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Database: UniProt
Entry: GRAA_HUMAN
LinkDB: GRAA_HUMAN
Original site: GRAA_HUMAN 
ID   GRAA_HUMAN              Reviewed;         262 AA.
AC   P12544; A4PHN1; Q6IB36;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   24-JAN-2024, entry version 219.
DE   RecName: Full=Granzyme A {ECO:0000303|PubMed:3263427};
DE            EC=3.4.21.78 {ECO:0000269|PubMed:12819770, ECO:0000269|PubMed:32299851, ECO:0000269|PubMed:34022140, ECO:0000269|PubMed:36157507};
DE   AltName: Full=CTL tryptase {ECO:0000303|PubMed:3047119};
DE   AltName: Full=Cytotoxic T-lymphocyte proteinase 1 {ECO:0000303|PubMed:3047119};
DE   AltName: Full=Fragmentin-1;
DE   AltName: Full=Granzyme-1 {ECO:0000303|PubMed:3262682};
DE   AltName: Full=Hanukkah factor {ECO:0000303|PubMed:3257574};
DE            Short=H factor {ECO:0000303|PubMed:3257574};
DE            Short=HF {ECO:0000303|PubMed:3257574};
DE   Flags: Precursor;
GN   Name=GZMA {ECO:0000303|PubMed:32299851, ECO:0000312|HGNC:HGNC:4708};
GN   Synonyms=CTLA3, HFSP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, SUBCELLULAR LOCATION,
RP   AND VARIANT THR-121.
RC   TISSUE=T-cell;
RX   PubMed=3257574; DOI=10.1073/pnas.85.4.1184;
RA   Gershenfeld H.K., Hershberger R.J., Shows T.B., Weissman I.L.;
RT   "Cloning and chromosomal assignment of a human cDNA encoding a T cell- and
RT   natural killer cell-specific trypsin-like serine protease.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:1184-1188(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), AND VARIANT
RP   THR-121.
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), AND VARIANT
RP   THR-121.
RC   TISSUE=Blood;
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 [GENOMIC DNA] OF 1-72, NUCLEOTIDE SEQUENCE [MRNA] OF
RP   1-34 (ISOFORM BETA), ALTERNATIVE PROMOTER USAGE, AND INDUCTION.
RX   PubMed=17180578; DOI=10.1007/s10038-006-0099-9;
RA   Ruike Y., Katsuma S., Hirasawa A., Tsujimoto G.;
RT   "Glucocorticoid-induced alternative promoter usage for a novel 5' variant
RT   of granzyme A.";
RL   J. Hum. Genet. 52:172-178(2007).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23.
RA   Goralski T.J., Krensky A.M.;
RT   "The upstream region of the human granzyme A locus contains both positive
RT   and negative transcriptional regulatory elements.";
RL   Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   PROTEIN SEQUENCE OF 29-53.
RX   PubMed=3047119; DOI=10.1016/s0021-9258(18)37694-4;
RA   Poe M., Bennett C.D., Biddison W.E., Blake J.T., Norton G.P., Rodkey J.A.,
RA   Sigal N.H., Turner R.V., Wu J.K., Zweerink H.J.;
RT   "Human cytotoxic lymphocyte tryptase. Its purification from granules and
RT   the characterization of inhibitor and substrate specificity.";
RL   J. Biol. Chem. 263:13215-13222(1988).
RN   [8]
RP   PROTEIN SEQUENCE OF 29-40, AND FUNCTION.
RX   PubMed=3262682;
RA   Hameed A., Lowrey D.M., Lichtenheld M., Podack E.R.;
RT   "Characterization of three serine esterases isolated from human IL-2
RT   activated killer cells.";
RL   J. Immunol. 141:3142-3147(1988).
RN   [9]
RP   PROTEIN SEQUENCE OF 29-39, AND FUNCTION.
RX   PubMed=3263427;
RA   Kraehenbuhl O., Rey C., Jenne D.E., Lanzavecchia A., Groscurth P.,
RA   Carrel S., Tschopp J.;
RT   "Characterization of granzymes A and B isolated from granules of cloned
RT   human cytotoxic T lymphocytes.";
RL   J. Immunol. 141:3471-3477(1988).
