GRAA_MOUSE
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 03-AUG-2022, entry version 191.
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.
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. It
CC cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its
CC oxidative repair activity. Cleaves the nucleosome assembly protein SET
CC after 'Lys-189', which disrupts its nucleosome assembly activity and
CC allows the SET complex to translocate into the nucleus to nick and
CC degrade the DNA. {ECO:0000250|UniProtKB:P12544}.
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:0000250|UniProtKB:P12544}. 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}.
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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_010370.2. [P11032-1]
DR AlphaFoldDB; P11032; -.
DR SMR; P11032; -.
DR STRING; 10090.ENSMUSP00000023897; -.
DR MEROPS; S01.135; -.
DR GlyGen; P11032; 2 sites.
DR PhosphoSitePlus; P11032; -.
DR EPD; P11032; -.
DR MaxQB; P11032; -.
DR PaxDb; P11032; -.
DR PeptideAtlas; P11032; -.
DR PRIDE; P11032; -.
DR ProteomicsDB; 271284; -. [P11032-1]
DR ProteomicsDB; 271285; -. [P11032-2]
DR Antibodypedia; 11050; 383 antibodies from 39 providers.
DR DNASU; 14938; -.
DR Ensembl; ENSMUST00000023897; ENSMUSP00000023897; ENSMUSG00000023132. [P11032-1]
DR Ensembl; ENSMUST00000224282; ENSMUSP00000153593; ENSMUSG00000023132. [P11032-2]
DR GeneID; 14938; -.
DR KEGG; mmu:14938; -.
DR UCSC; uc007rxc.1; mouse. [P11032-1]
DR UCSC; uc011zeu.1; mouse. [P11032-2]
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 PhylomeDB; P11032; -.
DR TreeFam; TF333630; -.
DR BRENDA; 3.4.21.78; 3474.
DR BioGRID-ORCS; 14938; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Gzma; mouse.
DR PRO; PR:P11032; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P11032; protein.
DR Bgee; ENSMUSG00000023132; Expressed in gastrula and 84 other tissues.
DR ExpressionAtlas; P11032; baseline and differential.
DR Genevisible; P11032; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:MGI.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:1902483; P:cytotoxic T cell pyroptotic process; ISS:UniProtKB.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0032078; P:negative regulation of endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP: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 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
