Q08048 (HGF_MOUSE) 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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.13
Subunit structure	Dimer of an alpha chain and a beta chain linked by a disulfide bond.
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.
Sequence caution	The sequence CAA51054.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
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 direct assay PubMed 15314156. Source: MGI cell chemotaxis Inferred from electronic annotation. Source: Compara cell morphogenesis Inferred from direct assay PubMed 12130561. Source: MGI cellular response to hepatocyte growth factor stimulus Inferred from electronic annotation. Source: Compara hepatocyte growth factor receptor signaling pathway Inferred from direct assay PubMed 15314156. Source: MGI liver development Inferred from direct assay PubMed 16880525. Source: MGI myoblast proliferation Inferred from direct assay PubMed 11061428. Source: MGI negative regulation of apoptotic process Inferred from direct assay PubMed 15314156. Source: MGI negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of hydrogen peroxide-mediated programmed cell death Inferred from electronic annotation. Source: Compara negative regulation of release of cytochrome c from mitochondria Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of DNA biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: InterPro regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling Inferred from mutant phenotype PubMed 14517989. Source: MGI
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: Q08048-1)

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 Short (identifier: Q08048-2)

The sequence of this isoform differs from the canonical sequence as follows:
     163-167: Missing.

Isoform NK1 (identifier: Q08048-3)

The sequence of this isoform differs from the canonical sequence as follows:
     210-211: VE → GK
     212-728: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 32

32

By similarity

Chain

33 – 495

463

Hepatocyte growth factor alpha chain

PRO_0000028093

Chain

496 – 728

233

Hepatocyte growth factor beta chain

PRO_0000028094

Regions

Domain

38 – 124

87

PAN

Domain

129 – 207

79

Kringle 1

Domain

212 – 289

78

Kringle 2

Domain

306 – 384

79

Kringle 3

Domain

392 – 470

79

Kringle 4

Domain

496 – 724

229

Peptidase S1

Amino acid modifications

Modified residue

33

1

Pyrrolidone carboxylic acid By similarity

Glycosylation

295

1

N-linked (GlcNAc...) Potential

Glycosylation

403

1

N-linked (GlcNAc...) Potential

Glycosylation

569

1

N-linked (GlcNAc...) Potential

Glycosylation

656

1

N-linked (GlcNAc...) Potential

Disulfide bond

71 ↔ 97

Ref.12 Ref.13

Disulfide bond

75 ↔ 85

Ref.12 Ref.13

Disulfide bond

129 ↔ 207

Ref.12 Ref.13

Disulfide bond

150 ↔ 190

Ref.12 Ref.13

Disulfide bond

178 ↔ 202

Ref.12 Ref.13

Disulfide bond

212 ↔ 289

By similarity

Disulfide bond

233 ↔ 272

By similarity

Disulfide bond

261 ↔ 284

By similarity

Disulfide bond

306 ↔ 384

By similarity

Disulfide bond

327 ↔ 366

By similarity

Disulfide bond

355 ↔ 378

By similarity

Disulfide bond

392 ↔ 470

By similarity

Disulfide bond

413 ↔ 453

By similarity

Disulfide bond

441 ↔ 465

By similarity

Disulfide bond

488 ↔ 607

Interchain (between alpha and beta chains) By similarity

Disulfide bond

520 ↔ 536

By similarity

Disulfide bond

615 ↔ 682

By similarity

Disulfide bond

645 ↔ 661

By similarity

Disulfide bond

672 ↔ 700

By similarity

Natural variations

Alternative sequence

163 – 167

5

Missing in isoform Short.

VSP_005408

Alternative sequence

210 – 211

2

VE → GK in isoform NK1.

VSP_044345

Alternative sequence

212 – 728

517

Missing in isoform NK1.

VSP_044346

Experimental info

Sequence conflict

189

1

W → K AA sequence Ref.9

Sequence conflict

344

1

N → K in AAB31855. Ref.2

Sequence conflict

378

1

C → E AA sequence Ref.9

Sequence conflict

380

1

Q → E AA sequence Ref.9

Sequence conflict

479

1

V → L in AAB31855. Ref.2

Sequence conflict

513

1

K → L AA sequence Ref.10

Sequence conflict

518

1

H → T AA sequence Ref.11

Sequence conflict

564

1

R → H in CAA51054. Ref.3

Secondary structure

1

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728

Helix Strand Turn

Details...

