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KLK3 kallikrein related peptidase 3 [ Homo sapiens (human) ]

Gene ID: 354, updated on 5-Mar-2024

Summary

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Official Symbol
KLK3provided by HGNC
Official Full Name
kallikrein related peptidase 3provided by HGNC
Primary source
HGNC:HGNC:6364
See related
Ensembl:ENSG00000142515 MIM:176820; AllianceGenome:HGNC:6364
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
APS; PSA; hK3; KLK2A1
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. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]
Expression
Restricted expression toward prostate (RPKM 4286.7) See more
Orthologs
all
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Genomic context

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See KLK3 in Genome Data Viewer
Location:
19q13.33
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (50854915..50860764)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (53944547..53950396)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (51358171..51364020)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15002 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10980 Neighboring gene kallikrein 1 Neighboring gene uncharacterized LOC105372441 Neighboring gene kallikrein related peptidase 15 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15003 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10982 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:51343676-51343863 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:51347149-51347671 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:51347672-51348193 Neighboring gene KLK3 upstream enhancer/promoter region Neighboring gene KLK2 upstream enhancer/promoter region Neighboring gene origin of replication 20mer2 Neighboring gene kallikrein related peptidase 2 Neighboring gene kallikrein pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15005

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. Prostate-Specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death. Tilki D, et al. J Clin Oncol, 2023 May 1. PMID 36857638, Free PMC Article
  2. [Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)]. Desbène C, et al. Ann Biol Clin (Paris), 2023 Mar 15. PMID 36757372
  3. KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression. Xu J, et al. Prostate Cancer Prostatic Dis, 2022 Apr. PMID 35149774
  4. Age-Adjusted Reference Values for Prostate Specific Antigen - A Systematic Review and Meta-Analysis. Matti B, et al. Clin Genitourin Cancer, 2022 Apr. PMID 34969631
  5. KLK3 in the Regulation of Angiogenesis-Tumorigenic or Not? Koistinen H, et al. Int J Mol Sci, 2021 Dec 17. PMID 34948344, Free PMC Article

See all (470) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Ki67 and prostate specific antigen are prognostic in metastatic hormone naive prostate cancer.
    Title: Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer.
  2. RNA-binding protein 14 promotes phase separation to sustain prostate specific antigen expression under androgen deprivation in human prostate cancer.
    Title: RNA-binding protein 14 promotes phase separation to sustain prostate specific antigen expression under androgen deprivation in human prostate cancer.
  3. Association of Kallikrein Related Peptidase 3 (KLK3) gene with dermatophytosis in the UK biobank cohort.
    Title: Association of Kallikrein Related Peptidase 3 (KLK3) gene with dermatophytosis in the UK biobank cohort.
  4. The effect of encomir-93 mimic transfection on the expression of miR-93 and PSA and androgen receptor in prostate cancer LNcap cell line.
    Title: The effect of encomir-93 mimic transfection on the expression of miR-93 and PSA and androgen receptor in prostate cancer LNcap cell line.
  5. Prostate-Specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death.
    Title: Prostate-Specific Antigen Level at the Time of Salvage Therapy After Radical Prostatectomy for Prostate Cancer and the Risk of Death.
  6. [Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)].
    Title: [Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)].
  7. Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.
    Title: Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients.
  8. KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression.
    Title: KLK3 germline mutation I179T complements DNA repair genes for predicting prostate cancer progression.
  9. Correlation analysis between CD133, Klk3 and grhl2 expression and tumor characteristics in prostate cancer.
    Title: Correlation analysis between CD133, Klk3 and grhl2 expression and tumor characteristics in prostate cancer.
  10. Age-Adjusted Reference Values for Prostate Specific Antigen - A Systematic Review and Meta-Analysis.
    Title: Age-Adjusted Reference Values for Prostate Specific Antigen - A Systematic Review and Meta-Analysis.
Submit: New GeneRIF Correction See all GeneRIFs (368)

