P14210 (HGF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hepatocyte growth factor

Alternative name(s):
Hepatopoietin-A
Scatter factor
Short name=SF

Cleaved into the following 2 chains:

1. Hepatocyte growth factor alpha chain
2. Hepatocyte growth factor beta chain

Gene names

Name:	HGF
Synonyms:	HPTA

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	728 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	Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Ref.22 Ref.23
Subunit structure	Dimer of an alpha chain and a beta chain linked by a disulfide bond. Ref.22
Involvement in disease	Deafness, autosomal recessive, 39 (DFNB39) [MIM:608265]: A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19
Sequence similarities	Belongs to the peptidase S1 family. Plasminogen subfamily. Contains 4 kringle domains. Contains 1 PAN domain. Contains 1 peptidase S1 domain.
Caution	Has lost two of the three essential catalytic residues and so probably has no enzymatic activity.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Non-syndromic deafness
Domain	Kringle Repeat Signal
Molecular function	Growth factor Serine protease homolog
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPK activity Inferred from electronic annotation. Source: Compara cell chemotaxis Inferred from direct assay PubMed 21245381. Source: BHF-UCL cellular response to hepatocyte growth factor stimulus Inferred from direct assay PubMed 21245381. Source: BHF-UCL epithelial to mesenchymal transition Traceable author statement PubMed 14679171. Source: HGNC hepatocyte growth factor receptor signaling pathway Inferred from direct assay PubMed 21245381. Source: BHF-UCL liver development Inferred from electronic annotation. Source: Compara mitosis Non-traceable author statement Ref.2. Source: UniProtKB myoblast proliferation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 20655899. Source: BHF-UCL negative regulation of hydrogen peroxide-mediated programmed cell death Inferred from direct assay PubMed 20655899. Source: BHF-UCL negative regulation of release of cytochrome c from mitochondria Inferred from direct assay PubMed 20655899. Source: BHF-UCL organ regeneration Inferred from electronic annotation. Source: Compara platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of DNA biosynthetic process Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of cell migration Inferred from direct assay PubMed 21245381. Source: BHF-UCL positive regulation of osteoblast differentiation Non-traceable author statement PubMed 22521434. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 21245381. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 20655899. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Non-traceable author statement PubMed 22521434. Source: BHF-UCL regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Inferred from direct assay PubMed 14517989. Source: MGI
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	catalytic activity Inferred from electronic annotation. Source: InterPro chemoattractant activity Inferred from direct assay PubMed 21245381. Source: BHF-UCL growth factor activity Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MET	P08581	4	EBI-1039104,EBI-1039152
Met	P16056	2	EBI-1039104,EBI-1798780	From a different organism.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P14210-1)

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: P14210-2)

The sequence of this isoform differs from the canonical sequence as follows:
     289-290: AD → ET
     291-728: Missing.

Isoform 3 (identifier: P14210-3)

The sequence of this isoform differs from the canonical sequence as follows:
     161-165: Missing.

Isoform 4 (identifier: P14210-4)

Also known as: HGF/NK2;

The sequence of this isoform differs from the canonical sequence as follows:
     287-296: TCADNTMNDT → NMRDITWALN
     297-728: Missing.

Note: Acts as a competitive antagonist in MET-signaling.

Isoform 5 (identifier: P14210-5)

The sequence of this isoform differs from the canonical sequence as follows:
     161-165: Missing.
     289-290: AD → ET
     291-728: Missing.

Note: No experimental confirmation available.

Isoform 6 (identifier: P14210-6)

Also known as: HGF/NK1;

The sequence of this isoform differs from the canonical sequence as follows:
     209-210: VE → GK
     211-728: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Chain

32 – 494

463

Hepatocyte growth factor alpha chain

PRO_0000028091

Chain

495 – 728

234

Hepatocyte growth factor beta chain

PRO_0000028092

Regions

Domain

37 – 123

87

PAN

Domain

128 – 206

79

Kringle 1

Domain

211 – 288

78

Kringle 2

Domain

305 – 383

79

Kringle 3

Domain

391 – 469

79

Kringle 4

Domain

495 – 721

227

Peptidase S1

Amino acid modifications

Modified residue

32

1

Pyrrolidone carboxylic acid

Glycosylation

294

1

N-linked (GlcNAc...) (complex)

