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SPINT2 serine peptidase inhibitor, Kunitz type 2 [ Homo sapiens (human) ]

Gene ID: 10653, updated on 29-Mar-2023

Summary

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Official Symbol
SPINT2provided by HGNC
Official Full Name
serine peptidase inhibitor, Kunitz type 2provided by HGNC
Primary source
HGNC:HGNC:11247
See related
Ensembl:ENSG00000167642 MIM:605124; AllianceGenome:HGNC:11247
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
PB; Kop; HAI2; DIAR3; HAI-2
Summary
This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Expression
Broad expression in colon (RPKM 172.2), thyroid (RPKM 135.2) and 22 other tissues See more
Orthologs
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Genomic context

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See SPINT2 in Genome Data Viewer
Location:
19q13.2
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (38264573..38292615)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (41066744..41094785)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (38755213..38783255)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38752767-38753703 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38753844-38754761 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38785153-38785654 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38788840-38789473

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. Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction. Murphy CN, et al. Int J Mol Sci, 2021 Jul 12. PMID 34299087, Free PMC Article
  2. The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity. Ramirez Alvarez C, et al. PLoS Pathog, 2021 Jun. PMID 34181691, Free PMC Article
  3. Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells. Barndt RB, et al. Hum Mol Genet, 2021 Sep 15. PMID 34089062, Free PMC Article
  4. Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea. Ernst J, et al. Am J Med Genet A, 2021 Apr. PMID 33547739
  5. SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses. Straus MR, et al. Virology, 2020 Apr. PMID 32056846, Free PMC Article

See all (102) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.
    Title: Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.
  2. Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.
    Title: Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.
  3. 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.
  4. Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.
    Title: Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.
  5. Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
    Title: Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
  6. The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity.
    Title: The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity.
  7. The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
    Title: The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
  8. Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.
    Title: Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.
  9. SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.
    Title: SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.
  10. down-regulation in SPINT2/HAI-2 gene expression, due to methylation in myelodysplastic syndromes (MDS)-bone marrow mesenchymal stromal cell (BMMSC) and de novo acute myeloid leukaemia -BMMSC, provides novel insights into the pathogenic role of the leukemic bone marrow microenvironment.
    Title: Up-regulation of SPINT2/HAI-2 by Azacytidine in bone marrow mesenchymal stromal cells affects leukemic stem cell survival and adhesion.
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

Associated conditions

Description Tests
Congenital secretory sodium diarrhea 3
MedGen: C5441927 OMIM: 270420 GeneReviews: Not available
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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

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ45571

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables serine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables serine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in basement membrane organization IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to BMP stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in epithelial cell morphogenesis involved in placental branching IEA
Inferred from Electronic Annotation
more info
  
involved_in establishment or maintenance of cell polarity IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within negative regulation of cell motility IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within negative regulation of cell-cell adhesion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neural precursor cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of peptidase activity IEA
Inferred from Electronic Annotation
more info
  
involved_in neural tube closure IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
 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
 PubMed 

General protein information

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Preferred Names
kunitz-type protease inhibitor 2
Names
HGF activator inhibitor 2
Kunitz domain containing protein overexpressed in pancreatic cancer
hepatocyte growth factor activator inhibitor type 2
hepatocyte growth factor activator inhibitor-2
serine protease inhibitor, Kunitz type, 2
testicular tissue protein Li 183

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_013372.1 RefSeqGene

    Range
    5116..33158
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166103.2 → NP_001159575.1  kunitz-type protease inhibitor 2 isoform b precursor

    See identical proteins and their annotated locations for NP_001159575.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) lacks an alternate in-frame exon in the 5' coding region, compared to variant a. The resulting isoform (b) lacks an internal segment near the N-terminus, compared to isoform a.
    Source sequence(s)
    AC011479, AI199013, AK297154, AW275313
    Consensus CDS
    CCDS54261.1
    UniProtKB/Swiss-Prot
    O43291
    UniProtKB/TrEMBL
    A0A140VJV6
    Related
    ENSP00000389788.2, ENST00000454580.7
    Conserved Domains (1) summary
    pfam00014
    Location:75 → 126
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

  2. NM_021102.4 → NP_066925.1  kunitz-type protease inhibitor 2 isoform a precursor

    See identical proteins and their annotated locations for NP_066925.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AC011479, AW275313, BC001668
    Consensus CDS
    CCDS12510.1
    UniProtKB/Swiss-Prot
    O43291, Q969E0
    Related
    ENSP00000301244.5, ENST00000301244.12
    Conserved Domains (1) summary
    pfam00014
    Location:37 → 88
    Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    38264573..38292615
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    41066744..41094785
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43291.2 GenPept UniProtKB/Swiss-Prot:O43291

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