More distant orthologs, including "Xenopus tropicalis", do have significantly more proline residues than expected. TMEM171 has 3 hydrophobic segments, which correspond with transmembrane regions. TMEM171 has a conserved domain, pfam15471 (aa4:318), whose structure and function are not yet characterized. Within the domain, there are 4 transmembrane domains, 2 non-cytosolic domains, and 3 cytosolic domains. The structure of TMEM171 consists of approximately 25% beta strands and 15% alpha helices, with coils and disordered regions making up the rest of the structure. The tertiary structure includes 2 predicted disulfide bridges, which occur between highly conserved cysteine residues in the non-cytosolic domains. TMEM171 undergoes methionine cleavage and N-terminal acetylation, which is one of the most common modifications of eukaryotic proteins. N-linked glycosylation is predicted at a highly conserved NETD sequence within a non-cytosolic domain. S-palmitoylation, which enhances surface hydrophobicity and membrane affinity, is predicted at 2 cytosolic cysteine residues in TMEM171. TMEM171 is phosphorylated by unspecified kinases at several sites. It also undergoes O-ß-GlcNAc modification at 4 sites, 3 of which are Yin-Yang sites due to O-ß-GlcNAc modification and phosphorylation competing for control of protein activation or deactivation. TMEM171's predicted location is in the plasma membrane, with both the N- and C-termini located inside the cell. The proteins that are most likely to interact with TMEM171, based on affinity chromatography and two hybrid arrays, are MIER1, EMSY, CHPT1, HDLBP, NEDD4, WWOX, and TTHY3. There is strong evidence for a direct interaction between TMEM171 an MIER1, which is a transcriptional repressor that is associated with central hypothyroidism. TMEM171 is down-regulated in papillary thyroid carcinoma and two SNPs, with the non-synonymous mutations R86G and N139K, are identified risk SNPs for papillary thyroid carcinoma. TMEM171 is also down-regulated in gastric cancer and colon cancer. More specifically, it is down-regulated in right-sided colon cancer relative to left-sided colon cancer, which typically has a better prognosis.