Reviewed, UniProtKB/Swiss-Prot P08581 (MET_HUMAN)

Names and origin

Protein names

Recommended name:
    Hepatocyte growth factor receptor
      Short name=HGF receptor
    EC=2.7.10.1
Alternative name(s):
    Scatter factor receptor
      Short name=SF receptor
    HGF/SF receptor
    Met proto-oncogene tyrosine kinase
    c-Met

Gene names

Name:

MET

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1390 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity. Functions in cell proliferation, scattering, morphogenesis and survival. Ref.7 Ref.12
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterodimer formed of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1 and GRB2. Interacts with SPSB1, SPSB2 and SPSB4 By similarity. 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.
Subcellular location	Membrane; Single-pass type I membrane protein.
Domain	The kinase domain is involved in SPSB1 binding.
Involvement in disease	Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:114550]. Ref.25 Defects in MET are a cause of hereditary papillary renal carcinoma (HPRC) [MIM:605074]; also known as papillary renal cell carcinoma 2 (RCCP2). HPRC is a form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumors. The pattern of inheritance is consistent with autosomal dominant transmission with reduced penetrance. Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Genetic variations in MET may be associated with susceptibility to autism type 9 (AUTS9) [MIM:611015]. Autism is a neurodevelopmental disorder characterized by disturbance in language, perception and socialization. The disorder is classically defined by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior. Ref.31
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
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	basal plasma membrane Ref.12 Inferred from direct assay. Source: MGI integral to plasma membrane Ref.7 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW hepatocyte growth factor receptor activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HGF	P14210	2	EBI-1039152,EBI-1039104
inlB	P25147	3	EBI-1039152,EBI-1379295	From a different organism.
PTPN12	Q05209	1	EBI-1039152,EBI-2266035
PTPN3	P26045	1	EBI-1039152,EBI-1047946
PTPRC	P08575	1	EBI-1039152,EBI-1341
PTPRG	P23470	1	EBI-1039152,EBI-2258115
PTPRJ	Q12913	1	EBI-1039152,EBI-2264500
PTPRK	Q15262	1	EBI-1039152,EBI-474052
PTPRO	Q16827	1	EBI-1039152,EBI-723739
YWHAZ	P63104	1	EBI-1039152,EBI-347088

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P08581-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P08581-2)

The sequence of this isoform differs from the canonical sequence as follows:
     755-755: S → STWWKEPLNIVSFLFCFAS

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 1390

1366

Hepatocyte growth factor receptor

PRO_0000024440

Regions

Topological domain

25 – 932

908

Extracellular Potential

Transmembrane

933 – 955

23

Potential

Topological domain

956 – 1390

435

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 – 1390

179

Interaction with RANBP9

Region

1320 – 1359

40

Interaction with MUC20

Sites

Active site

1204

1

Proton acceptor By similarity

Binding site

1110

1

ATP

Site

307 – 308

2

Cleavage Potential

Site

1009 – 1010

2

Breakpoint for translocation to form TPR-MET oncogene

Amino acid modifications

Modified residue

966

1

Phosphoserine Ref.16

Modified residue

977

1

Phosphothreonine Ref.16 Ref.15

Modified residue

988

1

Phosphoserine Ref.16 Ref.15

Modified residue

990

1

Phosphoserine Ref.16 Ref.15 Ref.17

Modified residue

997

1

Phosphoserine Ref.16 Ref.17

Modified residue

1000

1

Phosphoserine Ref.16 Ref.17

Modified residue

1003

1

Phosphotyrosine Ref.16 Ref.15 Ref.14

Modified residue

1230

1

Phosphotyrosine Ref.14

Modified residue

1234

1

Phosphotyrosine Ref.14

Modified residue

1235

1

Phosphotyrosine; by autocatalysis Ref.14 Ref.8

Modified residue

1356

1

Phosphotyrosine Ref.13

Glycosylation

45

1

N-linked (GlcNAc...) Potential

Glycosylation

106

1

N-linked (GlcNAc...) Ref.19

Glycosylation

149

1

N-linked (GlcNAc...) Potential

Glycosylation

202

1

N-linked (GlcNAc...)

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

Natural variations

Alternative sequence

755

1

S → STWWKEPLNIVSFLFCFAS in isoform 2.

VSP_005005

Natural variant

143

1

R → Q Ref.32

VAR_041738

Natural variant

156

1

S → L Ref.32

VAR_041739

Natural variant

168

1

E → D Ref.32

VAR_041740

Natural variant

238

1

L → S: dbSNP rs34349517.

