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SPINK5 Gene(Protein Coding)

Serine Peptidase Inhibitor, Kazal Type 5

GCID:
GC05P148025
GIFtS:
51
Genes Participants
UDN Logo

Aliases for SPINK5 Gene

Aliases for SPINK5 Gene

  • Serine Peptidase Inhibitor, Kazal Type 5 2 3 5
  • Lympho-Epithelial Kazal-Type-Related Inhibitor 3 4
  • Lymphoepithelial Kazal-Type-Related Inhibitor 2 3
  • LEKTI 3 4
  • Serine Protease Inhibitor, Kazal Type 5 2
  • Serine Protease Inhibitor Kazal-Type 5 3
  • LETKI 3
  • VAKTI 3
  • NETS 3
  • NS 3

External Ids for SPINK5 Gene

Previous GeneCards Identifiers for SPINK5 Gene

  • GC05P147475
  • GC05P147472
  • GC05P147423
  • GC05P142590

Summaries for SPINK5 Gene

Entrez Gene Summary for SPINK5 Gene

  • 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]

GeneCards Summary for SPINK5 Gene

SPINK5 (Serine Peptidase Inhibitor, Kazal Type 5) is a Protein Coding gene. Diseases associated with SPINK5 include Netherton Syndrome and Ige Responsiveness, Atopic. Among its related pathways are Keratinization and Cell adhesion_Plasmin signaling. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and peptidase inhibitor activity.

UniProtKB/Swiss-Prot for SPINK5 Gene

  • Serine protease inhibitor, probably important for the anti-inflammatory and/or antimicrobial protection of mucous epithelia. Contribute to the integrity and protective barrier function of the skin by regulating the activity of defense-activating and desquamation-involved proteases. Inhibits KLK5, its major target, in a pH-dependent manner. Inhibits KLK7, KLK14 CASP14, and trypsin.

Gene Wiki entry for SPINK5 Gene

Additional gene information for SPINK5 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPINK5 Gene

Genomics for SPINK5 Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for SPINK5 Gene

Promoters and enhancers for SPINK5 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH05I148063 Promoter 0.5 EPDnew 550.3 +38.3 38278 0.1 SPINK5 GC05M147950
GH05I148011 Enhancer 0.8 ENCODE 34.7 -13.5 -13534 1.6 FEZF1 RAD21 SCRT2 FOS RCOR1 OVOL3 CEBPB ELF1 ZNF217 MAFF SPINK5 PIR41093 GC05M147950
GH05I148089 Enhancer 0.6 ENCODE 25.2 +65.5 65518 2.8 ELK4 PKNOX1 CEBPB EP300 RFX5 JUND MAFF ZKSCAN8 SMARCC2 STAT3 SPINK5 SPINK7 GC05M147950
GH05I148032 Enhancer 0.5 ENCODE 22 +8.0 7998 1.7 RFX1 CEBPB NFE2 EP300 SPINK5 GC05M147950
GH05I148012 Enhancer 0.2 ENCODE 19.9 -12.7 -12650 0.2 SPINK5 PIR41093 GC05M147950
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around SPINK5 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SPINK5 gene promoter:

Genomic Locations for SPINK5 Gene

Genomic Locations for SPINK5 Gene
chr5:148,025,683-148,137,366
(GRCh38/hg38)
Size:
111,684 bases
Orientation:
Plus strand
chr5:147,405,246-147,516,925
(GRCh37/hg19)

Genomic View for SPINK5 Gene

Genes around SPINK5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPINK5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPINK5 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for SPINK5 Gene

Proteins for SPINK5 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for SPINK5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQ38-ISK5_HUMAN
    Recommended name:
    Serine protease inhibitor Kazal-type 5
    Protein Accession:
    Q9NQ38
    Secondary Accessions:
    • A8MYE8
    • B7WPB7
    • D6REN5
    • O75770
    • Q3LX95
    • Q3LX96
    • Q3LX97
    • Q96PP2
    • Q96PP3

    Protein attributes for SPINK5 Gene

    Size:
    1064 amino acids
    Molecular mass:
    120714 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for SPINK5 Gene

    Alternative splice isoforms for SPINK5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SPINK5 Gene

Protein Expression for SPINK5 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for SPINK5 Gene

  • Proteolytically processed by furin in individual domains (D1, D5, D6, D8 through D11, and D9 through D15) exhibiting various inhibitory potentials for multiple proteases.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SPINK5 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for SPINK5 (LEKTI/SPINK5)
  • Abcam antibodies for SPINK5

No data available for DME Specific Peptides for SPINK5 Gene

Domains & Families for SPINK5 Gene

Gene Families for SPINK5 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for SPINK5 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for SPINK5 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9NQ38

