SPINK5 serine peptidase inhibitor Kazal type 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SPINK5provided by HGNC
Official Full Name: serine peptidase inhibitor Kazal type 5provided by HGNC
Primary source: HGNC:HGNC:15464
See related: Ensembl:ENSG00000133710 MIM:605010; AllianceGenome:HGNC:15464
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: NS; NETS; LEKTI; LETKI; VAKTI
Summary: This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
Expression: Biased expression in esophagus (RPKM 472.7) and skin (RPKM 127.7) See more
Orthologs: mouse all
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Genomic context

Location:: 5q32

Exon count:: 36

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (148063980..148137382)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (148599687..148673088)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (147443543..147516945)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.
Title: SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.
Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.
Title: Comparative analyses of Netherton syndrome patients and Spink5 conditional knock-out mice uncover disease-relevant pathways.
Inhibition of the Tumor Suppressor Gene SPINK5 via EHMT2 Induces the Oral Squamous Cell Carcinoma Development.
Title: Inhibition of the Tumor Suppressor Gene SPINK5 via EHMT2 Induces the Oral Squamous Cell Carcinoma Development.
Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.
Title: Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.
MiR-375-3p alleviates the severity of inflammation through targeting YAP1/LEKTI pathway in HaCaT cells.
Title: MiR-375-3p alleviates the severity of inflammation through targeting YAP1/LEKTI pathway in HaCaT cells.
LEKTI domains D6, D7 and D8+9 serve as substrates for transglutaminase 1: implications for targeted therapy of Netherton syndrome.
Title: LEKTI domains D6, D7 and D8+9 serve as substrates for transglutaminase 1: implications for targeted therapy of Netherton syndrome.
Exonic mutations associated with atopic dermatitis disrupt lympho-epithelial Kazal-type related inhibitor action and enhance its degradation.
Title: Exonic mutations associated with atopic dermatitis disrupt lympho-epithelial Kazal-type related inhibitor action and enhance its degradation.
Genetic polymorphisms in serine protease inhibitor Kazal-type 5 and risk of atopic dermatitis: A meta-analysis.
Title: Genetic polymorphisms in serine protease inhibitor Kazal-type 5 and risk of atopic dermatitis: A meta-analysis.
Our study shows that SPINK5 can inhibit the proliferation, migration, and invasion of esophageal cancer cells by inhibiting Wnt/beta-catenin signaling pathway, and thus plays an important role in the development of esophageal cancer, and may serve as a treatment target of esophageal cancer.
Title: A novel tumor suppressor SPINK5 targets Wnt/β-catenin signaling pathway in esophageal cancer.
TNF-alpha and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and atopic dermatitis (AD) lesions. TNF-alpha and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under infla...
Title: TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes.

Submit: New GeneRIF Correction See all GeneRIFs (68)

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
Netherton syndrome MedGen: C5574950 OMIM: 256500 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

RH65250 (e-PCR)
- UniSTS:41334

D5S2598 (e-PCR)
- UniSTS:72639

Clone Names

FLJ21544, FLJ97536, FLJ97596, FLJ99794, DKFZp686K19184

Gene Ontology Provided by GOA

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	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in epidermal cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in epithelial cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in extracellular matrix organization	TAS Traceable Author Statement more info	PubMed
involved_in hair cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of angiogenesis	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of antibacterial peptide production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of T cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in regulation of timing of anagen	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell cortex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in epidermal lamellar body	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine protease inhibitor Kazal-type 5

Names: lympho-epithelial Kazal-type-related inhibitor; lymphoepithelial Kazal-type-related inhibitor

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_009633.1 RefSeqGene

Range

5001..78391

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GenBank, FASTA, Sequence Viewer (Graphics), LRG_110

mRNA and Protein(s)

NM_001127698.2 → NP_001121170.1 serine protease inhibitor Kazal-type 5 isoform a preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as SPINK5l) represents the longest transcript and encodes the longest isoform (a, also known as the LEKTIl or long isoform).

Source sequence(s)

AC116334, AI341060, AK025197, AK307588, AK307648, BI256857, DQ149928, DR421881

Consensus CDS

CCDS47300.1

UniProtKB/TrEMBL

B4DWS3

Related

ENSP00000352936.3, ENST00000359874.7

Conserved Domains (3) summary

smart00280
Location:787 → 827

KAZAL; Kazal type serine protease inhibitors

cd01327
Location:1032 → 1076

KAZAL_PSTI; Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the ...

cl00097
Location:310 → 346

KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...
NM_001127699.2 → NP_001121171.1 serine protease inhibitor Kazal-type 5 isoform c preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as SPINK5sh) differs in the 3' UTR and lacks several exons in the 3' coding region, compared to variant 1. The resulting protein (isoform c, also known as the LEKTIsh or short isoform) has a distinct C-terminus and is shorter than isoform a.

Source sequence(s)

AC008722, AK025197, AK307588, AK307648, DQ149929

Consensus CDS

CCDS47301.1

UniProtKB/TrEMBL

B4DWS3

Related

ENSP00000381472.1, ENST00000398454.5

Conserved Domains (3) summary

smart00280
Location:787 → 827

KAZAL; Kazal type serine protease inhibitors

cd01327
Location:107 → 151

KAZAL_PSTI; Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the ...

pfam07648
Location:311 → 348

Kazal_2; Kazal-type serine protease inhibitor domain
NM_006846.4 → NP_006837.2 serine protease inhibitor Kazal-type 5 isoform b preproprotein

See identical proteins and their annotated locations for NP_006837.2

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as SPINK5f-l) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform b, also known as the LEKTIf-l isoform), compared to isoform a.

Source sequence(s)

AC116334, AI341060, AK025197, AK307588, AK307648, DQ149927, DR421881

Consensus CDS

CCDS43382.1

UniProtKB/Swiss-Prot

A8MYE8, B7WPB7, D6REN5, O75770, Q3LX95, Q3LX96, Q3LX97, Q96PP2, Q96PP3, Q9NQ38

UniProtKB/TrEMBL

B4DWS3

Related

ENSP00000256084.7, ENST00000256084.8

Conserved Domains (3) summary

smart00280
Location:787 → 827

KAZAL; Kazal type serine protease inhibitors

cd01327
Location:1002 → 1046

KAZAL_PSTI; Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the ...

cl00097
Location:310 → 348

KAZAL_FS; Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

148063980..148137382

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047416662.1 → XP_047272618.1 serine protease inhibitor Kazal-type 5 isoform X1
XM_011537551.3 → XP_011535853.1 serine protease inhibitor Kazal-type 5 isoform X2

Conserved Domains (3) summary

smart00280
Location:759 → 799

KAZAL; Kazal type serine protease inhibitors

cd01327
Location:1004 → 1048

KAZAL_PSTI; Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the ...

pfam07648
Location:283 → 320

Kazal_2; Kazal-type serine protease inhibitor domain
XM_047416663.1 → XP_047272619.1 serine protease inhibitor Kazal-type 5 isoform X3