VAR_032478

Natural variant

316

1

I → M: dbSNP rs35225896.

VAR_032479

Natural variant

320

1

A → V: dbSNP rs35776110. Ref.22

VAR_006285

Natural variant

375

1

N → S: dbSNP rs33917957. Ref.32

VAR_032480

Natural variant

773

1

P → L in gastric cancer. Ref.29

VAR_032481

Natural variant

970

1

R → C: dbSNP rs34589476. Ref.31 Ref.32

VAR_032482

Natural variant

991

1

P → S in gastric cancer; prolonged tyrosine phosphorylation in response to HGF/SF; transforming activity in athymic nude mice. Ref.28

VAR_032483

Natural variant

992

1

T → I Low transforming activity in athymic nude mice. Ref.31 Ref.32 Ref.28

VAR_032484

Natural variant

1092

1

V → I in HPRC; constitutive autophosphorylation. Ref.24 Ref.26 Ref.27

VAR_032485

Natural variant

1094

1

H → L in HPRC; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.23 Ref.24 Ref.27

VAR_032486

Natural variant

1094

1

H → R in HPRC; causes malignant transformation in cell lines. Ref.23 Ref.24 Ref.27

VAR_032487

Natural variant

1094

1

H → Y in HPRC; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.23 Ref.24 Ref.27

VAR_032488

Natural variant

1106

1

H → D in HPRC; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.24 Ref.27

VAR_032489

Natural variant

1131

1

M → T in HPRC; germline mutation. Ref.22 Ref.24

VAR_006286

Natural variant

1173

1

T → I in HCC. Ref.25

VAR_032490

Natural variant

1188

1

V → L in HPRC; germline mutation. Ref.22 Ref.24

VAR_006287

Natural variant

1195

1

L → V in HPRC; somatic mutation. Ref.22

VAR_006288

Natural variant

1220

1

V → I in HPRC; germline mutation. Ref.22

VAR_006289

Natural variant

1228

1

D → H in HPRC; somatic mutation. Ref.22

VAR_006291

Natural variant

1228

1

D → N in HPRC; germline mutation. Ref.22

VAR_006290

Natural variant

1230

1

Y → C in HPRC; germline mutation. Ref.22 Ref.24 Ref.27

VAR_006292

Natural variant

1230

1

Y → D in HPRC; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.22 Ref.24 Ref.27

VAR_032491

Natural variant

1230

1

Y → H in HPRC; somatic mutation. Ref.22 Ref.24 Ref.27

VAR_006293

Natural variant

1244

1

K → R in HCC. Ref.25

VAR_032492

Natural variant

1250

1

M → I in HCC. Ref.25

VAR_032493

Natural variant

1250

1

M → T in HPRC; somatic mutation. Ref.22 Ref.24

VAR_006294

Experimental info

Sequence conflict

1191

1

G → A in AAA59591. Ref.2

Sequence conflict

1272

1

V → L in AAC60383. Ref.3

Sequence conflict

1272

1

V → L Ref.4

Secondary structure

1

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1390

Helix Strand Turn

Details...

