U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

HGFAC HGF activator [ Homo sapiens (human) ]

Gene ID: 3083, updated on 5-Mar-2024

Summary

Go to the top of the page Help
Official Symbol
HGFACprovided by HGNC
Official Full Name
HGF activatorprovided by HGNC
Primary source
HGNC:HGNC:4894
See related
Ensembl:ENSG00000109758 MIM:604552; AllianceGenome:HGNC:4894
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HGFA
Summary
This gene encodes a member of the peptidase S1 protein family. The encoded protein is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing. It acts as serine protease that converts hepatocyte growth factor to the active form. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression
Restricted expression toward liver (RPKM 27.9) See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See HGFAC in Genome Data Viewer
Location:
4p16.3
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (3441005..3449486)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (3440789..3449270)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (3443695..3451213)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene regulator of G protein signaling 12 Neighboring gene X antigen family member 3 pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:3319084-3319638 Neighboring gene ribosomal protein L7a pseudogene 29 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3374529-3375457 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21222 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21223 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3411075-3411982 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:3417810-3419009 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3422145-3422646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3425913-3426412 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3434795-3435296 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3435297-3435796 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3436172-3437070 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3437071-3437969 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3438515-3439015 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15205 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3450782-3451585 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:3463811-3464658 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3467576-3468185 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3469405-3470012 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:3474943-3475654 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:3476364-3476557 Neighboring gene vegetative cell wall protein gp1-like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3481667-3482258 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:3482478-3483445 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3483446-3484412 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:3486115-3487314 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:3487316-3488282 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15206 Neighboring gene docking protein 7 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:3494329-3494850 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:3510576-3511775 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:3516456-3517655 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3517921-3518540 Neighboring gene LDL receptor related protein associated protein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3528991-3529881 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:3529882-3530771 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15207 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21225

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. HGFAC expression decreased in liver cancer and its low expression correlated with DNA hypermethylation and poor prognosis. Yin L, et al. J Cell Biochem, 2019 Jun. PMID 30635948
  2. Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma. Tjin EP, et al. Blood, 2006 Jan 15. PMID 16189274
  3. Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene--phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator. Miyazawa K, et al. Eur J Biochem, 1998 Dec 1. PMID 9874200
  4. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. Miyazawa K, et al. J Biol Chem, 1993 May 15. PMID 7683665
  5. A novel protease obtained from FBS-containing culture supernatant, that processes single chain form hepatocyte growth factor to two chain form in serum-free culture. Shimomura T, et al. Cytotechnology, 1992. PMID 1368819

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. miR-4270 suppresses hepatocellular carcinoma progression by inhibiting DNMT3A-mediated methylation of HGFAC promoter.
    Title: miR-4270 suppresses hepatocellular carcinoma progression by inhibiting DNMT3A-mediated methylation of HGFAC promoter.
  2. Role of hypoxia on microRNA-dependant regulation of HGFA - HGF - c-Met signalling pathway in human progenitor and mature endothelial cells.
    Title: Role of hypoxia on microRNA-dependant regulation of HGFA - HGF - c-Met signalling pathway in human progenitor and mature endothelial cells.
  3. HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis.
    Title: HGFAC is a ChREBP-regulated hepatokine that enhances glucose and lipid homeostasis.
  4. Hypermethylation around the promoter region contributed to the decreased expression of HGFAC. HGFAC may be a useful and predictive biomarker for the prognosis of liver cancer patients.
    Title: HGFAC expression decreased in liver cancer and its low expression correlated with DNA hypermethylation and poor prognosis.
  5. Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis, discovered 5 common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) and 4 variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC.[Meta-analysis]
    Title: Trans-ethnic meta-analysis identifies common and rare variants associated with hepatocyte growth factor levels in the Multi-Ethnic Study of Atherosclerosis (MESA).
  6. Observational study of gene-disease association. (HuGE Navigator)
    Title: L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms.
  7. Results suggest that hepatocyte growth factor activator is a major serum activator of pro-macrophage-stimulating protein.
    Title: Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein.
  8. the activated form of HGFA is present at high levels in serum and bone marrow of myeloma patients, thus providing a necessary prerequisite for the activation of HGF.
    Title: Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma.
  9. Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer.
    Title: Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer.
  10. KLK4 and KLK5 activate pro-HGFA.
    Title: Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • MGC138395, MGC138397

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type peptidase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in blood coagulation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis TAS
Traceable Author Statement
more info
 PubMed 
involved_in zymogen activation IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in rough endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

Go to the top of the page Help
Preferred Names
hepatocyte growth factor activator
NP_001284368.1
NP_001519.1
XP_047306111.1
XP_054205836.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001297439.2 → NP_001284368.1  hepatocyte growth factor activator isoform 1 preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK314099, BC112190, D14012
    Consensus CDS
    CCDS75098.1
    UniProtKB/TrEMBL
    D6RAR4
    Related
    ENSP00000421801.1, ENST00000511533.1
    Conserved Domains (7) summary
    smart00059
    Location:102 → 148
    FN2; Fibronectin type 2 domain
    smart00020
    Location:414 → 648
    Tryp_SPc; Trypsin-like serine protease
    cd00054
    Location:162 → 197
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    cd00061
    Location:200 → 240
    FN1; Fibronectin type 1 domain, approximately 40 residue long with two conserved disulfide bridges. FN1 is one of three types of internal repeats which combine to form larger domains within fibronectin. Fibronectin, a plasma protein that binds cell surfaces ...
    cd00190
    Location:415 → 650
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00051
    Location:286 → 367
    Kringle; Kringle domain
    pfam15671
    Location:34 → 169
    PRR18; Proline-rich protein family 18

  2. NM_001528.4 → NP_001519.1  hepatocyte growth factor activator isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_001519.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
    Source sequence(s)
    BC112190, D14012
    Consensus CDS
    CCDS3369.1
    UniProtKB/Swiss-Prot
    Q04756, Q14726, Q2M1W7, Q53X47
    Related
    ENSP00000372224.4, ENST00000382774.8
    Conserved Domains (7) summary
    smart00059
    Location:102 → 148
    FN2; Fibronectin type 2 domain
    smart00020
    Location:407 → 641
    Tryp_SPc; Trypsin-like serine protease
    cd00054
    Location:162 → 197
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    cd00061
    Location:200 → 240
    FN1; Fibronectin type 1 domain, approximately 40 residue long with two conserved disulfide bridges. FN1 is one of three types of internal repeats which combine to form larger domains within fibronectin. Fibronectin, a plasma protein that binds cell surfaces ...
    cd00190
    Location:408 → 643
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00051
    Location:286 → 367
    Kringle; Kringle domain
    pfam15671
    Location:34 → 169
    PRR18; Proline-rich protein family 18

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    3441005..3449486
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047450155.1 → XP_047306111.1  hepatocyte growth factor activator isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    3440789..3449270
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054349861.1 → XP_054205836.1  hepatocyte growth factor activator isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q04756.1 GenPept UniProtKB/Swiss-Prot:Q04756

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous