KLK2 (human kallikrein 2, hK2) is a trypsin-like, arginine-selective serine protease of the tissue kallikrein family, expressed predominantly in prostate luminal epithelium under androgen control and secreted into seminal plasma. It is synthesized as a pre-pro-enzyme with an 18-residue signal peptide and a short activation peptide. In seminal fluid, hK2 activates the zymogens of prostate-specific antigen (pro-PSA/KLK3), itself (pro-hK2) and urokinase-type plasminogen activator, and it is controlled by serpins such as protein C inhibitor, PAI-1 and PI-6, with which it forms covalent complexes. hK2 is a secreted extracellular protein and an established prostate cancer biomarker.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003073 regulation of systemic arterial blood pressure | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Blood pressure regulation propagated from the kallikrein (KLK1-like kininogenase) clade. Reason: The blood-pressure role belongs to tissue kallikrein KLK1 and rodent glandular kallikreins through kinin release. hK2 is prostate-restricted, secreted into seminal fluid, and has no demonstrated role in systemic blood pressure; its characterized substrates are seminal zymogens. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000668785 SUPPORTS SOURCE BUT NOT TARGET Kallikrein node supported by mouse Klk1-family kininogenase phenotypes; prostate hK2 acts in seminal fluid. Supporting Evidence: PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0004252 serine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: hK2 is an active trypsin-like serine endopeptidase. Reason: Purified seminal plasma hK2 hydrolyzes Arg/Lys substrates and forms covalent complexes with serpins; it has the catalytic triad of the S1 family and activates protease zymogens by limited proteolysis. Supporting Evidence: PMID:9042371 the recovered free hK2 is a trypsin-like enzyme and that it can form molecular complexes with many of the major serum proteinase inhibitors PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0004252 serine-type endopeptidase activity | IDA PMID:9042371 Purification of enzymatically active kallikrein hK2 from hum... | ACCEPT | Summary: hK2 is an active trypsin-like serine endopeptidase. Reason: Purified seminal plasma hK2 hydrolyzes Arg/Lys substrates and forms covalent complexes with serpins; it has the catalytic triad of the S1 family and activates protease zymogens by limited proteolysis. Supporting Evidence: PMID:9042371 the recovered free hK2 is a trypsin-like enzyme and that it can form molecular complexes with many of the major serum proteinase inhibitors PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: hK2 is an active trypsin-like serine endopeptidase. Reason: Purified seminal plasma hK2 hydrolyzes Arg/Lys substrates and forms covalent complexes with serpins; it has the catalytic triad of the S1 family and activates protease zymogens by limited proteolysis. Supporting Evidence: PMID:9042371 the recovered free hK2 is a trypsin-like enzyme and that it can form molecular complexes with many of the major serum proteinase inhibitors PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0004252 serine-type endopeptidase activity | TAS PMID:10463585 Identification of a novel complex between human kallikrein 2... | ACCEPT | Summary: hK2 is an active trypsin-like serine endopeptidase. Reason: Purified seminal plasma hK2 hydrolyzes Arg/Lys substrates and forms covalent complexes with serpins; it has the catalytic triad of the S1 family and activates protease zymogens by limited proteolysis. Supporting Evidence: PMID:9042371 the recovered free hK2 is a trypsin-like enzyme and that it can form molecular complexes with many of the major serum proteinase inhibitors PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: hK2 is secreted into seminal plasma. Reason: hK2 has a signal peptide and is purified from human seminal plasma, where it acts on extracellular zymogens. Supporting Evidence: PMID:9042371 Purification of enzymatically active kallikrein hK2 from human seminal plasma. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1592398 | ACCEPT | Summary: hK2 is secreted into seminal plasma. Reason: hK2 has a signal peptide and is purified from human seminal plasma, where it acts on extracellular zymogens. Supporting Evidence: PMID:9042371 Purification of enzymatically active kallikrein hK2 from human seminal plasma. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5625883 | ACCEPT | Summary: hK2 is secreted into seminal plasma. Reason: hK2 has a signal peptide and is purified from human seminal plasma, where it acts on extracellular zymogens. Supporting Evidence: PMID:9042371 Purification of enzymatically active kallikrein hK2 from human seminal plasma. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Generic proteolysis from InterPro. Reason: Correct but general; the characterized proteolytic process of hK2 is zymogen activation (pro-PSA, pro-hK2, pro-uPA), already annotated. Proposed replacements: zymogen activation Supporting Evidence: PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) |
| GO:0030141 secretory granule | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Storage in secretory granules, inferred from kallikrein family members. Reason: As a secreted prostatic protease hK2 transits the regulated secretory pathway of luminal epithelial cells, but secretory-granule storage has not been shown directly for hK2. Supporting Evidence: PMID:10463585 Human kallikrein (hK) 2 is an arginine-selective serine protease expressed predominantly in the prostate |
| GO:0031638 zymogen activation | IBA GO_REF:0000033 | ACCEPT | Summary: hK2 activates the zymogens pro-PSA, pro-hK2 and pro-uPA. Reason: hK2 performs the activating cleavage itself, directly shown with recombinant pro-PSA and single-chain uPA; this is a core biological role in seminal fluid. Supporting Evidence: PMID:10209959 Unlike PSA, hK2 activates pro-PSA , pro-hK2 and the zymogen form of urokinase-type plasminogen activator (uPA) PMID:9261179 The recombinant pro-PSA was also activated by recombinant human glandular kallikrein, another prostate-specific serine protease |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Detected in proteomics of exosomes from expressed prostatic secretions. Reason: High-throughput detection in prostatic exosome preparations is consistent with abundant secretion into prostatic fluid; the protein is primarily soluble in seminal plasma. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected. |
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Download this section (compressed HTML)Q: Is hK2 the physiological activator of pro-PSA in seminal fluid, given redundancy with other prostatic proteases?
Experiment: Measure pro-PSA activation and semen liquefaction in seminal fluid immunodepleted of hK2 or treated with selective hK2 inhibitors.
Type: biochemical depletion
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