Beta strand

45 – 47

3

Beta strand

52 – 58

7

Beta strand

61 – 66

6

Beta strand

69 – 74

6

Turn

75 – 77

3

Beta strand

80 – 85

6

Beta strand

89 – 91

3

Beta strand

93 – 95

3

Beta strand

97 – 99

3

Beta strand

102 – 104

3

Beta strand

111 – 113

3

Beta strand

117 – 123

7

Beta strand

125 – 145

21

Beta strand

154 – 160

7

Beta strand

182 – 189

8

Beta strand

192 – 199

8

Beta strand

213 – 219

7

Helix

231 – 233

3

Helix

241 – 244

4

Beta strand

248 – 255

8

Beta strand

258 – 264

7

Beta strand

276 – 282

7

Beta strand

292 – 299

8

Beta strand

319 – 323

5

Helix

327 – 332

6

Beta strand

341 – 349

9

Beta strand

353 – 366

14

Helix

367 – 375

9

Turn

387 – 389

3

Beta strand

392 – 394

3

Turn

395 – 398

4

Beta strand

418 – 422

5

Beta strand

424 – 427

4

Turn

431 – 436

6

Beta strand

439 – 447

9

Beta strand

450 – 457

8

Beta strand

460 – 466

7

Beta strand

469 – 471

3

Beta strand

486 – 495

10

Turn

496 – 498

3

Beta strand

499 – 506

8

Beta strand

509 – 516

8

Helix

517 – 520

4

Helix

526 – 530

5

Helix

534 – 536

3

Beta strand

539 – 541

3

Beta strand

544 – 546

3

Helix

548 – 550

3

Helix

1055 – 1057

3

Helix

1060 – 1066

7

Helix

1067 – 1069

3

Helix

1073 – 1075

3

Beta strand

1076 – 1087

12

Beta strand

1090 – 1097

8

Beta strand

1105 – 1112

8

Helix

1118 – 1132

15

Beta strand

1144 – 1148

5

Turn

1149 – 1151

3

Beta strand

1152 – 1158

7

Helix

1165 – 1170

6

Helix

1178 – 1197

20

Helix

1207 – 1209

3

Beta strand

1210 – 1212

3

Beta strand

1218 – 1220

3

Helix

1224 – 1226

3

Turn

1229 – 1233

5

Helix

1247 – 1249

3

Helix

1252 – 1257

6

Helix

1262 – 1277

16

Helix

1293 – 1297

5

Helix

1310 – 1319

10

Helix

1324 – 1326

3

Helix

1330 – 1342

13

Turn

1354 – 1358

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 1992. Version 3. Checksum: 96F896D13D390E04	FASTA	1,390	155,527
	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 ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 190 200 210 220 230 240 GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE 250 260 270 280 290 300 FRDSYPIKYV HAFESNNFIY FLTVQRETLD 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 ARRDEYRTEF 430 440 450 460 470 480 TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 490 500 510 520 530 540 LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 550 560 570 580 590 600 CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK 610 620 630 640 650 660 TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT 670 680 690 700 710 720 SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 730 740 750 760 770 780 AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV 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 ISTALLLLLG FFLWLKKRKQ 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 VVLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 1330 1340 1350 1360 1370 1380 HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD 1390 TRPASFWETS
	Isoform 2. Checksum: CFF64DCBA613C74F	FASTA	1,408	157,698
	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 ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL 190 200 210 220 230 240 GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE 250 260 270 280 290 300 FRDSYPIKYV HAFESNNFIY FLTVQRETLD 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 ARRDEYRTEF 430 440 450 460 470 480 TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL 490 500 510 520 530 540 LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW 550 560 570 580 590 600 CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK 610 620 630 640 650 660 TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT 670 680 690 700 710 720 SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF 730 740 750 760 770 780 AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISTWWKE PLNIVSFLFC FASGGSTITG 790 800 810 820 830 840 VGKNLNSVSV PRMVINVHEA GRNFTVACQH RSNSEIICCT TPSLQQLNLQ LPLKTKAFFM 850 860 870 880 890 900 LDGILSKYFD LIYVHNPVFK PFEKPVMISM GNENVLEIKG NDIDPEAVKG EVLKVGNKSC 910 920 930 940 950 960 ENIHLHSEAV LCTVPNDLLK LNSELNIEWK QAISSTVLGK VIVQPDQNFT GLIAGVVSIS 970 980 990 1000 1010 1020 TALLLLLGFF LWLKKRKQIK DLGSELVRYD ARVHTPHLDR LVSARSVSPT TEMVSNESVD 1030 1040 1050 1060 1070 1080 YRATFPEDQF PNSSQNGSCR QVQYPLTDMS PILTSGDSDI SSPLLQNTVH IDLSALNPEL 1090 1100 1110 1120 1130 1140 VQAVQHVVIG PSSLIVHFNE VIGRGHFGCV YHGTLLDNDG KKIHCAVKSL NRITDIGEVS 1150 1160 1170 1180 1190 1200 QFLTEGIIMK DFSHPNVLSL LGICLRSEGS PLVVLPYMKH GDLRNFIRNE THNPTVKDLI 1210 1220 1230 1240 1250 1260 GFGLQVAKGM KYLASKKFVH RDLAARNCML DEKFTVKVAD FGLARDMYDK EYYSVHNKTG 1270 1280 1290 1300 1310 1320 AKLPVKWMAL ESLQTQKFTT KSDVWSFGVV LWELMTRGAP PYPDVNTFDI TVYLLQGRRL 1330 1340 1350 1360 1370 1380 LQPEYCPDPL YEVMLKCWHP KAEMRPSFSE LVSRISAIFS TFIGEHYVHV NATYVNVKCV 1390 1400 APYPSLLSSE DNADDEVDTR PASFWETS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors." Park M., Dean M., Kaul K., Braun M.J., Gonda M.A., Vande Woude G. Proc. Natl. Acad. Sci. U.S.A. 84:6379-6383(1987) [PubMed: 2819873] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	Giordano S. Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Primary structure of the met protein tyrosine kinase domain." Chan A.M.-L., King H.W.S., Tempest P.R., Deakin E.A., Cooper C.S., Brookes P. Oncogene 1:229-233(1987) [PubMed: 3325883] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1010-1390.
[5]	"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes." Lee S.-T., Strunk K.M., Spritz R.A. Oncogene 8:3403-3410(1993) [PubMed: 8247543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1206-1264.
[6]	"The human met oncogene is related to the tyrosine kinase oncogenes." Dean M., Park M., le Beau M.M., Robins T.S., Diaz M.O., Rowley J.D., Blair D.G., Vande Woude G.F. Nature 318:385-388(1985) [PubMed: 4069211] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1267-1390.
[7]	"Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product." Bottaro D.P., Rubin J.S., Faletto D.L., Chan A.M.-L., Kmiecik T.E., Vande Woude G.F., Aaronson S.A. Science 251:802-804(1991) [PubMed: 1846706] [Abstract] Cited for: FUNCTION.
[8]	"Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase." Ferracini R., Longati P., Naldini L., Vigna E., Comoglio P.M. J. Biol. Chem. 266:19558-19564(1991) [PubMed: 1655790] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1235, ATP-BINDING SITE LYS-1110.
[9]	"Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM." Wang D., Li Z., Messing E.M., Wu G. J. Biol. Chem. 277:36216-36222(2002) [PubMed: 12147692] [Abstract] Cited for: INTERACTION WITH RANBP9.
[10]	"The semaphorin 4D receptor controls invasive growth by coupling with Met." Giordano S., Corso S., Conrotto P., Artigiani S., Gilestro G., Barberis D., Tamagnone L., Comoglio P.M. Nat. Cell Biol. 4:720-724(2002) [PubMed: 12198496] [Abstract] Cited for: INTERACTION WITH PLXNB1.
[11]	"A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling." Wang D., Li Z., Schoen S.R., Messing E.M., Wu G. Biochem. Biophys. Res. Commun. 313:320-326(2004) [PubMed: 14684163] [Abstract] Cited for: INTERACTION WITH RANBP9 AND RANBP10.
[12]	"MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met." Higuchi T., Orita T., Katsuya K., Yamasaki Y., Akiyama K., Li H., Yamamoto T., Saito Y., Nakamura M. Mol. Cell. Biol. 24:7456-7468(2004) [PubMed: 15314156] [Abstract] Cited for: FUNCTION, INTERACTION WITH MUC20.
[13]	"The SH2-domian-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met directly via tyrosine residue 1356 and involves hepatocyte growth factor (HGF)-induced lamellipodium formation, cell scattering and cell spreading." Koch A., Mancini A., El Bounkari O., Tamura T. Oncogene 24:3436-3447(2005) [PubMed: 15735664] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1356, INTERACTION WITH INPPL1.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1003; TYR-1230; TYR-1234 AND TYR-1235, MASS SPECTROMETRY.
[15]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-977; SER-988; SER-990 AND TYR-1003, MASS SPECTROMETRY.
[16]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-966; THR-977; SER-988; SER-990; SER-997; SER-1000 AND TYR-1003, MASS SPECTROMETRY.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990; SER-997 AND SER-1000, MASS SPECTROMETRY.
[18]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202, MASS SPECTROMETRY. Tissue: Liver.
[19]	"Identification of N-glycosylation sites on secreted proteins of human hepatocellular carcinoma cells with a complementary proteomics approach." Cao J., Shen C., Wang H., Shen H., Chen Y., Nie A., Yan G., Lu H., Liu Y., Yang P. J. Proteome Res. 8:662-672(2009) [PubMed: 19196183] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106, MASS SPECTROMETRY.
[20]	"Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex." Schiering N., Casale E., Caccia P., Giordano P., Battistini C. Biochemistry 39:13376-13382(2000) [PubMed: 11063574] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1356-1359 IN COMPLEX WITH GRB2.
