Applewood Immigration & Settlement Services Incorporation has been successfully serving immigration clients since 1998. In this period, we have enjoyed tremendous growth, due to the value of quality of our services provided through the exceptional performance of our staff.
Canada will accept 330,000 new permanent residents in 2019. That number will grow to 340,000 in 2020, trending towards one percent of the population.
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Our President Mr. Izhar H. Zaidi, is a member of Immigration Consultants of Canada Regulatory Council (ICCRC), Canadian Association of Professional Immigration Consultants (CAPIC) and United Citizenship and Immigration Consultants Association (UCICA).
Please visit www.iccrc-crcic.ca by clicking on the link. His Membership ID # is R421959.
Interested in immigrating to Canada? Our instant "Comprehensive Ranking System (CRS)" Evaluation Too is available to assess your eligibility to apply for Canadian immigration in the Federal Skilled Worker category.
You will be asked few simple questions (your age, your education, your experience, your skills in English and or French, whether you have a valid job offer, your marital status and your adaptability). You will instantly get the score as you will get in the Express Entry Pool of IRCC.


text:
← Ethiopian Security Strategy: Upgrades Overdue
A Turkish attack on Afrin could spark a full-fledged war in Northern Syria →
Monitoring Economic Indicators from 500 Kilometers Up: Egyptian Oil and Gas Terminals
by Chris Biggers. This article was first published at Planet Stories.
Ain Sokhna Port, south of the Suez Canal. Image ©2017 Planet Labs, Inc. Left: Jun 2017 / Right: Feb 2016
From space, satellites monitor the movement of commodities that can affect the health of national economies.
In Egypt, they track Liquefied Petroleum Gas (LPG), one of Egypt's most important commodities. With a rapidly growing population — more than 89 million — it remains crucial to many of the country's domestic activities, particularly heating water and cooking. According to the World LPG Association, per capita consumption of the fuel is one of the highest in the world.
In the years following the Global Economic Crisis and the Arab Spring movement, access to fuel for cooking has proved challenging, but nonetheless continues to be a priority for the country. According to the World Bank, more than 75% of Egyptian households rely on LPG. The country consumes approximately 4.3 million tonnes of the fuel each year, of which 1.47 million tonnes is produced domestically while another 2.18 million tonnes is imported from abroad.
And more and more LPG may be making its way into Egypt from outside the country. At Planet, we've been observing the expansion of Egypt's oil and gas infrastructure at Ain Sokhna — a port located about 40 km south of Egypt's strategically important Suez canal. It's there, Planet's 3–5 meter resolution imaging satellites show Egypt in the process of building a third basin and expanding a liquid bulk terminal. The space snapshots show the erection of six new storage tanks to be associated with the expanded terminal which, upon completion, will hold additional LPG and gasoil. At the time of capture, the tanks were in various states of build.
Moreover, the port also happens to be home to Egypt's Floating Storage Regasification Units (FSRUs) which pump about 20 million m3 per day of foreign natural gas to feed Egypt's grid and commercial sector. They were chartered in 2015 for a five year period. In February, Egypt announced plans to push between 100 and 108 liquified natural gas (LNG) cargos through the terminals in 2017. Planet's high cadence imagery has already captured these vessels arriving alongside the FSRUs at the port.
In recent years, natural gas has become a competitor to LPG as Egypt has moved to connect additional households to the natural gas grid through a prior World Bank funded project. Accordingly, over 355,000 consumers have been connected to the gas grid in the Greater Cairo area, alone. Through the project, the state plans to connect about 1.5 million households in 11 of Egypt's 27 governorates. Most recently, France, an important partner in the region, pledged another 68 million euros to expand gas connections to 2.4 million households. However, overall progress has been slow.
Both imported LNG and LPG will likely be integral to reducing the magnitude of Egypt's energy security problems, especially until Zohr — a "super giant" gas field in the Mediterranean — begins production in earnest. Zohr is estimated to contain a reserve of approximately 850 billion m3 of natural gas. Eni, an Italian energy group which discovered the field in 2015, projects costs for development around $14 billion, a substantial sum given gas companies are reducing global expenditures.
Egypt LNG terminal near Idku. Captured June 15, 2017. Image ©2017 Planet Labs, Inc.
If all goes according to plan, Eni believes the field will produce 70 million m3 of gas per day by 2019. That gas may further support domestic consumption, further easing pressure on Egypt's energy demands — especially if more households are connected to the grid. However, depending on price, Egypt could restart significant exports and still use LPG as it continues to construct additional storage capacity and import infrastructure. If that occurs, Planet's imaging fleet stand ready to capture Egypt's LNG liquefaction terminals near Damietta and Idku.
As of 2017, Damietta's LNG terminal remains offline as Egypt sends more domestic gas production to the grid, a policy that's helped ease electricity shortages. The situation is unlikely to change in the short term as disputes persist around Egypt's decision to declare force majeure in 2014. However, as Zohr's production increases in 2018, we could see significantly more cargoes leaving from Idku. In 2016 for example, Planet's imagery captured 7 of the reported 9 cargoes at port while another 4 have already been observed in 2017.
In the meantime, despite returning GDP growth and an IMF-led economic reform program, the North African country remains under stress with high levels of unemployment, inflation, and increasing public debt. GDP numbers from the first quarter show a 1.7% decline compared to last year and consumption of LPG and other fuels remain taxing on the state's coffers. In the first half of FY 17, Egypt has already seen a $2.11 billion fuel subsidy bill, a jump of 46% over the same time last year. According to Egypt's Petroleum Minister, 50% of the subsidy is spent on diesel, 20% for LPG, 20% for gasoline, and another 10% for fuel oil and petroleum derivatives. Egypt's officials expect to spend more than $8 billion over FY17–18 for the bill.
Satellite Imagery Confirms Qatari Isolation Left: Planet imagery of Qatar's As Salwa Border Crossing dated 07JUN17 / Right: 05JUN17 As the diplomatic crisis between Qatar...
The Future of Election Monitoring in Southeast Asia by Paul Pryce. Paul Pryce is a Junior Research Fellow at the Atlantic Council of Canada. With degrees in political...
China's Liaoning Departs Qingdao China's aircraft carrier, the Liaoning, has departed its home port of Qingdao, recent imagery acquired by Planet confirms. China's Ministry...
North Korea Opens Russian Financed Wharf Satellite imagery acquired by DigitalGlobe shows the recently renovated wharf at North Korea's Rajin Port located on the east coast....
Stratfor – Economic Effects of a Syria Strike This video by Stratfor Vice President of Global Analysis Reva Bhalla examines the regional economic effect of a limited intervention...
This entry was posted in Chris B, Egypt, English, Intelligence.

redpajama_set_name: RedPajamaCommonCrawl


200 tests of the 6 key parameters. Integral test tube rack for ease of use.
200 tests of the 6 key parameters. Integral test tube rack for ease of use. The main factor in successful fish keeping lies in the maintenance of good water quality; pH, ammonia and nitrite levels in the aquarium should be checked regularly, weekly in a new aquarium and fortnightly in an established mature aquarium.
The NT Labs Aquarium Lab Multi-test Kit comprises over 200 tests of the 6 key parameters to test in your aquarium. Ammonia, Nitrite, Nitrate, pH, GH and KH. All the tests are liquid drop tests from a callobrated dropper bottle so all the drops are the same size. All you have to do is add your aquarium water to the test tube and count the drops needed, simple.
The back of the box details clear pictorial instructions so you can see what to do from the start. A booklet of colour coded stickers is provided to label both the test tubes and test tube lids so you always conduct the same test in the same test tube. The reason for this? Well for example the GH reagents may contaminate the test tube and could give you a false reading if you were to conduct an ammonia test in the same tube.


Brazil (officially the Federative Republic of Brazil (Portuguese: República Federativa do Brasil, About this sound listen , is the largest country in both South America and the Latin American region. It is the world's fifth-largest country, both by geographical area and by population. It is the largest Portuguese-speaking country in the world, and the only one in the Americas. Bounded by the Atlantic Ocean on the east, Brazil has a coastline of 7,491 km (4,655 mi).It borders all other South American countries except Ecuador and Chile and occupies 47.3 percent of the continent of South America. Its Amazon River basin includes a vast tropical forest, home to diverse wildlife, a variety of ecological systems, and extensive natural resources spanning numerous protected habitats. This unique environmental heritage makes Brazil one of 17 mega diverse countries, and is the subject of significant global interest and debate regarding deforestation and environmental protection.
Christ the Redeemer is the famous statue of Jesus Christ in Rio de Janeiro. Located at the peak of the 700 meters (2,300 ft) Corcovado mountain, it provides a sweeping panorama from the interior of Guanabara bay to the north, to Lagoa Rodrigo de Freitas to the south. The Christ the Redeemer statue stands 39.6 meters (130 ft) tall, including its 9.5 meters (31 ft) pedestal and has become an icon of Rio and Brazil.
One of the great natural wonders of the world, Iguaçu Falls is situated on the border between Brazil and Argentina. The waterfall system consists of 275 falls along the Iguazu River. The most impressive of them all is the Devil's Throat a U-shaped with a height of 82 meter (269 ft). The falls can be reached from the cities Foz do Iguaçu in Brazil and Puerto Iguazú in Argentina, as well as from Ciudad del Este in Paraguay. On the Brazilian side there is a long walkway along the canyon with an extension to the lower base of the Devil's Throat.
At approximately 6,400 km (4,000 miles) the Amazon River is the second longest river in the world, just slightly shorter than the Nile, and the largest river by volume. The Amazon has over 3,000 recognized species of fish and new species are still being discovered. The Amazon Basin is covered by half of the planet's remaining rainforests. Although a tenth of the world's estimated 10 million living species live in the Amazon rainforest, jungle tours are more about the boating upriver into the damp, buzzing, oppressive ambience than actually spotting animals.


