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

    Gene ID: 354, updated on 30-Apr-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. Prostate-specific antigen: An unfamiliar protein in the human salivary glands.
      Title: Prostate-specific antigen: An unfamiliar protein in the human salivary glands.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. [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)].
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (369)

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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