[21]	"Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a." Schiering N., Knapp S., Marconi M., Flocco M.M., Cui J., Perego R., Rusconi L., Cristiani C. Proc. Natl. Acad. Sci. U.S.A. 100:12654-12659(2003) [PubMed: 14559966] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1049-1360 IN COMPLEX WITH INHIBITOR.
[22]	"Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas." Schmidt L., Duh F.-M., Chen F., Kishida T., Glenn G., Choyke P., Scherer S.W., Zhuang Z., Lubensky I., Dean M., Allikmets R., Chidambaram A., Bergerheim U.R., Feltis J.T., Casadevall C., Zamarron A., Bernues M., Richard S. , Lips C.J.M., Walther M.M., Tsui L.-C., Geil L., Orcutt M.L., Stackhouse T., Lipan J., Slife L., Brauch H., Decker J., Niehans G., Hughson M.D., Moch H., Storkel S., Lerman M.I., Linehan W.M., Zbar B. Nat. Genet. 16:68-73(1997) [PubMed: 9140397] [Abstract] Cited for: VARIANTS HPRC THR-1131; LEU-1188; VAL-1195; ILE-1220; HIS-1228; ASN-1228; CYS-1230; HIS-1230 AND THR-1250, VARIANT VAL-320.
[23]	"Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene." Schmidt L., Junker K., Weirich G., Glenn G., Choyke P., Lubensky I., Zhuang Z., Jeffers M., Vande Woude G., Neumann H., Walther M., Linehan W.M., Zbar B. Cancer Res. 58:1719-1722(1998) [PubMed: 9563489] [Abstract] Cited for: VARIANT HPRC ARG-1094, CHARACTERIZATION OF VARIANT HPRC ARG-1094.
[24]	"Hereditary and sporadic papillary renal carcinomas with c-met mutations share a distinct morphological phenotype." Lubensky I.A., Schmidt L., Zhuang Z., Weirich G., Pack S., Zambrano N., Walther M.M., Choyke P., Linehan W.M., Zbar B. Am. J. Pathol. 155:517-526(1999) [PubMed: 10433944] [Abstract] Cited for: VARIANTS HPRC ILE-1092; ARG-1094; ASP-1106; THR-1131; LEU-1188; ASP-1230; CYS-1230 AND THR-1250.
[25]	"Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas." Park W.S., Dong S.M., Kim S.Y., Na E.Y., Shin M.S., Pi J.H., Kim B.J., Bae J.H., Hong Y.K., Lee K.S., Lee S.H., Yoo N.J., Jang J.J., Pack S., Zhuang Z., Schmidt L., Zbar B., Lee J.Y. Cancer Res. 59:307-310(1999) [PubMed: 9927037] [Abstract] Cited for: VARIANTS HCC ILE-1173; ARG-1244 AND ILE-1250.
[26]	"Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family." Olivero M., Valente G., Bardelli A., Longati P., Ferrero N., Cracco C., Terrone C., Rocca-Rossetti S., Comoglio P.M., Di Renzo M.F. Int. J. Cancer 82:640-643(1999) [PubMed: 10417759] [Abstract] Cited for: VARIANT HPRC ILE-1092, CHARACTERIZATION OF VARIANT HPRC ILE-1092.
[27]	"Novel mutations of the MET proto-oncogene in papillary renal carcinomas." Schmidt L., Junker K., Nakaigawa N., Kinjerski T., Weirich G., Miller M., Lubensky I., Neumann H.P.H., Brauch H., Decker J., Vocke C., Brown J.A., Jenkins R., Richard S., Bergerheim U., Gerrard B., Dean M., Linehan W.M., Zbar B. Oncogene 18:2343-2350(1999) [PubMed: 10327054] [Abstract] Cited for: VARIANTS HPRC ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230, CHARACTERIZATION OF VARIANTS HPRC ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230.
[28]	"A novel germ line juxtamembrane Met mutation in human gastric cancer." Lee J.-H., Han S.-U., Cho H., Jennings B., Gerrard B., Dean M., Schmidt L., Zbar B., Vande Woude G.F.V. Oncogene 19:4947-4953(2000) [PubMed: 11042681] [Abstract] Cited for: VARIANT GASTRIC CANCER SER-991, VARIANT ILE-992, CHARACTERIZATION OF VARIANT GASTRIC CANCER SER-991, CHARACTERIZATION OF VARIANT ILE-992.
[29]	"A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer." Kim I.-J., Park J.-H., Kang H.C., Shin Y., Lim S.-B., Ku J.-L., Yang H.-K., Lee K.U., Park J.-G. J. Med. Genet. 40:E97-E97(2003) [PubMed: 12920089] [Abstract] Cited for: VARIANT GASTRIC CANCER LEU-773.
[30]	"The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway." Wang D., Li Z., Messing E.M., Wu G. J. Biol. Chem. 280:16393-16401(2005) [PubMed: 15713673] [Abstract] Cited for: INTERACTION WITH SPSB1; SPSB2; SPSB3 AND SPSB4.
[31]	"A genetic variant that disrupts MET transcription is associated with autism." Campbell D.B., Sutcliffe J.S., Ebert P.J., Militerni R., Bravaccio C., Trillo S., Elia M., Schneider C., Melmed R., Sacco R., Persico A.M., Levitt P. Proc. Natl. Acad. Sci. U.S.A. 103:16834-16839(2006) [PubMed: 17053076] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO AUTS9, VARIANTS CYS-970 AND ILE-992.
[32]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-143; LEU-156; ASP-168; SER-375; CYS-970 AND ILE-992.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Wikipedia