text:
Information Technology Acts Paper
Submitted By sarabelle08
Sara Murphy
BIS/220 Introduction to Computer Application and Systems
Instructor V. Wade
Information Technology Acts Paper As technology continuously advances, basic human privacy diminishes. People input personal information on various websites and willingly give out identifiers to random people. Unfortunately, much of this information gets collected and sold, bringing on unwanted contact from solicitors. In turn, the government keeps creating new Acts to at least lessen the solicitation. Two such acts are the Do Not Call Implementation Act of 2003 and the Controlling the Assault of Non-solicited Pornography and Marketing (CAN-SPAM) Ac of 2003.	Telemarketing is generally considered a nuisance, especially when the telemarketers call multiple times a day or become rude. In 2003, the Do Not Call Implementation Act was signed into law by President George W. Bush. The law was put in effect in order to give the people of the United States an opportunity to limit the amount of telemarketing calls they receive. According to Tauzin, some telemarketing practices can be intrusive, invasive of privacy, and can confuse consumers (2003). Tauzin also states that some telemarketers have been known to take advantage of confused consumers and commit fraud (2003). The Federal Trade Commission (FTC) also reports over a one-thousand percent increase in unwanted telemarketing calls between 1998 and 2002 (Tauzin, 2003). With the employment of the Do Not Call Implementation Act, people are able to put their phone numbers on the National Do Not Call Registry, thereby allowing them to avoid the majority of unwanted telemarketing calls. If one has an email, chances are their SPAM folder fills up fairly quickly, with not an idea of how so many sources got their email address. President Bush signed the Controlling the Assault of Non-solicited Pornography and Marketing (CAN-SPAM) Act into effect in 2003. According to 15 U.S. Code & 7701 – Congressional findings and policy, Congress found that unsolicited emails account for more than half of all electronic mail sent, which was an estimated seven percent increase from 2001 (2003). Congress also found that much of the material contained vulgar or pornographic material. The SPAM also contains misleading information, which can be confusing for consumers. The implementation of the CAN-SPAM Act, however, is supposed to aid in lessening the amount of…
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I was not physically at the location where the job was done but I dealt with Donna over the phone and she was very helpful and made me feel comfortable that the job would get done properly. Thank you!


titleist 915 driver australia Maybe not next month at Quail Hollow, but he'll get one. At least one. He'll slap it all over Bethpage (2019) or Harding Park (2020), get up and down for birdie from behind a tree, make some 30-footers and drive fellow competitors bonkers with his fortuitous breaks.
http://www.lowpricegolfaus.com/Callawa....49.html Woods had a real chance, but Spieth isn't Tiger Woods. And, on top of that, the equipment is so good, even golfers outside the top 200 can be a contender on the right week. (Pour one out for Y.E. Yang and Michael Campbell.) The obstacles are too many.
titleist 915 d2 driver australia It seems foolish to put a number on how many majors Spieth might be able to win. Eventually, he'll probably get married and potentially have a family, and with that, a whole new set of priorities and challenges will arise.


As with the surrounding suburbs in the western Cook County, the local residents can count on us when it comes to reliable flood prevention.
Once known as Grossdale, a suburban community of nearly 20 thousand, and the location of the famous Brookfield Zoo. Brookfield is a nice place to live or visit, with an easy and close connection with the city of Chicago. Before 1803 this area was mostly covered by prairie grasses, forests and farms. The first settlement in the Village dates back to 1889 by Samuel Eberly Gross, a Chicago lawyer turned real estate agent. At this time Mr. Gross began investing in the land and offered a suburban lifestyle that was affordable for working-class families. In 1952 Brookfield received the All-American City award from the National Municipal League and LOOK magazine.
On July 24th, 2010 however, it was reported the village was hit with around 7 inches of rain in a period of 24 hours. Several residents woke up to see their basements flooded with storm or storm and sewer water, and some of their neighborhood streets covered with several inches of water. Some areas near Salt Creek were reportedly suffered the most damage. Parks' would be happy to come out and give residents a free estimate for our Double Guard Valve Flood Control.
Brookfield does not currently offer any shared cost or reimbursement programs for residents.


Feeling a little homesick? Are you far away from your home, hometown, or, in extreme cases, home planet? Use an old real estate agent's trick and bake up some fresh Chocolate Chip Cookies! That sweet, dense smell will waft through your nose, bringing memories of rainy days by the fireplace, after-school milk-dunking moments, and all the delightful joy of being somewhere warm and comfy! Anywhere you take a Chocolate Chip Cookie is a bit like home! 15 squishy inches of home sweet home, polyester fiber, ages 3 and up!


Are you even aware that duality exists?
This might sound silly to ask such a question in this day and age, but many people still live primarily all their life in make believe, so it's totally possible that they haven't even observed that the physical world is dual.
By duality, I mean that everything is broken up into two parts by the mind. It cannot be any other way or else the physical world would not exist. Things such as life and death, good and bad, happy and sad, self and other, all are aspects of the same thing. This can be seen if you take the time to observe life from outside of the mind.
This could be a super powerful realization for you to have, but it must be experienced and not just thought up, because knowing it through conceptualizations won't do much as that's how you know it now.
When you start touching unity (detaching from your mind self), you finally start seeing that most people, including you get deluded by their mind into thinking that somehow they can escape the other aspect of what they are seeking. Duality cannot be escaped when trapped in the mind, and if you continue to seek just the one aspect, you will suffer every time when the thing that you have been seeking transforms into it's other half.
The key is to start accepting that the physical world is indeed dual and only then the mind will not be able to continually fool you, that if you go towards one side of the coin you somehow will be able to avoid the other. I am not saying to give up playing this game of teeter totter either, I am just saying be aware that you are playing this game and it will always be this way when you are living from the mind self.
One must truly spend a good amount of time contemplating this subject and learning to dis-identify from the mind realm to get this, or otherwise you will just know it intellectually and that is still a mind thing.
If this is something that you would like to pursue, then a meditation practice is vital. You don't have to become a mystical yogi that lives in the woods, just 5 minutes a day to start will get you moving in the right direction. When unity is experienced directly, the way you view the world will change drastically, because no longer will you see fragments everywhere as are seen through the mind.


He was also a noted solo artist. regala un corso di cucina milano juni 2006 in san gran premio del canada 2008 francisco, kalifornien) war ein us-amerikanischer keyboarder. i am the blues: dixon, willie (1992) concert posters and music memorabilia. 12-22-02 – duration: seinen ersten auftritt bei …. the willie dixon story. februar 1951 in phoenix, arizona; † 2. he had regalo di natale perfetto per la mamma five good years with the band. the hobbit premiere 2018 rest in peace when vince welnick signed on to play keyboards for the grateful dead, some people said it vince welnick grave probably saved his life. 1,750 likes · 4 vince welnick grave svendita poste italiane talking about this. johnnie johnson. vince welnick.


While the Mid-Atlantic has been getting pummeled with inches upon inches of snow, we've been sitting up in Southern Maine with hardly a flake insight. Amazingly it is February and there is more grass to be seen than piels of snow. I'm sure we'll get hit with a doozy of a storm as soon as I post this, but in the meantime, Mr. Cleaver and I have been taking advantage of this February Sunshine.
Last weekend we took my first trip to the Maine Audubon sanctuary in Falmouth. In the past, Mr. Cleaver has gone to the sanctuary to cross-country ski, but we just wandered the trails, holding hands.
It was still cold and breezy, but the sun was so nice we sat on the ground and soaked it in.
I didn't think it possible, but this weekend was even nicer - so we went to the beach.
We picked up pizza and pier fries at Lisa's Pizza and took a walk along the shore at Old Orchard Beach - one of those places that is crawling with tourists in the summer, but lovely and quiet in the winter.
We're currently at a 50% chance of snow for Tuesday, but in a Maine winter, you take what sunny days you can.


text:
Q: How to manage `maxLength` of `textfield` with two dependent fileds in `extjs` How to set maxLength of two dependent fields in one textfield?
get_input_field: function (target_field, name) {
    return ({
        xtype: "textfield",
        name: name,
        width: 100,
        autoCreate: {
            tag: "input",
            maxLength: 10,
            type: "text",
            size: "20",
            autoComplete: "off"
        },
        value: this[name],
        listeners: this.get_listeners(target_field)

    })
}

the dependent fields are:
 this.get_input_field("dependentField1", "upperValue")
 this.get_input_field("dependentField2", "lowerValue")

Please help me how to fix maxLength based on these two fields.
Thanks in advance.

redpajama_set_name: RedPajamaStackExchange


With the greatest difficulty, the Captain contrived to regain the Ship, when, without losing a moment of time, he ordered the long boat to be launched and that care should be taken to prevent a similar accident to that which had just befallen them, by two [sic] many endeavouring to force their way into her. After having taken the utmost caution, the long boat was at length pushed off; but scarcely had they got away from the Ship, when she was upset by the violence of the surf, and the whole party precipitated into the sea.
The master and the chief mate, being good swimmers once more succeeded in saving themselves from the death which appeared to be inevitable. With extreme difficulty they managed to reach the ship, but scarcely had they got on board, when a new horror awaited them. The vessel went to pieces, and every hope of preservation vanished like an unsubstantial dream.
The scene at this moment was most awful. The vessel had been divided into four parts, each of which,, was covered with the terror-stricken females in the light dress in which they had just before simultaneously rushed from their beds; clingly wildly to parts of the wreck, and screaming for help in the most piteous manner. This was, indeed, a moment of terror, which would have appalled even the boldest. Situated as they were, upon a frail and shaking wreck, not one gleam of hope broke in to cheer or inspire them. Beneath, and all around, were the lashing waves, roaring aloud as if eager to engulf them. Every plank and joint creaked as the contending elements warred furiously with each other, and insecure as this place of refuge seemed, the hearts of the poor creatures quailed lest it should sink and bury them in the yawning abyss of water.  The vessel soon afterwards went to pieces, the final work of destruction was complete, and the whole of those on board were precipitated, shrieking with horror, into the raging ocean.
In this perilous situation, nearly the whole of the unfortunate sufferers were consigned to an untimely death. About 22 persons, however, consisting of some of the crew and 5 passengers were carried, by clinging to various disjointed portions of the wreck, to a small uninhabited Island, which was situated at the distance of about 9 miles from the spot where this distressing accident took place. Of these 22 suffering creatures seven shortly afterwards died, from exhaustion and the fatigue to which they had for so long a period been subjected.
After having buried the bodies of their unfortunate companions, and in some degree, recovered from the cold and fatigue they had endured, the remaining 15 succeeded in erecting a temporary tent of the few things that were occasionally washed ashore from the wreck. In this dreadful situation they were not suffered to perish, a few provisions were washed ashore from the vessel, and upon the scanty supply thus afforded, they contrived with economy to subsist for about 15 days.
During this time they had employed themselves in constructing, from the numerous portions of the wreck which were found washed ashore, a raft, on which they hoped to make their escape to King's Island, which they supposed to be about 150 miles distant. Actuated by curiosity, and a desire to ascertain whether any more of the crew had escaped, 5 of the survivors commenced a journey round the Island, in order to satisfy themselves; they encountered perils and fatigue of no ordinary kind, and after a search of 4 days, returned to their fellow victims of adversity.
The crew of the Tartar had been accompanied by a sealer, a passenger in that vessel, who had luckily saved several of his hunting dogs. With the assistance of these sagacious animals they soon succeeded in taking a wallaby, upon which the persons on the Island lived. Whilst some of the party were employed to see if any vessel passed, others were engaged in erecting tents for their shelter from the inclement season, which had just set in, in those latitudes.
The sufferings to which these poor creatures were subjected, it would be impossible to describe. Thoughts of home and distant friends were ever flitting through their minds. They remembered the happiness that had once been theirs, and contrasting it with the misery to which they were at present doomed, despair at last yielded to the hopes they had once formed of escaping from the wretched situation in which their lot was cast, and they wished that the raging elements which had destroyed so many of their companions, had involved them in the same dreadful fate.
At last on the 15th of June, exactly 1 month from the time of the wreck taken place, they left this inhospitable Island, and committed themselves to the dangers of the deep on the fragile raft they had constructed, when awful to relate, fresh, and more horrible disasters awaited them. In 3 days their whole stock of provisions were exhausted - 2 days passed without tasting a morsel. What followed next? Nothing, but what devouring famine could have suggested. It was agreed that one should die to support the rest, and they accordingly cast lots; the first lot fell upon Patrick Lidane, who requested, that for their immediate subsistance, they would only take the calves of his legs; representing that Providence might do more for them than they expected. His request was granted, and after cutting away the flesh, which they eat raw, and of which he begged a morsel for himself, but was refused, he was permitted to live 30 hours. The second person who suffered was Brian Flaherty. Of these two bodies which were eaten raw, without any drink, but what rain-water they could catch in the skulls of the killed, the rest subsisted. In this interval, three of them who had escaped the lot, after languishing for a considerable time, expired on the raft.
On the following morning 8 others in despair jumped into the sea. Next morning the raft was descried by some persons on King's Island, who had them conveyed on shore, and although the greatest care was extended to the two unfortunate survivors, the Captain died in 30 hours after.
John M'Daniel, the only person saved of the ill-fated crew, as soon as he was able to travel, made the best of his way home to Galway, to fulfil the dying injunctions of the men who fell by lot, and relate to their friends their miserable sufferings and sad catastrophe.


