Q07DZ1 (MET_COLGU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatocyte growth factor receptor
Short name=HGF receptor
EC=2.7.10.1

Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name=SF receptor
Tyrosine-protein kinase Met

Gene names

Name:

MET

Organism

Colobus guereza (Mantled guereza) (Eastern black-and-white colobus monkey)

Taxonomic identifier

33548 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Cercopithecoidea › Cercopithecidae › Colobinae › Colobus

Protein attributes

Sequence length	1381 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

General annotation (Comments)

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 By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity By similarity.
Subunit structure	Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein By similarity.
Domain	The kinase domain is involved in SPSB1 binding By similarity. The beta-propeller Sema domain mediates binding to HGF By similarity.
Post-translational modification	Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site By similarity. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365 By similarity. Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 3 IPT/TIG domains. Contains 1 protein kinase domain. Contains 1 Sema domain.

Ontologies

Keywords
Cellular component	Membrane
Disease	Proto-oncogene
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological_process	multicellular organismal development Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 1381	1357	Hepatocyte growth factor receptor		PRO_0000260420
Regions
	Topological domain	25 – 932	908	Extracellular Potential
	Transmembrane	933 – 955	23	Helical; Potential
	Topological domain	956 – 1381	426	Cytoplasmic Potential
	Domain	27 – 515	489	Sema
	Domain	563 – 655	93	IPT/TIG 1
	Domain	657 – 739	83	IPT/TIG 2
	Domain	742 – 836	95	IPT/TIG 3
	Domain	1078 – 1345	268	Protein kinase
	Nucleotide binding	1084 – 1092	9	ATP By similarity
	Region	1212 – 1381	170	Interaction with RANBP9 By similarity
	Region	1320 – 1359	40	Interaction with MUC20 By similarity
Sites
	Active site	1204	1	Proton acceptor By similarity
	Binding site	1110	1	ATP By similarity
	Site	307 – 308	2	Cleavage Potential
Amino acid modifications
	Modified residue	977	1	Phosphothreonine By similarity
	Modified residue	990	1	Phosphoserine By similarity
	Modified residue	997	1	Phosphoserine By similarity
	Modified residue	1000	1	Phosphoserine By similarity
	Modified residue	1003	1	Phosphotyrosine By similarity
	Modified residue	1230	1	Phosphotyrosine By similarity
	Modified residue	1234	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1235	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1289	1	Phosphothreonine By similarity
	Modified residue	1349	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1356	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1365	1	Phosphotyrosine By similarity
	Glycosylation	45	1	N-linked (GlcNAc...) Potential
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Glycosylation	149	1	N-linked (GlcNAc...) Potential
	Glycosylation	202	1	N-linked (GlcNAc...) Potential
	Glycosylation	399	1	N-linked (GlcNAc...) Potential
	Glycosylation	405	1	N-linked (GlcNAc...) Potential
	Glycosylation	607	1	N-linked (GlcNAc...) Potential
	Glycosylation	635	1	N-linked (GlcNAc...) Potential
	Glycosylation	785	1	N-linked (GlcNAc...) Potential
	Glycosylation	879	1	N-linked (GlcNAc...) Potential
	Glycosylation	930	1	N-linked (GlcNAc...) Potential
	Disulfide bond	95 ↔ 101		By similarity
	Disulfide bond	98 ↔ 160		By similarity
	Disulfide bond	133 ↔ 141		By similarity
	Disulfide bond	172 ↔ 175		By similarity
	Disulfide bond	298 ↔ 363		By similarity
	Disulfide bond	385 ↔ 397		By similarity
	Disulfide bond	520 ↔ 538		By similarity
	Disulfide bond	526 ↔ 561		By similarity
	Disulfide bond	529 ↔ 545		By similarity
	Disulfide bond	541 ↔ 551		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q07DZ1 [UniParc]. Last modified October 31, 2006. Version 1. Checksum: 488C5AA28E9F32D0	FASTA	1,381	154,313
	10 20 30 40 50 60 MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH 70 80 90 100 110 120 HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD CSSKANLSGG VWKDNINMAL 130 140 150 160 170 180 VVDTYYDDQL ISCGSGNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 190 200 210 220 230 240 GAKVLSSVKD RFINFFVGNT INSSYFPHHP LHSISVRRLK ETKDGFVFLT DQSYIDVLPE 250 260 270 280 290 300 FRDSYPIKYV HAFESNNFIY FLSVQRETLN AQTFHTRIIR FCSINSGLHS YMEMPLECIL 310 320 330 340 350 360 TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK PDSAEPMDRS 370 380 390 400 410 420 AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR TLLRNSSGCE ARRDEYRAEF 430 440 450 460 470 480 TTALQRVDLF MGQFSEVLLT SISTFVKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 490 500 510 520 530 540 LDSHPVSPEV IVEHPLNQNG YTLVVTGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 550 560 570 580 590 600 CQDKCVRSED CPSGTWTQQI CLPAIYKVFP TSAPLEGGTR LTICGWDFGF RRNNKFDLKK 610 620 630 640 650 660 TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPIIT 670 680 690 700 710 720 SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 730 740 750 760 770 780 AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLHSV SVPRMVINVH 790 800 810 820 830 840 EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV 850 860 870 880 890 900 FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL 910 920 930 940 950 960 LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISIALLLLLG LFLWLKKRKQ 970 980 990 1000 1010 1020 IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS 1030 1040 1050 1060 1070 1080 CRQVQYPLTD MSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF 1090 1100 1110 1120 1130 1140 NEVIGRGHFG CVYHGTLLDN DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL 1150 1160 1170 1180 1190 1200 SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF 1210 1220 1230 1240 1250 1260 VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF 1270 1280 1290 1300 1310 1320 TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 1330 1340 1350 1360 1370 1380 HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD T

