P08581 (MET_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [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 › Hominoidea › Hominidae › Homininae › 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 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. Ref.14 Ref.17 Ref.25 Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells. Ref.14 Ref.17 Ref.25
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.
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 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. Interacts with GRB10. Ref.12 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.26 Ref.34 Ref.48
Subcellular location	Membrane; Single-pass type I membrane protein. Isoform 3: Secreted.
Tissue specificity	Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. Ref.11 Ref.13
Domain	The kinase domain is involved in SPSB1 binding. The beta-propeller Sema domain mediates binding to HGF.
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. Ref.15 Ref.16 Ref.23 Ref.26 Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Ref.15 Ref.16 Ref.23 Ref.26 Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. Ref.21
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. Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.43 Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.41 Ref.42 Ref.44 Ref.45 A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies. Ref.51
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 Secreted
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation 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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPK activity Inferred from electronic annotation. Source: Compara adult behavior Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement. Source: Reactome brain development Inferred from electronic annotation. Source: Compara branching morphogenesis of an epithelial tube Inferred from mutant phenotype PubMed 16153003. Source: UniProtKB cell proliferation Traceable author statement PubMed 10871856. Source: ProtInc glucose homeostasis Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara muscle cell migration Inferred from electronic annotation. Source: Compara myoblast proliferation Inferred from electronic annotation. Source: Compara myotube differentiation Inferred from electronic annotation. Source: Compara negative regulation of hydrogen peroxide-mediated programmed cell death Inferred from mutant phenotype PubMed 20655899. Source: BHF-UCL placenta development Inferred from electronic annotation. Source: Compara positive regulation of glucose transport Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 22521434. Source: BHF-UCL protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Inferred from electronic annotation. Source: Compara
Cellular_component	basal plasma membrane Inferred from direct assay Ref.25. Source: MGI extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.14. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW hepatocyte growth factor-activated receptor activity Traceable author statement PubMed 10871856. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNAJA3	Q96EY1-2	2	EBI-1039152,EBI-3952284
EGFR	P00533	4	EBI-1039152,EBI-297353
HGF	P14210	4	EBI-1039152,EBI-1039104
HGF	P14210-6	2	EBI-1039152,EBI-6280319
inlB	P25147	4	EBI-1039152,EBI-1379295	From a different organism.
KDR	P35968	3	EBI-1039152,EBI-1005487
Kdr	P35918	3	EBI-1039152,EBI-1555005	From a different organism.
PLXNB1	O43157	7	EBI-1039152,EBI-1111488
PLXNB2	O15031	2	EBI-1039152,EBI-722004
PLXNB3	Q9ULL4	2	EBI-1039152,EBI-311073
PTK2	Q00944	5	EBI-1039152,EBI-2896409	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional soluble isoforms seem to exist.

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.

Isoform 3 (identifier: P08581-3)

Also known as: Soluble MET variant 4;

The sequence of this isoform differs from the canonical sequence as follows:
     755-764: SGGSTITGVG → RHVNIALIQR
     765-1390: Missing.

