KLK4 kallikrein related peptidase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLK4provided by HGNC
Official Full Name: kallikrein related peptidase 4provided by HGNC
Primary source: HGNC:HGNC:6365
See related: Ensembl:ENSG00000167749 MIM:603767; AllianceGenome:HGNC:6365
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: ARM1; EMSP; PSTS; AI2A1; EMSP1; KLK-L1; PRSS17; kallikrein
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 a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]
Expression: Restricted expression toward prostate (RPKM 123.8) See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.41

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (50906351..50911395, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (53994435..53999407, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (51409607..51414651, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Kallikrein-Related Peptidase 4 Promotes Proliferation, Migration, Invasion, and Pro-Angiogenesis of Endometrial Stromal Cells via Regulation of Brain-Derived Neurotrophic Factor Production in Endometriosis.
Title: Kallikrein-Related Peptidase 4 Promotes Proliferation, Migration, Invasion, and Pro-Angiogenesis of Endometrial Stromal Cells via Regulation of Brain-Derived Neurotrophic Factor Production in Endometriosis.
Loss of KLK4::KLKP1 pseudogene expression by RNA chromogenic in-situ hybridization is associated with PTEN loss and increased risk of biochemical recurrence in a cohort of middle eastern men with prostate cancer.
Title: Loss of KLK4::KLKP1 pseudogene expression by RNA chromogenic in-situ hybridization is associated with PTEN loss and increased risk of biochemical recurrence in a cohort of middle eastern men with prostate cancer.
KLK4 Silencing Inhibits the Growth of Chromophobe Renal Cell Carcinoma through ERK/AKT Signaling Pathway.
Title: KLK4 Silencing Inhibits the Growth of Chromophobe Renal Cell Carcinoma through ERK/AKT Signaling Pathway.
lncRNA IGF2-AS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by sponging miR-3,126-5p to upregulate KLK4.
Title: lncRNA IGF2-AS promotes the osteogenic differentiation of bone marrow mesenchymal stem cells by sponging miR-3,126-5p to upregulate KLK4.
MicroRNA-378-3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4.
Title: MicroRNA-378-3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4.
MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression.
Title: MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression.
miR-378a-5p suppressed angiogenesis of oral squamous cell carcinoma at least partly by the regulation of KLK4.
Title: MiR-378a-5p inhibits angiogenesis of oral squamous cell carcinoma by targeting KLK4.
crystals of KLK4 obtained belonged to space group P1, contained four molecules in the asymmetric unit and diffracted to 1.64 A resolution
Title: Crystal structure of the inhibitor-free form of the serine protease kallikrein-4.
Study found a significant association of elevated KLK4 mRNA expression levels with shortened overall survival (OS) analyzing a homogenous cohort of advanced high-grade serous ovarian cancer patients (FIGO stage III/IV). Multivariable model showed that KLK4 remains an independent unfavorable predictive biomarker for OS in ovarian cancer.
Title: Characterization of kallikrein-related peptidase 4 (KLK4) mRNA expression in tumor tissue of advanced high-grade serous ovarian cancer patients.
Circular RNA (hsa_circ_0051240) promotes cell proliferation, migration and invasion in ovarian cancer through miR-637/KLK4 axis
Title: Circular RNA (hsa_circ_0051240) promotes cell proliferation, migration and invasion in ovarian cancer through miR-637/KLK4 axis.

Submit: New GeneRIF Correction See all GeneRIFs (63)

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
Amelogenesis imperfecta type 2A1 MedGen: C2673922 OMIM: 204700 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-treated vaginal epithelial cells show downregulation of kallikrein-related peptidase 4 (KLK4) expression as compared to untreated control	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:483897

PMC15904P1 (e-PCR)
- UniSTS:271439

NoName (e-PCR)
- UniSTS:480639

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables serine-type peptidase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in amelogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in amelogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in biomineral tissue development	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix disassembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info	PubMed
is_active_in secretory granule	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: kallikrein-4

Names: androgen-regulated message 1; enamel matrix serine protease 1; enamel matrix serine proteinase 1; kallikrein-like protein 1; prostase; serine protease 17

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_012154.2 RefSeqGene

Range

4344..9388

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001302961.2 → NP_001289890.1 kallikrein-4 isoform 2

See identical proteins and their annotated locations for NP_001289890.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' end, which results in a frameshift, compared to variant 1. It encodes isoform 2, which is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

AC011483, AF113140, AF259969, AY923170

UniProtKB/Swiss-Prot

Q9Y5K2

UniProtKB/TrEMBL

Q5BQA0

Conserved Domains (2) summary

smart00020
Location:1 → 152

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:1 → 155

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_004917.5 → NP_004908.4 kallikrein-4 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_004908.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC011483, AF113140, BC069403, CA425532

Consensus CDS

CCDS12809.1

UniProtKB/Swiss-Prot

Q4VB16, Q96RU5, Q9GZL6, Q9UBJ6, Q9Y5K2

UniProtKB/TrEMBL

A0A0C4DFQ5, Q4VB17

Related

ENSP00000326159.1, ENST00000324041.6

Conserved Domains (1) summary

cd00190
Location:31 → 250

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 ...

RNA

NR_126566.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses two alternate splice junctions compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC011483, AF113140, BC096176

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

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

50906351..50911395 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011527545.4 → XP_011525847.1 kallikrein-4 isoform X1

UniProtKB/TrEMBL

Q96PT1

Conserved Domains (2) summary

smart00020
Location:31 → 162

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:31 → 159

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 ...