ID GRAA_MOUSE Reviewed; 260 AA. AC P11032; P15118; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 2. DT 02-SEP-2026, entry version 209. DE RecName: Full=Granzyme A; DE EC=3.4.21.78; DE AltName: Full=Autocrine thymic lymphoma granzyme-like serine protease; DE AltName: Full=CTLA-3; DE AltName: Full=Fragmentin-1; DE AltName: Full=T cell-specific serine protease 1; DE Short=TSP-1; DE Flags: Precursor; GN Name=Gzma; Synonyms=Ctla-3, Ctla3, Mtsp-1; 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]. RC STRAIN=C57BL/6J; RX PubMed=2976140; RA Bogenberger J., Haas M.; RT "cDNA clones from autocrine thymic lymphoma cells encode two mitogenic RT proteins, a serine protease and a truncated T-cell receptor beta-chain."; RL Oncogene Res. 3:301-312(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=1639378; DOI=10.1016/0888-7543(92)90117-b; RA Ebnet K., Kramer M.D., Simon M.M.; RT "Organization of the gene encoding the mouse T-cell-specific serine RT proteinase 'granzyme A'."; RL Genomics 13:502-508(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS HF1 AND HF2), AND TISSUE RP SPECIFICITY. RX PubMed=1460043; DOI=10.1016/s0021-9258(19)74067-8; RA Hershberger R.J., Gershenfeld H.K., Weissman I.L., Su L.; RT "Genomic organization of the mouse granzyme A gene. Two mRNAs encode the RT same mature granzyme A with different leader peptides."; RL J. Biol. Chem. 267:25488-25493(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM HF1). 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 [MRNA] OF 1-37. RX PubMed=3292396; DOI=10.1111/j.1600-065x.1988.tb00749.x; RA Jenne D.E., Tschopp J.; RT "Granzymes, a family of serine proteases released from granules of RT cytolytic T lymphocytes upon T cell receptor stimulation."; RL Immunol. Rev. 103:53-71(1988). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-260. RX PubMed=2422755; DOI=10.1126/science.2422755; RA Gershenfeld H.K., Weissman I.L.; RT "Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T RT lymphocyte."; RL Science 232:854-858(1986). RN [7] RP PROTEIN SEQUENCE OF 29-48, FUNCTION, AND SUBCELLULAR LOCATION. 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 [8] RP PROTEIN SEQUENCE OF 29-53. RX PubMed=3533635; DOI=10.1016/0014-5793(86)81537-x; RA Masson D., Zamai M., Tschopp J.; RT "Identification of granzyme A isolated from cytotoxic T-lymphocyte-granules RT as one of the proteases encoded by CTL-specific genes."; RL FEBS Lett. 208:84-88(1986). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-46. RX PubMed=3260181; DOI=10.1002/eji.1830180605; RA Simon H.G., Fruth U., Eckerskorn C., Lottspeich F., Kramer M.D., Nerz G., RA Simon M.M.; RT "Induction of T cell serine proteinase 1 (TSP-1)-specific mRNA in mouse T RT lymphocytes."; RL Eur. J. Immunol. 18:855-861(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:3555842). It cleaves after Lys or Arg (By similarity). Cleaves CC APEX1 after 'Lys-31' and destroys its oxidative repair activity (By CC similarity). Cleaves the nucleosome assembly protein SET after 'Lys- CC 189', which disrupts its nucleosome assembly activity and allows the CC SET complex to translocate into the nucleus to nick and degrade the DNA CC (By similarity). {ECO:0000250|UniProtKB:P12544, CC ECO:0000269|PubMed:3555842}. 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:0000269|PubMed:3555842}. Note=Delivered into CC the target cell by perforin. {ECO:0000250|UniProtKB:P12544}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=HF1; CC IsoId=P11032-1; Sequence=Displayed; CC Name=HF2; CC IsoId=P11032-2; Sequence=VSP_005373; CC -!- TISSUE SPECIFICITY: Found in cytotoxic lymphocytes and in normal CC lymphoid tissues such as thymus and spleen. CC {ECO:0000269|PubMed:1460043}. CC -!- TISSUE SPECIFICITY: [Isoform HF1]: More abundant in lymphoid tissues CC than isoform HF2. {ECO:0000269|PubMed:1460043}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- CAUTION: [Isoform HF2]: The predicted cleavage site for the activation CC peptide of HF2 is uncertain. It could have either 2 (ER) or 7 (KRGGCER) CC AA. {ECO:0000305|PubMed:1460043}. 