UniProtKB/Swiss-Prot:

ISK5_HUMAN :
  • Contains at least one active inhibitory domain for trypsin (domain 6).
Domain:
  • Contains at least one active inhibitory domain for trypsin (domain 6).
genes like me logo Genes that share domains with SPINK5: view

Function for SPINK5 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for SPINK5 Gene

UniProtKB/Swiss-Prot Function:
Serine protease inhibitor, probably important for the anti-inflammatory and/or antimicrobial protection of mucous epithelia. Contribute to the integrity and protective barrier function of the skin by regulating the activity of defense-activating and desquamation-involved proteases. Inhibits KLK5, its major target, in a pH-dependent manner. Inhibits KLK7, KLK14 CASP14, and trypsin.

Phenotypes From GWAS Catalog for SPINK5 Gene

Gene Ontology (GO) - Molecular Function for SPINK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IEA,IDA 10419450
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with SPINK5: view
genes like me logo Genes that share phenotypes with SPINK5: view

Human Phenotype Ontology for SPINK5 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SPINK5 Gene

MGI Knock Outs for SPINK5:

Animal Model Products

miRNA for SPINK5 Gene

miRTarBase miRNAs that target SPINK5

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SPINK5 Gene

Localization for SPINK5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPINK5 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPINK5 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
cytosol 5
plasma membrane 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SPINK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005737 cytoplasm IDA 12915442
GO:0005783 endoplasmic reticulum IDA 15680911
GO:0005789 endoplasmic reticulum membrane IDA 15680911
GO:0005829 cytosol IDA 15680911
genes like me logo Genes that share ontologies with SPINK5: view

Pathways & Interactions for SPINK5 Gene

genes like me logo Genes that share pathways with SPINK5: view

Pathways by source for SPINK5 Gene

1 GeneGo (Thomson Reuters) pathway for SPINK5 Gene

Interacting Proteins for SPINK5 Gene

STRING Interaction Network Preview (showing 2 interactants - click image to see details)
http://version10.5.string-db.org/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000352936%0d%0a9606.ENSP00000308720%0d%0a9606.ENSP00000240851%0d%0a
Selected Interacting proteins: Q9NQ38-ISK5_HUMAN ENSP00000352936 for SPINK5 Gene via IID STRING

Gene Ontology (GO) - Biological Process for SPINK5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002787 negative regulation of antibacterial peptide production IEA --
GO:0009913 epidermal cell differentiation IDA 12915442
GO:0010466 negative regulation of peptidase activity IEA --
GO:0016525 negative regulation of angiogenesis TAS 15680911
GO:0030155 regulation of cell adhesion IEA --
genes like me logo Genes that share ontologies with SPINK5: view

No data available for SIGNOR curated interactions for SPINK5 Gene

Drugs & Compounds for SPINK5 Gene

Products:

  1. Drug

(1) Drugs for SPINK5 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with SPINK5: view

Transcripts for SPINK5 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for SPINK5 Gene

(4) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(90) Selected AceView cDNA sequences:
(9) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for SPINK5 Gene

Serine peptidase inhibitor, Kazal type 5:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SPINK5 Gene

No ASD Table

Relevant External Links for SPINK5 Gene

GeneLoc Exon Structure for
SPINK5
ECgene alternative splicing isoforms for
SPINK5

Expression for SPINK5 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SPINK5 Gene

mRNA expression in normal human tissues for SPINK5 Gene
mRNA expression by GTEx for SPINK5 GenemRNA expression by BioGPS for SPINK5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SPINK5 Gene

This gene is overexpressed in Esophagus - Mucosa (x22.8), Vagina (x11.4), Cervix - Ectocervix (x7.5), and Skin - Sun Exposed (Lower leg) (x4.2).

Protein differential expression in normal tissues from HIPED for SPINK5 Gene

This gene is overexpressed in Cervix (42.4) and Skin (12.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for SPINK5 Gene



NURSA nuclear receptor signaling pathways regulating expression of SPINK5 Gene:

SPINK5

SOURCE GeneReport for Unigene cluster for SPINK5 Gene:

Hs.331555

mRNA Expression by UniProt/SwissProt for SPINK5 Gene:

Q9NQ38-ISK5_HUMAN
Tissue specificity: Highly expressed in the thymus and stratum corneum. Also found in the oral mucosa, parathyroid gland, Bartholins glands, tonsils, and vaginal epithelium. Very low levels are detected in lung, kidney, and prostate.

