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 27-MAR-2024, entry version 210. DE RecName: Full=Granzyme B(G,H); DE EC=3.4.21.79 {ECO:0000269|PubMed:35705808}; 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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=35705808; DOI=10.1038/s41586-022-04825-8; RA Nozaki K., Maltez V.I., Rayamajhi M., Tubbs A.L., Mitchell J.E., RA Lacey C.A., Harvest C.K., Li L., Nash W.T., Larson H.N., McGlaughon B.D., RA Moorman N.J., Brown M.G., Whitmire J.K., Miao E.A.; RT "Caspase-7 activates ASM to repair gasdermin and perforin pores."; RL Nature 0:0-0(2022). RN [8] 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 CC (PubMed:35705808). It cleaves after Asp (PubMed:35705808). Once CC delivered into the target cell, acts by catalyzing cleavage of CC gasdermin-E (GSDME), releasing the pore-forming moiety of GSDME, CC thereby triggering pyroptosis and target cell death (By similarity). CC Seems to be linked to an activation cascade of caspases (aspartate- CC specific cysteine proteases) responsible for apoptosis execution (By CC similarity). Cleaves caspase-3 and -9 (CASP3 and CASP9, respectively) CC to give rise to active enzymes mediating apoptosis (PubMed:35705808). CC Cleaves and activates CASP7 in response to bacterial infection, CC promoting plasma membrane repair (PubMed:35705808). CC {ECO:0000250|UniProtKB:P10144, ECO:0000269|PubMed:35705808}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|- CC Xaa-, -Ser-|-Xaa-.; EC=3.4.21.79; CC Evidence={ECO:0000269|PubMed:35705808}; 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; 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 GlyCosmos; P04187; 2 sites, No reported glycans. DR GlyGen; P04187; 2 sites. DR iPTMnet; P04187; -. DR PhosphoSitePlus; P04187; -. DR EPD; P04187; -. DR PaxDb; 10090-ENSMUSP00000015581; -. DR PeptideAtlas; P04187; -. DR ProteomicsDB; 271286; -. DR DNASU; 14939; -. DR Ensembl; ENSMUST00000015581.6; ENSMUSP00000015581.5; ENSMUSG00000015437.6. DR GeneID; 14939; -. DR KEGG; mmu:14939; -. DR UCSC; uc007ubv.1; mouse. DR AGR; MGI:109267; -. 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; 2540265at2759; -. 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 80 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 37 other cell types or tissues. DR ExpressionAtlas; P04187; baseline and differential. 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:0005769; C:early endosome; ISO:MGI. DR GO; GO:0005615; C:extracellular space; IDA:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA: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:0042742; P:defense response to bacterium; IDA:UniProt. DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; IDA:MGI. DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW. DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISS:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. 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; Trypsin-like serine proteases; 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 PANTHER; PTHR24271:SF81; GRANZYME B; 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. DR Genevisible; P04187; MM. 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 //