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    HGFAC HGF activator [ Homo sapiens (human) ]

    Gene ID: 3083, updated on 10-Dec-2024

    Summary

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    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
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    Genomic context

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    See HGFAC in Genome Data Viewer
    Location:
    4p16.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (3441005..3449486)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (3440789..3449270)
    RS_2024_09 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

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. 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
    2. 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
    3. 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
    4. 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
    5. 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

    See all (33) 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

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    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

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    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

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    Preferred Names
    hepatocyte growth factor activator
    NP_001284368.1
    NP_001519.1
    XP_047306111.1
    XP_054205836.1

    NCBI Reference Sequences (RefSeq)

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    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_2024_08

    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.

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