Location of mutations identified in MET oncogene. The MET protein is 1390 amino acids long (NM_000245.2, NP_000236.2). The pre-protein is cleaved into alpha and beta chains that are joined by a disulfide bond to create the extracellular receptor. The extracellular region (blue and yellow) contains a Sema domain, followed by a PSI and four IPT domains and are encoded in exons 2-12 of the mRNA. The transmembrane domain (green) is encoded in exon 13. The intracellular domain (red) is encoded in exons 14-21. Serine 985 (red star) down regulates kinase activity when phosphorylated, tyrosine 1234 and 1235 (green stars) positively modulate enzyme activity when phosphorylated, and tyrosine 1349 and 1356 (blue stars) recruit signal transducers when phosphorylated. Catalog of Somatic Mutations in Cancer (COSMIC) reports mutations in amino acids 130-370 of the extracellular domain, and 960-1340 of the intracellular tyrosine kinase domain. Amino acid changes responsible for Hereditary Papillary Renal Carcinoma (HPRC) are found between amino acids 1110 and 1268. Sequencing traces of the germline DNA mutations in the colon cancer sibling pair population are shown with their approximate location on the gene.