CAR_000021

Glycosylation

402

1

N-linked (GlcNAc...) (complex)

CAR_000022

Glycosylation

476

1

O-linked (GalNAc...) Ref.17

CAR_000023

Glycosylation

566

1

N-linked (GlcNAc...) (complex)

CAR_000024

Glycosylation

653

1

N-linked (GlcNAc...) (complex)

CAR_000025

Disulfide bond

70 ↔ 96

Ref.22 Ref.23

Disulfide bond

74 ↔ 84

Ref.22 Ref.23

Disulfide bond

128 ↔ 206

Ref.22 Ref.23

Disulfide bond

149 ↔ 189

Ref.22 Ref.23

Disulfide bond

177 ↔ 201

Ref.22 Ref.23

Disulfide bond

211 ↔ 288

By similarity

Disulfide bond

232 ↔ 271

By similarity

Disulfide bond

260 ↔ 283

By similarity

Disulfide bond

305 ↔ 383

By similarity

Disulfide bond

326 ↔ 365

By similarity

Disulfide bond

354 ↔ 377

By similarity

Disulfide bond

391 ↔ 469

By similarity

Disulfide bond

412 ↔ 452

By similarity

Disulfide bond

440 ↔ 464

By similarity

Disulfide bond

487 ↔ 604

Interchain (between alpha and beta chains) By similarity

Disulfide bond

519 ↔ 535

By similarity

Disulfide bond

612 ↔ 679

By similarity

Disulfide bond

642 ↔ 658

By similarity

Disulfide bond

669 ↔ 697

By similarity

Natural variations

Alternative sequence

161 – 165

5

Missing in isoform 3 and isoform 5.

VSP_009617

Alternative sequence

209 – 210

2

VE → GK in isoform 6.

VSP_009618

Alternative sequence

211 – 728

518

Missing in isoform 6.

VSP_009619

Alternative sequence

287 – 296

10

TCADNTMNDT → NMRDITWALN in isoform 4.

VSP_009620

Alternative sequence

289 – 290

2

AD → ET in isoform 2 and isoform 5.

VSP_009622

Alternative sequence

291 – 728

438

Missing in isoform 2 and isoform 5.

VSP_009623

Alternative sequence

297 – 728

432

Missing in isoform 4.

VSP_009621

Natural variant

153

1

S → I.
Corresponds to variant rs17566 [ dbSNP | Ensembl ].

VAR_014570

Natural variant

304

1

E → K. Ref.11
Corresponds to variant rs5745687 [ dbSNP | Ensembl ].

VAR_019199

Natural variant

330

1

D → Y. Ref.11
Corresponds to variant rs5745688 [ dbSNP | Ensembl ].

VAR_019200

Experimental info

Mutagenesis

494

1

R → Q: Loss of activity due to absence of proteolytic cleavage. Ref.9

Sequence conflict

32 – 33

2

QR → HK in CAA34387. Ref.2

Sequence conflict

78

1

K → N in CAA34387. Ref.2

Sequence conflict

180

1

P → T AA sequence Ref.6

Sequence conflict

293

1

M → V in CAA34387. Ref.2

Sequence conflict

300

1

L → M in CAA34387. Ref.2

Sequence conflict

317

1

V → A in CAA34387. Ref.2

Sequence conflict

336

1

E → K in CAA34387. Ref.2

Sequence conflict

387

1

H → N in CAA34387. Ref.2

Sequence conflict

416

1

D → N in CAA34387. Ref.2

Sequence conflict

505

1

I → V in CAA34387. Ref.2

Sequence conflict

509

1

V → I in CAA34387. Ref.2

Sequence conflict

558

1

D → E in CAA34387. Ref.2

Sequence conflict

561

1

C → R in CAA34387. Ref.2

Sequence conflict

592

1

D → N AA sequence Ref.6

Sequence conflict

595

1

S → N in CAA34387. Ref.2

Secondary structure

1

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728

Helix Strand Turn

Details...