C-MET entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

J02958 mRNA. Translation: AAA59591.1.
X54559 mRNA. Translation: CAB56793.1.
AC002080 Genomic DNA. Translation: AAB54047.1.
AC002543 Genomic DNA. Translation: AAC60383.1.
AC004416 Genomic DNA. Translation: AAF66137.2.
U08818 mRNA. Translation: AAB60323.1. Sequence problems.
M35074 mRNA. Translation: AAA59590.1.

IPI

IPI00029273.
IPI00294528.

PIR

TVHUME. A40175.

RefSeq

NP_000236.2.
NP_001120972.1.

UniGene

Hs.132966

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FYR	X-ray	2.40	I/J/K/L	1356-1359	[»]
1R0P	X-ray	1.80	A	1049-1360	[»]
1R1W	X-ray	1.80	A	1049-1360	[»]
1SHY	X-ray	3.22	B	25-567	[»]
1SSL	NMR	-	A	519-562	[»]
1UX3	model	-	A	25-656	[»]
2G15	X-ray	2.15	A	1038-1346	[»]
2RFN	X-ray	2.50	A/B	1048-1351	[»]
2RFS	X-ray	2.20	A	1048-1351	[»]
2UZX	X-ray	2.80	B/D	25-740	[»]
2UZY	X-ray	4.00	B/D	25-740	[»]
2WD1	X-ray	2.00	A	1055-1346	[»]
3BUX	X-ray	1.35	A/C	997-1009	[»]
3CE3	X-ray	2.40	A	1049-1360	[»]
3CTH	X-ray	2.30	A	1049-1360	[»]
3CTJ	X-ray	2.50	A	1049-1360	[»]
3EFJ	X-ray	2.60	A/B	1048-1351	[»]
3EFK	X-ray	2.20	A/B	1048-1351	[»]
3F66	X-ray	1.40	A/B	1052-1349	[»]
3F82	X-ray	2.50	A	1049-1360	[»]

DisProt

DP00317.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6023N.

IntAct

P08581. 11 interactions.

PTM databases

PhosphoSite

P08581.

2-D gel databases

OGP

P08581.

Proteomic databases

PRIDE

P08581.

Genome annotation databases

Ensembl

ENSG00000105976. Homo sapiens. [Contig view]

GeneID

4233.

KEGG

hsa:4233.

Organism-specific databases

GeneCards

GC07P116099.

H-InvDB

HIX0007019.

HGNC

HGNC:7029. MET.

HPA

CAB005282.

MIM

114550. phenotype.
164860. gene.
605074. phenotype.
611015. phenotype.

Orphanet

106. Autism.
33402. Hepatocellular carcinoma of childhood.
47044. Renal cell carcinoma, papillary, familial.

PharmGKB

PA24993.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P08581.

HOVERGEN

P08581.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
arf6cyclingpathway. Arf6 signaling events.
faspathway. FAS signaling pathway (CD95).
fgf_pathway. FGF signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
syndecan_1_pathway. Syndecan-1-mediated signaling events.

Gene expression databases

ArrayExpress

P08581.

Bgee

P08581.

CleanEx

HS_MET.

GermOnline

ENSG00000105976. Homo sapiens.

Family and domain databases

InterPro

IPR002909. IPT_TIG_rcpt.
IPR003659. Plexin-like.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001627. Semaphorin/CD100_Ag.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
IPR016244. TyrPK_HGF-R.
IPR015943. WD40/YVTN_repeat-like.
[Graphical view]

Gene3D

G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.

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.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

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...

Other Resources

NextBio

16689.

SOURCE

Search...

Entry information

Entry name

MET_HUMAN

Accession

Primary (citable) accession number: P08581
Secondary accession number(s): O60366 , Q12875, Q9UDX7, Q9UPL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	December 1, 1992
Last modified:	June 16, 2009
This is version 135 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)