Hepatocyte growth factor receptor
Protein
Protein
-------

MET is a [receptor tyrosine kinase](/wiki/Receptor_tyrosine_kinase "Receptor tyrosine kinase") (RTK) that is produced as a single\-chain precursor. The precursor is proteolytically cleaved at a [furin](/wiki/Furin "Furin") site to yield a highly glycosylated extracellular α\-subunit and a transmembrane β\-subunit, which are linked together by a [disulfide bridge](/wiki/Disulfide_bridge "Disulfide bridge").

### Extracellular

* Region of homology to [semaphorins](/wiki/Semaphorin "Semaphorin") (Sema domain), which includes the full α\-chain and the N\-terminal part of the β\-chain
* Cysteine\-rich MET\-related sequence (MRS domain)
* Glycine\-proline\-rich repeats (G\-P repeats)
* Four immunoglobulin\-like structures (Ig domains), a typical protein\-protein interaction region.

### Intracellular

A juxtamembrane segment that contains:

* A serine residue (Ser 985\), which inhibits the receptor kinase activity upon phosphorylation
* A tyrosine residue (Tyr 1003\), which is responsible for MET [polyubiquitination](/wiki/Polyubiquitination "Polyubiquitination"), [endocytosis](/wiki/Endocytosis "Endocytosis"), and degradation upon interaction with the [ubiquitin ligase](/wiki/Ubiquitin_ligase "Ubiquitin ligase") CBL
* Tyrosine kinase domain, which mediates MET biological activity. Following MET activation, transphosphorylation occurs on Tyr 1234 and Tyr 1235
* C\-terminal region contains two crucial tyrosines (Tyr 1349 and Tyr 1356\), which are inserted into the multisubstrate docking site, capable of recruiting downstream adapter proteins with [Src homology\-2](/wiki/SH2_domain "SH2 domain") (SH2\) domains. The two tyrosines of the docking site have been reported to be necessary and sufficient for the signal transduction both *in vitro*.

How many Ig domains does MET have?