Helix

39 – 41

3

Beta strand

42 – 52

11

Beta strand

55 – 57

3

Beta strand

60 – 63

4

Helix

67 – 76

10

Turn

77 – 79

3

Beta strand

80 – 82

3

Beta strand

86 – 90

5

Turn

91 – 94

4

Beta strand

95 – 100

6

Beta strand

105 – 107

3

Beta strand

108 – 121

14

Helix

122 – 124

3

Beta strand

128 – 132

5

Beta strand

148 – 150

3

Beta strand

156 – 158

3

Helix

164 – 167

4

Turn

168 – 171

4

Beta strand

187 – 193

7

Beta strand

198 – 200

3

Helix

206 – 209

4

Beta strand

211 – 213

3

Beta strand

239 – 241

3

Turn

247 – 249

3

Turn

251 – 254

4

Beta strand

270 – 274

5

Beta strand

279 – 282

4

Beta strand

508 – 525

18

Beta strand

528 – 532

5

Helix

533 – 535

3

Beta strand

537 – 539

3

Helix

541 – 543

3

Beta strand

544 – 549

6

Beta strand

551 – 554

4

Turn

557 – 561

5

Beta strand

563 – 572

10

Beta strand

579 – 586

8

Beta strand

591 – 593

3

Beta strand

611 – 618

8

Beta strand

630 – 637

8

Helix

639 – 641

3

Turn

646 – 648

3

Beta strand

656 – 660

5

Beta strand

662 – 664

3

Turn

670 – 674

5

Beta strand

676 – 680

5

Beta strand

682 – 691

10

Beta strand

695 – 698

4

Beta strand

704 – 708

5

Helix

709 – 712

4

Helix

713 – 720

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 2. Checksum: 2D997938295ADD2F	FASTA	728	83,134
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP 190 200 210 220 230 240 RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP 250 260 270 280 290 300 HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKTCAD NTMNDTDVPL 310 320 330 340 350 360 ETTECIQGQG EGYRGTVNTI WNGIPCQRWD SQYPHEHDMT PENFKCKDLR ENYCRNPDGS 370 380 390 400 410 420 ESPWCFTTDP NIRVGYCSQI PNCDMSHGQD CYRGNGKNYM GNLSQTRSGL TCSMWDKNME 430 440 450 460 470 480 DLHRHIFWEP DASKLNENYC RNPDDDAHGP WCYTGNPLIP WDYCPISRCE GDTTPTIVNL 490 500 510 520 530 540 DHPVISCAKT KQLRVVNGIP TRTNIGWMVS LRYRNKHICG GSLIKESWVL TARQCFPSRD 550 560 570 580 590 600 LKDYEAWLGI HDVHGRGDEK CKQVLNVSQL VYGPEGSDLV LMKLARPAVL DDFVSTIDLP 610 620 630 640 650 660 NYGCTIPEKT SCSVYGWGYT GLINYDGLLR VAHLYIMGNE KCSQHHRGKV TLNESEICAG 670 680 690 700 710 720 AEKIGSGPCE GDYGGPLVCE QHKMRMVLGV IVPGRGCAIP NRPGIFVRVA YYAKWIHKII LTYKVPQS
	Isoform 2 [UniParc]. Checksum: C8A18A6F0D63200A	FASTA	290	33,766
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP 190 200 210 220 230 240 RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP 250 260 270 280 290 HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKTCET
	Isoform 3 [UniParc]. Checksum: 627B1EF99FAD931B	FASTA	723	82,602
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SYRGKDLQEN YCRNPRGEEG 190 200 210 220 230 240 GPWCFTSNPE VRYEVCDIPQ CSEVECMTCN GESYRGLMDH TESGKICQRW DHQTPHRHKF 250 260 270 280 290 300 LPERYPDKGF DDNYCRNPDG QPRPWCYTLD PHTRWEYCAI KTCADNTMND TDVPLETTEC 310 320 330 340 350 360 IQGQGEGYRG TVNTIWNGIP CQRWDSQYPH EHDMTPENFK CKDLRENYCR NPDGSESPWC 370 380 390 400 410 420 FTTDPNIRVG YCSQIPNCDM SHGQDCYRGN GKNYMGNLSQ TRSGLTCSMW DKNMEDLHRH 430 440 450 460 470 480 IFWEPDASKL NENYCRNPDD DAHGPWCYTG NPLIPWDYCP ISRCEGDTTP TIVNLDHPVI 490 500 510 520 530 540 SCAKTKQLRV VNGIPTRTNI GWMVSLRYRN KHICGGSLIK ESWVLTARQC FPSRDLKDYE 550 560 570 580 590 600 AWLGIHDVHG RGDEKCKQVL NVSQLVYGPE GSDLVLMKLA RPAVLDDFVS TIDLPNYGCT 610 620 630 640 650 660 IPEKTSCSVY GWGYTGLINY DGLLRVAHLY IMGNEKCSQH HRGKVTLNES EICAGAEKIG 670 680 690 700 710 720 SGPCEGDYGG PLVCEQHKMR MVLGVIVPGR GCAIPNRPGI FVRVAYYAKW IHKIILTYKV PQS
	Isoform 4 (HGF/NK2) [UniParc]. Checksum: A45E456B87AE03BE	FASTA	296	34,547
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP 190 200 210 220 230 240 RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP 250 260 270 280 290 HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKNMRD ITWALN