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

Helical; 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

977

1

Phosphothreonine Ref.28

Modified residue

990

1

Phosphoserine Ref.29

Modified residue

997

1

Phosphoserine Ref.29

Modified residue

1000

1

Phosphoserine Ref.29

Modified residue

1003

1

Phosphotyrosine Ref.28 Ref.31

Modified residue

1230

1

Phosphotyrosine Ref.23

Modified residue

1234

1

Phosphotyrosine; by autocatalysis Ref.23

Modified residue

1235

1

Phosphotyrosine; by autocatalysis Ref.15 Ref.23

Modified residue

1289

1

Phosphothreonine Ref.31

Modified residue

1349

1

Phosphotyrosine; by autocatalysis Ref.16 Ref.23

Modified residue

1356

1

Phosphotyrosine; by autocatalysis Ref.16 Ref.26

Modified residue

1365

1

Phosphotyrosine Ref.23

Glycosylation

45

1

N-linked (GlcNAc...) Potential

Glycosylation

106

1

N-linked (GlcNAc...) Ref.30

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

Ref.37 Ref.38 Ref.39

Disulfide bond

98 ↔ 160

Ref.37 Ref.38 Ref.39

Disulfide bond

133 ↔ 141

Ref.37 Ref.38 Ref.39

Disulfide bond

172 ↔ 175

Ref.37 Ref.38 Ref.39

Disulfide bond

298 ↔ 363

Ref.37 Ref.38 Ref.39

Disulfide bond

385 ↔ 397

Ref.37 Ref.38 Ref.39

Disulfide bond

520 ↔ 538

Ref.37 Ref.38 Ref.39

Disulfide bond

526 ↔ 561

Ref.37 Ref.38 Ref.39

Disulfide bond

529 ↔ 545

Ref.37 Ref.38 Ref.39

Disulfide bond

541 ↔ 551

Ref.37 Ref.38 Ref.39

Natural variations

Alternative sequence

755 – 764

10

SGGSTITGVG → RHVNIALIQR in isoform 3.

VSP_042447

Alternative sequence

755

1

S → STWWKEPLNIVSFLFCFAS in isoform 2.

VSP_005005

Alternative sequence

765 – 1390

626

Missing in isoform 3.

VSP_042448

Natural variant

143

1

R → Q. Ref.50
Corresponds to variant rs35469582 [ dbSNP | Ensembl ].

VAR_041738

Natural variant

150

1

H → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.51

VAR_064855

Natural variant

156

1

S → L. Ref.50
Corresponds to variant rs56311081 [ dbSNP | Ensembl ].

VAR_041739

Natural variant

168

1

E → D Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.50 Ref.51
Corresponds to variant rs55985569 [ dbSNP | Ensembl ].

VAR_041740

Natural variant

238

1

L → S.
Corresponds to variant rs34349517 [ dbSNP | Ensembl ].

VAR_032478

Natural variant

316

1

I → M.
Corresponds to variant rs35225896 [ dbSNP | Ensembl ].

VAR_032479

Natural variant

320

1

A → V. Ref.40
Corresponds to variant rs35776110 [ dbSNP | Ensembl ].

VAR_006285

Natural variant

375

1

N → S. Ref.50
Corresponds to variant rs33917957 [ dbSNP | Ensembl ].

VAR_032480

Natural variant

385

1

C → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.51

VAR_064856

Natural variant

773

1

P → L in gastric cancer. Ref.47

VAR_032481

Natural variant

970

1

R → C. Ref.49 Ref.50
Corresponds to variant rs34589476 [ dbSNP | Ensembl ].

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.46

VAR_032483

Natural variant

992

1

T → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.46 Ref.49 Ref.50 Ref.51
Corresponds to variant rs56391007 [ dbSNP | Ensembl ].

