GRAA_BOVIN
ID GRAA_BOVIN Reviewed; 258 AA.
AC Q7YRZ7;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Granzyme A;
DE EC=3.4.21.78;
DE Flags: Precursor;
GN Name=GZMA;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jenne D.E.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Abundant protease in the cytosolic granules of cytotoxic T-
CC cells and NK-cells which activates caspase-independent pyroptosis when
CC delivered into the target cell through the immunological synapse. It
CC cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its
CC oxidative repair activity. Cleaves the nucleosome assembly protein SET
CC after 'Lys-189', which disrupts its nucleosome assembly activity and
CC allows the SET complex to translocate into the nucleus to nick and
CC degrade the DNA. {ECO:0000250|UniProtKB:P12544}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins, including fibronectin, type IV
CC collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-
CC Xaa- >> -Phe-|-Xaa- in small molecule substrates.; EC=3.4.21.78;
CC Evidence={ECO:0000250|UniProtKB:P12544};
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with APEX1.
CC {ECO:0000250|UniProtKB:P12544}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P12544}.
CC Cytoplasmic granule {ECO:0000250|UniProtKB:P12544}. Note=Delivered into
CC the target cell by perforin. {ECO:0000250|UniProtKB:P12544}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; AJ544059; CAD66427.1; -; mRNA.
DR RefSeq; NP_001001142.1; NM_001001142.1.
DR AlphaFoldDB; Q7YRZ7; -.
DR SMR; Q7YRZ7; -.
DR STRING; 9913.ENSBTAP00000039959; -.
DR MEROPS; S01.135; -.
DR PaxDb; Q7YRZ7; -.
DR PRIDE; Q7YRZ7; -.
DR Ensembl; ENSBTAT00000040181; ENSBTAP00000039959; ENSBTAG00000027865.
DR GeneID; 407178; -.
DR KEGG; bta:407178; -.
DR CTD; 3001; -.
DR VEuPathDB; HostDB:ENSBTAG00000027865; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000167010; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; Q7YRZ7; -.
DR OMA; NKYLNWI; -.
DR OrthoDB; 1105435at2759; -.
DR TreeFam; TF333630; -.
DR Proteomes; UP000009136; Chromosome 20.
DR Bgee; ENSBTAG00000027865; Expressed in caecum and 42 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:1902483; P:cytotoxic T cell pyroptotic process; ISS:UniProtKB.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0032078; P:negative regulation of endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript level;
KW Cytolysis; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000250"
FT PROPEP 27..28
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000027397"
FT CHAIN 29..258
FT /note="Granzyme A"
FT /id="PRO_0000027398"
FT DOMAIN 29..255
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 67
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P12544"
FT ACT_SITE 112
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P12544"
FT ACT_SITE 211
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P12544"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..68
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 146..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 178..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 207..230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 258 AA; 28070 MW; 042707AD8C87624E CRC64;
MNIPFPFSFP PAICLLLIPG VFPVSCEGII GGNEVAPHTR RYMALIKGLK LCAGALIKEN
WVLTAAHCDL KGNPQVILGA HSTSHKEKLD QVFSIKKAIP YPCFDPQTFE GDLQLLQLEG
KATMTKAVGI LQLPRTEDDV KPHTKCHVAG WGSTKKDACQ MSNALREANV TVIDRKICND
AQHYNFNPVI DLSMICAGGR KGEDDSCEGD SGSPLICDNV FRGVTSFGKC GNPQKPGIYI
LLTKKHLNWI KKTIAGAI
