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

Gene ID: 3817, updated on 11-Apr-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 
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

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