VAR_032484

Natural variant

1092

1

V → I in RCCP; constitutive autophosphorylation. Ref.42 Ref.44 Ref.45

VAR_032485

Natural variant

1094

1

H → L in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.45

VAR_032486

Natural variant

1094

1

H → R in RCCP; causes malignant transformation in cell lines. Ref.41 Ref.42

VAR_032487

Natural variant

1094

1

H → Y in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.45

VAR_032488

Natural variant

1106

1

H → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.42 Ref.45

VAR_032489

Natural variant

1131

1

M → T in RCCP; germline mutation. Ref.40 Ref.42

VAR_006286

Natural variant

1173

1

T → I in HCC. Ref.43

VAR_032490

Natural variant

1188

1

V → L in RCCP; germline mutation. Ref.40 Ref.42

VAR_006287

Natural variant

1195

1

L → V in RCCP; somatic mutation. Ref.40

VAR_006288

Natural variant

1220

1

V → I in RCCP; germline mutation. Ref.40

VAR_006289

Natural variant

1228

1

D → H in RCCP; somatic mutation. Ref.40

VAR_006291

Natural variant

1228

1

D → N in RCCP; germline mutation. Ref.40

VAR_006290

Natural variant

1230

1

Y → C in RCCP; germline mutation. Ref.40 Ref.42

VAR_006292

Natural variant

1230

1

Y → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. Ref.42 Ref.45

VAR_032491

Natural variant

1230

1

Y → H in RCCP; somatic mutation. Ref.40

VAR_006293

Natural variant

1244

1

K → R in HCC. Ref.43

VAR_032492

Natural variant

1250

1

M → I in HCC. Ref.43

VAR_032493

Natural variant

1250

1

M → T in RCCP; somatic mutation. Ref.40 Ref.42

VAR_006294

Natural variant

1294

1

V → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. Ref.51

VAR_064857

Experimental info

Sequence conflict

237

1

V → A in ACF47606. Ref.3

Sequence conflict

508

1

K → R in ACF47606. Ref.3

Sequence conflict

720

1

F → S in ACF47606. Ref.3

Sequence conflict

1191

1

G → A in AAA59591. Ref.1

Sequence conflict

1272

1

L → V in AAA59591. Ref.1

Sequence conflict

1272

1

L → V in CAB56793. Ref.2

Sequence conflict

1272

1

L → V in AAA59590. Ref.6

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 – 84

5

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

119 – 123

5

Beta strand

125 – 133

9

Beta strand

135 – 139

5

Beta strand

141 – 145

5

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

239 – 241

3

Turn

242 – 244

3

Beta strand

247 – 255

9

Beta strand

258 – 268

11

Beta strand

272 – 274

3

Beta strand

277 – 281

5

Beta strand

284 – 286

3

Beta strand

292 – 300

9

Beta strand

312 – 314

3

Beta strand

316 – 323

8

Helix

327 – 333

7

Beta strand

341 – 349

9

Beta strand

356 – 366

11

Helix

367 – 374

8

Helix

387 – 390

4

Beta strand

392 – 394

3

Turn

395 – 398

4

Beta strand

418 – 422

5

Beta strand

424 – 427

4

Turn

429 – 436

8

Beta strand

439 – 447

9

Beta strand

450 – 457

8

Beta strand

462 – 466

5

Beta strand

469 – 471

3

Beta strand

490 – 493

4

Turn

496 – 498

3

Beta strand

501 – 506

6

Beta strand

509 – 514

6

Helix

517 – 520

4

Helix

526 – 531

6

Helix

534 – 536

3

Beta strand

538 – 540

3

Beta strand

545 – 548

4

Beta strand

552 – 554

3

Beta strand

557 – 559

3

Beta strand

564 – 572

9

Beta strand

580 – 586

7

Beta strand

590 – 592

3

Beta strand

595 – 598

4

Beta strand

602 – 605

4

Helix

614 – 616

3

Beta strand

619 – 625

7

Beta strand

637 – 641

5

Beta strand

646 – 650

5

Turn

1048 – 1052

5

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

1100 – 1102

3

Beta strand

1105 – 1112

8

Helix

1118 – 1132

15

Beta strand

1144 – 1146

3

Beta strand

1149 – 1151

3

Beta strand

1154 – 1158

5

Helix

1165 – 1170

6

Turn

1172 – 1174

3

Helix

1178 – 1197

20

Helix

1207 – 1209

3

Beta strand

1210 – 1212

3

Beta strand

1218 – 1220

3

Helix

1224 – 1226

3

Helix

1232 – 1234

3

Helix

1237 – 1239

3

Beta strand

1241 – 1245

5

Helix

1247 – 1249

3

Helix

1252 – 1257

6

Helix

1262 – 1277

16

Beta strand

1285 – 1287

3

Turn

1289 – 1291

3

Helix

1292 – 1297

6

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 July 7, 2009. Version 4. Checksum: 9CF896D1273905C3	FASTA	1,390	155,541
	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 VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW 1330 1340 1350 1360 1370 1380 HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD 1390 TRPASFWETS
	Isoform 2 [UniParc]. Checksum: C5F64DCBBC13CC88	FASTA	1,408	157,712
	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 KSDVWSFGVL LWELMTRGAP PYPDVNTFDI TVYLLQGRRL 1330 1340 1350 1360 1370 1380 LQPEYCPDPL YEVMLKCWHP KAEMRPSFSE LVSRISAIFS TFIGEHYVHV NATYVNVKCV 1390 1400 APYPSLLSSE DNADDEVDTR PASFWETS
	Isoform 3 (Soluble MET variant 4) [UniParc]. Checksum: BBCBC4197C9C18DE	FASTA	764	85,745
	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 AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFIRHVNIA LIQR

