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    SPINT1 serine peptidase inhibitor, Kunitz type 1 [ Homo sapiens (human) ]

    Gene ID: 6692, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SPINT1provided by HGNC
    Official Full Name
    serine peptidase inhibitor, Kunitz type 1provided by HGNC
    Primary source
    HGNC:HGNC:11246
    See related
    Ensembl:ENSG00000166145 MIM:605123; AllianceGenome:HGNC:11246
    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
    HAI; HAI1; MANSC2
    Summary
    The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in placenta (RPKM 87.0), duodenum (RPKM 69.0) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPINT1 in Genome Data Viewer
    Location:
    15q15.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (40844048..40858207)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (38650076..38664232)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (41136246..41150405)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene DnaJ heat shock protein family (Hsp40) member C17 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9264 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9265 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9266 Neighboring gene zinc finger FYVE-type containing 19 Neighboring gene protein phosphatase 1 regulatory inhibitor subunit 14D Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:41117412-41117912 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:41117913-41118413 Neighboring gene Sharpr-MPRA regulatory region 7770 Neighboring gene SPINT1 antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:41135684-41135866 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:41135819-41136390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6344 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9267 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9268 Neighboring gene uncharacterized LOC124903475 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6345 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9269 Neighboring gene ras homolog family member V Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6346 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6348 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9270 Neighboring gene VPS18 core subunit of CORVET and HOPS complexes

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Suppression of hepatocyte growth factor activator inhibitor-1 leads to a more aggressive phenotype of prostate cancer cells in vitro. Sanders AJ, et al. Int J Mol Med, 2007 Oct. PMID 17786295
    2. Expression of Hepatocyte growth factor activator inhibitor type-1 (HAI-1) in prostate cancer. Yasuda K, et al. Anticancer Res, 2013 Feb. PMID 23393351
    3. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells. Fukushima T, et al. Cancer Sci, 2011 Feb. PMID 21166957, Free PMC Article
    4. Down-regulation of HAI-1 is associated with poor-differentiation status of colorectal cancer. Ye J, et al. Hum Cell, 2013 Dec. PMID 23979832
    5. Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model. Ye J, et al. Cancer Sci, 2014 Jan. PMID 24147538, Free PMC Article

    See all (94) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.
      Title: HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.
    2. Role of the polycystic kidney disease domain in matriptase chaperone activity and localization of hepatocyte growth factor activator inhibitor-1.
      Title: Role of the polycystic kidney disease domain in matriptase chaperone activity and localization of hepatocyte growth factor activator inhibitor-1.
    3. Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells.
      Title: Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells.
    4. Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.
      Title: Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.
    5. HAI-1 is an independent predictor of lung cancer mortality and is required for M1 macrophage polarization.
      Title: HAI-1 is an independent predictor of lung cancer mortality and is required for M1 macrophage polarization.
    6. Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.
      Title: Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.
    7. Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction.
      Title: Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction.
    8. Hypomethylation of the HAI-1 promoter contributed to the elevated HAI-1 expression in HCC tissues. In addition, the hypomethylation of the HAI-1 promoter region correlated with poor differentiation status of HCC tissues.
      Title: Promoter Hypomethylation Is Responsible for Upregulated Expression of HAI-1 in Hepatocellular Carcinoma.
    9. CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. We find that CDX2 is not required for the basal ST14 and SPINT1 gene expression; however changes in CDX2 expression affects the ST14/SPINT1 mRNA ratio.
      Title: Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2.
    10. show that HA activation by the TMPRSS11A-related enzymes human airway tryptase and DESC1, but not TMPRSS11A itself, is blocked by the cellular serine protease inhibitor hepatocyte growth factor activator inhibitor type-1 (HAI-1).
      Title: TMPRSS11A activates the influenza A virus hemagglutinin and the MERS coronavirus spike protein and is insensitive against blockade by HAI-1.
    Submit: New GeneRIF Correction See all GeneRIFs (62)

    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
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in branching involved in labyrinthine layer morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to BMP stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epidermis development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in epithelium development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in extracellular matrix organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of neural precursor cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in placenta blood vessel development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of glial cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular space HDA PubMed 
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    kunitz-type protease inhibitor 1
    Names
    HAI-1
    hepatocyte growth factor activator inhibitor type 1
    serine protease inhibitor, Kunitz type 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.