	Isoform 5 [UniParc]. Checksum: 0A93B073EA86EA61	FASTA	285	33,234
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SYRGKDLQEN YCRNPRGEEG 190 200 210 220 230 240 GPWCFTSNPE VRYEVCDIPQ CSEVECMTCN GESYRGLMDH TESGKICQRW DHQTPHRHKF 250 260 270 280 LPERYPDKGF DDNYCRNPDG QPRPWCYTLD PHTRWEYCAI KTCET
	Isoform 6 (HGF/NK1) [UniParc]. Checksum: 94A6EE9C50DE5A86	FASTA	210	24,116
	10 20 30 40 50 60 MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK 70 80 90 100 110 120 TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE 130 140 150 160 170 180 NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP 190 200 210 RGEEGGPWCF TSNPEVRYEV CDIPQCSEGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor." Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K., Gohda E., Daikuhara Y., Kitamura N. Biochem. Biophys. Res. Commun. 163:967-973(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Molecular cloning and expression of human hepatocyte growth factor." Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Nature 342:440-443(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 55-73 AND 495-520. Tissue: Liver.
[3]	"Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte." Seki T., Ihara I., Sugimura A., Shimonishi M., Nishizawa T., Asami O., Hagiya M., Nakamura T., Shimizu S. Biochem. Biophys. Res. Commun. 172:321-327(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Leukocyte.
[4]	"Organization of the human hepatocyte growth factor-encoding gene." Seki T., Hagiya M., Shimonishi M., Nakamura T., Shimizu S. Gene 102:213-219(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]	"An alternatively processed mRNA generated from human hepatocyte growth factor gene." Miyazawa K., Kitamura A., Naka D., Kitamura N. Eur. J. Biochem. 197:15-22(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Placenta.
[6]	"A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor." Rubin J.S., Chan A.M.-L., Bottaro D.P., Burgess W.H., Taylor W.G., Cech A.C., Hirschfield D.W., Wong J., Miki T., Finch P.W., Aaronson S.A. Proc. Natl. Acad. Sci. U.S.A. 88:415-419(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PROTEIN SEQUENCE OF 583-592. Tissue: Lung fibroblast.
[7]	"Evidence for the identity of human scatter factor and human hepatocyte growth factor." Weidner K.M., Arakaki N., Hartmann G., Vandekerckhove J., Weingart S., Rieder H., Fonatsch C., Tsubouchi H., Hishida T., Daikuhara Y., Birchmeier W. Proc. Natl. Acad. Sci. U.S.A. 88:7001-7005(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryonic fibroblast.
[8]	"Identification of a competitive HGF antagonist encoded by an alternative transcript." Chan A.M.-L., Rubin J.S., Bottaro D.P., Hirschfield D.W., Chedid M., Aaronson S.A. Science 254:1382-1385(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[9]	"A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis." Hartmann G., Naldini L., Weidner K.M., Sachs M., Vigna E., Comoglio P.M., Birchmeier W. Proc. Natl. Acad. Sci. U.S.A. 89:11574-11578(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), MUTAGENESIS OF ARG-494.
[10]	"Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF/scatter factor variant with partial agonist/antagonist activity." Cioce V., Csaky K.G., Chan A.M.-L., Bottaro D.P., Taylor W.G., Jensen R., Aaronson S.A., Rubin J.S. J. Biol. Chem. 271:13110-13115(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
[11]	NIEHS SNPs program Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-304 AND TYR-330.
[12]	"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].
[13]	"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].