References

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[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] [Europe PMC] [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]	"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis." Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M. Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1010-1390.
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1206-1264.
[10]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1267-1390.
[11]	"The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors." Prat M., Narsimhan R.P., Crepaldi T., Nicotra M.R., Natali P.G., Comoglio P.M. Int. J. Cancer 49:323-328(1991) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase." Graziani A., Gramaglia D., Cantley L.C., Comoglio P.M. J. Biol. Chem. 266:22087-22090(1991) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PIK3R1.
[13]	"Expression of the Met/HGF receptor in normal and neoplastic human tissues." Di Renzo M.F., Narsimhan R.P., Olivero M., Bretti S., Giordano S., Medico E., Gaglia P., Zara P., Comoglio P.M. Oncogene 6:1997-2003(1991) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1235, ATP-BINDING SITE LYS-1110.
[16]	"A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family." Ponzetto C., Bardelli A., Zhen Z., Maina F., dalla Zonca P., Giordano S., Graziani A., Panayotou G., Comoglio P.M. Cell 77:261-271(1994) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION AT TYR-1349 AND TYR-1356, INTERACTION WITH SRC; PLCG1 AND GRB2.
[17]	"Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium." Nusrat A., Parkos C.A., Bacarra A.E., Godowski P.J., Delp-Archer C., Rosen E.M., Madara J.L. J. Clin. Invest. 93:2056-2065(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN WOUND HEALING.
[18]	"Induction of epithelial tubules by growth factor HGF depends on the STAT pathway." Boccaccio C., Ando M., Tamagnone L., Bardelli A., Michieli P., Battistini C., Comoglio P.M. Nature 391:285-288(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAT3.
[19]	"Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis." Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., Swamy O.R., Leone M.E., Riedel H. Mol. Cell. Biol. 19:6217-6228(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB10.
[20]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RANBP9.
[21]	"c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination." Taher T.E., Tjin E.P., Beuling E.A., Borst J., Spaargaren M., Pals S.T. J. Immunol. 169:3793-3800(2002) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[22]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLXNB1.
[23]	"Hepatocyte growth factor receptor tyrosine kinase met is a substrate of the receptor protein-tyrosine phosphatase DEP-1." Palka H.L., Park M., Tonks N.K. J. Biol. Chem. 278:5728-5735(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1230; TYR-1234; TYR-1235; TYR-1349 AND TYR-1365, DEPHOSPHORYLATION BY PTPRJ AT TYR-1349 AND TYR-1365.
[24]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RANBP9 AND RANBP10.
[25]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MUC20.
[26]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-1356, INTERACTION WITH INPPL1.
[27]	"Invasive growth: a MET-driven genetic programme for cancer and stem cells." Boccaccio C., Comoglio P.M. Nat. Rev. Cancer 6:637-645(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN ANGIOGENESIS.
[28]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-977 AND TYR-1003, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990; SER-997 AND SER-1000, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[30]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106, MASS SPECTROMETRY. Tissue: Hepatoma.