text:
The domain within your query sequence starts at position 352 and ends at position 434; the E-value for the SH2 domain shown below is 7.33e-26.
KTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGF
AEPYNLYSSLKELVLHYQHTSLV
Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.
The Src homology 2 (SH2) domain is a protein domain of about 100 amino-acid residues first identified as a conserved sequence region between the oncoproteins Src and Fps [ (PUBMED:3025655) ]. Similar sequences were later found in many other intracellular signal-transducing proteins [ (PUBMED:1377638) ]. SH2 domains function as regulatory modules of intracellular signalling cascades by interacting with high affinity to phosphotyrosine-containing target peptides in a sequence-specific, SH2 domains recognise between 3-6 residues C-terminal to the phosphorylated tyrosine in a fashion that differs from one SH2 domain to another, and strictly phosphorylation-dependent manner [ (PUBMED:7883800) (PUBMED:15335710) (PUBMED:14731533) (PUBMED:7531822) ]. They are found in a wide variety of protein contexts e.g., in association with catalytic domains of phospholipase Cy (PLCy) and the non-receptor protein tyrosine kinases; within structural proteins such as fodrin and tensin; and in a group of small adaptor molecules, i.e Crk and Nck. The domains are frequently found as repeats in a single protein sequence and will then often bind both mono- and di-phosphorylated substrates.
The structure of the SH2 domain belongs to the alpha+beta class, its overall shape forming a compact flattened hemisphere. The core structural elements comprise a central hydrophobic anti-parallel beta-sheet, flanked by 2 short alpha-helices. The loop between strands 2 and 3 provides many of the binding interactions with the phosphate group of its phosphopeptide ligand, and is hence designated the phosphate binding loop, the phosphorylated ligand binds perpendicular to the beta-sheet and typically interacts with the phosphate binding loop and a hydrophobic binding pocket that interacts with a pY+3 side chain. The N- and C-termini of the domain are close together in space and on the opposite face from the phosphopeptide binding surface and it has been speculated that this has facilitated their integration into surface-exposed regions of host proteins [ (PUBMED:11911873) ].
There are 58927 SH2 domains in 53279 proteins in SMART's nrdb database.
Binding / catalysis: phosphotyrosine-containing peptide-binding
Mandiyan V, Andreev J, Schlessinger J, Hubbard SR
Crystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-associated protein beta.
ADP ribosylation factors (ARFs), which are members of the Ras superfamily of GTP-binding proteins, are critical components of vesicular trafficking pathways in eukaryotes. Like Ras, ARFs are active in their GTP-bound form, and their duration of activity is controlled by GTPase-activating proteins (GAPs), which assist ARFs in hydrolyzing GTP to GDP. PAPbeta, a protein that binds to and is phosphorylated by the non-receptor tyrosine kinase PYK2, contains several modular signaling domains including a pleckstrin homology domain, an SH3 domain, ankyrin repeats and an ARF-GAP domain. Sequences of ARF-GAP domains show no recognizable similarity to those of other GAPs, and contain a characteristic Cys-X(2)-Cys-X(16-17)-Cys-X(2)-Cys motif. The crystal structure of the PAPbeta ARF-GAP domain and the C-terminal ankyrin repeats has been determined at 2.1 A resolution. The ARF-GAP domain comprises a central three-stranded beta-sheet flanked by five alpha-helices, with a Zn(2+) ion coordinated by the four cysteines of the cysteine-rich motif. Four ankyrin repeats are also present, the first two of which form an extensive interface with the ARF-GAP domain. An invariant arginine and several nearby hydrophobic residues are solvent exposed and are predicted to be the site of interaction with ARFs. Site-directed mutagenesis of these residues confirms their importance in ARF-GAP activity.
Smalla M et al.
Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.
Protein Sci. 1999; 8: 1954-61
The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize and to mediate specific protein-protein interactions. A highly conserved subclass of SAM domains is present at the intracellular C-terminus of more than 40 Eph receptor tyrosine kinases that are involved in the control of axonal pathfinding upon ephrin-induced oligomerization and activation in the event of cell-cell contacts. These SAM domains appear to participate in downstream signaling events via interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor SAM domain and studied its association behavior. The structure consists of five helices forming a compact structure without binding pockets or exposed conserved aromatic residues. Concentration-dependent chemical shift changes of NMR signals reveal two distinct well-separated areas on the domains' surface sensitive to the formation of homotypic oligomers in solution. These findings are supported by analytical ultracentrifugation studies. The conserved Tyr932, which was reported to be essential for the interaction with SH2 domains after phosphorylation, is buried in the hydrophobic core of the structure. The weak capability of the isolated EphB2 receptor SAM domain to form oligomers is supposed to be relevant in vivo when the driving force of ligand binding induces receptor oligomerization. A formation of SAM tetramers is thought to provide an appropriate contact area for the binding of a low-molecular-weight phosphotyrosine phosphatase and to initiate further downstream responses.
Stapleton D, Balan I, Pawson T, Sicheri F
The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.
Nat Struct Biol. 1999; 6: 44-9
The sterile alpha motif (SAM) domain is a novel protein module of approximately 70 amino acids that is found in a variety of signaling molecules including tyrosine and serine/threonine protein kinases, cytoplasmic scaffolding and adaptor proteins, regulators of lipid metabolism, and GTPases as well as members of the ETS family of transcription factors. The SAM domain can potentially function as a protein interaction module through the ability to homo- and hetero-oligomerize with other SAM domains. This functional property elicits the oncogenic activation of chimeric proteins arising from translocation of the SAM domain of TEL to coding regions of the betaPDGF receptor, Abl, JAK2 protein kinase and the AML1 transcription factor. Here we describe the 2.0 A X-ray crystal structure of a SAM domain homodimer from the intracellular region of the EphA4 receptor tyrosine kinase. The structure reveals a mode of dimerization that we predict is shared amongst the SAM domains of the Eph receptor tyrosine kinases and possibly other SAM domain containing proteins. These data indicate a mechanism through which an independently folding protein module can form homophilic complexes that regulate signaling events at the membrane and in the nucleus.
Thanos CD, Goodwill KE, Bowie JU
Oligomeric structure of the human EphB2 receptor SAM domain.
The sterile alpha motif (SAM) domain is a protein interaction module that is present in diverse signal-transducing proteins. SAM domains are known to form homo- and hetero-oligomers. The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one interface, adjacent monomers exchange amino-terminal peptides that insert into a hydrophobic groove on each neighbor. A second interface is composed of the carboxyl-terminal helix and a nearby loop. A possible oligomer, constructed from a combination of these binding modes, may provide a platform for the formation of larger protein complexes.
Whisstock JC, Lesk AM
SH3 domains in prokaryotes.
Trends Biochem Sci. 1999; 24: 132-3
Barford D, Neel BG
Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2.
Structure. 1998; 6: 249-54
The crystal structure of the protein tyrosine phosphatase SHP-2 reveals the mechanism of auto-inhibition of phosphatase activity by its SH2 domains. Phosphotyrosine peptide stimulation of the phosphatase activity, resulting from peptide binding to the N-terminal SH2 domain, is linked to conformational changes within the protein, including an unprecedented allosteric transition of the N-terminal SH2 domain.
Sticht H, Pickford AR, Potts JR, Campbell ID
Solution structure of the glycosylated second type 2 module of fibronectin.
Fibronectin is an extracellular matrix glycoprotein that plays a role in a number of physiological processes involving cell adhesion and migration. The modules of the fibronectin monomer are organized into proteolytically resistant domains that in isolation retain their affinity for various ligands. The tertiary structure of the glycosylated second type 2 module (2F2) from the gelatin-binding domain of fibronectin was determined by two-dimensional nuclear magnetic resonance spectroscopy and simulated annealing. The structure is well defined with an overall fold typical of F2 modules, showing two double-stranded antiparallel beta-sheets and a partially solvent-exposed hydrophobic cluster. An N-terminal beta-sheet, that was not present in previously determined F2 module structures, may be important for defining the relative orientation of adjacent F2 modules in fibronectin. This is the first three-dimensional structure of a glycosylated module of fibronectin, and provides insight into the possible role of the glycosylation in protein stability, protease resistance and modulation of collagen binding. Based on the structures of the isolated modules, models for the 1F22F2 pair were generated by randomly changing the orientation of the linker peptide between the modules. The models suggest that the two putative collagen binding sites in the pair form discrete binding sites, rather than combining to form a single binding site.
Williams JC, Wierenga RK, Saraste M
Insights into Src kinase functions: structural comparisons.
Trends Biochem Sci. 1998; 23: 179-84
Recent structures of Src tyrosine kinases reveal complex mechanisms for regulation of enzymatic activity. The regulatory SH3 and SH2 domains bind to the back of the catalytic kinase domain via a linker region that joins the SH2 domain to the catalytic domain. Members of a subgroup of the Src kinase family show distinct features in this linker and in the loops that interact with it. Hydrophobicity of key residues in this region is important for intramolecular regulation. The kinases Abl, Btk and Csk seem to have the same molecular architecture as Src. Structural comparisons between serine/threonine and tyrosine kinases indicate a specific twisting mechanism involving the N- and C-terminal lobes of the catalytic domain. This motion could provide insights into the various mechanisms used to regulate kinase activity.
Carugo KD, Banuelos S, Saraste M
Crystal structure of a calponin homology domain.
Nat Struct Biol. 1997; 4: 175-9
The three-dimensional structure of the calponin homology domain present in many actin binding cytoskeletal and signal-transducing proteins has been determined at 2.0 A resolution.
Konrat R, Weiskirchen R, Krautler B, Bister K
Solution structure of the carboxyl-terminal LIM domain from quail cysteine-rich protein CRP2.