[14]	"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] (ISOFORMS 1; 5 AND 6). Tissue: Brain.
[15]	"Structural organization and the transcription initiation site of the human hepatocyte growth factor gene." Miyazawa K., Kitamura A., Kitamura N. Biochemistry 30:9170-9176(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-208 AND 249-695 (ISOFORM 1).
[16]	"Identification of the N-terminal residue of the heavy chain of both native and recombinant human hepatocyte growth factor." Yoshiyama Y., Arakaki N., Naka D., Takahashi K., Hirono S., Kondo J., Nakayama H., Gohda E., Kitamura N., Tsubouchi H., Ishii T., Hishida T., Daikuhara Y. Biochem. Biophys. Res. Commun. 175:660-667(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SIGNAL SEQUENCE CLEAVAGE SITE.
[17]	"Hepatocyte growth factor is linked by O-glycosylated oligosaccharide on the alpha chain." Shimizu N., Hara H., Sogabe T., Sakai H., Ihara I., Inoue H., Nakamura T., Shimizu S. Biochem. Biophys. Res. Commun. 189:1329-1335(1992) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-476.
[18]	"Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding." Lokker N.A., Mark M.R., Luis E.A., Bennett G.L., Robbins K.A., Baker J.B., Godowski P.J. EMBO J. 11:2503-2510(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[19]	"Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39." Schultz J.M., Khan S.N., Ahmed Z.M., Riazuddin S., Waryah A.M., Chhatre D., Starost M.F., Ploplis B., Buckley S., Velasquez D., Kabra M., Lee K., Hassan M.J., Ali G., Ansar M., Ghosh M., Wilcox E.R., Ahmad W. , Merlino G., Leal S.M., Riazuddin S., Friedman T.B., Morell R.J. Am. J. Hum. Genet. 85:25-39(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DFNB39.
[20]	"The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site." Zhou H., Mazzulla M.J., Kaufman J.D., Stahl S.J., Wingfield P.T., Rubin J.S., Bottaro D.P., Byrd R.A. Structure 6:109-116(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 31-127.
[21]	"Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0-A resolution." Ultsch M., Lokker N.A., Godowski P.J., de Vos A.M. Structure 6:1383-1393(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 35-210.
[22]	"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 495-728 IN COMPLEX WITH MET, FUNCTION, SUBUNIT, DISULFIDE BONDS.
[23]	"Structural basis for agonism and antagonism of hepatocyte growth factor." Tolbert W.D., Daugherty-Holtrop J., Gherardi E., Vande Woude G., Xu H.E. Proc. Natl. Acad. Sci. U.S.A. 107:13264-13269(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 28-289, DISULFIDE BONDS, FUNCTION.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Hepatocyte growth factor entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M29145 mRNA. Translation: AAA52650.1.
X16323 mRNA. Translation: CAA34387.1.
M60718 mRNA. Translation: AAA52648.1.
D90334 Genomic DNA. Translation: BAA14348.1.
X57574 mRNA. Translation: CAA40802.1.
M55379 mRNA. No translation available.
M73239 mRNA. Translation: AAA64239.1.
M73240 mRNA. Translation: AAA64297.1.
M77227 mRNA. Translation: AAA35980.1.
L02931 mRNA. Translation: AAA52649.1.
U46010 mRNA. Translation: AAC50539.1.
AY246560 Genomic DNA. Translation: AAO61091.1.
AC004960 Genomic DNA. Translation: AAC71655.1.
CH236949 Genomic DNA. Translation: EAL24189.1.
BC022308 mRNA. Translation: AAH22308.1.
BC063485 mRNA. Translation: AAH63485.1.
BC105797 mRNA. Translation: AAI05798.1.
BC130284 mRNA. Translation: AAI30285.1.
BC130286 mRNA. Translation: AAI30287.1.
M75971 , M75967, M75966, M75968, M75969 Genomic DNA. Translation: AAG53459.1.
M75983 , M75972, M75973, M75974, M75975, M75976, M75977, M75978, M75979, M75980, M75981, M75982 Genomic DNA. Translation: AAG53460.1.

