ID   GRAK_RAT                Reviewed;         258 AA.
AC   P49864;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   04-NOV-2026, entry version 140.
DE   RecName: Full=Granzyme K;
DE            EC=3.4.21.- {ECO:0000250|UniProtKB:P49863};
DE   AltName: Full=NK-tryptase-2;
DE            Short=NK-Tryp-2;
DE   Flags: Precursor;
GN   Name=Gzmk;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND PROTEIN SEQUENCE OF
RP   26-58.
RC   STRAIN=Fischer 344; TISSUE=Lymphocyte;
RX   PubMed=8133042; DOI=10.4049/jimmunol.152.5.2289;
RA   Sayers T.J., Wiltrout T.A., Smyth M.J., Ottaway K.S., Pilaro A.M.,
RA   Sowder R., Henderson L.E., Sprenger H., Lloyd A.R.;
RT   "Purification and cloning of a novel serine protease, RNK-Tryp-2, from the
RT   granules of a rat NK cell leukemia.";
RL   J. Immunol. 152:2289-2297(1994).
CC   -!- FUNCTION: Serine protease that initiates the GZMK pathway of the
CC       complement system, a cascade of proteins directly activated by CD8(+)
CC       T-cells that leads to phagocytosis and breakdown of pathogens and
CC       signaling that strengthens the adaptive immune system. GZMK is
CC       specifically secreted by CD8(+) T-cells and mediates both recognition
CC       and initiation steps of GZMK complement pathway. First acts as a
CC       pattern recognition receptor, which specifically recognizes and binds
CC       heparan sulfate glycosaminoglycans on the pathogen surface to drive
CC       opsonization. It then initiates the complement pathway cascade by
CC       catalyzing cleavage and activation of C2 and C4, the next components of
CC       the complement pathway. GZMK-mediated complement activation is an
CC       important contributor to tissue inflammation. Also able to cleave and
CC       activate F2R/PAR1 and PAR2/F2RL1, possibly promoting interleukin
CC       release. May also regulate apoptosis by catalyzing cleavage and
CC       activation of BID, thereby promoting cytochrome C release from
CC       mitochrondria. {ECO:0000250|UniProtKB:P49863}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P49863}. Cell
CC       surface {ECO:0000250|UniProtKB:P49863}. Cytoplasmic granule
CC       {ECO:0000250|UniProtKB:P49863}. Note=Constitutively secreted by CD8(+)
CC       T-cells in the absence of TCR stimulation. Specifically binds heparan
CC       sulfate glycosaminoglycans on the surface of pathogens.
CC       {ECO:0000250|UniProtKB:P49863}.
CC   -!- TISSUE SPECIFICITY: Speen, lungs and liver non-parenchymal cells.
CC       {ECO:0000269|PubMed:8133042}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR   EMBL; L19694; AAA42057.1; -; mRNA.
DR   PIR; I56220; I56220.
DR   RefSeq; NP_058815.1; NM_017119.2.
DR   AlphaFoldDB; P49864; -.
DR   SMR; P49864; -.
DR   BioGRID; 247846; 1.
DR   FunCoup; P49864; 138.
DR   IntAct; P49864; 1.
DR   STRING; 10116.ENSRNOP00000014319; -.
DR   ChEMBL; CHEMBL4557; -.
DR   MEROPS; S01.146; -.
DR   CarbonylDB; P49864; -.
DR   PhosphoSitePlus; P49864; -.
DR   PaxDb; 10116-ENSRNOP00000014319; -.
DR   GeneID; 29165; -.
DR   KEGG; rno:29165; -.
DR   AGR; RGD:68401; -.
DR   CTD; 3003; -.
DR   RGD; 68401; Gzmk.
DR   eggNOG; KOG3627; Eukaryota.
DR   InParanoid; P49864; -.
DR   OMA; AAHCEQY; -.
DR   OrthoDB; 49450at9989; -.
DR   PhylomeDB; P49864; -.
DR   BRENDA; 3.4.21.B4; 5301.
DR   PRO; PR:P49864; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR   GO; GO:0106139; C:symbiont cell surface; ISS:UniProtKB.
DR   GO; GO:0005539; F:glycosaminoglycan binding; ISS:UniProtKB.
DR   GO; GO:0038187; F:pattern recognition receptor activity; ISS:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0008236; F:serine-type peptidase activity; IDA:RGD.
DR   GO; GO:0160257; P:complement activation, GZMK pathway; ISS:UniProtKB.
DR   GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; IBA:GO_Central.
DR   GO; GO:0008228; P:opsonization; ISS:UniProtKB.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR   GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR   GO; GO:0051604; P:protein maturation; ISS:UniProtKB.
DR   GO; GO:0031638; P:zymogen activation; ISS:UniProtKB.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   FunFam; 2.40.10.10:FF:000003; Transmembrane serine protease 3; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24271:SF52; GRANZYME K; 1.
DR   PANTHER; PTHR24271; KALLIKREIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Hydrolase; Immunity;
KW   Inflammatory response; Innate immunity; Protease; Reference proteome;
KW   Secreted; Serine protease; Signal; Zymogen.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PROPEP          24..25
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:8133042"
FT                   /id="PRO_0000027419"
FT   CHAIN           26..258
FT                   /note="Granzyme K"
FT                   /id="PRO_0000027420"
FT   DOMAIN          26..253
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        66
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P49863"
FT   ACT_SITE        110
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P49863"
FT   ACT_SITE        208
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:P49863"
FT   DISULFID        51..67
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        143..214
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        175..193
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        204..228
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ   SEQUENCE   258 AA;  28465 MW;  988AD71DB08AFBB4 CRC64;
     MSFSSSALVF LVAGIYMSSE SFHTEIIGGR EVQPHSRPFM ASIQYRGKHI CGGVLIHPQW
     VLTAAHCYSR GHSPTVVLGA HSLSKNEPMK QTFEIKEFIP FSGFKSGTND IMLIKLRTAA
     ELNKHVQLLH LRSKNYIRDG TKCQVTGWGS TKPDVLTTSD TLQEVTVTII SRKRCNSQSY
     YNHKPVITKD MICAGDRRGE KDSCKGDSGG PLICKGVFHA LVSGGYKCGI SNKPGVYTLL
     TKKYQTWIKS KLAPSSAH
//