UniProtKB - P04187 (GRAB_MOUSE)
Granzyme B(G,H)
Gzmb
Functioni
Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse. It cleaves after Asp. Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-E (GSDME), releasing the pore-forming moiety of GSDME, thereby triggering pyroptosis and target cell death. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis.
By similarityCatalytic activityi
- Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-.By similarity EC:3.4.21.79
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 64 | Charge relay systemBy similarity | 1 | |
Active sitei | 108 | Charge relay systemBy similarity | 1 | |
Active sitei | 203 | Charge relay systemBy similarity | 1 | |
Sitei | 228 | Mediates preference for Asp-containing substratesBy similarity | 1 |
GO - Molecular functioni
- serine-type endopeptidase activity Source: UniProtKB
- serine-type peptidase activity Source: MGI
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cytolysis Source: UniProtKB-KW
- granzyme-mediated programmed cell death signaling pathway Source: MGI
- natural killer cell mediated cytotoxicity Source: UniProtKB
- negative regulation of translation Source: MGI
- proteolysis involved in cellular protein catabolic process Source: UniProtKB
- pyroptosis Source: UniProtKB
- T cell mediated cytotoxicity Source: MGI
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Biological process | Apoptosis, Cytolysis |
Enzyme and pathway databases
BRENDAi | 3.4.21.79, 3474 |
Reactomei | R-MMU-5620971, Pyroptosis R-MMU-75108, Activation, myristolyation of BID and translocation to mitochondria |
Protein family/group databases
MEROPSi | S01.136 |
Names & Taxonomyi
Protein namesi | Recommended name: Granzyme B(G,H) (EC:3.4.21.79)Alternative name(s): CTLA-1 Cytotoxic cell protease 1 Short name: CCP1 Fragmentin-2 |
Gene namesi | Name:Gzmb Synonyms:Ctla-1, Ctla1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109267, Gzmb |
VEuPathDBi | HostDB:ENSMUSG00000015437 |
Subcellular locationi
Lysosome
- Cytolytic granule By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Delivered into the target cell by perforin.By similarity
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Lysosome
- cytolytic granule Source: MGI
Other locations
- cytoplasm Source: MGI
- intracellular membrane-bounded organelle Source: GO_Central
Keywords - Cellular componenti
Lysosome, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
PropeptideiPRO_0000027401 | 19 – 20 | Activation peptide1 Publication | 2 | |
ChainiPRO_0000027402 | 21 – 247 | Granzyme B(G,H)Add BLAST | 227 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 49 ↔ 65 | PROSITE-ProRule annotation | ||
Glycosylationi | 71 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 142 ↔ 209 | PROSITE-ProRule annotation | ||
Disulfide bondi | 173 ↔ 188 | PROSITE-ProRule annotation | ||
Glycosylationi | 182 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, ZymogenProteomic databases
EPDi | P04187 |
PaxDbi | P04187 |
PeptideAtlasi | P04187 |
PRIDEi | P04187 |
ProteomicsDBi | 271286 |
PTM databases
GlyGeni | P04187, 2 sites |
iPTMneti | P04187 |
PhosphoSitePlusi | P04187 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000015437, Expressed in decidua and 77 other tissues |
ExpressionAtlasi | P04187, baseline and differential |
Genevisiblei | P04187, MM |
Interactioni
Protein-protein interaction databases
BioGRIDi | 200135, 6 interactors |
STRINGi | 10090.ENSMUSP00000015581 |
Miscellaneous databases
RNActi | P04187, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 21 – 245 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 225 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT01030000234551 |
HOGENOMi | CLU_006842_1_0_1 |
InParanoidi | P04187 |
OMAi | PAYNPEK |
OrthoDBi | 1076876at2759 |
PhylomeDBi | P04187 |
TreeFami | TF333630 |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MKILLLLLTL SLASRTKAGE IIGGHEVKPH SRPYMALLSI KDQQPEAICG
60 70 80 90 100
GFLIREDFVL TAAHCEGSII NVTLGAHNIK EQEKTQQVIP MVKCIPHPDY
110 120 130 140 150
NPKTFSNDIM LLKLKSKAKR TRAVRPLNLP RRNVNVKPGD VCYVAGWGRM
160 170 180 190 200
APMGKYSNTL QEVELTVQKD RECESYFKNR YNKTNQICAG DPKTKRASFR
210 220 230 240
GDSGGPLVCK KVAAGIVSYG YKDGSPPRAF TKVSSFLSWI KKTMKSS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X04072 mRNA Translation: CAA27715.1 M12302 mRNA Translation: AAA37383.1 M22526 Genomic DNA Translation: AAB61756.1 BC002085 mRNA Translation: AAH02085.1 U05707 Genomic DNA Translation: AAB60470.1 |
CCDSi | CCDS27147.1 |
PIRi | A94288, PRMSCL |
RefSeqi | NP_038570.1, NM_013542.3 |
Genome annotation databases
Ensembli | ENSMUST00000015581; ENSMUSP00000015581; ENSMUSG00000015437 |
GeneIDi | 14939 |
KEGGi | mmu:14939 |
UCSCi | uc007ubv.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X04072 mRNA Translation: CAA27715.1 M12302 mRNA Translation: AAA37383.1 M22526 Genomic DNA Translation: AAB61756.1 BC002085 mRNA Translation: AAH02085.1 U05707 Genomic DNA Translation: AAB60470.1 |
CCDSi | CCDS27147.1 |
PIRi | A94288, PRMSCL |
RefSeqi | NP_038570.1, NM_013542.3 |
3D structure databases
SMRi | P04187 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200135, 6 interactors |
STRINGi | 10090.ENSMUSP00000015581 |
Protein family/group databases
MEROPSi | S01.136 |
PTM databases
GlyGeni | P04187, 2 sites |
iPTMneti | P04187 |
PhosphoSitePlusi | P04187 |
Proteomic databases
EPDi | P04187 |
PaxDbi | P04187 |
PeptideAtlasi | P04187 |
PRIDEi | P04187 |
ProteomicsDBi | 271286 |
Protocols and materials databases
DNASUi | 14939 |
Genome annotation databases
Ensembli | ENSMUST00000015581; ENSMUSP00000015581; ENSMUSG00000015437 |
GeneIDi | 14939 |
KEGGi | mmu:14939 |
UCSCi | uc007ubv.1, mouse |
Organism-specific databases
CTDi | 3002 |
MGIi | MGI:109267, Gzmb |
VEuPathDBi | HostDB:ENSMUSG00000015437 |
Phylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT01030000234551 |
HOGENOMi | CLU_006842_1_0_1 |
InParanoidi | P04187 |
OMAi | PAYNPEK |
OrthoDBi | 1076876at2759 |
PhylomeDBi | P04187 |
TreeFami | TF333630 |
Enzyme and pathway databases
BRENDAi | 3.4.21.79, 3474 |
Reactomei | R-MMU-5620971, Pyroptosis R-MMU-75108, Activation, myristolyation of BID and translocation to mitochondria |
Miscellaneous databases
BioGRID-ORCSi | 14939, 1 hit in 65 CRISPR screens |
ChiTaRSi | Gzmb, mouse |
PROi | PR:P04187 |
RNActi | P04187, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000015437, Expressed in decidua and 77 other tissues |
ExpressionAtlasi | P04187, baseline and differential |
Genevisiblei | P04187, MM |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GRAB_MOUSE | |
Accessioni | P04187Primary (citable) accession number: P04187 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 20, 1987 |
Last sequence update: | March 20, 1987 | |
Last modified: | February 23, 2022 | |
This is version 199 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families