For example, the SH2 domain of SOCS1 binds to a tyrosine in the activation loop of JAKs, which prevents JAKs from phosphorylating each other.[1] The SH2 domains of SOCS2, SOCS3 and CIS bind directly to receptors themselves.[2] Also, SOCS1 and SOCS3 can prevent JAK-STAT signalling by binding to JAKs, using segments called kinase inhibitory regions (KIRs) and stopping JAKs binding to other proteins.[50] The exact details of how other SOCS function is less understood.[4]