Proteins of the cysteine-rich protein (CRP) family (CRP1, CRP2, and CRP3) are implicated in diverse processes linked to cellular differentiation and growth control. CRP proteins contain two LIM domains, each formed by two zinc-binding modules of the CCHC and CCCC type, respectively. The solution structure of the carboxyl-terminal LIM domain (LIM2) from recombinant quail CRP2 was determined by multidimensional homo- and heteronuclear magnetic resonance spectroscopy. The folding topology retains both independent zinc binding modules (CCHC and CCCC). Each module consists of two orthogonally arranged antiparallel beta-sheets, and the carboxyl-terminal CCCC module is terminated by an alpha-helix. 15N magnetic relaxation data indicate that the modules differ in terms of conformational flexibility. They pack together via a hydrophobic core region. In addition, Arg122 in the CCHC module and Glu155 in the CCCC module are linked by an intermodular hydrogen bond and/or salt bridge. These residues are absolutely conserved in the CRP family of LIM proteins, and their interaction might contribute to the relative orientation of the two zinc-binding modules in CRP LIM2 domains. The global fold of quail CRP2 LIM2 is very similar to that of the carboxyl-terminal LIM domain of the related but functionally distinct CRP family member CRP1, analyzed recently. The carboxyl-terminal CCCC module is structurally related to the DNA-binding domain of the erythroid transcription factor GATA-1. In the two zinc-binding modules of quail CRP2 LIM2, flexible loop regions made up of conserved amino acid residues are located on the same side of the LIM2 domain and may cooperate in macromolecular recognition.
Liepinsh E, Ilag LL, Otting G, Ibanez CF
NMR structure of the death domain of the p75 neurotrophin receptor.
EMBO J. 1997; 16: 4999-5005
The intracellular domain of the p75 neurotrophin receptor (p75ICD) lacks catalytic activity but contains a motif similar to death domains found in the cytoplasmic regions of members of the tumor necrosis factor receptor family and their downstream targets. Although some aspects of the signaling pathways downstream of p75 have been elucidated recently, mechanisms of receptor activation and proximal signaling events are unknown. Here we report the nuclear magnetic resonance (NMR) structure of the 145 residue long p75ICD. The death domain of p75ICD consists of two perpendicular sets of three helices packed into a globular structure. The polypeptide segment connecting the transmembrane and death domains as well as the serine/threonine-rich C-terminal end are highly flexible in p75ICD. Unlike the death domains involved in signaling by the TNF receptor and Fas, p75ICD does not self-associate in solution. A surface area devoid of charged residues in the p75ICD death domain may indicate a potential site of interaction with downstream targets.
Zhang ZY
Structure, mechanism, and specificity of protein-tyrosine phosphatases.
Curr Top Cell Regul. 1997; 35: 21-68
Worthington MT, Amann BT, Nathans D, Berg JM
Metal binding properties and secondary structure of the zinc-binding domain of Nup475.
Nup475 is a nuclear zinc-binding protein of unknown function that is induced in mammalian cells by growth factor mitogens. Nup475 contains two tandemly repeated sequences YKTELCX8CX5CX3H (Cys3His repeats) that are thought to be zinc-bindin domains. Similar sequences have been found in a number of proteins from various species of eukaryotes. To determine the metal binding properties and secondary structure of the putative zinc-binding domains of Nup475, we have used synthetic or recombinant peptides that contain one or two domain sequences. The peptide with a single domain bound 1.0 +/- 0.1 equivalents of Co2+, and the peptide with two domains bound 1.7 +/- 0.4 equivalents of Co2+. Both peptides bound Co2+ and Zn2+ with affinities similar to those of classical zinc finger peptides. In each case, the Co2+ complex exhibited strong d-d transitions characteristic of tetrahedral coordination. For structural studies by nuclear magnetic resonance spectroscopy, we used a more soluble two-domain peptide that had a single amino acid substitution in a nonconserved amino acid residue in the second Cys3His repeat. The mutant peptide unexpectedly showed loss of one of its metal binding sites and displayed ordered structure for only the first Cys3His sequence. On the basis of the nuclear magnetic resonance data, we propose a structure for the Nup475 metal-binding domain in which the zinc ion is coordinated by the conserved cysteines and histidine, and the conserved YKTEL motif forms a parallel sheet-like structure with the C terminus of this domain. This structure is unlike that of any previously described class of metal binding domain.
Bork P, Margolis B
A phosphotyrosine interaction domain.
Cell. 1995; 80: 693-4
Jia Z, Barford D, Flint AJ, Tonks NK
Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B.
The crystal structures of a cysteine-215-->serine mutant of protein tyrosine phosphatase 1B complexed with high-affinity peptide substrates corresponding to an autophosphorylation site of the epidermal growth factor receptor were determined. Peptide binding to the protein phosphatase was accompanied by a conformational change of a surface loop that created a phosphotyrosine recognition pocket and induced a catalytically competent form of the enzyme. The phosphotyrosine side chain is buried within the period and anchors the peptide substrate to its binding site. Hydrogen bonds between peptide main-chain atoms and the protein contribute to binding affinity, and specific interactions of acidic residues of the peptide with basic residues on the surface of the enzyme confer sequence specificity.
Kavanaugh WM, Turck CW, Williams LT
PTB domain binding to signaling proteins through a sequence motif containing phosphotyrosine.
Src homology 2 (SH2) domains mediate assembly of signaling complexes by binding specifically to tyrosine-phosphorylated proteins. A phosphotyrosine binding (PTB) domain has been identified which also binds specifically to tyrosine-phosphorylated targets, but is structurally different from SH2 domains. Expression cloning was used to identify targets of PTB domains. PTB domains bound to phosphotyrosine within a sequence motif, asparagine-X1-X2-phosphotyrosine (where X represents any amino acid), that is found in many signaling proteins and is not recognized by SH2 domains. Mutational studies indicated that high affinity binding of PTB domains may require a specific conformation of the motif.
Ponting CP
SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins.
Single copies of an approximately 65-70 residue domain are shown to be present in the sequences of 14 eukaryotic proteins, including yeast byr2, STE11, ste4, and STE50, which are essential participants in sexual differentiation. This domain, named SAM (sterile alpha motif), appears to participate in other developmental processes because it is also present in Drosophila polyhomeotic gene product and related homologues, which are thought to regulate determination of segmental specification in early embryogenesis. Its appearance in byr2 and STE11, which are MEK kinases, and in proteins containing pleckstrain homology, src homology 3, and discs-large homologous region domains, suggests possible participation in signal transduction pathways.
vanderGeer P, Pawson T
The PTB domain: a new protein module implicated in signal transduction.
Src homology 2 (SH2) domains have been identified in a large number of proteins involved in signal transduction downstream of receptor tyrosine kinases. They allow cytoplasmic signalling proteins to bind specifically to other polypeptides that are phosphorylated on tyrosine in response to growth factor stimulation. A novel phosphotyrosine-binding (PTB) domain has been identified recently in the amino terminus of Shc, an adaptor molecule that appears to be involved in Ras activation PTB domains are longer than SH2 domains, and recognize phosphotyrosine in the context of amino-terminal residues, in contrast to SH2 domains, which recognize them in the context of carboxy-terminal residues.
Xiao B et al.
Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways.
A broad range of organisms and tissues contain 14-3-3 proteins, which have been associated with many diverse functions including critical roles in signal transduction pathways, exocytosis and cell cycle regulation. We report here the crystal structure of the human T-cell 14-3-3 isoform (tau) dimer at 2.6 A resolution. Each monomer (Mr 28K) is composed of an unusual arrangement of nine antiparallel alpha-helices organized as two structural domains. The dimer creates a large, negatively charged channel approximately 35 A broad, 35 A wide and 20 A deep. Overall, invariant residues line the interior of this channel whereas the more variable residues are distributed on the outer surface. At the base of this channel is a 16-residue segment of 14-3-3 which has been implicated in the binding of 14-3-3 to protein kinase C.
Zhou MM et al.
Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.
Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor.
She is a widely expressed adapter protein that plays an important role in signaling via a variety of cell surface receptors and has been implicated in coupling the stimulation of growth factor, cytokine, and antigen receptors to the Ras signaling pathway. She interacts with several tyrosine-phosphorylated receptors through its C-terminal SH2 domain, and one of the mechanisms of T-cell receptor-mediated Ras activation involves the interaction of the Shc SH2 domain with the tyrosine-phosphorylated zeta chain of the T-cell receptor. Here we describe a high-resolution NMR structure of the Shc SH2 domain complexed to a phosphopeptide (GHDGLpYQGLSTATK) corresponding to a portion of the zeta chain of the T-cell receptor. Although the overall architecture of the protein is similar to other SH2 domains, distinct structural differences were observed in the smaller beta-sheet, BG loop, (pY + 3) phosphopeptide-binding site, and relative position of the bound phosphopeptide.
Barford D, Flint AJ, Tonks NK
Crystal structure of human protein tyrosine phosphatase 1B.
Science. 1994; 263: 1397-404
Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of phosphotyrosine residues and are characterized by homologous catalytic domains. The crystal structure of a representative member of this family, the 37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 A resolution. The enzyme consists of a single domain with the catalytic site located at the base of a shallow cleft. The phosphate recognition site is created from a loop that is located at the amino-terminus of an alpha helix. This site is formed from an 11-residue sequence motif that is diagnostic of PTPs and the dual specificity phosphatases, and that contains the catalytically essential cysteine and arginine residues. The position of the invariant cysteine residue within the phosphate binding site is consistent with its role as a nucleophile in the catalytic reaction. The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.
Carr MD, Bauer CJ, Gradwell MJ, Feeney J
