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

Summary

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: mouse all
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Genomic context

Location:: 19q13.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (38264573..38292615)
RS_2023_10	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_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
Title: Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
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.
The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
Title: The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
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.
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.
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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

A007F08 (e-PCR)
- UniSTS:10913

WI-14931 (e-PCR)
- UniSTS:76232

D19S897 (e-PCR), detects polymorphism
- UniSTS:14816

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
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 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
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

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

NG_013372.1 RefSeqGene

Range

5116..33158

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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/TrEMBL

A0A140VJV6, K7EM91

Related

ENSP00000389788.2, ENST00000454580.7

Conserved Domains (1) summary

pfam00014
Location:75 → 126

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain
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

A8K667, B4DLU1, O00271, O14895, O43291, Q5TZQ3, Q969E0

UniProtKB/TrEMBL

Q6LEU8

Related

ENSP00000301244.5, ENST00000301244.12

Conserved Domains (1) summary

pfam00014
Location:37 → 88

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain