Details of the BTS | SYNBIP

General Information of Binding Target of SBP (BTS) (ID: ST00067)
BTS Name	Hepatocyte growth factor receptor
Synonyms	HGF receptor; EC 2.7.10.1; HGF/SF receptor; Proto-oncogene c-Met; Scatter factor receptor; SF receptor; Tyrosine-protein kinase Met
BTS Type	Protein
Family	Protein kinase superfamily; Tyr protein kinase family
Gene Name	MET
Organism	Homo sapiens (Human)
Function	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity).; (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells.
UniProt ID	P08581
UniProt Entry	MET_HUMAN
PFam	PF07714 ; PF01437 ; PF01403 ; PF01833
Gene ID	4233
Sequence	MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE FRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECIL TEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEF TTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFL LDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKK TRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVIT SISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVH EAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPV FKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQ IKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGS CRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHF NEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVL SLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKF VHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKF TTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCW HPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVD TRPASFWETS
Sequence Length	1390

Synthetic Binding Protein (SBP) Targeting This BTS

SBP Name	Highest Status	Mechanism	Affinity	Application	Details	Ref
Anticalin anti-HGFR PRS-110	Research	Antagonist	Kd: 0.6 nM	Research tool	SBP Info	[1], [2]
Avimer anti-HGFR C426	Research	Inhibitor	Kd: <0.1 nM	Research tool	SBP Info	[3]
Centyrin anti-HGFR P114-A3	Research	Inhibitor	Kd: 0.4 nM	Research tool	SBP Info	[4]
Diabody anti-c-Met/PD-1 Diabody-mp	Research	inhibitor	Kd: 0.63 nM	Tumors [ICD-11: XH1N44]	SBP Info	[5]
Diabody anti-c-Met/PD-1 Diabody-pm	Research	inhibitor	Kd: 32.48 nM	Tumors [ICD-11: XH1N44]	SBP Info	[5]

References

1	Recent advances in the development of novel protein scaffolds based therapeutics. Int J Biol Macromol. 2017 Sep;102:630-641.
2	In vivo visualization of MET tumor expression and anticalin biodistribution with the MET-specific anticalin 89Zr-PRS-110 PET tracer. J Nucl Med. 2014 Apr;55(4):665-71.
3	Mult ivalent avimer proteins evolved by exon shuffling of a family of human receptor. Nat Biotechnol. 2005 Dec;23(12):1556-61.
4	Selection of high-affinity Centyrin FN3 domains from a simple library diversified at a combination of strand and loop positions. Protein Eng Des Sel. 2014 Oct;27(10):419-29.
5	Development of bispecific anti-c-Met/PD-1 diabodies for the treatment of solid tumors and the effect of c-Met binding affinity on efficacy. Oncoimmunology. 2021 Jul 21;10(1):1914954.