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Q08048 (HGF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte growth factor
Alternative name(s):
Hepatopoietin-A
Scatter factor
Short name=SF
Gene names
Name:Hgf
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length728 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Interacts with SRPX2; the interaction increases HGF mitogenic activity.

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 diversityAlternative splicing
   DomainKringle
Repeat
Signal
   Molecular functionGrowth factor
Serine protease homolog
   PTMDisulfide bond
Glycoprotein
Pyrrolidone carboxylic acid
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPK activity

Inferred from direct assay PubMed 15314156. Source: MGI

cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis

Inferred from direct assay PubMed 12130561. Source: MGI

cell proliferation

Inferred from direct assay PubMed 12130561PubMed 15314156. Source: MGI

cellular response to hepatocyte growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

hepatocyte growth factor receptor signaling pathway

Inferred from direct assay PubMed 15314156. Source: MGI

hyaluronan metabolic process

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay PubMed 15314156. Source: MGI

negative regulation of hydrogen peroxide-mediated programmed cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling

Inferred from mutant phenotype PubMed 14517989. Source: MGI

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchemoattractant activity

Inferred from electronic annotation. Source: Ensembl

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 By similarity
Chain33 – 495463Hepatocyte growth factor alpha chain
PRO_0000028093
Chain496 – 728233Hepatocyte growth factor beta chain
PRO_0000028094

Regions

Domain38 – 12487PAN
Domain129 – 20779Kringle 1
Domain212 – 28978Kringle 2
Domain306 – 38479Kringle 3
Domain392 – 47079Kringle 4
Domain496 – 724229Peptidase S1

Amino acid modifications

Modified residue331Pyrrolidone carboxylic acid By similarity
Glycosylation2951N-linked (GlcNAc...) Potential
Glycosylation4031N-linked (GlcNAc...) Potential
Glycosylation5691N-linked (GlcNAc...) Potential
Glycosylation6561N-linked (GlcNAc...) Potential
Disulfide bond71 ↔ 97 Ref.12 Ref.13
Disulfide bond75 ↔ 85 Ref.12 Ref.13
Disulfide bond129 ↔ 207 Ref.12 Ref.13
Disulfide bond150 ↔ 190 Ref.12 Ref.13
Disulfide bond178 ↔ 202 Ref.12 Ref.13
Disulfide bond212 ↔ 289 By similarity
Disulfide bond233 ↔ 272 By similarity
Disulfide bond261 ↔ 284 By similarity
Disulfide bond306 ↔ 384 By similarity
Disulfide bond327 ↔ 366 By similarity
Disulfide bond355 ↔ 378 By similarity
Disulfide bond392 ↔ 470 By similarity
Disulfide bond413 ↔ 453 By similarity
Disulfide bond441 ↔ 465 By similarity
Disulfide bond488 ↔ 607Interchain (between alpha and beta chains) By similarity
Disulfide bond520 ↔ 536 By similarity
Disulfide bond615 ↔ 682 By similarity
Disulfide bond645 ↔ 661 By similarity
Disulfide bond672 ↔ 700 By similarity

Natural variations

Alternative sequence163 – 1675Missing in isoform Short.
VSP_005408
Alternative sequence210 – 2112VE → GK in isoform NK1.
VSP_044345
Alternative sequence212 – 728517Missing in isoform NK1.
VSP_044346

Experimental info

Sequence conflict1891W → K AA sequence Ref.9
Sequence conflict3441N → K in AAB31855. Ref.2
Sequence conflict3781C → E AA sequence Ref.9
Sequence conflict3801Q → E AA sequence Ref.9
Sequence conflict4791V → L in AAB31855. Ref.2
Sequence conflict5131K → L AA sequence Ref.10
Sequence conflict5181H → T AA sequence Ref.11
Sequence conflict5641R → H in CAA51054. Ref.3

Secondary structure

............................................ 728
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: A0381FC497534328

FASTA72882,945
        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 

« Hide

Isoform Short [UniParc].

Checksum: 7BC19A16C399EDD2
Show »

FASTA72382,413
Isoform NK1 [UniParc].

Checksum: 758BD0687A835F48
Show »

FASTA21124,308

References

« Hide '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.
CCDSCCDS19097.1. [Q08048-1]
PIRA60185. JC2117.
RefSeqNP_001276387.1. NM_001289458.1. [Q08048-1]
NP_001276388.1. NM_001289459.1. [Q08048-1]
NP_001276389.1. NM_001289460.1. [Q08048-3]
NP_001276390.1. NM_001289461.1. [Q08048-2]
NP_034557.3. NM_010427.5. [Q08048-1]
XP_006535691.1. XM_006535628.1. [Q08048-1]
UniGeneMm.267078.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QJ4X-ray2.50A/B29-210[»]
3HMRX-ray2.00A31-127[»]
4IUAX-ray3.05A/B/C/D/E/F/G/H31-290[»]
ProteinModelPortalQ08048.
SMRQ08048. Positions 37-476, 496-724.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-46456N.

Protein family/group databases

MEROPSS01.982.

PTM databases

PhosphoSiteQ08048.

Proteomic databases

PRIDEQ08048.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030683; ENSMUSP00000030683; ENSMUSG00000028864. [Q08048-1]
GeneID15234.
KEGGmmu:15234.
UCSCuc008wne.1. mouse.
uc008wnf.1. mouse. [Q08048-1]
uc008wnj.1. mouse. [Q08048-2]

Organism-specific databases

CTD3082.
MGIMGI:96079. Hgf.

Phylogenomic databases

eggNOGCOG5640.
GeneTreeENSGT00740000115022.
HOGENOMHOG000112892.
HOVERGENHBG004381.
InParanoidQ08048.
KOK05460.
OMAGSESPWC.
OrthoDBEOG75B84T.
PhylomeDBQ08048.
TreeFamTF329901.

Gene expression databases

BgeeQ08048.
CleanExMM_HGF.
GenevestigatorQ08048.

Family and domain databases

Gene3D2.40.20.10. 4 hits.
InterProIPR027284. 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]
PfamPF00051. Kringle. 4 hits.
PF00024. PAN_1. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF500183. Hepatocyte_GF. 1 hit.
PIRSF001152. HGF_MST1. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00130. KR. 4 hits.
SM00473. PAN_AP. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57440. SSF57440. 4 hits.
PROSITEPS00021. KRINGLE_1. 4 hits.
PS50070. KRINGLE_2. 4 hits.
PS50948. PAN. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ08048.
NextBio287831.
PROQ08048.
SOURCESearch...

Entry information

Entry nameHGF_MOUSE
AccessionPrimary (citable) accession number: Q08048
Secondary accession number(s): O55027 expand/collapse secondary AC list , Q53WS5, Q61662, Q64007, Q6LBE6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot