KLK8 kallikrein related peptidase 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLK8provided by HGNC
Official Full Name: kallikrein related peptidase 8provided by HGNC
Primary source: HGNC:HGNC:6369
See related: Ensembl:ENSG00000129455 MIM:605644; AllianceGenome:HGNC:6369
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: NP; HNP; NRPN; PRSS19; TADG14
Summary: Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in tandem in a gene cluster on chromosome 19. The encoded protein may be involved in proteolytic cascade in the skin and may serve as a biomarker for ovarian cancer. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
Annotation information: Note: The KLK9 gene is immediately upstream of the KLK8 gene. There are a few transcripts (DQ267419, DQ267420, AY566267, and BC040887) that span the gap between these two genes and which suggest the presence of a bicistronic transcript. However, there is no published support for that, so they will continue to be represented as separate genes. [13 Feb 2013]
Expression: Biased expression in skin (RPKM 32.0) and esophagus (RPKM 29.8) See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.41

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (50996008..51001604, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (54084477..54090075, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (51499264..51504860, complement)

Chromosome 19 - NC_000019.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma.
Title: Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma.
circSSPO boosts growth of esophageal squamous cell carcinoma through upregulation of micrRNA-6820-5p-mediated KLK8 and PKD1 expression.
Title: circSSPO boosts growth of esophageal squamous cell carcinoma through upregulation of micrRNA-6820-5p-mediated KLK8 and PKD1 expression.
Kallikrein 8: A key sheddase to strengthen and stabilize neural plasticity.
Title: Kallikrein 8: A key sheddase to strengthen and stabilize neural plasticity.
DNA methylation of the KLK8 gene in depression symptomatology.
Title: DNA methylation of the KLK8 gene in depression symptomatology.
KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1.
Title: KLK8 promotes the proliferation and metastasis of colorectal cancer via the activation of EMT associated with PAR1.
The association of serum Kallikrein-8 with cognitive function in vascular dementia.
Title: The association of serum Kallikrein-8 with cognitive function in vascular dementia.
Extracellular acidityinduced expression of Kallikreinrelated peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.
Title: Extracellular acidity‑induced expression of Kallikrein‑related peptidases 7 and 8 is involved in increased invasiveness of gastric cancer cells.
Blood KLK8 was a similarly strong discriminator for mild cognitive impairment but slightly weaker for Alzheimer's disease
Title: CSF and blood Kallikrein-8: a promising early biomarker for Alzheimer's disease.
Study findings provide a comprehensive picture of the molecular mechanisms underlying the enzyme activity of recombinant human KLK8. Enzyme kinetics with optimized substrates showed stimulation by Ca2+ and inhibition by Zn2+, which are physiological regulators. Crystal structures of KLK8 with a ligand-free active site and with the inhibitor leupeptin explain the subsite specificity and display Ca2+ bound to the 75-loop.
Title: Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin.
KLK8 levels are higher in female brain and female sex hormone increases KLK8 in neuronal/glial cells. Hippocampal KLK8 protein levels were drastically increased in women patients.
Title: Higher levels of kallikrein-8 in female brain may increase the risk for Alzheimer's disease.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in keratinocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein maturation	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of synapse organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISS Inferred from Sequence or Structural Similarity more info
is_active_in secretory granule	IBA Inferred from Biological aspect of Ancestor more info
part_of serine protease inhibitor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: kallikrein-8

Names: ovasin; serine protease 19; serine protease TADG-14; tumor-associated differentially expressed gene 14 protein

NP_001268360.1

EC 3.4.21.118

NP_009127.1

EC 3.4.21.118

NP_653088.1

EC 3.4.21.118

NP_653089.1

EC 3.4.21.118

NP_653090.1

EC 3.4.21.118

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_001281431.2 → NP_001268360.1 kallikrein-8 isoform 5

See identical proteins and their annotated locations for NP_001268360.1

Status: REVIEWED

Description

Transcript Variant: This variant (5, also known as T5) lacks an alternate exon in the 5' coding region and initiates translation at a downstream start codon, compared to variant 2. It encodes isoform 5 which is shorter at the N-terminus, compared to isoform 2. This variant is based on data in PMID: 20360129.

Source sequence(s)

AA587273, AB009849, AY359036

Consensus CDS

CCDS74433.1

UniProtKB/TrEMBL

A0A0A0MQY9

Related

ENSP00000291726.8, ENST00000291726.11

Conserved Domains (1) summary

smart00020
Location:1 → 131

Tryp_SPc; Trypsin-like serine protease
NM_007196.4 → NP_009127.1 kallikrein-8 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_009127.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as T1) uses an alternate splice site in the 5' coding region, compared to variant 2. It encodes isoform 1, which is shorter than isoform 2.

Source sequence(s)

AA587273, AY359036

Consensus CDS

CCDS12813.1

UniProtKB/Swiss-Prot

O60259, Q5V9X1, Q5V9X2, Q8IW69, Q9HCB3, Q9NR68, Q9NR69, Q9UIL9, Q9UQ47

UniProtKB/TrEMBL

A0A1R3UD89

Related

ENSP00000512260.1, ENST00000695909.1

Conserved Domains (1) summary

smart00020
Location:32 → 252

Tryp_SPc; Trypsin-like serine protease
NM_144505.3 → NP_653088.1 kallikrein-8 isoform 2 precursor

See identical proteins and their annotated locations for NP_653088.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as T2) represents the longest transcript and encodes the longest isoform (2).

Source sequence(s)

AA587273, AB008927, AF095742

Consensus CDS

CCDS42600.1

UniProtKB/TrEMBL

A0A1R3UD89

Related

ENSP00000375682.1, ENST00000391806.6

Conserved Domains (2) summary

smart00020
Location:77 → 297

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:78 → 300

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
NM_144506.3 → NP_653089.1 kallikrein-8 isoform 3 precursor

See identical proteins and their annotated locations for NP_653089.1

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as T3) lacks two alternate exons in the coding region, compared to variant 2. It encodes isoform 3, which lacks an in-frame segment and is shorter than isoform 2.

Source sequence(s)

AA587273, AY359036, BM845575

Consensus CDS

CCDS12814.1

UniProtKB/TrEMBL

A0A2H4GDC0

Related

ENSP00000341555.3, ENST00000347619.8

Conserved Domains (1) summary

smart00020
Location:25 → 111

Tryp_SPc; Trypsin-like serine protease
NM_144507.3 → NP_653090.1 kallikrein-8 isoform 4

See identical proteins and their annotated locations for NP_653090.1

Status: REVIEWED

Description

Transcript Variant: This variant (4, also known as T4) lacks three exons in the coding region, which results in a frameshift and an early stop codon, compared to variant 2. The encoded isoform (4) is shorter and has a distinct C-terminus, compared to isoform 2. This variant is based on data in PMID: 11309326 and 20360129.

Source sequence(s)

AA320217, AA587273, AY359036

Consensus CDS

CCDS12815.1

UniProtKB/Swiss-Prot

O60259

Related

ENSP00000325072.5, ENST00000320838.9

RNA

NR_104008.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6, also known as T6) lacks an alternate internal exon, compared to variant 2. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 2, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD). This variant is based on data in PMID: 20360129.

Source sequence(s)

AA587273, AB008390, AY359036