[31]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1003 AND THR-1289, MASS SPECTROMETRY.
[32]	"The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas." Mahtouk K., Tjin E.P., Spaargaren M., Pals S.T. Biochim. Biophys. Acta 1806:208-219(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[33]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]	"Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET." Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., Bodepudi S., Ashkenazi A. J. Biol. Chem. 286:32762-32774(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GAB1.
[35]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1356-1359 IN COMPLEX WITH GRB2.
[36]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1049-1360 IN COMPLEX WITH INHIBITOR.
[37]	"Insights into function of PSI domains from structure of the Met receptor PSI domain." Kozlov G., Perreault A., Schrag J.D., Park M., Cygler M., Gehring K., Ekiel I. Biochem. Biophys. Res. Commun. 321:234-240(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 519-562, DISULFIDE BONDS.
[38]	"Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor." Stamos J., Lazarus R.A., Yao X., Kirchhofer D., Wiesmann C. EMBO J. 23:2325-2335(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.22 ANGSTROMS) OF 25-567 IN COMPLEX WITH HGF, DISULFIDE BONDS.
[39]	"Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB." Niemann H.H., Jager V., Butler P.J., van den Heuvel J., Schmidt S., Ferraris D., Gherardi E., Heinz D.W. Cell 130:235-246(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-740 IN COMPLEX WITH L.MONOCYTOGENES INLB, DISULFIDE BONDS.
[40]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS RCCP THR-1131; LEU-1188; VAL-1195; ILE-1220; HIS-1228; ASN-1228; CYS-1230; HIS-1230 AND THR-1250, VARIANT VAL-320.
[41]	"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] [Europe PMC] [Abstract] Cited for: VARIANT RCCP ARG-1094, CHARACTERIZATION OF VARIANT RCCP ARG-1094.
[42]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS RCCP ILE-1092; ARG-1094; ASP-1106; THR-1131; LEU-1188; ASP-1230; CYS-1230 AND THR-1250.
[43]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS HCC ILE-1173; ARG-1244 AND ILE-1250.
[44]	"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] [Europe PMC] [Abstract] Cited for: VARIANT RCCP ILE-1092, CHARACTERIZATION OF VARIANT RCCP ILE-1092.
[45]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230, CHARACTERIZATION OF VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230.
[46]	"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] [Europe PMC] [Abstract] Cited for: VARIANT GASTRIC CANCER SER-991, VARIANT ILE-992, CHARACTERIZATION OF VARIANT GASTRIC CANCER SER-991, CHARACTERIZATION OF VARIANT ILE-992.
[47]	"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] [Europe PMC] [Abstract] Cited for: VARIANT GASTRIC CANCER LEU-773.
[48]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPSB1; SPSB2; SPSB3 AND SPSB4.
[49]	"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] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO AUTS9, VARIANTS CYS-970 AND ILE-992.
[50]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-143; LEU-156; ASP-168; SER-375; CYS-970 AND ILE-992.
[51]	"MET mutations in cancers of unknown primary origin (CUPs)." Stella G.M., Benvenuti S., Gramaglia D., Scarpa A., Tomezzoli A., Cassoni P., Senetta R., Venesio T., Pozzi E., Bardelli A., Comoglio P.M. Hum. Mutat. 32:44-50(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, CHARACTERIZATION OF VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, POSSIBLE INVOLVEMENT IN CUP.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Wikipedia

