Spint2 serine protease inhibitor, Kunitz type 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Spint2provided by MGI
Official Full Name: serine protease inhibitor, Kunitz type 2provided by MGI
Primary source: MGI:MGI:1338031
See related: Ensembl:ENSMUSG00000074227 AllianceGenome:MGI:1338031
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: HAI-2
Summary: Predicted to enable serine-type endopeptidase inhibitor activity. Acts upstream of or within basement membrane organization; chordate embryonic development; and establishment or maintenance of cell polarity. Predicted to be located in cytoplasm. Is expressed in several structures, including alimentary system; brain; genitourinary system; respiratory system; and sensory organ. Used to study congenital secretory sodium diarrhea 3. Human ortholog(s) of this gene implicated in congenital secretory sodium diarrhea 3. Orthologous to human SPINT2 (serine peptidase inhibitor, Kunitz type 2). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in colon adult (RPKM 448.1), duodenum adult (RPKM 435.7) and 13 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 B1; 7 16.94 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (28955755..28981484, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (29256330..29282059, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

matriptase is a causative agent in the development of congenital tufting enteropathy (CTE) and may provide a new target for the treatment of CTE in individuals carrying SPINT2 mutation
Title: Matriptase drives early-onset intestinal failure in a mouse model of congenital tufting enteropathy.
Hai-2 is an essential protease inhibitor for epithelial integrity, Epcam homeostasis and mucosal organization of the intestinal tract.
Title: Hepatocyte growth factor activator inhibitor-2 stabilizes Epcam and maintains epithelial organization in the mouse intestine.
Intestines of HAI-2 deficient mice showed altered expression of epithelial junctional proteins, including reduced levels of EpCAM, E-cadherin, occludin, claudin-1 and -7, as well as an increased level of claudin-4, indicating that the loss of HAI-2 compromises intestinal epithelial barrier function.
Title: Loss of HAI-2 in mice with decreased prostasin activity leads to an early-onset intestinal failure resembling congenital tufting enteropathy.
HAI-1 regulates the activity of activated matriptase, whereas HAI-2 has an essential role in regulating prostasin-dependent matriptase zymogen activation.
Title: The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin.
mutations in Prss8 restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos.
Title: Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation.
HAI-1 and -2 are overexpressed in the liver in cholangiopathies with ductular reactions and are possibly involved in liver fibrosis and hepatic differentiation.
Title: Persistent elevation of hepatocyte growth factor activator inhibitors in cholangiopathies affects liver fibrosis and differentiation.
Inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis.
Title: Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice.
Unlike HAI-1 and matriptase, HAI-2 expression is detected in non-epithelial cells of brain and lymph nodes, suggesting that HAI-2 may also be involved in inhibition of serine proteases other than matriptase
Title: Potent inhibition and global co-localization implicate the transmembrane Kunitz-type serine protease inhibitor hepatocyte growth factor activator inhibitor-2 in the regulation of epithelial matriptase activity.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1)
Gene trapped (1) 1 citation
Targeted (1) 1 citation

General gene information

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Markers

RH125952 (e-PCR)
- UniSTS:162664

NoName (e-PCR)
- UniSTS:235639

Spint2 (e-PCR), detects polymorphism
- UniSTS:531094

Spint1 (e-PCR), detects polymorphism
- UniSTS:502733

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables serine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase inhibitor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within basement membrane organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within epithelial cell morphogenesis involved in placental branching	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within epithelial cell morphogenesis involved in placental branching	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within establishment or maintenance of cell polarity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of cell motility	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell-cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neural precursor cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neural tube closure	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within neural tube closure	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
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: hepatocyte growth factor activator inhibitor type 2

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)

NM_001082548.1 → NP_001076017.1 kunitz-type protease inhibitor 2 isoform b precursor

See identical proteins and their annotated locations for NP_001076017.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate exon, in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform b), compared to isoform a.

Source sequence(s)

AI227451, AK007792, BQ174562, CB196296

Consensus CDS

CCDS39869.1

UniProtKB/TrEMBL

Q9D8Q8

Related

ENSMUSP00000103871.4, ENSMUST00000108236.5

Conserved Domains (1) summary

cd00109
Location:80 → 126

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
NM_011464.2 → NP_035594.1 kunitz-type protease inhibitor 2 isoform a precursor

See identical proteins and their annotated locations for NP_035594.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a).

Source sequence(s)

AI227451, AK007792, BQ174562, CB196296

Consensus CDS

CCDS39870.1

UniProtKB/Swiss-Prot

Q5D0F2, Q9WU03, Q9WU04, Q9WU05

Related

ENSMUSP00000096204.5, ENSMUST00000098604.12

Conserved Domains (2) summary

cd00109
Location:137 → 183

KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.

pfam00014
Location:38 → 88

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000073.7 Reference GRCm39 C57BL/6J

Range

28955755..28981484 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017322072.3 → XP_017177561.1 kunitz-type protease inhibitor 2 isoform X1

Conserved Domains (1) summary

pfam00014
Location:38 → 88

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain