HGF

Protein identityUniProt · HPA

UniProt accession

P14210

Gene

HGF

Ensembl

ENSG00000019991

Chromosome

7

Canonical length

728 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted secreted proteins, RAS pathway related proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate alpha and beta chains, which form the mature heterodimer. This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. This protein also plays a role in angiogenesis, tumorogenesis, and tissue regeneration. Although the encoded protein is a member of the peptidase S1 family of serine proteases, it lacks peptidase activity. Mutations in this gene are associated with nonsyndromic hearing loss. [provided by RefSeq, Nov 2015]

Canonical amino-acid sequenceUniProt

728 residues, UniProt reviewed canonical sequence.

>P14210|HGF
     1  MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK
    61  TKKVNTADQC ANRCTRNKGL PFTCKAFVFD KARKQCLWFP FNSMSSGVKK EFGHEFDLYE
   121  NKDYIRNCII GKGRSYKGTV SITKSGIKCQ PWSSMIPHEH SFLPSSYRGK DLQENYCRNP
   181  RGEEGGPWCF TSNPEVRYEV CDIPQCSEVE CMTCNGESYR GLMDHTESGK ICQRWDHQTP
   241  HRHKFLPERY PDKGFDDNYC RNPDGQPRPW CYTLDPHTRW EYCAIKTCAD NTMNDTDVPL
   301  ETTECIQGQG EGYRGTVNTI WNGIPCQRWD SQYPHEHDMT PENFKCKDLR ENYCRNPDGS
   361  ESPWCFTTDP NIRVGYCSQI PNCDMSHGQD CYRGNGKNYM GNLSQTRSGL TCSMWDKNME
   421  DLHRHIFWEP DASKLNENYC RNPDDDAHGP WCYTGNPLIP WDYCPISRCE GDTTPTIVNL
   481  DHPVISCAKT KQLRVVNGIP TRTNIGWMVS LRYRNKHICG GSLIKESWVL TARQCFPSRD
   541  LKDYEAWLGI HDVHGRGDEK CKQVLNVSQL VYGPEGSDLV LMKLARPAVL DDFVSTIDLP
   601  NYGCTIPEKT SCSVYGWGYT GLINYDGLLR VAHLYIMGNE KCSQHHRGKV TLNESEICAG
   661  AEKIGSGPCE GDYGGPLVCE QHKMRMVLGV IVPGRGCAIP NRPGIFVRVA YYAKWIHKII
   721  LTYKVPQS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HGF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

293 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HGF.

Disease | AllUniProt

Conditions HGF is implicated in, by any mechanism.

• Deafness, autosomal recessive, 39 (DFNB39) MIM:608265

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 327 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive nonsyndromic hearing loss 39
• Sensorineural hearing loss disorder

ReferencesPubMed · IEDB

Publications for HGF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.25

gnomAD pLI

1

gnomAD missense Z

1.85

DepMap mean gene effect

0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell chemotaxis
• cell morphogenesis
• cellular response to hepatocyte growth factor stimulus
• epithelial cell proliferation
• epithelial to mesenchymal transition
• hepatocyte growth factor receptor signaling pathway
• liver development
• mitotic cell cycle
• myoblast proliferation
• negative regulation of apoptotic process
• negative regulation of autophagy
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• negative regulation of hydrogen peroxide-mediated programmed cell death
• negative regulation of inflammatory response
• negative regulation of interleukin-6 production
• negative regulation of release of cytochrome c from mitochondria
• positive regulation of cell migration
• positive regulation of DNA biosynthetic process
• positive regulation of interleukin-10 production
• positive regulation of MAPK cascade
• positive regulation of osteoblast differentiation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of transcription by RNA polymerase II
• regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling
• regulation of p38MAPK cascade
• skeletal muscle cell proliferation

Molecular functions

• chemoattractant activity
• growth factor activity
• identical protein binding
• signaling receptor binding

Cellular components

• extracellular region
• extracellular space
• membrane
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• Kringle
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• PAN/Apple domain
• Peptidase S1, PA clan
• Kringle-like fold
• Kringle, conserved site
• Hepatocyte growth factor/Macrophage stimulatory protein
• Kringle superfamily
• Serine proteases and regulators with kringle domains
• PAN domain
• Kringle domain
• Trypsin
• Hepatocyte growth factor

KeywordsUniProt

• Deafness
• Disulfide bond
• Glycoprotein
• Growth factor
• Kringle
• Non-syndromic deafness
• Pyrrolidone carboxylic acid
• Repeat
• Serine protease homolog
• Signal

InteractionsUniProt · HPA

Protein binding partners of HGF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SRPX2
• MET