    Genomic

    1. NG_029239.1 RefSeqGene

      Range
      5001..19160
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001032367.2 → NP_001027539.1  kunitz-type protease inhibitor 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001027539.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has multiple differences in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC012476, AI684245
      Consensus CDS
      CCDS45231.1
      UniProtKB/TrEMBL
      B2RBU9
      Conserved Domains (3) summary
      smart00192
      Location:318 → 350
      LDLa; Low-density lipoprotein receptor domain class A
      pfam00014
      Location:375 → 426
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    2. NM_001386873.1 → NP_001373802.1  kunitz-type protease inhibitor 1 isoform 1 precursor

      Status: REVIEWED

      Source sequence(s)
      AC012476
      Consensus CDS
      CCDS10067.1
      UniProtKB/Swiss-Prot
      O43278, Q7Z7D2
      UniProtKB/TrEMBL
      B2RBU9
      Conserved Domains (3) summary
      smart00192
      Location:334 → 366
      LDLa; Low-density lipoprotein receptor domain class A
      pfam00014
      Location:391 → 442
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    3. NM_001386874.1 → NP_001373803.1  kunitz-type protease inhibitor 1 isoform 3 precursor

      Status: REVIEWED

      Source sequence(s)
      AC012476
      UniProtKB/TrEMBL
      B2RBU9
      Conserved Domains (2) summary
      pfam00014
      Location:349 → 400
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    4. NM_001386875.1 → NP_001373804.1  kunitz-type protease inhibitor 1 isoform 4 precursor

      Status: REVIEWED

      Source sequence(s)
      AC012476
      UniProtKB/TrEMBL
      B2RBU9
      Conserved Domains (2) summary
      pfam00014
      Location:333 → 384
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    5. NM_003710.4 → NP_003701.1  kunitz-type protease inhibitor 1 isoform 2 precursor

      See identical proteins and their annotated locations for NP_003701.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2).
      Source sequence(s)
      AC012476, AI684245, BC018702, BM763214
      Consensus CDS
      CCDS45231.1
      UniProtKB/TrEMBL
      B2RBU9
      Related
      ENSP00000457076.1, ENST00000562057.6
      Conserved Domains (3) summary
      smart00192
      Location:318 → 350
      LDLa; Low-density lipoprotein receptor domain class A
      pfam00014
      Location:375 → 426
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    6. NM_181642.3 → NP_857593.1  kunitz-type protease inhibitor 1 isoform 1 precursor

      See identical proteins and their annotated locations for NP_857593.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as HAI-1B, encodes the longer isoform (1).
      Source sequence(s)
      AC012476, AI684245, AY358969, BM763214
      Consensus CDS
      CCDS10067.1
      UniProtKB/Swiss-Prot
      O43278, Q7Z7D2
      UniProtKB/TrEMBL
      B2RBU9
      Related
      ENSP00000342098.4, ENST00000344051.8
      Conserved Domains (3) summary
      smart00192
      Location:334 → 366
      LDLa; Low-density lipoprotein receptor domain class A
      pfam00014
      Location:391 → 442
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
      pfam07502
      Location:50 → 139
      MANEC; MANEC domain

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      40844048..40858207
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432969.1 → XP_047288925.1  kunitz-type protease inhibitor 1 isoform X2

      UniProtKB/TrEMBL
      B2RBU9

    2. XM_047432968.1 → XP_047288924.1  kunitz-type protease inhibitor 1 isoform X1

      UniProtKB/TrEMBL
      B2RBU9

    3. XM_047432970.1 → XP_047288926.1  kunitz-type protease inhibitor 1 isoform X3

      UniProtKB/TrEMBL
      B2RBU9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      38650076..38664232
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054378667.1 → XP_054234642.1  kunitz-type protease inhibitor 1 isoform X2

      UniProtKB/TrEMBL
      B2RBU9

    2. XM_054378666.1 → XP_054234641.1  kunitz-type protease inhibitor 1 isoform X1

      UniProtKB/TrEMBL
      B2RBU9

    3. XM_054378668.1 → XP_054234643.1  kunitz-type protease inhibitor 1 isoform X3

      UniProtKB/TrEMBL
      B2RBU9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43278.2 GenPept UniProtKB/Swiss-Prot:O43278

    Gene LinkOut

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

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