GZMK

Granzyme K (GrK) is a protein that is encoded by the GZMK gene on chromosome 5 in humans.^[5][6] Granzymes are a family of serine proteases which have various intracellular and extracellular roles. GrK is found in granules of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), and is traditionally described as being cytotoxic towards targeted foreign, infected, or cancerous cells. NK cells and CTLs can induce apoptosis through the granule secretory pathway, which involves the secretion of granzymes along with perforin at immunological synapses.

GZMK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1MZA, 1MZD
Identifiers
Aliases	GZMK, TRYP2, granzyme K
External IDs	OMIM: 600784; MGI: 1298232; HomoloGene: 20485; GeneCards: GZMK; OMA:GZMK - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q11.2 Start 55,024,256 bp[1] End 55,034,570 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D2.2 Start 113,308,142 bp[2] End 113,362,442 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lymph node granulocyte spleen blood appendix testicle gallbladder trabecular bone epithelium of nasopharynx thymus Top expressed in tail of embryo Region II of hippocampus proper submandibular gland supramammillary nucleus medial amygdaloid nucleus CA3 field central amygdaloid nucleus blood gastrula lymph node More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity Cellular component extracellular region Biological process proteolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3003 14945 Ensembl ENSG00000113088 ENSMUSG00000042385 UniProt P49863 O35205 RefSeq (mRNA) NM_002104 NM_008196 RefSeq (protein) NP_002095 NP_032222 Location (UCSC) Chr 5: 55.02 – 55.03 Mb Chr 13: 113.31 – 113.36 Mb PubMed search [3] [4]
Wikidata
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Intracellularly, GrK may cleave a variety of substrates, such as the nucleosome assembly protein (NAP),^[7] HMG2,^[7] and Ape1^[8] in the ER-associated SET complex, along with other targets that have downstream cytotoxic effects. Compared to in vitro studies of GrK cytotoxicity in rats and humans, in vitro mouse studies show no cytotoxic potential in the absence of perforin, making the role of GrK controversial.^[9][10] In vitro studies show potential extracellular targets for GrK such as the cleavage and activation of protease activated receptors (PAR)-1^[11][12] and PAR-2.^[13] Grk binds lipopolysaccharides (LPS) in vitro separately from GrK's catalytic activity.^[14] Both PAR and LPS activation by GrK induce cytokine production in human in vitro studies.

GrK is important in bacterial and viral^[15] infection control. GrK-expressing CD8+ T cells may be associated with inflammation and aging.^[16]