Spint1 serine protease inhibitor, Kunitz type 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Spint1provided by MGI
Official Full Name: serine protease inhibitor, Kunitz type 1provided by MGI
Primary source: MGI:MGI:1338033
See related: Ensembl:ENSMUSG00000027315 AllianceGenome:MGI:1338033
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-1
Summary: Predicted to enable serine-type endopeptidase inhibitor activity. Acts upstream of or within extracellular matrix organization; neural tube closure; and placenta development. Located in plasma membrane. Is expressed in several structures, including alimentary system; brain; extraembryonic component; genitourinary system; and sensory organ. Orthologous to human SPINT1 (serine peptidase inhibitor, Kunitz type 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in duodenum adult (RPKM 111.5), small intestine adult (RPKM 107.4) and 11 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 E5; 2 59.97 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (119067841..119079995)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (119237360..119249535)

Chromosome 2 - NC_000068.8 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: 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?

ese results suggest that serine proteases promote intestinal carcinogenesis through activation of PAR-2, and that HAI-1 plays a critical tumor suppressor role as an inhibitor of matriptase, kallikreins, and other PAR-2 activating proteases.
Title: Protease-activated receptor-2 accelerates intestinal tumor formation through activation of nuclear factor-κB signaling and tumor angiogenesis in Apc(Min/+) mice.
We propose that Spint1 contributes to the tumor-suppressive function of HIF-2a in tumor-associated macrophages in breast tumor development
Title: Macrophage HIF-2α regulates tumor-suppressive Spint1 in the tumor microenvironment.
Grhl2 regulation of SPINT1 expression controls salivary gland development
Title: Grhl2 regulation of SPINT1 expression controls salivary gland development.
Results suggest that insufficient hepatocyte growth factor activator inhibitor type 1 (HAI-1) function promotes intestinal carcinogenesis by activating nuclear factor-kappaB (NF-kappaB) signaling.
Title: Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the ApcMin/+ model.
By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor
Title: Crystal Structure of a Two-domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: FUNCTIONAL INTERACTIONS BETWEEN THE KUNITZ-TYPE INHIBITOR DOMAIN-1 AND THE NEIGHBORING POLYCYSTIC KIDNEY DISEASE-LIKE DOMAIN.
HAI-1 may have a critical role in maintaining normal keratinocyte morphology through regulation of PAR-2-dependent p38 mitogen-activated protein kinase signaling.
Title: Hepatocyte growth factor activator inhibitor type 1 maintains the assembly of keratin into desmosomes in keratinocytes by regulating protease-activated receptor 2-dependent p38 signaling.
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.
HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP sign
Title: Hepatocyte growth factor activator inhibitor-1 is induced by bone morphogenetic proteins and regulates proliferation and cell fate of neural progenitor cells.
HAI-1/SPINT1 has a crucial role in suppressing intestinal tumorigenesis, which implies a novel link between epithelial cell surface serine protease inhibitors and protection from carcinogenic stimuli.
Title: Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis.
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.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Variation

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Alleles

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

Endonuclease-mediated (2)
Gene trapped (1) 1 citation
Targeted (5) 1 citation

General gene information

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Markers

Spint1 (e-PCR), detects polymorphism
- UniSTS:531093

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

Gene Ontology Provided by MGI

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

Process	Evidence Code	Pubs
acts_upstream_of_or_within branching involved in labyrinthine layer morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within embryonic placenta development	IMP Inferred from Mutant Phenotype more info	PubMed
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
acts_upstream_of_or_within extracellular matrix organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neural precursor cell proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neural tube closure	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within placenta blood vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glial cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within symbiont entry into host cell	ISO Inferred from Sequence Orthology more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: kunitz-type protease inhibitor 1

Names: hepatocyte growth factor activator inhibitor 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.

mRNA and Protein(s)

NM_001412660.1 → NP_001399589.1 kunitz-type protease inhibitor 1 precursor

Status: VALIDATED

Source sequence(s)

AL929318

UniProtKB/Swiss-Prot

Q99J04, Q9R097

Related

ENSMUSP00000106440.2, ENSMUST00000110816.8
NM_001412661.1 → NP_001399590.1 kunitz-type protease inhibitor 1 precursor

Status: VALIDATED

Source sequence(s)

AL929318

UniProtKB/Swiss-Prot

Q99J04, Q9R097

Related

ENSMUSP00000106441.3, ENSMUST00000110817.3
NM_016907.3 → NP_058603.2 kunitz-type protease inhibitor 1 precursor

See identical proteins and their annotated locations for NP_058603.2

Status: VALIDATED

Source sequence(s)

AL929318

Consensus CDS

CCDS16597.1

UniProtKB/Swiss-Prot

Q99J04, Q9R097

UniProtKB/TrEMBL

Q9D3K4

Related

ENSMUSP00000028783.8, ENSMUST00000028783.14

Conserved Domains (3) summary

smart00192
Location:313 → 344

LDLa; Low-density lipoprotein receptor domain class A

pfam00014
Location:368 → 419

Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

pfam07502
Location:42 → 133

MANEC; MANEC domain