KLK3

Protein identityUniProt · HPA

UniProt accession

P07288

Gene

KLK3

Ensembl

ENSG00000142515

Chromosome

19

Canonical length

261 aa

Protein class

Cancer-related genes, Enzymes, FDA approved drug targets, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted in male reproductive system

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

261 residues, UniProt reviewed canonical sequence.

>P07288|KLK3
     1  MWVPVVFLTL SVTWIGAAPL ILSRIVGGWE CEKHSQPWQV LVASRGRAVC GGVLVHPQWV
    61  LTAAHCIRNK SVILLGRHSL FHPEDTGQVF QVSHSFPHPL YDMSLLKNRF LRPGDDSSHD
   121  LMLLRLSEPA ELTDAVKVMD LPTQEPALGT TCYASGWGSI EPEEFLTPKK LQCVDLHVIS
   181  NDVCAQVHPQ KVTKFMLCAG RWTGGKSTCS GDSGGPLVCN GVLQGITSWG SEPCALPERP
   241  SLYTKVVHYR KWIKDTIVAN P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KLK3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

7,518 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KLK3.

Disease | ImmuneIEDB

Conditions an epitope on KLK3 was assayed in.

• prostate cancer B and T cell
• prostatitis T cell
• prostate adenocarcinoma T cell
• castration-resistant prostate carcinoma B and T cell
• leiomyosarcoma B and T cell
• biliary tract cancer B and T cell
• triple-receptor negative breast cancer B and T cell
• Her2-receptor negative breast cancer B and T cell
• Her2-receptor positive breast cancer B and T cell
• colorectal cancer B and T cell
• clear cell sarcoma B and T cell
• lung cancer B and T cell
• esophageal cancer B and T cell
• prostatic urethral cancer B and T cell
• cancer B cell
• pancreatic carcinoma B cell
• lung small cell carcinoma B cell
• adult hepatocellular carcinoma B cell
• hematologic cancer B cell
• hepatocellular carcinoma B cell

ReferencesPubMed · IEDB

Publications for KLK3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.46

gnomAD pLI

0

gnomAD missense Z

-0.25

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of angiogenesis
• positive regulation of antibacterial peptide production
• proteolysis
• regulation of systemic arterial blood pressure
• zymogen activation

Molecular functions

• endopeptidase activity
• hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
• serine-type endopeptidase activity
• serine-type peptidase activity

Cellular components

• extracellular exosome
• extracellular region
• extracellular space
• nucleus
• protein-containing complex
• secretory granule

Protein domainsUniProt · Pfam · InterPro

• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Peptidase S1, PA clan
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Trypsin

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Hydrolase
• Protease
• Secreted
• Serine protease
• Signal
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of KLK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AR