GRAB_RAT
ID GRAB_RAT Reviewed; 248 AA.
AC P18291;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Granzyme B;
DE EC=3.4.21.79;
DE AltName: Full=Fragmentin;
DE AltName: Full=Natural killer cell protease 1;
DE AltName: Full=RNKP-1;
DE Flags: Precursor;
GN Name=Gzmb;
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].
RC TISSUE=T-cell;
RX PubMed=2307850;
RA Zunino S.J., Bleackley R.C., Martinez J., Hudig D.;
RT "RNKP-1, a novel natural killer-associated serine protease gene cloned from
RT RNK-16 cytotoxic lymphocytes.";
RL J. Immunol. 144:2001-2009(1990).
RN [2]
RP PROTEIN SEQUENCE OF 21-53.
RX PubMed=1727874;
RA Sayers T.J., Wiltrout T.A., Sowder R., Munger W.L., Smyth M.J.,
RA Henderson L.E.;
RT "Purification of a factor from the granules of a rat natural killer cell
RT line (RNK) that reduces tumor cell growth and changes tumor morphology.
RT Molecular identity with a granule serine protease (RNKP-1).";
RL J. Immunol. 148:292-300(1992).
RN [3]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=1732416; DOI=10.1084/jem.175.2.553;
RA Shi L., Kraut R.P., Aebersold R., Greenberg A.H.;
RT "A natural killer cell granule protein that induces DNA fragmentation and
RT apoptosis.";
RL J. Exp. Med. 175:553-566(1992).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-248 IN COMPLEX WITH E.COLI
RP ECOTIN, ACTIVE SITE, AND DISULFIDE BONDS.
RX PubMed=10966646; DOI=10.1038/78992;
RA Waugh S.M., Harris J.L., Fletterick R., Craik C.S.;
RT "The structure of the pro-apoptotic protease granzyme B reveals the
RT molecular determinants of its specificity.";
RL Nat. Struct. Biol. 7:762-765(2000).
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 Asp. Once delivered into the target cell, acts by
CC catalyzing cleavage of gasdermin-E (GSDME), releasing the pore-forming
CC moiety of GSDME, thereby triggering pyroptosis and target cell death.
CC Seems to be linked to an activation cascade of caspases (aspartate-
CC specific cysteine proteases) responsible for apoptosis execution.
CC Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes
CC mediating apoptosis. {ECO:0000250|UniProtKB:P10144}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-
CC Xaa-, -Ser-|-Xaa-.; EC=3.4.21.79;
CC Evidence={ECO:0000250|UniProtKB:P10144};
CC -!- ACTIVITY REGULATION: Inactivated by the serine protease inhibitor
CC diisopropylfluorophosphate. {ECO:0000250|UniProtKB:P10144}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P10144}.
CC Cytolytic granule {ECO:0000250|UniProtKB:P10144}. Note=Delivered into
CC the target cell by perforin. {ECO:0000250|UniProtKB:P10144}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M34097; AAA42055.1; -; mRNA.
DR PIR; A43520; A43520.
DR RefSeq; NP_612526.2; NM_138517.3.
DR RefSeq; XP_002728303.2; XM_002728257.5.
DR RefSeq; XP_017460403.1; XM_017604914.1.
DR PDB; 1FI8; X-ray; 2.20 A; A/B=21-248.
DR PDBsum; 1FI8; -.
DR AlphaFoldDB; P18291; -.
DR SMR; P18291; -.
DR IntAct; P18291; 1.
DR STRING; 10116.ENSRNOP00000040429; -.
DR MEROPS; S01.091; -.
DR PaxDb; P18291; -.
DR PRIDE; P18291; -.
DR Ensembl; ENSRNOT00000041430; ENSRNOP00000040429; ENSRNOG00000049976.
DR GeneID; 171528; -.
DR KEGG; rno:171528; -.
DR UCSC; RGD:620018; rat.
DR CTD; 3002; -.
DR RGD; 620018; Gzmb.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01030000234551; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; P18291; -.
DR OrthoDB; 1076876at2759; -.
DR PhylomeDB; P18291; -.
DR TreeFam; TF333630; -.
DR BRENDA; 3.4.21.79; 5301.
DR Reactome; R-RNO-5620971; Pyroptosis.
DR Reactome; R-RNO-75108; Activation, myristolyation of BID and translocation to mitochondria.
DR EvolutionaryTrace; P18291; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000045973; Expressed in jejunum and 11 other tissues.
DR ExpressionAtlas; P18291; baseline and differential.
DR Genevisible; P18291; RN.
DR GO; GO:0044194; C:cytolytic granule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:RGD.
DR GO; GO:0008236; F:serine-type peptidase activity; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0060545; P:positive regulation of necroptotic process; IMP:RGD.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; ISO:RGD.
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 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytolysis; Direct protein sequencing;
KW Disulfide bond; Hydrolase; Lysosome; Protease; Reference proteome;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..20
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:1727874"
FT /id="PRO_0000027425"
FT CHAIN 21..248
FT /note="Granzyme B"
FT /id="PRO_0000027426"
FT DOMAIN 21..246
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 65
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:10966646"
FT ACT_SITE 109
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:10966646"
FT ACT_SITE 204
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:10966646"
FT SITE 229
FT /note="Mediates preference for Asp-containing substrates"
FT /evidence="ECO:0000269|PubMed:10966646"
FT DISULFID 50..66
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:10966646"
FT DISULFID 143..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:10966646"
FT DISULFID 174..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:10966646"
FT CONFLICT 98
FT /note="H -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="K -> D (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:1FI8"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 69..76
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:1FI8"
FT TURN 103..106
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:1FI8"
FT HELIX 171..177
FT /evidence="ECO:0007829|PDB:1FI8"
FT TURN 178..181
FT /evidence="ECO:0007829|PDB:1FI8"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 213..222
FT /evidence="ECO:0007829|PDB:1FI8"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:1FI8"
FT HELIX 234..237
FT /evidence="ECO:0007829|PDB:1FI8"
FT HELIX 238..245
FT /evidence="ECO:0007829|PDB:1FI8"
SQ SEQUENCE 248 AA; 27326 MW; 6F52089DDACCC88C CRC64;
MKLLLLLLSF SLAPKTEAGE IIGGHEAKPH SRPYMAYLQI MDEYSGSKKC GGFLIREDFV
LTAAHCSGSK INVTLGAHNI KEQEKMQQII PVVKIIPHPA YNSKTISNDI MLLKLKSKAK
RSSAVKPLNL PRRNVKVKPG DVCYVAGWGK LGPMGKYSDT LQEVELTVQE DQKCESYLKN
YFDKANEICA GDPKIKRASF RGDSGGPLVC KKVAAGIVSY GQNDGSTPRA FTKVSTFLSW
IKKTMKKS
