GZMK
entrez
3003
canonical
uniprot
P49863
canonical
ensembl
ENSG00000113088
resolver
ensp
ENSP00000231009
resolver
enst
ENST00000231009
resolver
genesymbol
GZMK
resolver
genesymbol_syn
TRYP2
resolver
hgnc
HGNC:4711
resolver
uniprot
B2R563
resolver
uniprot_entry
GRAK_HUMAN
resolver
uniprot_sec
B2R563
resolver
activity_regulation
ACTIVITY REGULATION: Specifically inhibited by D-Phe-Pro-Arg-chloromethylketone (PPACK) synthetic drug. {ECO:0000269|PubMed:10480954, ECO:0000269|PubMed:39814882}.
uniprot
proteins
amino_acid_sequence
MTKFSSFSLFFLIVGAYMTHVCFNMEIIGGKEVSPHSRPFMASIQYGGHHVCGGVLIDPQWVLTAAHCQYRFTKGQSPTVVLGAHSLSKNEASKQTLEIKKFIPFSRVTSDPQSNDIMLVKLQTAAKLNKHVKMLHIRSKTSLRSGTKCKVTGWGATDPDSLRPSDTLREVTVTVLSRKLCNSQSYYNGDPFITKDMVCAGDAKGQKDSCKGDSGGPLICKGVFHAIVSGGHECGVATKPGIYTLLTKKYQTWIKSNLVPPHTN
uniprot
proteins
ec_number
3.4.21.-
uniprot
proteins
function
FUNCTION: Serine protease that initiates the GZMK pathway of the complement system, a cascade of proteins directly activated by CD8(+) T-cells that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:3262682, PubMed:39814882, PubMed:39914456). GZMK is specifically secreted by CD8(+) T-cells and mediates both recognition and initiation steps of GZMK complement pathway (PubMed:39914456). First acts as a pattern recognition receptor, which specifically recognizes and binds heparan sulfate glycosaminoglycans on the pathogen surface to drive opsonization (PubMed:39914456). It then initiates the complement pathway cascade by catalyzing cleavage and activation of C2 and C4, the next components of the complement pathway (PubMed:39814882, PubMed:39914456). GZMK-mediated complement activation is an important contributor to tissue inflammation (PubMed:24711407, PubMed:33271118, PubMed:35704599, PubMed:39614076, PubMed:39814882, PubMed:39914456). Also able to cleave and activate F2R/PAR1 and PAR2/F2RL1, possibly promoting interleukin release (PubMed:21760880, PubMed:26936634, PubMed:35881628). May also regulate apoptosis by catalyzing cleavage and activation of BID, thereby promoting cytochrome C release from mitochrondria (PubMed:17308307). {ECO:0000269|PubMed:17308307, ECO:0000269|PubMed:21760880, ECO:0000269|PubMed:24711407, ECO:0000269|PubMed:26936634, ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:33271118, ECO:0000269|PubMed:35704599, ECO:0000269|PubMed:35881628, ECO:0000269|PubMed:39614076, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456}.
uniprot
proteins
mass_dalton
28882
uniprot
proteins
mutagenesis
MUTAGEN 214; /note="S->A: Abolished serine protease activity, preventing activation of the GZMK complement pathway."; /evidence="ECO:0000269|PubMed:39814882
uniprot
proteins
protein_family
Granzyme subfamily
uniprot
proteins
protein_family
Peptidase S1 family
uniprot
proteins
pubmed
10480954
uniprot
proteins
pubmed
12384499
uniprot
proteins
pubmed
1460416
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17308307
uniprot
proteins
pubmed
19059912
uniprot
proteins
pubmed
21760880
uniprot
proteins
pubmed
24711407
uniprot
proteins
pubmed
26936634
uniprot
proteins
pubmed
3262682
uniprot
proteins
pubmed
33271118
uniprot
proteins
pubmed
35704599
uniprot
proteins
pubmed
35881628
uniprot
proteins
pubmed
36347862
uniprot
proteins
pubmed
39614076
uniprot
proteins
pubmed
39814882
uniprot
proteins
pubmed
39914456
uniprot
proteins
pubmed
7758581
uniprot
proteins
pubmed
8656064
uniprot
proteins
sequence_length
264
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:39914456}. Cell surface {ECO:0000269|PubMed:24711407, ECO:0000269|PubMed:39914456}. Cytoplasmic granule {ECO:0000269|PubMed:1460416}. Note=Constitutively secreted by CD8(+) T-cells in the absence of TCR stimulation (PubMed:39914456). Specifically binds heparan sulfate glycosaminoglycans on the surface of pathogens (PubMed:39914456). {ECO:0000269|PubMed:39914456}.
uniprot
proteins