Solution structure of a trefoil-motif-containing cell growth factor, porcine spasmolytic protein.
Proc Natl Acad Sci U S A. 1994; 91: 2206-10
The porcine spasmolytic protein (pSP) is a 106-residue cell growth factor that typifies a family of eukaryotic proteins that contain at least one copy of an approximately 40-amino acid protein domain known as the trefoil motif. In fact, pSP contains two highly homologous trefoil domains. We have determined the complete three-dimensional solution structure of pSP by using a combination of two- and three-dimensional 1H NMR spectroscopy and distance geometry calculations. pSP is a relatively elongated molecule, consisting of two compact globular domains joined via a small interface. The protein's two trefoil domains adopt the same tertiary structure and contain a core C-terminal two-stranded antiparallel beta-sheet, preceded by a 6-residue helix that packs against the N-terminal beta-strand. The remainder of the protein backbone is taken up by two short loops that lie on either side of the beta-hairpin and are linked by an extended region that wraps around the C-terminal beta-strand. The topology of the protein backbone observed for the trefoil domains in pSP represents an unusual polypeptide fold. A striking feature of both trefoil domains is a surface patch formed from five conserved residues that have no obvious structural role. The two patches are located at the far ends of the protein molecule, and we propose that these residues form at least part of the receptor binding site, or sites, on pSP.
Kavanaugh WM, Williams LT
An alternative to SH2 domains for binding tyrosine-phosphorylated proteins.
Src homology 2 (SH2) domains bind specifically to tyrosine-phosphorylated proteins that participate in signaling by growth factors and oncogenes. A protein domain was identified that bound specifically to the tyrosine-phosphorylated form of its target protein but differs from known SH2 sequences. Phosphotyrosine-binding (PTB) domains were found in two proteins: SHC, a protein implicated in signaling through Ras; and SCK, encoded by a previously uncharacterized gene. The PTB domain of SHC specifically bound to a tyrosine-phosphorylated 145-kilodalton protein. PTB domains are an alternative to SH2 domains for specifically recruiting tyrosine-phosphorylated proteins into signaling complexes and are likely to take part in signaling by many growth factors.
Lee CH et al.
Crystal structures of peptide complexes of the amino-terminal SH2 domain of the Syp tyrosine phosphatase.
BACKGROUND: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a sequence-specific manner, and thereby couple tyrosine phosphorylation to changes in the localization or catalytic activity of signal transducing molecules. Current understanding of SH2 specificity is based on the structures of SH2-peptide complexes of the closely-related Src and Lck tyrosine kinases. The tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent from those of the tyrosine kinases, with distinct target specificities, and is thus well suited for structural studies aimed at extending our understanding of SH2 specificity. RESULTS: Crystal structures of the amino-terminal SH2 domain of Syp in separate complexes with two high-affinity peptides, in complex with a non-specific peptide and in the uncomplexed form have been determined at between 2 A and 3 A resolution. The structure of the SH2 domain and the mode of high-affinity peptide binding is essentially similar to that seen in the Src and Lck structures. However, the binding interface is more extensive in Syp. CONCLUSIONS: Most SH2 targets have hydrophobic residues at the third position following the phosphotyrosine, and the Syp structure confirms that the peptide is anchored to the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp structure has revealed that sequence specificity can extend across the five residues following the phosphotyrosine, and has shown how the SH2 domain's surface topography can be altered with resulting changes in specificity, while conserving the structure of the central core of the domain.
Pascal SM et al.
Nuclear magnetic resonance structure of an SH2 domain of phospholipase C-gamma 1 complexed with a high affinity binding peptide.
The solution structure of the C-terminal SH2 domain of phospholipase C-gamma 1 (PLC-gamma 1), in complex with a phosphopeptide corresponding to its Tyr-1021 high affinity binding site on the platelet-derived growth factor receptor, has been determined by nuclear magnetic resonance spectroscopy. The topology of the SH2-phosphopeptide complex is similar to previously reported Src and Lck SH2 complexes. However, the binding site for residues C-terminal to the phosphotyrosine (pTyr) is an extended groove that contacts peptide residues at the +1 to +6 positions relative to the pTyr. This striking difference from Src and Lck reflects the fact that the PLC-gamma 1 complex involves binding of a phosphopeptide with predominantly hydrophobic residues C-terminal to the pTyr and therefore serves as a prototype for a second class of SH2-phosphopeptide interactions.
Yoon HS, Hajduk PJ, Petros AM, Olejniczak ET, Meadows RP, Fesik SW
Solution structure of a pleckstrin-homology domain.
Pleckstrin, the major protein kinase C substrate of platelets, contains domains of about 100 amino acids at the amino and carboxy termini that have been found in a number of proteins, including serine/threonine kinases, GTPase-activating proteins, phospholipases and cytoskeletal proteins. These conserved sequences, termed pleckstrin-homology (PH) domains, are thought to be involved in signal transduction. But the details of the function and binding partners of the PH domains have not been characterized. Here we report the solution structure of the N-terminal pleckstrin-homology domain of pleckstrin determined using heteronuclear three-dimensional nuclear magnetic resonance spectroscopy. The structure consists of an up-and-down beta-barrel of seven antiparallel beta-strands and a C-terminal amphiphilic alpha-helix that caps one end of the barrel. The overall topology of the domain is similar to that of the retinol-binding protein family of structures.
Maclennan AJ, Shaw G
A yeast SH2 domain.
Overduin M, Rios CB, Mayer BJ, Baltimore D, Cowburn D
Three-dimensional solution structure of the src homology 2 domain of c-abl.
Cell. 1992; 70: 697-704
SH2 regions are protein motifs capable of binding target protein sequences that contain a phosphotyrosine. The solution structure of the abl SH2 product, a protein of 109 residues and 12.1 kd, has been determined by multidimensional nuclear magnetic resonance spectroscopy. It is a compact spherical domain with a pair of three-stranded antiparallel beta sheets and a C-terminal alpha helix enclosing the hydrophobic core. Three arginines project from a short N-terminal alpha helix and one beta sheet into the putative phosphotyrosine-binding site, which lies on a face distal from the termini. Comparison with other SH2 sequences supports a common global fold and mode of phosphotyrosine binding for this family.
Mayer BJ, Hamaguchi M, Hanafusa H
A novel viral oncogene with structural similarity to phospholipase C.
Numerous oncogenes have been isolated from acutely transforming retroviruses. To date, the products of these viral oncogenes have been protein kinases, nuclear proteins, growth factors, or GTP-binding proteins. We have cloned the previously uncharacterized avian sarcoma virus CT10 and sequenced its genome. This virus encodes a protein, p47gag-crk, that has blocks of sequence similarity to the amino-terminal, non-catalytic region of the non-receptor class of tyrosine kinases. In addition, the structure of p47gag-crk has striking similarity to a 180-amino acid region of bovine brain phospholipase C. Biochemical data suggest that p47gag-crk activates one or several endogenous tyrosine kinases.
Stahl ML, Ferenz CR, Kelleher KL, Kriz RW, Knopf JL
Sequence similarity of phospholipase C with the non-catalytic region of src.
The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific phospholipase C (PLC) enzymes. Here we report the cloning of a bovine brain complementary DNA encoding an enzyme PLC-148 that is characterized by calcium-dependent and phosphatidylinositol-specific phospholipase C activity when expressed in mammalian cells. Bovine brain messenger RNA contains a 7.5-kilobase transcript corresponding to the isolated cDNA; a related transcript of the same size is present in mRNA from some but not all human cell lines tested. Southern blot analysis of the bovine genome indicated that one or possibly two genes hybridize to the cloned PLC-148 cDNA. There is a striking sequence similarity between specific regions of PLC-148 and the non-catalytic domain of the non-receptor tyrosine kinases. The newly characterized crk transforming gene of the avian sarcoma virus CT10 also contains extensive sequence similarities with PLC-148.
Sadowski I, Stone JC, Pawson T
A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps.
Mol Cell Biol. 1986; 6: 4396-408
Proteins encoded by oncogenes such as v-fps/fes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the cell. These proteins possess two contiguous regions of sequence identity: a C-terminal catalytic domain of 260 residues with homology to other tyrosine-specific and serine-threonine-specific protein kinases, and a unique domain of approximately 100 residues which is located N terminal to the kinase region and is absent from kinases that span the plasma membrane. In-frame linker insertion mutations in Fujinami avian sarcoma virus which introduced dipeptide insertions into the most stringently conserved segment of this N-terminal domain in P130gag-fps impaired the ability of Fujinami avian sarcoma virus to transform rat-2 cells. The P130gag-fps proteins encoded by these transformation-defective mutants were deficient in protein-tyrosine kinase activity in rat cells. However v-fps polypeptides derived from the mutant Fujinami avian sarcoma virus genomes and expressed in Escherichia coli as trpE-v-fps fusion proteins displayed essentially wild-type enzymatic activity, even though they contained the mutated sites. Deletion of the N-terminal domain from wild-type and mutant v-fps bacterial proteins had little effect on autophosphorylating activity. The conserved N-terminal domain of P130gag-fps is therefore not required for catalytic activity, but can profoundly influence the adjacent kinase region. The presence of this noncatalytic domain in all known cytoplasmic tyrosine kinases of higher and lower eucaryotes argues for an important biological function. The relative inactivity of the mutant proteins in rat-2 cells compared with bacteria suggests that the noncatalytic domain may direct specific interactions of the enzymatic region with cellular components that regulate or mediate tyrosine kinase function.
Tyrosine-protein kinase BTK (Q06187) (SMART) OMIM:300300: Agammaglobulinemia, type 1, X-linked ; ?XLA and isolated growth hormone deficiency
SH2 domain-containing protein 1A (O60880) (SMART) OMIM:308240: Lymphoproliferative syndrome, X-linked
Ras GTPase-activating protein 1 (P20936) (SMART) OMIM:139150: Basal cell carcinoma
