GRAB_MOUSE
ID GRAB_MOUSE Reviewed; 247 AA.
AC P04187;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Granzyme B(G,H);
DE EC=3.4.21.79;
DE AltName: Full=CTLA-1;
DE AltName: Full=Cytotoxic cell protease 1;
DE Short=CCP1;
DE AltName: Full=Fragmentin-2;
DE Flags: Precursor;
GN Name=Gzmb; Synonyms=Ctla-1, Ctla1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3518058; DOI=10.1126/science.3518058;
RA Lobe C.G., Finlay B.B., Paranchych W., Paetkau V.H., Bleackley R.C.;
RT "Novel serine proteases encoded by two cytotoxic T lymphocyte-specific
RT genes.";
RL Science 232:858-861(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3264185; DOI=10.1021/bi00418a040;
RA Lobe C.G., Upton C., Duggan B., Ehrman N., Letellier M., Bell J.,
RA McFadden G., Bleackley R.C.;
RT "Organization of two genes encoding cytotoxic T lymphocyte-specific serine
RT proteases CCPI and CCPII.";
RL Biochemistry 27:6941-6946(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3090449; DOI=10.1038/322268a0;
RA Brunet J.-F., Dosseto M., Denizot F., Mattei M.-G., Clark W.R., Haqqi T.M.,
RA Ferrier P., Nabholz M., Schmitt-Verhulst A.-M., Luciani M.-F., Golstein P.;
RT "The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1
RT sequence and gene localization to mouse chromosome 14.";
RL Nature 322:268-271(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 227-247.
RC STRAIN=C57BL/6J;
RX PubMed=8043949; DOI=10.1007/bf00356553;
RA Ko M.S., Wang X., Horton J.H., Hagen M.D., Takahashi N., Maezaki Y.,
RA Nadeau J.H.;
RT "Genetic mapping of 40 cDNA clones on the mouse genome by PCR.";
RL Mamm. Genome 5:349-355(1994).
RN [6]
RP PROTEIN SEQUENCE OF 21-40.
RX PubMed=3555842; DOI=10.1016/0092-8674(87)90544-7;
RA Masson D., Tschopp J.;
RT "A family of serine esterases in lytic granules of cytolytic T
RT lymphocytes.";
RL Cell 49:679-685(1987).
RN [7]
RP 3D-STRUCTURE MODELING.
RX PubMed=3237717; DOI=10.1002/prot.340040306;
RA Murphy M.E.P., Moult J., Bleackley R.C., Gershenfeld H., Weissman I.L.,
RA James M.N.G.;
RT "Comparative molecular model building of two serine proteinases from
RT cytotoxic T lymphocytes.";
RL Proteins 4:190-204(1988).
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}.
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DR EMBL; X04072; CAA27715.1; -; mRNA.
DR EMBL; M12302; AAA37383.1; -; mRNA.
DR EMBL; M22526; AAB61756.1; -; Genomic_DNA.
DR EMBL; BC002085; AAH02085.1; -; mRNA.
DR EMBL; U05707; AAB60470.1; -; Genomic_DNA.
DR CCDS; CCDS27147.1; -.
DR PIR; A94288; PRMSCL.
DR RefSeq; NP_038570.1; NM_013542.3.
DR AlphaFoldDB; P04187; -.
DR SMR; P04187; -.
DR BioGRID; 200135; 6.
DR STRING; 10090.ENSMUSP00000015581; -.
DR MEROPS; S01.136; -.
DR GlyGen; P04187; 2 sites.
DR iPTMnet; P04187; -.
DR PhosphoSitePlus; P04187; -.
DR EPD; P04187; -.
DR PaxDb; P04187; -.
DR PeptideAtlas; P04187; -.
DR PRIDE; P04187; -.
DR ProteomicsDB; 271286; -.
DR DNASU; 14939; -.
DR Ensembl; ENSMUST00000015581; ENSMUSP00000015581; ENSMUSG00000015437.
DR GeneID; 14939; -.
DR KEGG; mmu:14939; -.
DR UCSC; uc007ubv.1; mouse.
DR CTD; 3002; -.
DR MGI; MGI:109267; Gzmb.
DR VEuPathDB; HostDB:ENSMUSG00000015437; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01030000234551; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; P04187; -.
DR OMA; PAYNPEK; -.
DR OrthoDB; 1076876at2759; -.
DR PhylomeDB; P04187; -.
DR TreeFam; TF333630; -.
DR BRENDA; 3.4.21.79; 3474.
DR Reactome; R-MMU-5620971; Pyroptosis.
DR Reactome; R-MMU-75108; Activation, myristolyation of BID and translocation to mitochondria.
DR BioGRID-ORCS; 14939; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Gzmb; mouse.
DR PRO; PR:P04187; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P04187; protein.
DR Bgee; ENSMUSG00000015437; Expressed in gastrula and 36 other tissues.
DR ExpressionAtlas; P04187; baseline and differential.
DR Genevisible; P04187; MM.
DR GO; GO:0044194; C:cytolytic granule; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
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; IMP:MGI.
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 Apoptosis; Cytolysis; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Lysosome; Protease; Reference proteome; Secreted;
KW 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:3555842"
FT /id="PRO_0000027401"
FT CHAIN 21..247
FT /note="Granzyme B(G,H)"
FT /id="PRO_0000027402"
FT DOMAIN 21..245
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 64
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P18291"
FT ACT_SITE 108
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P18291"
FT ACT_SITE 203
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P18291"
FT SITE 228
FT /note="Mediates preference for Asp-containing substrates"
FT /evidence="ECO:0000250|UniProtKB:P18291"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 142..209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 173..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
SQ SEQUENCE 247 AA; 27470 MW; 996BCD199965C6D6 CRC64;
MKILLLLLTL SLASRTKAGE IIGGHEVKPH SRPYMALLSI KDQQPEAICG GFLIREDFVL
TAAHCEGSII NVTLGAHNIK EQEKTQQVIP MVKCIPHPDY NPKTFSNDIM LLKLKSKAKR
TRAVRPLNLP RRNVNVKPGD VCYVAGWGRM APMGKYSNTL QEVELTVQKD RECESYFKNR
YNKTNQICAG DPKTKRASFR GDSGGPLVCK KVAAGIVSYG YKDGSPPRAF TKVSSFLSWI
KKTMKSS