Evidence on tissue expression from TISSUES for SPINK5 Gene

  • Skin(4.7)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SPINK5 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • face
  • forehead
  • head
  • lip
  • mouth
  • neck
  • scalp
  • tongue
Thorax:
  • bronchus
  • lung
Abdomen:
  • intestine
  • large intestine
  • small intestine
Limb:
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • hair
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with SPINK5: view

No data available for Protein tissue co-expression partners for SPINK5 Gene

Orthologs for SPINK5 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SPINK5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia SPINK5 33
  • 99.12 (n)
dog
(Canis familiaris)
 Mammalia SPINK5 33 34
  • 84.6 (n)
cow
(Bos Taurus)
 Mammalia SPINK5 33 34
  • 75.62 (n)
mouse
(Mus musculus)
 Mammalia Spink5 16 34 33
  • 69.89 (n)
rat
(Rattus norvegicus)
 Mammalia LOC100910851 33
  • 68.54 (n)
oppossum
(Monodelphis domestica)
 Mammalia SPINK5 34
  • 54 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 34
  • 51 (a)
 OneToMany
-- 34
  • 46 (a)
 OneToMany
chicken
(Gallus gallus)
 Aves SPINK7 33
  • 47.87 (n)
SPINK5 34
  • 28 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia SPINK5 34
  • 30 (a)
 OneToOne
Species where no ortholog for SPINK5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for SPINK5 Gene

ENSEMBL:
Gene Tree for SPINK5 (if available)
TreeFam:
Gene Tree for SPINK5 (if available)

Paralogs for SPINK5 Gene

(8) SIMAP similar genes for SPINK5 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with SPINK5: view

No data available for Paralogs for SPINK5 Gene

Variants for SPINK5 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for SPINK5 Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs114635730 conflicting-interpretations-of-pathogenicity, Netherton syndrome 148,125,737(+) A/G coding_sequence_variant, genic_downstream_transcript_variant, synonymous_variant
rs114784178 likely-benign, Netherton syndrome 148,089,617(+) C/T coding_sequence_variant, synonymous_variant
rs115366845 conflicting-interpretations-of-pathogenicity, Netherton syndrome 148,133,895(+) C/T genic_downstream_transcript_variant, intron_variant
rs115504632 benign, conflicting-interpretations-of-pathogenicity, not specified, Netherton syndrome 148,107,109(+) C/T coding_sequence_variant, missense_variant
rs115820034 conflicting-interpretations-of-pathogenicity, Netherton syndrome 148,125,847(+) T/C coding_sequence_variant, genic_downstream_transcript_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for SPINK5 Gene

Variant ID Type Subtype PubMed ID
dgv3188n106 CNV deletion 24896259
esv1953564 CNV deletion 18987734
esv2569672 CNV deletion 19546169
esv2730894 CNV deletion 23290073
esv3357612 CNV insertion 20981092
esv3555 CNV loss 18987735
esv3566789 CNV deletion 23714750
esv3570489 CNV loss 25503493
esv3607101 CNV loss 21293372
esv3607102 CNV loss 21293372
esv8009 CNV loss 19470904
nsv1033838 CNV loss 25217958
nsv1074337 CNV deletion 25765185
nsv327946 CNV deletion 16902084
nsv328025 CNV deletion 16902084
nsv477853 CNV novel sequence insertion 20440878
nsv830515 CNV gain+loss 17160897
nsv955839 CNV deletion 24416366

Variation tolerance for SPINK5 Gene

Residual Variation Intolerance Score: 69.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 29.30; 99.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPINK5 Gene

Human Gene Mutation Database (HGMD)
SPINK5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPINK5

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPINK5 Gene

Disorders for SPINK5 Gene

MalaCards: The human disease database

(15) MalaCards diseases for SPINK5 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

ISK5_HUMAN
  • Netherton syndrome (NETH) [MIM:256500]: An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration. {ECO:0000269 PubMed:10835624}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SPINK5

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SPINK5: view

No data available for Genatlas for SPINK5 Gene

Publications for SPINK5 Gene

  1. A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population. (PMID: 19534795) Liu Q … Gong Y (BMC medical genetics 2009) 3 22 44 58
  2. Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk. (PMID: 18774391) Weidinger S … Irvine AD (The Journal of allergy and clinical immunology 2008) 3 22 44 58
  3. Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort. (PMID: 17989887) Hubiche T … Boralevi F (Acta dermato-venereologica 2007) 3 22 44 58
  4. SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. (PMID: 16374478) Tartaglia-Polcini A … D'Alessio M (The Journal of investigative dermatology 2006) 3 4 22 58
  5. Rapid detection of the SPINK5 polymorphism Glu420Lys by real-time PCR technology. (PMID: 15820494) Rihs HP … Brüning T (Clinica chimica acta; international journal of clinical chemistry 2005) 3 22 44 58

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