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

Summary

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

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

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

RH47591 (e-PCR)
- UniSTS:37415

STS-R72769 (e-PCR)
- UniSTS:50501

G62007 (e-PCR)
- UniSTS:139081

RH103600 (e-PCR)
- UniSTS:97925

RH80144 (e-PCR)
- UniSTS:92624

WI-21808 (e-PCR)
- UniSTS:66526

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 more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info	PubMed
located_in extracellular space	HDA 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

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

NG_029239.1 RefSeqGene

Range

5001..19160

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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
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