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; X14799; CAA32905.1; -; mRNA. DR EMBL; X62542; CAA44426.1; -; Genomic_DNA. DR EMBL; X62543; CAA44426.1; JOINED; Genomic_DNA. DR EMBL; X60310; CAA44426.1; JOINED; Genomic_DNA. DR EMBL; X60311; CAA44426.1; JOINED; Genomic_DNA. DR EMBL; L01429; AAA99898.1; -; Genomic_DNA. DR EMBL; L01426; AAA99898.1; JOINED; Genomic_DNA. DR EMBL; L01427; AAA99898.1; JOINED; Genomic_DNA. DR EMBL; L01441; AAA99898.1; JOINED; Genomic_DNA. DR EMBL; L01429; AAA99897.1; -; Genomic_DNA. DR EMBL; L01426; AAA99897.1; JOINED; Genomic_DNA. DR EMBL; L01427; AAA99897.1; JOINED; Genomic_DNA. DR EMBL; L01441; AAA99897.1; JOINED; Genomic_DNA. DR EMBL; BC061146; AAH61146.1; -; mRNA. DR EMBL; M26183; AAA37735.1; -; mRNA. DR EMBL; M13226; AAA40134.1; -; mRNA. DR CCDS; CCDS26782.1; -. [P11032-1] DR PIR; A24807; A24807. DR PIR; A45061; A45061. DR PIR; B45061; B45061. DR RefSeq; NP_034500.1; NM_010370.3. [P11032-1] DR AlphaFoldDB; P11032; -. DR SMR; P11032; -. DR BioGRID; 200134; 1. DR FunCoup; P11032; 980. DR STRING; 10090.ENSMUSP00000023897; -. DR MEROPS; S01.135; -. DR GlyCosmos; P11032; 2 sites, No reported glycans. DR GlyGen; P11032; 3 sites, 3 N-linked glycans (3 sites). DR PhosphoSitePlus; P11032; -. DR PaxDb; 10090-ENSMUSP00000023897; -. DR PeptideAtlas; P11032; -. DR ProteomicsDB; 271284; -. [P11032-1] DR ProteomicsDB; 271285; -. [P11032-2] DR Antibodypedia; 11050; 396 antibodies from 42 providers. DR DNASU; 14938; -. DR Ensembl; ENSMUST00000023897.7; ENSMUSP00000023897.6; ENSMUSG00000023132.9. [P11032-1] DR Ensembl; ENSMUST00000224282.2; ENSMUSP00000153593.2; ENSMUSG00000023132.9. [P11032-2] DR GeneID; 14938; -. DR KEGG; mmu:14938; -. DR UCSC; uc007rxc.1; mouse. [P11032-1] DR UCSC; uc011zeu.1; mouse. [P11032-2] DR AGR; MGI:109266; -. DR CTD; 3001; -. DR MGI; MGI:109266; Gzma. DR VEuPathDB; HostDB:ENSMUSG00000023132; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000159928; -. DR HOGENOM; CLU_006842_1_0_1; -. DR InParanoid; P11032; -. DR OMA; YPCYDPA; -. DR OrthoDB; 6755574at2759; -. DR PhylomeDB; P11032; -. DR BRENDA; 3.4.21.78; 3474. DR BioGRID-ORCS; 14938; 0 hits in 79 CRISPR screens. DR PRO; PR:P11032; -. DR Proteomes; UP000000589; Chromosome 13. DR RNAct; P11032; protein. DR Bgee; ENSMUSG00000023132; Expressed in gastrula and 84 other cell types or tissues. DR ExpressionAtlas; P11032; baseline and differential. DR GO; GO:0044194; C:cytolytic granule; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISO:GO_Central. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. 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:1902483; P:cytotoxic T cell pyroptotic cell death; ISS:UniProtKB. DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB. DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; ISO:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB. DR GO; GO:0051604; P:protein maturation; ISO:GO_Central. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR GO; GO:0070269; P:pyroptotic inflammatory response; ISS:UniProtKB. DR GO; GO:0009617; P:response to bacterium; IEP:MGI. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000120; Putative serine protease; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF69; GRANZYME A; 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. PE 1: Evidence at protein level; KW Alternative splicing; Cytolysis; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hydrolase; Protease; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1..26 FT PROPEP 27..28 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:3533635, FT ECO:0000269|PubMed:3555842" FT /id="PRO_0000027395" FT CHAIN 29..260 FT /note="Granzyme A" FT /id="PRO_0000027396" FT DOMAIN 29..257 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 69 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P12544" FT ACT_SITE 113 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 157 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 169 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 54..70 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 147..217 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 178..196 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 207..232 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT VAR_SEQ 1..23 FT /note="MRNASGPRGPSLATLLFLLLIPE -> MSKEMNEILLSWEINLSSKR (in FT isoform HF2)" FT /evidence="ECO:0000305" FT /id="VSP_005373" SQ SEQUENCE 260 AA; 28599 MW; 7705352F08DEED8D CRC64; MRNASGPRGP SLATLLFLLL IPEGGCERII GGDTVVPHSR PYMALLKLSS NTICAGALIE KNWVLTAAHC NVGKRSKFIL GAHSINKEPE QQILTVKKAF PYPCYDEYTR EGDLQLVRLK KKATVNRNVA ILHLPKKGDD VKPGTRCRVA GWGRFGNKSA PSETLREVNI TVIDRKICND EKHYNFHPVI GLNMICAGDL RGGKDSCNGD SGSPLLCDGI LRGITSFGGE KCGDRRWPGV YTFLSDKHLN WIKKIMKGSV //