IPI

IPI00025767.
IPI00400878.
IPI00400879.
IPI00400880.
IPI00400881.
IPI00941852.

PIR

JH0579.

RefSeq

NP_000592.3. NM_000601.4.
NP_001010931.1. NM_001010931.1.
NP_001010932.1. NM_001010932.1.
NP_001010933.1. NM_001010933.1.
NP_001010934.1. NM_001010934.1.

UniGene

Hs.396530.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BHT	X-ray	2.00	A/B	35-210	[»]
1GMN	X-ray	2.30	A/B	30-210	[»]
1GMO	X-ray	3.00	A/B/C/D/E/F/G/H	30-210	[»]
1GP9	X-ray	2.50	A/B/C/D	40-210	[»]
1NK1	X-ray	2.50	A/B	30-210	[»]
1SHY	X-ray	3.22	A	495-728	[»]
1SI5	X-ray	2.53	H	495-728	[»]
2HGF	NMR	-	A	31-127	[»]
2QJ2	X-ray	1.81	A/B	28-209	[»]
3HMS	X-ray	1.70	A	28-126	[»]
3HMT	X-ray	2.00	A/B	28-126	[»]
3HN4	X-ray	2.60	A	28-289	[»]
3MKP	X-ray	2.81	A/B/C/D	28-210	[»]
3SP8	X-ray	1.86	A/B	28-288	[»]

ProteinModelPortal

P14210.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37535N.

IntAct

P14210. 3 interactions.

MINT

MINT-219560.

Protein family/group databases

MEROPS

S01.976.

PTM databases

GlycoSuiteDB

P14210.

PhosphoSite

P14210.

Polymorphism databases

DMDM

123116.

Proteomic databases

PaxDb

P14210.

PRIDE

P14210.

Protocols and materials databases

DNASU

3082.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222390; ENSP00000222390; ENSG00000019991.
ENST00000423064; ENSP00000413829; ENSG00000019991.
ENST00000444829; ENSP00000389854; ENSG00000019991.
ENST00000453411; ENSP00000408270; ENSG00000019991.
ENST00000457544; ENSP00000391238; ENSG00000019991.

GeneID

3082.

KEGG

hsa:3082.

UCSC

uc003uhl.3. human.
uc003uhm.3. human.
uc003uhn.1. human.
uc003uho.1. human.
uc003uhp.3. human.

Organism-specific databases

CTD

3082.

GeneCards

GC07M081328.

HGNC

HGNC:4893. HGF.

HPA

CAB010333.
HPA040360.
HPA044088.

MIM

142409. gene.
608265. phenotype.

neXtProt

NX_P14210.

Orphanet

90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.

PharmGKB

PA29269.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOVERGEN

HBG004381.

InParanoid

P14210.

KO

K05460.

OMA

GSESPWC.

OrthoDB

EOG4R7V94.

PhylomeDB

P14210.

Enzyme and pathway databases

Pathway_Interaction_DB

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_604. Hemostasis.
REACT_6900. Immune System.

SignaLink

P14210.

Gene expression databases

ArrayExpress

P14210.

Bgee

P14210.

Genevestigator

P14210.

GermOnline

ENSG00000019991. Homo sapiens.

Family and domain databases

Gene3D

2.40.20.10. 4 hits.

InterPro

IPR027284. Hepatocyte_GF.
IPR024174. HGF_MST1.
IPR000001. Kringle.
IPR013806. Kringle-like.
IPR018056. Kringle_CS.
IPR003014. PAN-1_domain.
IPR003609. Pan_app.
IPR001254. Peptidase_S1.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00051. Kringle. 4 hits.
PF00024. PAN_1. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]

PIRSF

PIRSF500183. Hepatocyte_GF. 1 hit.
PIRSF001152. HGF_MST1. 1 hit.

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00130. KR. 4 hits.
SM00473. PAN_AP. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF57440. Kringle-like. 4 hits.
SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS00021. KRINGLE_1. 4 hits.
PS50070. KRINGLE_2. 4 hits.
PS50948. PAN. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5479.

ChiTaRS

HGF. human.

EvolutionaryTrace

P14210.

GenomeRNAi

3082.

NextBio

12211.

PMAP-CutDB

P14210.

SOURCE

Search...

Entry information

Entry name

HGF_HUMAN

Accession

Primary (citable) accession number: P14210
Secondary accession number(s): A1L3U6 , Q02935, Q13494, Q14519, Q3KRB2, Q8TCE2, Q9BYL9, Q9BYM0, Q9UDU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	August 1, 1991
Last modified:	May 29, 2013
This is version 171 of the entry and version 2 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.