References

[1]

"NISC comparative sequencing initiative." Antonellis A., Ayele K., Benjamin B., Blakesley R.W., Boakye A., Bouffard G.G., Brinkley C., Brooks S., Chu G., Coleman H., Engle J., Gestole M., Greene A., Guan X., Gupta J., Haghighi P., Han J., Hansen N. , Ho S.-L., Hu P., Hunter G., Hurle B., Idol J.R., Kwong P., Laric P., Larson S., Lee-Lin S.-Q., Legaspi R., Madden M., Maduro Q.L., Maduro V.B., Margulies E.H., Masiello C., Maskeri B., McDowell J., Mojidi H.A., Mullikin J.C., Oestreicher J.S., Park M., Portnoy M.E., Prasad A., Puri O., Reddix-Dugue N., Schandler K., Schueler M.G., Sison C., Stantripop S., Stephen E., Taye A., Thomas J.W., Thomas P.J., Tsipouri V., Ung L., Vogt J.L., Wetherby K.D., Young A., Green E.D. Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	DP000193 Genomic DNA. Translation: ABJ08851.1.
3D structure databases
ProteinModelPortal	Q07DZ1.
SMR	Q07DZ1. Positions 40-741, 1046-1346.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG006348.
Family and domain databases
Gene3D	2.130.10.10. 1 hit. 2.60.40.10. 3 hits.
InterPro	IPR013783. Ig-like_fold. IPR014756. Ig_E-set. IPR002909. IPT_TIG_rcpt. IPR011009. Kinase-like_dom. IPR003659. Plexin-like. IPR016201. Plexin-like_fold. IPR002165. Plexin_repeat. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001627. Semaphorin/CD100_Ag. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016244. Tyr_kinase_HGF/MSP_rcpt. IPR015943. WD40/YVTN_repeat-like_dom. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF01437. PSI. 1 hit. PF01403. Sema. 1 hit. PF01833. TIG. 3 hits. [Graphical view]
PIRSF	PIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00429. IPT. 4 hits. SM00423. PSI. 1 hit. SM00630. Sema. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF81296. Ig_E-set. 3 hits. SSF56112. Kinase_like. 1 hit. SSF103575. Plexin-like_fold. 1 hit. SSF101912. Sema. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS51004. SEMA. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

MET_COLGU

Accession

Primary (citable) accession number: Q07DZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	October 31, 2006
Last modified:	March 6, 2013
This is version 48 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program