2.00 map04920 Adipocytokine signaling pathway
1.20 map04120 Ubiquitin mediated proteolysis
0.04 map00970 Aminoacyl-tRNA biosynthesis
0.04 map00251 Glutamate metabolism
1a07 C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-MALONYL TYR-GLU-(N,N-DIPENTYL AMINE)
1a08 C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-DIFLUORO PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a09 C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-FORMYL PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a1a C-SRC (SH2 DOMAIN WITH C188A MUTATION) COMPLEXED WITH ACE-FORMYL PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a1b C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a1c C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N-ME(-(CH2)3-CYCLOPENTYL))
1a1e C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(3-BUTYLPIPERIDINE)
1a81 CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF THE SYK KINASE BOUND TO A DUALLY TYROSINE-PHOSPHORYLATED ITAM
1ab2 THREE-DIMENSIONAL SOLUTION STRUCTURE OF THE SRC HOMOLOGY 2 DOMAIN OF C-ABL
1aot NMR STRUCTURE OF THE FYN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PEPTIDE, MINIMIZED AVERAGE STRUCTURE
1aou NMR STRUCTURE OF THE FYN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PEPTIDE, 22 STRUCTURES
1aya CRYSTAL STRUCTURES OF PEPTIDE COMPLEXES OF THE AMINO-TERMINAL SH2 DOMAIN OF THE SYP TYROSINE PHOSPHATASE
1ayb CRYSTAL STRUCTURES OF PEPTIDE COMPLEXES OF THE AMINO-TERMINAL SH2 DOMAIN OF THE SYP TYROSINE PHOSPHATASE
1ayc CRYSTAL STRUCTURES OF PEPTIDE COMPLEXES OF THE AMINO-TERMINAL SH2 DOMAIN OF THE SYP TYROSINE PHOSPHATASE
1ayd CRYSTAL STRUCTURES OF PEPTIDE COMPLEXES OF THE AMINO-TERMINAL SH2 DOMAIN OF THE SYP TYROSINE PHOSPHATASE
1bf5 TYROSINE PHOSPHORYLATED STAT-1/DNA COMPLEX
1bfi SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, 30 STRUCTURES
1bfj SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE
1bg1 TRANSCRIPTION FACTOR STAT3B/DNA COMPLEX
1bhf P56LCK SH2 DOMAIN INHIBITOR COMPLEX
1bhh FREE P56LCK SH2 DOMAIN
1bkl SELF-ASSOCIATED APO SRC SH2 DOMAIN
1bkm COCRYSTAL STRUCTURE OF D-AMINO ACID SUBSTITUTED PHOSPHOPEPTIDE COMPLEX
1blj NMR ENSEMBLE OF BLK SH2 DOMAIN, 20 STRUCTURES
1blk NMR ENSEMBLE OF BLK SH2 DOMAIN USING CHEMICAL SHIFT REFINEMENT, 20 STRUCTURES
1bm2 GRB2-SH2 DOMAIN IN COMPLEX WITH CYCLO-[N-ALPHA-ACETYL-L-THI ALYSYL-O-PHOSPHOTYROSYL-VALYL-ASPARAGYL-VALYL-PROLYL] (PKF273-791)
1bmb GRB2-SH2 DOMAIN IN COMPLEX WITH KPFY*VNVEF (PKF270-974)
1cj1 GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN (HUMAN) COMPLEXED WITH A PHOSPHOTYROSYL DERIVATIVE
1csy SYK TYROSINE KINASE C-TERMINAL SH2 DOMAIN COMPLEXED WITH A PHOSPHOPEPTIDEFROM THE GAMMA CHAIN OF THE HIGH AFFINITY IMMUNOGLOBIN G RECEPTOR, NMR
1csz SYK TYROSINE KINASE C-TERMINAL SH2 DOMAIN COMPLEXED WITH A PHOSPHOPEPTIDEFROM THE GAMMA CHAIN OF THE HIGH AFFINITY IMMUNOGLOBIN G RECEPTOR, NMR
1cwd HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE
1cwe HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE
1d1z CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP
1d4t CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH A SLAM PEPTIDE
1d4w CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH SLAM PHOSPHOPEPTIDE
1f1w SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN
1f2f SRC SH2 THREF1TRP MUTANT
1fbz Structure-based design of a novel, osteoclast-selective, nonpeptide Src SH2 inhibitor with in vivo anti-resorptive activity
1fhs THE THREE-DIMENSIONAL SOLUTION STRUCTURE OF THE SRC HOMOLOGY DOMAIN-2 OF THE GROWTH FACTOR RECEPTOR BOUND PROTEIN-2, NMR, 18 STRUCTURES
1fu5 NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGEN
1fu6 NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE
1fyr DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX
1ghu NMR SOLUTION STRUCTURE OF GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2 (GRB2) SH2 DOMAIN, 24 STRUCTURES
1h9o PHOSPHATIDYLINOSITOL 3-KINASE, P85-ALPHA SUBUNIT: C-TERMINAL SH2 DOMAIN COMPLEXED WITH A TYR751 PHOSPHOPEPTIDE FROM THE PDGF RECEPTOR, CRYSTAL STRUCTURE AT 1.79 A
1hcs NMR STRUCTURE OF THE HUMAN SRC SH2 DOMAIN COMPLEX
1hct NMR STRUCTURE OF THE HUMAN SRC SH2 DOMAIN COMPLEX
1i3z MURINE EAT2 SH2 DOMAIN IN COMPLEX WITH SLAM PHOSPHOPEPTIDE
1ijr Crystal structure of LCK SH2 complexed with nonpeptide phosphotyrosine mimetic
1is0 Crystal Structure of a Complex of the Src SH2 Domain with Conformationally Constrained Peptide Inhibitor
1jwo Crystal Structure Analysis of the SH2 Domain of the Csk Homologous Kinase CHK
1jyq Xray Structure of Grb2 SH2 Domain Complexed with a Highly Affine Phospho Peptide
1jyr Xray Structure of Grb2 SH2 Domain Complexed with a Phosphorylated Peptide
1jyu Xray Structure of Grb2 SH2 Domain
1ka6 SAP/SH2D1A bound to peptide n-pY
1ka7 SAP/SH2D1A bound to peptide n-Y-c
1kc2 structure of the triple (Lys(beta)D3Ala, Asp(beta)C8Ala, AspCD2Ala) mutant of the Src SH2 domain bound to the PQpYEEIPI peptide
1lcj SH2 (SRC HOMOLOGY-2) DOMAIN OF HUMAN P56-LCK TYROSINE KINASE COMPLEXED WITH THE 11 RESIDUE PHOSPHOTYROSYL PEPTIDE EPQPYEEIPIYL
1lkk HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-ILE (PYEEI PEPTIDE)
1lkl HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (PYEEG PEPTIDE)
1lui NMR Structures of Itk SH2 domain, Pro287cis isoform, ensemble of 20 low energy structures
1luk NMR Structure of the Itk SH2 domain, Pro287cis, Energy minimized average structure
1lum NMR Structure of the Itk SH2 domain, Pro287trans, 20 low energy structures
1lun NMR Structure of the Itk SH2 domain, Pro287trans, energy minimized average structure
1m61 Crystal structure of the apo SH2 domains of ZAP-70
1mil TRANSFORMING PROTEIN
1mw4 Solution structure of the human Grb7-SH2 domain in complex with a 10 amino acid peptide pY1139
1nrv Crystal structure of the SH2 domain of Grb10
1nzl Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYEpYIPI
1nzv Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA
1o41 CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78300.
1o44 Crystal structure of sh2 in complex with ru85052
1o4a CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82197.
1o4b CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU83876.
1o4c CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHOSPHATE.
1o4d CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78262.
1o4e CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78299.
1o4f CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79073.
1o4g CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH DPI59.
1o4h CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79072.
1o4i CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PAS219.
1o4j CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH ISO24.
1o4k CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PASBN.
1o4l CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH FRAGMENT2.
1o4m CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH MALONICACID.
1o4n CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH OXALIC ACID.
1o4o CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHENYLPHOSPHATE.
1o4p CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78791.
1o4q CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79256.
1o4r CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78783.
1oo3 P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase
1oo4 P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived from PDGFr
1p13 Crystal Structure of the Src SH2 Domain Complexed with Peptide (SDpYANFK)
1pic PHOSPHATIDYLINOSITOL 3-KINASE, P85-ALPHA SUBUNIT: C-TERMINAL SH2 DOMAIN COMPLEXED WITH A TYR751 PHOSPHOPEPTIDE FROM THE PDGF RECEPTOR, NMR, MINIMIZED MEAN STRUCTURE
1qad Crystal Structure of the C-Terminal SH2 Domain of the P85 alpha Regulatory Subunit of Phosphoinositide 3-Kinase: An SH2 domain mimicking its own substrate
1qg1 GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH AN SHC-DERIVED PEPTIDE
1r1p Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads
1r1q Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads
1r1s Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads
1rja Solution Structure and Backbone Dynamics of the Nonreceptor Tyrosine Kinase PTK6/Brk SH2 Domain
1rpy CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS
1rqq Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS
1sha CRYSTAL STRUCTURE OF THE PHOSPHOTYROSINE RECOGNITION DOMAIN SH2 OF V-SRC COMPLEXED WITH TYROSINE-PHOSPHORYLATED PEPTIDES
1shb CRYSTAL STRUCTURE OF THE PHOSPHOTYROSINE RECOGNITION DOMAIN SH2 OF V-SRC COMPLEXED WITH TYROSINE-PHOSPHORYLATED PEPTIDES
1shd PEPTIDE INHIBITORS OF SRC SH3-SH2-PHOSPHOPROTEIN INTERACTIONS
1skj COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX
1spr BINDING OF A HIGH AFFINITY PHOSPHOTYROSYL PEPTIDE TO THE SRC SH2 DOMAIN: CRYSTAL STRUCTURES OF THE COMPLEXED AND PEPTIDE-FREE FORMS
1sps BINDING OF A HIGH AFFINITY PHOSPHOTYROSYL PEPTIDE TO THE SRC SH2 DOMAIN: CRYSTAL STRUCTURES OF THE COMPLEXED AND PEPTIDE-FREE FORMS
1tce SOLUTION NMR STRUCTURE OF THE SHC SH2 DOMAIN COMPLEXED WITH A TYROSINE-PHOSPHORYLATED PEPTIDE FROM THE T-CELL RECEPTOR, MINIMIZED AVERAGE STRUCTURE
1tze SIGNAL TRANSDUCTION ADAPTOR GROWTH FACTOR, GRB2 SH2 DOMAIN COMPLEXED WITH PHOSPHOTYROSYL HEPTAPEPTIDE LYS-PRO-PHE-PTYR-VAL-ASN-VAL-NH2 (KFPPYVNC-NH2)
1uur Structure of an activated Dictyostelium STAT in its DNA-unbound form
1uus Structure of an activated Dictyostelium STAT in its DNA-unbound form
1wqu Solution structure of the human FES SH2 domain
1x0n NMR structure of growth factor receptor binding protein SH2 domain complexed with the inhibitor
1x6c Solution structures of the SH2 domain of human protein-tyrosine phosphatase SHP-1
1xa6 Crystal Structure of the Human Beta2-Chimaerin
1y1u Structure of unphosphorylated STAT5a
1yvl Structure of Unphosphorylated STAT1
1z3k Structural Insight into the Binding Diversity between the Tyr-Phosphorylated Human EphrinBs and Nck2 SH2 Domain
1zfp GROWTH FACTOR RECEPTOR BINDING PROTEIN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PENTAPEPTIDE
2aoa Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
2aob Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain
2aug Crystal structure of the Grb14 SH2 domain
2b3o Crystal structure of human tyrosine phosphatase SHP-1
2bbu solution structure of mouse socs3 in complex with a phosphopeptide from the gp130 receptor
2c9w CRYSTAL STRUCTURE OF SOCS-2 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 1.9A RESOLUTION
2ci8 sh2 domain of human nck1 adaptor protein - uncomplexed
2ci9 Nck1 SH2-domain in complex with a dodecaphosphopeptide from EPEC protein Tir
2cia human nck2 sh2-domain in complex with a decaphosphopeptide from translocated intimin receptor (tir) of epec
2cr4 Solution structure of the SH2 domain of human SH3BP2 protein
2crh Solution structure of the SH2 domain of human proto-oncogene protein VAV1
2cs0 Solution structure of the SH2 domain of human HSH2D protein
2dcr Fully automated solution structure determination of the Fes SH2 domain
2dly Solution structure of the SH2 domain of murine Fyn-related kinase
2dlz Solution structure of the SH2 domain of human protein vav-2
2dm0 Solution structure of the SH2 domain of human Tyrosine-protein kinase TXK
2dx0 Crystal structure of the N-terminal SH2 domain of mouse phospholipase C-gamma 2