Helix

40 – 42

3

Beta strand

43 – 52

10

Beta strand

55 – 57

3

Beta strand

61 – 64

4

Helix

68 – 77

10

Turn

78 – 80

3

Beta strand

87 – 91

5

Turn

92 – 95

4

Beta strand

96 – 101

6

Beta strand

106 – 108

3

Beta strand

110 – 122

13

Helix

123 – 125

3

Beta strand

129 – 133

5

Beta strand

149 – 151

3

Beta strand

157 – 159

3

Turn

165 – 167

3

Beta strand

188 – 194

7

Beta strand

198 – 201

4

Turn

207 – 209

3

Beta strand

240 – 242

3

Helix

248 – 250

3

Turn

252 – 255

4

Beta strand

271 – 275

5

Beta strand

280 – 283

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1995. Version 1. Checksum: A0381FC497534328	FASTA	728	82,945
	10 20 30 40 50 60 MMWGTKLLPV LLLQHVLLHL LLLHVAIPYA EGQKKRRNTL HEFKKSAKTT LTKEDPLLKI 70 80 90 100 110 120 KTKKVNSADE CANRCIRNRG FTFTCKAFVF DKSRKRCYWY PFNSMSSGVK KGFGHEFDLY 130 140 150 160 170 180 ENKDYIRNCI IGKGGSYKGT VSITKSGIKC QPWNSMIPHE HSFLPSSYRG KDLQENYCRN 190 200 210 220 230 240 PRGEEGGPWC FTSNPEVRYE VCDIPQCSEV ECMTCNGESY RGPMDHTESG KTCQRWDQQT 250 260 270 280 290 300 PHRHKFLPER YPDKGFDDNY CRNPDGKPRP WCYTLDPDTP WEYCAIKTCA HSAVNETDVP 310 320 330 340 350 360 METTECIQGQ GEGYRGTSNT IWNGIPCQRW DSQYPHKHDI TPENFKCKDL RENYCRNPDG 370 380 390 400 410 420 AESPWCFTTD PNIRVGYCSQ IPKCDVSSGQ DCYRGNGKNY MGNLSKTRSG LTCSMWDKNM 430 440 450 460 470 480 EDLHRHIFWE PDASKLNKNY CRNPDDDAHG PWCYTGNPLI PWDYCPISRC EGDTTPTIVN 490 500 510 520 530 540 LDHPVISCAK TKQLRVVNGI PTQTTVGWMV SLKYRNKHIC GGSLIKESWV LTARQCFPAR 550 560 570 580 590 600 NKDLKDYEAW LGIHDVHERG EEKRKQILNI SQLVYGPEGS DLVLLKLARP AILDNFVSTI 610 620 630 640 650 660 DLPSYGCTIP EKTTCSIYGW GYTGLINADG LLRVAHLYIM GNEKCSQHHQ GKVTLNESEL 670 680 690 700 710 720 CAGAEKIGSG PCEGDYGGPL ICEQHKMRMV LGVIVPGRGC AIPNRPGIFV RVAYYAKWIH KVILTYKL
	Isoform Short [UniParc]. Checksum: 7BC19A16C399EDD2	FASTA	723	82,413
	10 20 30 40 50 60 MMWGTKLLPV LLLQHVLLHL LLLHVAIPYA EGQKKRRNTL HEFKKSAKTT LTKEDPLLKI 70 80 90 100 110 120 KTKKVNSADE CANRCIRNRG FTFTCKAFVF DKSRKRCYWY PFNSMSSGVK KGFGHEFDLY 130 140 150 160 170 180 ENKDYIRNCI IGKGGSYKGT VSITKSGIKC QPWNSMIPHE HSYRGKDLQE NYCRNPRGEE 190 200 210 220 230 240 GGPWCFTSNP EVRYEVCDIP QCSEVECMTC NGESYRGPMD HTESGKTCQR WDQQTPHRHK 250 260 270 280 290 300 FLPERYPDKG FDDNYCRNPD GKPRPWCYTL DPDTPWEYCA IKTCAHSAVN ETDVPMETTE 310 320 330 340 350 360 CIQGQGEGYR GTSNTIWNGI PCQRWDSQYP HKHDITPENF KCKDLRENYC RNPDGAESPW 370 380 390 400 410 420 CFTTDPNIRV GYCSQIPKCD VSSGQDCYRG NGKNYMGNLS KTRSGLTCSM WDKNMEDLHR 430 440 450 460 470 480 HIFWEPDASK LNKNYCRNPD DDAHGPWCYT GNPLIPWDYC PISRCEGDTT PTIVNLDHPV 490 500 510 520 530 540 ISCAKTKQLR VVNGIPTQTT VGWMVSLKYR NKHICGGSLI KESWVLTARQ CFPARNKDLK 550 560 570 580 590 600 DYEAWLGIHD VHERGEEKRK QILNISQLVY GPEGSDLVLL KLARPAILDN FVSTIDLPSY 610 620 630 640 650 660 GCTIPEKTTC SIYGWGYTGL INADGLLRVA HLYIMGNEKC SQHHQGKVTL NESELCAGAE 670 680 690 700 710 720 KIGSGPCEGD YGGPLICEQH KMRMVLGVIV PGRGCAIPNR PGIFVRVAYY AKWIHKVILT YKL
	Isoform NK1 [UniParc]. Checksum: 758BD0687A835F48	FASTA	211	24,308
	10 20 30 40 50 60 MMWGTKLLPV LLLQHVLLHL LLLHVAIPYA EGQKKRRNTL HEFKKSAKTT LTKEDPLLKI 70 80 90 100 110 120 KTKKVNSADE CANRCIRNRG FTFTCKAFVF DKSRKRCYWY PFNSMSSGVK KGFGHEFDLY 130 140 150 160 170 180 ENKDYIRNCI IGKGGSYKGT VSITKSGIKC QPWNSMIPHE HSFLPSSYRG KDLQENYCRN 190 200 210 PRGEEGGPWC FTSNPEVRYE VCDIPQCSEG K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of mouse mammary fibroblast-derived mammary growth factor as hepatocyte growth factor." Sasaki M., Nishio M., Sasaki T., Enami J. Biochem. Biophys. Res. Commun. 199:772-779(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), PROTEIN SEQUENCE OF 496-504. Tissue: Mammary fibroblast.
[2]	"Structure, genetic mapping, and expression of the mouse Hgf/scatter factor gene." Lee C.C., Kozak C.A., Yamada K.M. Cell Adhes. Commun. 1:101-111(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Molecular cloning and characterization of cDNA encoding mouse hepatocyte growth factor." Liu Y., Michalopoulos G.K., Zarnegar R. Biochim. Biophys. Acta 1216:299-303(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo." Jakubczak J.L., LaRochelle W.J., Merlino G. Mol. Cell. Biol. 18:1275-1283(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NK1). Tissue: Lung.
[5]	Sharpe M.J.S., Lane K., Gherardi E. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Strain: Swiss. Tissue: Fibroblast.
[6]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-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] (ISOFORM LONG). Tissue: Brain.
[8]	"Characterisation of the scatter factor/hepatocyte growth factor gene promoter: positive and negative regulatory elements direct gene expression to mesenchymal cells." Plaschke-Schluetter A., Behrens J., Gherardi E., Birchmeier W. J. Biol. Chem. 270:830-836(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30. Strain: 129.
[9]	"Purified scatter factor stimulates epithelial and vascular endothelial cell migration." Rosen E.M., Meromsky L., Setter E., Vinter D.W., Goldberg I.D. Proc. Soc. Exp. Biol. Med. 195:34-43(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 184-197; 357-367; 375-383 AND 653-666.
[10]	"Hepatocytes and scatter factor." Gherardi E., Stoker M. Nature 346:228-228(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 496-519.
[11]	"Purification and characterization of biologically active scatter factor from ras-transformed NIH 3T3 conditioned medium." Coffer A., Fellows J., Young S., Pappin D., Rahman D. Biochem. J. 278:35-41(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 496-519.
[12]	"A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist." Tolbert W.D., Daugherty J., Gao C., Xie Q., Miranti C., Gherardi E., Woude G.V., Xu H.E. Proc. Natl. Acad. Sci. U.S.A. 104:14592-14597(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 29-210, DISULFIDE BONDS.
[13]	"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 (2.0 ANGSTROMS) OF 31-127, DISULFIDE BONDS, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D10212 mRNA. Translation: BAA01064.1.
D10213 mRNA. Translation: BAA01065.1.
S71816 mRNA. Translation: AAB31855.1.
X72307 mRNA. Translation: CAA51054.1. Different initiation.
AF042856 mRNA. Translation: AAC40051.1.
X84046 mRNA. Translation: CAA58865.1.
CH466586 Genomic DNA. Translation: EDL03238.1.
BC119228 mRNA. Translation: AAI19229.1.
X81630 Genomic DNA. Translation: CAA57286.1.