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

EBI GWAS Catalog

Description
A genome-wide association study of serum levels of prostate-specific antigen in the Japanese population.
EBI GWAS Catalog
A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease.
EBI GWAS Catalog
Genetic correction of PSA values using sequence variants associated with PSA levels.
EBI GWAS Catalog
Genetic variants at 1q32.1, 10q11.2 and 19q13.41 are associated with prostate-specific antigen for prostate cancer screening in two Korean population-based cohort studies.
EBI GWAS Catalog
Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies.
EBI GWAS Catalog
Genome-wide association scan for variants associated with early-onset prostate cancer.
EBI GWAS Catalog
Genome-wide association study identified novel genetic variant on SLC45A3 gene associated with serum levels prostate-specific antigen (PSA) in a Chinese population.
EBI GWAS Catalog
Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.
EBI GWAS Catalog
Multiple newly identified loci associated with prostate cancer susceptibility.
EBI GWAS Catalog

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

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of kallikrein-related peptidase 3 (KLK3) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

Go to the HIV-1, Human Interaction Database

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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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables serine-type endopeptidase activity TAS
Traceable Author Statement
more info
  
enables serine-type peptidase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of angiogenesis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in positive regulation of antibacterial peptide production IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein metabolic process TAS
Traceable Author Statement
more info
  
involved_in proteolysis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular exosome HDA 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 extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus HDA PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
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
prostate-specific antigen
Names
P-30 antigen
gamma-seminoprotein
kallikrein-3
semenogelase
seminin
NP_001025218.1
NP_001025219.1
NP_001639.1

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

  1. NG_011653.1 RefSeqGene

    Range
    5001..10850
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001030047.1 → NP_001025218.1  prostate-specific antigen isoform 3 preproprotein

    See identical proteins and their annotated locations for NP_001025218.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site at the end of a coding exon, that causes a frameshift. The resulting isoform (3) is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC011523, BC005307, M21896
    Consensus CDS
    CCDS33083.1
    UniProtKB/TrEMBL
    M0R294
    Related
    ENSP00000353829.2, ENST00000360617.7
    Conserved Domains (2) summary
    smart00020
    Location:24 → 209
    Tryp_SPc; Trypsin-like serine protease
    cd00190
    Location:25 → 209
    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 ...

  2. NM_001030048.1 → NP_001025219.1  prostate-specific antigen isoform 4 preproprotein

    See identical proteins and their annotated locations for NP_001025219.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site at the end of a coding exon. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC011523, BC005307, BQ932072
    Consensus CDS
    CCDS46155.1
    UniProtKB/TrEMBL
    Q6LDS3
    Related
    ENSP00000471155.1, ENST00000595952.5
    Conserved Domains (2) summary
    smart00020
    Location:24 → 210
    Tryp_SPc; Trypsin-like serine protease
    cd00190
    Location:25 → 213
    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 ...

  3. NM_001648.2 → NP_001639.1  prostate-specific antigen isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001639.1

    Status: REVIEWED

    Source sequence(s)
    X05332
    Consensus CDS
    CCDS12807.1
    UniProtKB/Swiss-Prot
    C9JXH3, G3V0H4, G3XAE3, P07288, Q15096, Q16272, Q86TG8, Q8IXI4
    UniProtKB/TrEMBL
    Q546G3, Q6LDS3
    Related
    ENSP00000314151.1, ENST00000326003.7
    Conserved Domains (1) summary
    cd00190
    Location:25 → 256
    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 ...

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_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    50854915..50860764
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    53944547..53950396
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001030049.1: Suppressed sequence

    Description
    NM_001030049.1: This RefSeq was permanently suppressed because it contains non-consensus splice sites that are poorly supported.

  2. NM_001030050.1: Suppressed sequence

    Description
    NM_001030050.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  3. NM_145864.1: Suppressed sequence

    Description
    NM_145864.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P07288.2 GenPept UniProtKB/Swiss-Prot:P07288

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