2ecd Solution structure of the human ABL2 SH2 domain
2ekx Solution structure of the human BMX SH2 domain
2el8 Solution structure of the human STAP2 SH2 domain
2eo3 Solution structure of the SH2 domain from human Crk-like protein
2eo6 Solution structure of the SH2 domain from mouse B-cell linker protein BLNK
2eob Solution structure of the second SH2 domain from rat PLC gamma-2
2etz The NMR minimized average structure of the Itk SH2 domain bound to a phosphopeptide
2eu0 The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide
2eyv SH2 domain of CT10-Regulated Kinase
2fci Structural basis for the requirement of two phosphotyrosines in signaling mediated by Syk tyrosine kinase
2ge9 Solution Structures of the SH2 domain of Bruton's Tyrosine Kinase
2gsb Solution structure of the second SH2 domain of human Ras GTPase-activating protein 1
2h46 Native domain-swapped dimer crystal structure of the Grb2 SH2 domain
2h5k Crystal Structure of Complex Between the Domain-Swapped Dimeric Grb2 SH2 Domain and Shc-Derived Ligand, Ac-NH-pTyr-Val-Asn-NH2
2hdv Crystal structure of the Src Homology-2 domain of the adapter protein SH2-B
2hdx Crystal structure of the Src homology-2 domain of SH2-B in complex with Jak2 pTyr813 phosphopeptide
2hmh Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.
2huw X-ray crystal structure of the Grb2 SH2 domain complexed to a constrained and cyclopropane-derived ligand
2iug Crystal structure of the PI3-kinase p85 N-terminal SH2 domain
2iuh Crystal structure of the PI3-kinase p85 N-terminal SH2 domain in complex with c-Kit phosphotyrosyl peptide
2iui Crystal structure of the PI3-kinase p85 N-terminal SH2 domain in complex with PDGFR phosphotyrosyl peptide
2izv CRYSTAL STRUCTURE OF SOCS-4 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 2.55A RESOLUTION
2jyq NMR structure of the apo v-Src SH2 domain
2kk6 Solution structure of sh2 domain of proto-oncogene tyrosine-protein kinase fer from homo sapiens, northeast structural genomics consortium (nesg) target hr3461d
2kno NMR Solution Structure of SH2 Domain of the Human Tensin Like C1 Domain Containing Phosphatase (TENC1)
2l3t Solution structure of tandem SH2 domain from Spt6
2l4k Water refined solution structure of the human Grb7-SH2 domain in complex with the 10 amino acid peptide pY1139
2l6k Solution Structure of a Nonphosphorylated Peptide Recognizing Domain
2lct Solution structure of the Vav1 SH2 domain complexed with a Syk-derived doubly phosphorylated peptide
2lnw Identification and structural basis for a novel interaction between Vav2 and Arap3
2lnx Solution structure of Vav2 SH2 domain
2mc1 Solution structure of the Vav1 SH2 domain complexed with a Syk-derived singly phosphorylated peptide
2mk2 Solution NMR structure of N-terminal domain (SH2 domain) of human Inositol polyphosphate phosphatase-like protein 1 (INPPL1) (fragment 20-117), Northeast Structural Genomics Consortium Target HR9134A
2mqi 2MQI
2mrj 2MRJ
2mrk 2MRK
2oq1 Tandem SH2 domains of ZAP-70 with 19-mer zeta1 peptide
2ozo Autoinhibited intact human ZAP-70
2pld NUCLEAR MAGNETIC RESONANCE STRUCTURE OF AN SH2 DOMAIN OF PHOSPHOLIPASE C-GAMMA1 COMPLEXED WITH A HIGH AFFINITY BINDING PEPTIDE
2ple NUCLEAR MAGNETIC RESONANCE STRUCTURE OF AN SH2 DOMAIN OF PHOSPHOLIPASE C-GAMMA1 COMPLEXED WITH A HIGH AFFINITY BINDING PEPTIDE
2pna STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE
2pnb STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE
2qms Crystal structure of a signaling molecule
2rd0 Structure of a human p110alpha/p85alpha complex
2rmx Solution structure of the SHP-1 C-terminal SH2 domain complexed with a tyrosine-phosphorylated peptide from NKG2A
2ror Solution structure of the VAV1 SH2 domain complexed with a tyrosine-phosphorylated peptide from SLP76
2rsy Solution structure of the SH2 domain of Csk in complex with a phosphopeptide from Cbp
2rvf 2RVF
2shp TYROSINE PHOSPHATASE SHP-2
2vif Crystal structure of SOCS6 SH2 domain in complex with a c-KIT phosphopeptide
2xp1 Structure of the tandem SH2 domains from Antonospora locustae transcription elongation factor Spt6
2y3a Crystal structure of p110beta in complex with icSH2 of p85beta and the drug GDC-0941
2ysx Solution structure of the human SHIP SH2 domain
2yu7 Solution structure of the SHP-1 C-terminal SH2 domain complexed with a tyrosine-phosphorylated peptide from NKG2A
3bkb Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)
3c7i X-RAY crystal structure of the complex between the grb2-sh2 domain and a flexible ligand, FPTVN.
3cbl Crystal structure of human feline sarcoma viral oncogene homologue (v-FES) in complex with staurosporine and a consensus peptide
3cd3 Crystal structure of phosphorylated human feline sarcoma viral oncogene homologue (v-FES) in complex with staurosporine and a consensus peptide
3cwg Unphosphorylated mouse STAT3 core fragment
3cxl Crystal structure of human chimerin 1 (CHN1)
3eac Crystal structure of SH2 domain of Human Csk (carboxyl-terminal src kinase), Oxidized form.
3eaz Crystal structure of SH2 domain of Human Csk (carboxyl-terminal src kinase), C122S mutant.
3gqi Crystal Structure of activated receptor tyrosine kinase in complex with substrates
3gxw Structure of the SH2 domain of the Candida glabrata transcription elongation factor Spt6, crystal form A
3gxx Structure of the SH2 domain of the Candida glabrata transcription elongation factor Spt6, crystal form B
3hck NMR ENSEMBLE OF THE UNCOMPLEXED HUMAN HCK SH2 DOMAIN, 20 STRUCTURES
3hhm Crystal structure of p110alpha H1047R mutant in complex with niSH2 of p85alpha and the drug wortmannin
3hiz Crystal structure of p110alpha H1047R mutant in complex with niSH2 of p85alpha
3imd Crystal Structure of the Grb2 SH2 Domain in Complex with a Flexible Ac-pY-Q-N-NH2 Tripeptide Mimic
3imj Crystal Structure of the Grb2 SH2 Domain in Complex with a Cyclopropyl-constrained Ac-pTyr-Ile-Asn-NH2 Tripeptide Mimic
3in7 Crystal Structure of the Grb2 SH2 Domain in Complex with a Cyclopropyl-constrained Ac-pY-Q-N-NH2 Tripeptide Mimic
3in8 Crystal Structure of the Grb2 SH2 Domain in Complex with a Flexible Ac-pTyr-Ile-Asn-NH2 Tripeptide Mimic
3k2m Crystal Structure of Monobody HA4/Abl1 SH2 Domain Complex
3kfj Crystal Structure of the Grb2 SH2 Domain in Complex with a Flexible Ac-pY-E-N-NH2 Tripeptide Mimic
3m7f Crystal structure of the Nedd4 C2/Grb10 SH2 complex
3maz Crystal Structure of the Human BRDG1/STAP-1 SH2 Domain in Complex with the NTAL pTyr136 Peptide
3mxc Structures of Grb2-SH2 Domain and AICD peptide Complexes Reveal a Conformational Switch and Their Functional Implications.
3mxy Structures of Grb2-SH2 Domain and AICD peptide Complexes Reveal a Conformational Switch and Their Functional Implications.
3n7y Crystal Structure of the Grb2 SH2 Domain in Complex with a 20-Membered Macrocyclic Ligand Having the Sequence pYVNV
3n84 Crystal Structure of the Grb2 SH2 Domain in Complex with a 23-Membered Macrocyclic Ligand Having the Sequence pYVNVP
3n8m Crystal Structure of the Grb2 SH2 Domain in Complex with An Acyclic Ligand Having the Sequence pYVNVP
3ov1 Crystal Structure of the Grb2 SH2 Domain in Complex with a pYXN-Derived Tripeptide
3ove Crystal Structure of the Grb2 SH2 Domain in Complex with a pYXN-Derived Tripeptide
3pfv Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide
3pjp A Tandem SH2 Domain in Transcription Elongation Factor Spt6 Binds the Phosphorylated RNA Polymerase II C-terminal Repeat Domain(CTD)
3pqz Grb7 SH2 with peptide
3ps5 Crystal structure of the full-length Human Protein Tyrosine Phosphatase SHP-1
3psi Crystal Structure of the Spt6 core domain from Saccharomyces cerevisiae, Form Spt6(239-1451)
3psj Crystal Structure of the Spt6 Tandem SH2 Domain from Saccharomyces cerevisiae, Form Se-Spt6 (1247-1451)
3psk Crystal Structure of the Spt6 Tandem SH2 Domain from Saccharomyces cerevisiae, Form Native Spt6 (1247-1451)
3s8l Protein-Ligand Interactions: Thermodynamic Effects Associated with Increasing Hydrophobic Surface Area
3s8n Crystal Structure of the Grb2 SH2 Domain in Complex with a pYXN-Derived Tripeptide
3s8o Crystal Structure of the Grb2 SH2 Domain in Complex with a pYXN-Derived Tripeptide
3s9k Crystal structure of the Itk SH2 domain.
3t04 Crystal structure of monobody 7c12/abl1 sh2 domain complex
3tkz Structure of the SHP-2 N-SH2 domain in a 1:2 complex with RVIpYFVPLNR peptide
3tl0 Structure of SHP2 N-SH2 domain in complex with RLNpYAQLWHR peptide
3us4 Crystal structure of a SH2 domain of a megakaryocyte-associated tyrosine kinase (MATK) from Homo sapiens at 1.50 A resolution
3uyo Crystal structure of monobody SH13/ABL1 SH2 domain complex
3vgo Crystal structure of the N-terminal fragment of Cbl-b
3wa4 Grb2 SH2 domain/CD28-derived peptide complex
3zni Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex
4a55 Crystal structure of p110alpha in complex with iSH2 of p85alpha and the inhibitor PIK-108
4dgp The wild-type Src homology 2 (SH2)-domain containing protein tyrosine phosphatase-2 (SHP2)
4dgx LEOPARD Syndrome-Associated SHP2/Y279C mutant
4e68 Unphosphorylated STAT3B core protein binding to dsDNA
4e93 Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684
4eih Crystal structure of Arg SH2 domain
4ey0 Structure of tandem SH2 domains from PLCgamma1
4f59 Triple mutant Src SH2 domain
4f5a Triple mutant Src SH2 domain bound to phosphate ion
4f5b Triple mutant Src SH2 domain bound to phosphotyrosine
4fbn Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains
4fl2 Structural and Biophysical Characterization of the Syk Activation Switch
4gl9 Crystal structure of inhibitory protein SOCS3 in complex with JAK2 kinase domain and fragment of GP130 intracellular domain
4gwf Crystal structure of the tyrosine phosphatase SHP-2 with Y279C mutation
4h1o Crystal structure of the tyrosine phosphatase SHP-2 with D61G mutation
4h34 Crystal structure of the tyrosine phosphatase SHP-2 with Q506P mutation
4je4 Crystal Structure of Monobody NSa1/SHP2 N-SH2 Domain Complex
4jeg Crystal Structure of Monobody CS1/SHP2 C-SH2 Domain Complex
4jgh Structure of the SOCS2-Elongin BC complex bound to an N-terminal fragment of Cullin5
4jmg Crystal structure of the synthetic protein in complex with pY peptide
4jmh Crystal structure of synthetic protein in complex with double pY peptide
4jps Co-crystal Structures of the Lipid Kinase PI3K alpha with Pan and Isoform Selective Inhibitors
4k2r Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker
4k44 Auto-inhibition and phosphorylation-induced activation of PLC-gamma isozymes
4l1b Crystal Structure of p110alpha complexed with niSH2 of p85alpha
4l23 Crystal Structure of p110alpha complexed with niSH2 of p85alpha and PI-103
4l2y Crystal Structure of p110alpha complexed with niSH2 of p85alpha and compound 9d
4nwf 4NWF
4nwg 4NWG
4ohd 4OHD
4ohe 4OHE
4ohh 4OHH
4ohi 4OHI
4ohl 4OHL
4ovu 4OVU
4ovv 4OVV
4p9v 4P9V
4p9z 4P9Z
4po6 Crystal structure of the human TYK2 FERM and SH2 domains with an IFNAR1 intracellular peptide
4qsy 4QSY
4roj 4ROJ
4tzi 4TZI
4u17 4U17
4u1p 4U1P
4waf 4WAF
4wwq 4WWQ
4x6s 4X6S
4xey 4XEY
4xz0 4XZ0
4y5u 4Y5U
4y5w 4Y5W
4ykn 4YKN
4zop 4ZOP
5aul 5AUL
5bo4 5BO4
5cdw 5CDW
5d0j 5D0J
5d39 5D39
5dc0 5DC0
5df6 5DF6
5eel 5EEL
5eeq 5EEQ
5eg3 5EG3
5ehp 5EHP
5ehr 5EHR
5fi4 5FI4
5i6v 5I6V
5ibm 5IBM
5ibs 5IBS
5itd 5ITD
5ixd 5IXD
5ixi 5IXI