C-MET entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02958 mRNA. Translation: AAA59591.1.
X54559 mRNA. Translation: CAB56793.1.
EU826570 mRNA. Translation: ACF47606.1.
AC002080 Genomic DNA. Translation: AAB54047.1.
AC002543 Genomic DNA. Translation: AAC60383.1.
AC004416 Genomic DNA. Translation: AAF66137.2.
CH236947 Genomic DNA. Translation: EAL24359.1.
CH471070 Genomic DNA. Translation: EAW83509.1.
BC130420 mRNA. Translation: AAI30421.1.
U08818 mRNA. Translation: AAB60323.1. Sequence problems.
M35074 mRNA. Translation: AAA59590.1.

IPI

IPI00029273.
IPI00294528.

PIR

TVHUME. A40175.

RefSeq

NP_000236.2. NM_000245.2.
NP_001120972.1. NM_001127500.1.

UniGene

Hs.132966.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
2WGJ	X-ray	2.00	A	1051-1348	[»]
2WKM	X-ray	2.20	A	1051-1348	[»]
3A4P	X-ray	2.54	A	1049-1360	[»]
3BUX	X-ray	1.35	A/C	997-1009	[»]
3C1X	X-ray	2.17	A	1049-1360	[»]
3CCN	X-ray	1.90	A	1048-1351	[»]
3CD8	X-ray	2.00	A	1048-1351	[»]
3CE3	X-ray	2.40	A	1049-1360	[»]
3CTH	X-ray	2.30	A	1049-1360	[»]
3CTJ	X-ray	2.50	A	1049-1360	[»]
3DKC	X-ray	1.52	A	1049-1360	[»]
3DKF	X-ray	1.80	A	1049-1360	[»]
3DKG	X-ray	1.91	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	[»]
3I5N	X-ray	2.00	A	1048-1351	[»]
3L8V	X-ray	2.40	A	1049-1360	[»]
3LQ8	X-ray	2.02	A	1051-1348	[»]
3Q6U	X-ray	1.60	A	1048-1348	[»]
3Q6W	X-ray	1.75	A	1048-1348	[»]
3QTI	X-ray	2.00	A/B	1050-1360	[»]
3R7O	X-ray	2.30	A	1048-1348	[»]
3RHK	X-ray	1.94	A/B	1038-1346	[»]
3U6H	X-ray	2.00	A	1048-1351	[»]
3U6I	X-ray	2.10	A	1048-1351	[»]
3ZXZ	X-ray	1.80	A	1051-1348	[»]
3ZZE	X-ray	1.87	A	1051-1348	[»]
4AOI	X-ray	1.90	A	1051-1348	[»]
4AP7	X-ray	1.80	A	1051-1348	[»]
4DEG	X-ray	2.00	A	1048-1351	[»]
4DEH	X-ray	2.00	A	1048-1351	[»]
4DEI	X-ray	2.05	A	1048-1351	[»]
4EEV	X-ray	1.80	A	1038-1346	[»]
4GG5	X-ray	2.42	A	1038-1346	[»]
4GG7	X-ray	2.27	A	1038-1346	[»]

DisProt

DP00317.

ProteinModelPortal

P08581.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6023N.

IntAct

P08581. 20 interactions.

MINT

MINT-4837114.

STRING

9606.ENSP00000317272.

PTM databases

PhosphoSite

P08581.

Polymorphism databases

DMDM

251757497.

2D gel databases

OGP

P08581.

Proteomic databases

PaxDb

P08581.

PRIDE

P08581.

Protocols and materials databases

DNASU

4233.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000318493; ENSP00000317272; ENSG00000105976.
ENST00000397752; ENSP00000380860; ENSG00000105976.
ENST00000436117; ENSP00000410980; ENSG00000105976.

GeneID

4233.

KEGG

hsa:4233.

UCSC

uc003vij.3. human.
uc010lkh.3. human.
uc011knc.1. human.

Organism-specific databases

CTD

4233.

GeneCards

GC07P116312.

HGNC

HGNC:7029. MET.

HPA

CAB005282.
CAB018577.

MIM

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

neXtProt

NX_P08581.

Orphanet

106. Autism.
47044. Familial papillary renal cell carcinoma.
33402. Hepatocellular carcinoma, childhood-onset.

PharmGKB

PA30763.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000220900.

HOVERGEN

HBG006348.

KO

K05099.

OMA

RVDLFMG.

OrthoDB

EOG466VK2.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

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.

Reactome

REACT_111045. Developmental Biology.

SignaLink

P08581.

Gene expression databases

ArrayExpress

P08581.

Bgee

P08581.

CleanEx

HS_MET.

Genevestigator

P08581.

GermOnline

ENSG00000105976. Homo sapiens.

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...

Other

BindingDB

P08581.

ChEMBL

CHEMBL3717.

ChiTaRS

MET. human.

EvolutionaryTrace

P08581.

GenomeRNAi

4233.

NextBio

16689.

SOURCE

Search...

Entry information

Entry name

MET_HUMAN

Accession

Primary (citable) accession number: P08581
Secondary accession number(s): A1L467 , B5A932, E7EQ94, O60366, Q12875, Q9UDX7, Q9UPL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	July 7, 2009
Last modified:	May 29, 2013
This is version 184 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.