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

Gene ID: 6692, updated on 3-Apr-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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Location:
15q15.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (40844048..40858207)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (38650076..38664232)
105.20220307 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. Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells. Izumi A, et al. Cancer Sci, 2022 Jun. PMID 35332604, Free PMC Article
  2. HAI-1 is an independent predictor of lung cancer mortality and is required for M1 macrophage polarization. Borowicz S, et al. PLoS One, 2021. PMID 34185790, Free PMC Article
  3. Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes. Lu DD, et al. Hum Cell, 2021 May. PMID 33486722
  4. Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction. Kaitu'u-Lino TJ, et al. Nat Commun, 2020 May 15. PMID 32415092, Free PMC Article
  5. Promoter Hypomethylation Is Responsible for Upregulated Expression of HAI-1 in Hepatocellular Carcinoma. Du X, et al. Dis Markers, 2019. PMID 31558918, Free PMC Article

See all (93) 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)

Genotypes

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 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_2023_10

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

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

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

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

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

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

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

Gene LinkOut

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