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SPINK6 serine peptidase inhibitor Kazal type 6 [ Homo sapiens (human) ]

Gene ID: 404203, updated on 5-Mar-2024

Summary

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Official Symbol
SPINK6provided by HGNC
Official Full Name
serine peptidase inhibitor Kazal type 6provided by HGNC
Primary source
HGNC:HGNC:29486
See related
Ensembl:ENSG00000178172 MIM:615868; AllianceGenome:HGNC:29486
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
BUSI2; UNQ844
Summary
The protein encoded by this gene is a Kazal-type serine protease inhibitor that acts on kallikrein-related peptidases in the skin. Two transcript variants the same protein have been found for this gene. [provided by RefSeq, Aug 2010]
Expression
Low expression observed in reference dataset See more
Orthologs
mouse all
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Genomic context

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Location:
5q32
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (148202778..148215137)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (148737170..148749644)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (147582341..147594700)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene serine peptidase inhibitor Kazal type 5 Neighboring gene uncharacterized LOC124901185 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_81997 Neighboring gene Sharpr-MPRA regulatory region 6578 Neighboring gene serine peptidase inhibitor Kazal type 14 (putative) Neighboring gene CAGE-defined high expression enhancer downstream of SPINK6 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:147609822-147611021 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 16 Neighboring gene MARCO like

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. SPINK6 inhibits human airway serine proteases and restricts influenza virus activation. Wang D, et al. EMBO Mol Med, 2022 Jan 11. PMID 34826211, Free PMC Article
  2. Serine protease inhibitor kazal-type 6 inhibits tumorigenesis of human hepatocellular carcinoma cells via its extracellular action. Ge K, et al. Oncotarget, 2017 Jan 24. PMID 27999203, Free PMC Article
  3. The solution structure of the kallikrein-related peptidases inhibitor SPINK6. Jung S, et al. Biochem Biophys Res Commun, 2016 Feb 26. PMID 26828269, Free PMC Article
  4. Cross-linking of SPINK6 by transglutaminases protects from epidermal proteases. Fischer J, et al. J Invest Dermatol, 2013 May. PMID 23303447
  5. Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. Meyer-Hoffert U, et al. J Biol Chem, 2010 Oct 15. PMID 20667819, Free PMC Article

See all (19) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.
    Title: SPINK6 inhibits human airway serine proteases and restricts influenza virus activation.
  2. Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium.
    Title: Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium.
  3. Study showed that the expression of SPINK6 is specifically suppressed in liver tumor tissues. The suppression could be even detected in the early stage tumors. As SPINK6 is a secretory protein, the extracellular protein level may be decreased because of tumor development. These results support that SPINK6 is an important tumor suppressor in liver.
    Title: Serine protease inhibitor kazal-type 6 inhibits tumorigenesis of human hepatocellular carcinoma cells via its extracellular action.
  4. our results identified a novel EGFR-activating mechanism in which SPINK6 has a critical role in promoting nasopharyngeal carcinoma metastasis
    Title: SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor.
  5. a significant fraction of SPINK6-sensitive proteases in healthy saliva and confirmed the ability of gingipains to inactivate SPINK6 under ex vivo conditions
    Title: Gingipains of Porphyromonas gingivalis Affect the Stability and Function of Serine Protease Inhibitor of Kazal-type 6 (SPINK6), a Tissue Inhibitor of Human Kallikreins.
  6. KLKs. Thereby, beside the conserved binding mode, we identified an alternate binding mode which has so far not been observed for SPINK inhibitors.
    Title: The solution structure of the kallikrein-related peptidases inhibitor SPINK6.
  7. Our study indicates that Spink6 is a potent inhibitor of kallikrein related peptidases and involved in skin barrier function.
    Title: Characterization of Spink6 in mouse skin: the conserved inhibitor of kallikrein-related peptidases is reduced by barrier injury.
  8. Cross-linked SPINK6 might protect specific substrates such as fibronectin from kallikrein-related peptidases cleavage and contribute to the regulation of proteases in the epidermis.
    Title: Cross-linking of SPINK6 by transglutaminases protects from epidermal proteases.
  9. Serine protease of Kazal-type (SPINK6) expressed in normal human skin is a potent natural inhibitor of Kallikrein-related peptidases, KLK12 and KLK13.
    Title: Inhibition of kallikrein-related peptidases by the serine protease inhibitor of Kazal-type 6.
  10. Data suggest that SPINK6 plays a role in modulating the activity of kallikreins in human skin.
    Title: Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases.
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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

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Homology

Clone Names

  • MGC21394

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables serine-type endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in extracellular region TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
serine protease inhibitor Kazal-type 6
Names
acrosin inhibitor
kallikrein inhibitor
protease inhibitor H

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)

  1. NM_001195290.2 → NP_001182219.1  serine protease inhibitor Kazal-type 6 precursor

    See identical proteins and their annotated locations for NP_001182219.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein.
    Source sequence(s)
    AC011346, AY358716, BE122852, GQ504704
    Consensus CDS
    CCDS34268.1
    UniProtKB/Swiss-Prot
    E0X656, Q6UWN8, Q8N5P0
    Related
    ENSP00000481309.1, ENST00000621437.4
    Conserved Domains (1) summary
    pfam00050
    Location:36 → 80
    Kazal_1; Kazal-type serine protease inhibitor domain

  2. NM_205841.4 → NP_995313.2  serine protease inhibitor Kazal-type 6 precursor

    See identical proteins and their annotated locations for NP_995313.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 both encode the same protein.
    Source sequence(s)
    AY358716, GQ504704
    Consensus CDS
    CCDS34268.1
    UniProtKB/Swiss-Prot
    E0X656, Q6UWN8, Q8N5P0
    Related
    ENSP00000324870.2, ENST00000325630.3
    Conserved Domains (1) summary
    pfam00050
    Location:36 → 80
    Kazal_1; Kazal-type serine protease inhibitor domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    148202778..148215137
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    148737170..148749644
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6UWN8.1 GenPept UniProtKB/Swiss-Prot:Q6UWN8

Gene LinkOut

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