text:
Pro Bono Publico
February 2, 2015 Non-FictionEditor East Coast Stories
The following is a true story as told by a New Jersey attorney Gene Mitchell to the Editor of East Cost Stories. Only the name of the career criminal has been changed.
All lawyers are expected to put in a certain amount "pro bono publico" (for the public good) hours each year. This consists of providing free legal work for people who can't afford it.
Although they never admit it openly, most lawyers hate doing pro bono work. It cuts directly into their income, and it brings them into contact with the type of people they usually try to avoid.
Gene is a corporate attorney specializing in tax work. A few years ago one of his firm's big clients switched to another law firm, temporarily making legal work sparse for the law firm Gene worked for. The managing partner of the firm "suggested" that this would be a good time for Gene to volunteer to do some pro bono work. The partner had arranged for Gene to do some work as a public defender.
Gene was not at all happy about this. It meant that he had to work for free defending criminal cases until his law firm could find some more new tax clients.
Gene's mood did not improve when he got the details of his first client. "Little Tony" Parker had been accused in the breaking and entering of a McDonald's restaurant. Gene took one look at the file and realized that Little Tony was not exactly a dream client. He was 30 years old, but had a record of different types of thefts going back to when he was a kid. He had been in and out of various jails and prisons for short sentences, but added together it came up to a significant part of his life.
He was called "Little Tony" since he was just under 5 feet tall and had a slight build. He was very sensitive about this, especially since his size tended to make him a prime target in whatever jail he happened to be in. He had been in numerous fights, and usually came out the loser.
Little Tony could be facing a long time in prison for his latest crime. Like many other States, New Jersey had passed statutes allowing judges to give extended sentences to "career criminals."
On top of all of that, Little Tony's latest endeavor was something the police were laughing at. One week earlier, at 2am, he had broken into a closed McDonald's to try to rob the safe. He did not realize that this McDonald's was still under construction, and would not have its Grand Opening for another week. There was no safe, no cash registers, no food. There was nothing to steal.
However, the restaurant did have its security cameras operating. They showed a clear view of Little Tony's face as he frantically scurried around the restaurant searching for something to take. He finally gave up and left.
The next day, the construction workers showed up, saw the door had been forced open and they called the police. The detectives immediately recognized Little Tony from the security tapes and drove directly to his apartment to arrest him.
Gene decided that the best defense was to try to get Little Tony off with as light a sentence as possible. In his favor was the fact that Little Tony had not actually stolen anything, and had not vandalized anything in the store. The only thing he had broken was a very cheap lock on the door. If this was a first-time offense, Tony would probably get a suspended sentence. However, with his past record, he could be looking at 5 years in prison.
Gene decided to really work hard on this just to show what a great lawyer he was, even when it was not a tax case. He had long conversations with Tony, and even had a friend who was a psychologist speak with Tony.
In the end, Gene wrote a beautiful brief for the Judge. He explained about Tony's horrible childhood, and about how Tony had continually been abused in the various juvenile facilities and jails he had been sent to. Gene submitted the psychologist's report which emphatically stated that the best way to make Tony a productive member of society was through treatment rather than prison.
In the end Gene had a resounding success. He was not sure if it was because of his legal work or if the courts were just too swamped with violent crime to care about a broken lock on a restaurant under construction. The judge gave Little Tony a suspended sentence, and the only penalty was that he had to pay $350 for repairs to the door of the McDonalds.
Gene was ecstatic. For the first time he actually felt good about doing pro bono work. He had made a real difference to a person's life. It was much more satisfying than any of his tax cases.
Gene had a long and serious conversation with Little Tony. He gave Tony a speech explaining that Tony should look at this as a new beginning. This was a real chance for Tony to do something different with his life. Gene walked Tony down the hall to the Court Clerk's office. The Gene decided to really help. Gene gave $350 cash to Little Tony and said,
"Tony, this is a new start for you. To help you on your way, I am even going to give you the money to pay the fine. Take this money, and wait in that line there. Give the clerk the cash and these documents, and then this case is over for you."
Little Tony was so moved he was almost in tears. He solemnly shook Gene's hand and told him how Gene was the fist person in his life who had ever given him a real break.
Gene left the court that day happier than he had been in a long time. A week later, Gene's law firm got a new tax client and Gene was back at work in corporate law. Gene was buried in spredsheets when his phone rang.
"Mr. Mitchell, this is Detective Hanson. I was wondering if you could tell me the whereabouts of Tony Parker. He moved out of his apartment, and we don't have any other address for him."
Gene was surprised, "No. I have no idea where he is. What is the problem?"
"The judge issued a bench warrant for him. He never paid the fine on that McDonald's break-in. The judge is really pissed off. Says he should have know better than to trust someone with that background."
It turns out that Little Tony was a career thief after all. After he had so warmly shaken Gene's hand, he had watched as gene left the court house. Then he had pocked the $350 Gene had given him, gotten out of line, and left without paying the fine. Apparently he had then used the $350 to skip town.
That was the last criminal case Gene ever handled. He now happily works on spreadsheets and corporate law. When he is forced to to pro bono work, he helps people with tax problems. He never offers to give them any money for their back taxes.
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Every Tuesday and Thursday through the end of February, Flatland will share stories of Kansas City's neighbors. Find them online here and on Flatland's Youtube page.