IPI

IPI00116509.
IPI00230423.

PIR

A60185. JC2117.

RefSeq

NP_034557.3. NM_010427.4.

UniGene

Mm.267078.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QJ4	X-ray	2.50	A/B	29-210	[»]
3HMR	X-ray	2.00	A	31-127	[»]
4IUA	X-ray	3.05	A/B/C/D/E/F/G/H	31-290	[»]

ProteinModelPortal

Q08048.

SMR

Q08048. Positions 35-476, 496-725.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46456N.

Protein family/group databases

MEROPS

S01.982.

PTM databases

PhosphoSite

Q08048.

Proteomic databases

PRIDE

Q08048.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000030683; ENSMUSP00000030683; ENSMUSG00000028864.

GeneID

15234.

KEGG

mmu:15234.

UCSC

uc008wnj.1. mouse.

Organism-specific databases

CTD

3082.

MGI

MGI:96079. Hgf.

Phylogenomic databases

eggNOG

COG5640.

GeneTree

ENSGT00700000104191.

HOGENOM

HOG000112892.

HOVERGEN

HBG004381.

InParanoid

Q08048.

KO

K05460.

OMA

GSESPWC.

OrthoDB

EOG4R7V94.

Enzyme and pathway databases

Reactome

REACT_107772. Immune System.

Gene expression databases

ArrayExpress

Q08048.

Bgee

Q08048.

CleanEx

MM_HGF.

Genevestigator

Q08048.

GermOnline

ENSMUSG00000028864. Mus musculus.

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

EvolutionaryTrace

Q08048.

NextBio

287831.

SOURCE

Search...

Entry information

Entry name

HGF_MOUSE

Accession

Primary (citable) accession number: Q08048
Secondary accession number(s): O55027 , Q53WS5, Q61662, Q64007, Q6LBE6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program