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    KLK2 kallikrein related peptidase 2 [ Homo sapiens (human) ]

    Gene ID: 3817, updated on 2-May-2024

    Summary

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    Official Symbol
    KLK2provided by HGNC
    Official Full Name
    kallikrein related peptidase 2provided by HGNC
    Primary source
    HGNC:HGNC:6363
    See related
    Ensembl:ENSG00000167751 MIM:147960; AllianceGenome:HGNC:6363
    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
    hK2; hGK-1; KLK2A2
    Summary
    This gene encodes a member of the grandular kallikrein protein family. Kallikreins are a subgroup of serine proteases that are clustered on chromosome 19. Members of this family are involved in a diverse array of biological functions. The protein encoded by this gene is a highly active trypsin-like serine protease that selectively cleaves at arginine residues. This protein is primarily expressed in prostatic tissue and is responsible for cleaving pro-prostate-specific antigen into its enzymatically active form. This gene is highly expressed in prostate tumor cells and may be a prognostic maker for prostate cancer risk. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Jan 2012]
    Expression
    Restricted expression toward prostate (RPKM 1047.4) See more
    Orthologs
    all
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    Genomic context

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    See KLK2 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 (50873439..50880567)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (53963071..53970199)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (51376695..51383823)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes 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 kallikrein related peptidase 3 Neighboring gene KLK2 upstream enhancer/promoter region Neighboring gene origin of replication 20mer2 Neighboring gene kallikrein pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15005 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15006 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15007 Neighboring gene kallikrein related peptidase 4

    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. Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG-negative prostate cancer. Bonk S, et al. Prostate, 2020 Sep. PMID 32628300
    2. A Single Glycan at the 99-Loop of Human Kallikrein-related Peptidase 2 Regulates Activation and Enzymatic Activity. Guo S, et al. J Biol Chem, 2016 Jan 8. PMID 26582203, Free PMC Article
    3. Trp(250) -hK2 is defective in intracellular trafficking and activates the unfolded protein response. Choi EJ, et al. Genes Cells, 2015 Jun. PMID 25847286
    4. Structure-function analyses of human kallikrein-related peptidase 2 establish the 99-loop as master regulator of activity. Skala W, et al. J Biol Chem, 2014 Dec 5. PMID 25326387, Free PMC Article
    5. Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell functional capacity. Yao Y, et al. Hum Gene Ther, 2012 Aug. PMID 22435954, Free PMC Article

    See all (86) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2.
      Title: Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2.
    2. Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2.
      Title: Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2.
    3. Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG-negative prostate cancer.
      Title: Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG-negative prostate cancer.
    4. Study report KLK2-FGFR2 fusion protein in 2 unrelated cases of metastatic prostate cancer. Expression of the KLK2-FGFR2 fusion protein in NIH3T3 cells induced a profound morphological change promoting enhanced migration and activation of downstream proteins in FGFR signaling pathways.
      Title: Characterization of a KLK2-FGFR2 fusion gene in two cases of metastatic prostate cancer.
    5. glycosylation changes the enzymatic activity of KLK2 in a drastically substrate-dependent manner.
      Title: A Single Glycan at the 99-Loop of Human Kallikrein-related Peptidase 2 Regulates Activation and Enzymatic Activity.
    6. The results indicated that W-hK2 had a defect in cellular trafficking due to its misfolding and that it activated the unfolded protein response, suggesting a mechanism to explain the association of the T allele with higher prostate cancer risk.
      Title: Trp(250) -hK2 is defective in intracellular trafficking and activates the unfolded protein response.
    7. The differential regulation of alternative transcripts (using KLK2, KLK3 and KLK4 as models) by androgens and anti-androgens as an indicator of prostate cancers, was investigated.
      Title: Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer.
    8. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in prostate cancer patients.
      Title: Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients.
    9. Structure-function analyses of KLK2 establish the 99-loop as master regulator of its activity.
      Title: Structure-function analyses of human kallikrein-related peptidase 2 establish the 99-loop as master regulator of activity.
    10. Predictions based on levels of four kallikrein markers, including KLK2, in blood distinguish between pathologically insignificant and aggressive disease after radical prostatectomy with good accuracy.
      Title: Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam.
    Submit: New GeneRIF Correction See all GeneRIFs (38)

    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 possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease.
    EBI GWAS Catalog
    Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.
    EBI GWAS Catalog
    Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA.
    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

    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

    Clone Names

    • FLJ17010, FLJ17011, MGC12201

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in secretory granule IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    kallikrein-2
    Names
    glandular kallikrein 2
    glandular kallikrein-1
    kallikrein 2, prostatic
    tissue kallikrein-2
    NP_001002231.1
    NP_001243009.1
    NP_005542.1

    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_031984.1 RefSeqGene

      Range
      5007..12135
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001002231.3 → NP_001002231.1  kallikrein-2 isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_001002231.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC037199, AF188745, AF188747, AK300527
      Consensus CDS
      CCDS42597.1
      Related
      ENSP00000350748.3, ENST00000358049.8
      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_001256080.2 → NP_001243009.1  kallikrein-2 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (3) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AC037199, AF188745, AK300549
      Consensus CDS
      CCDS58675.1
      UniProtKB/Swiss-Prot
      P20151
      UniProtKB/TrEMBL
      B4DU77
      Related
      ENSP00000375686.2, ENST00000391810.6
      Conserved Domains (2) summary
      smart00020
      Location:13 → 151
      Tryp_SPc; Trypsin-like serine protease
      cd00190
      Location:16 → 154
      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_005551.5 → NP_005542.1  kallikrein-2 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_005542.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC037199, AF188746, AK300527
      Consensus CDS
      CCDS12808.1
      UniProtKB/Swiss-Prot
      B4DU93, B4DUB0, F5H8L3, P20151, Q15946, Q9UJZ9
      UniProtKB/TrEMBL
      A0A024R4J4
      Related
      ENSP00000313581.2, ENST00000325321.8
      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 ...

    RNA

    1. NR_045762.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has multiple differences, 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)
      AC037199, AF188745
      Related
      ENST00000597439.1

    2. NR_045763.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site, compared to variant 1. This variant (5) is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC037199, AF188745, AK300527

    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
      50873439..50880567
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      53963071..53970199
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001002232.2: Suppressed sequence

      Description
      NM_001002232.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20151.1 GenPept UniProtKB/Swiss-Prot:P20151

    Gene LinkOut

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

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