RN   [10]
RP   FUNCTION AS SET PROTEASE.
RX   PubMed=11555662; DOI=10.1074/jbc.m108137200;
RA   Beresford P.J., Zhang D., Oh D.Y., Fan Z., Greer E.L., Russo M.L., Jaju M.,
RA   Lieberman J.;
RT   "Granzyme A activates an endoplasmic reticulum-associated caspase-
RT   independent nuclease to induce single-stranded DNA nicks.";
RL   J. Biol. Chem. 276:43285-43293(2001).
RN   [11]
RP   FUNCTION AS SET PROTEASE.
RX   PubMed=12628186; DOI=10.1016/s0092-8674(03)00150-8;
RA   Fan Z., Beresford P.J., Oh D.Y., Zhang D., Lieberman J.;
RT   "Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-
RT   mediated apoptosis, and the nucleosome assembly protein SET is its
RT   inhibitor.";
RL   Cell 112:659-672(2003).
RN   [12]
RP   FUNCTION, AND INTERACTION WITH APEX1.
RX   PubMed=12524539; DOI=10.1038/ni885;
RA   Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A.,
RA   Pommier Y., Lieberman J.;
RT   "Cleaving the oxidative repair protein Ape1 enhances cell death mediated by
RT   granzyme A.";
RL   Nat. Immunol. 4:145-153(2003).
RN   [13]
RP   FUNCTION AS SET PROTEASE.
RX   PubMed=16818237; DOI=10.1016/j.molcel.2006.06.005;
RA   Chowdhury D., Beresford P.J., Zhu P., Zhang D., Sung J.S., Demple B.,
RA   Perrino F.W., Lieberman J.;
RT   "The exonuclease TREX1 is in the SET complex and acts in concert with NM23-
RT   H1 to degrade DNA during granzyme A-mediated cell death.";
RL   Mol. Cell 23:133-142(2006).
RN   [14]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-170.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [15]
RP   SUBCELLULAR LOCATION.
RX   PubMed=20038786; DOI=10.1182/blood-2009-10-246116;
RA   Thiery J., Keefe D., Saffarian S., Martinvalet D., Walch M., Boucrot E.,
RA   Kirchhausen T., Lieberman J.;
RT   "Perforin activates clathrin- and dynamin-dependent endocytosis, which is
RT   required for plasma membrane repair and delivery of granzyme B for
RT   granzyme-mediated apoptosis.";
RL   Blood 115:1582-1593(2010).
RN   [16]
RP   FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, ACTIVE SITE, AND
RP   MUTAGENESIS OF SER-212.
RX   PubMed=32299851; DOI=10.1126/science.aaz7548;
RA   Zhou Z., He H., Wang K., Shi X., Wang Y., Su Y., Wang Y., Li D., Liu W.,
RA   Zhang Y., Shen L., Han W., Shen L., Ding J., Shao F.;
RT   "Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis
RT   in target cells.";
RL   Science 368:0-0(2020).
RN   [17]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=34022140; DOI=10.1016/j.cell.2021.04.036;
RA   Hansen J.M., de Jong M.F., Wu Q., Zhang L.S., Heisler D.B., Alto L.T.,
RA   Alto N.M.;
RT   "Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal
RT   functions.";
RL   Cell 184:3178-3191(2021).
RN   [18]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=36157507; DOI=10.1016/j.gendis.2021.12.022;
RA   Gong W., Liu P., Liu J., Li Y., Zheng T., Wu X., Zhao Y., Ren J.;
RT   "GSDMB N-terminal assembles in plasma membrane to execute pyroptotic cell
RT   death.";
RL   Genes Dis. 9:1405-1407(2022).
RN   [19]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=36899106; DOI=10.1038/s41418-023-01143-y;
RA   Oltra S.S., Colomo S., Sin L., Perez-Lopez M., Lazaro S., Molina-Crespo A.,
RA   Choi K.H., Ros-Pardo D., Martinez L., Morales S., Gonzalez-Paramos C.,
RA   Orantes A., Soriano M., Hernandez A., Lluch A., Rojo F., Albanell J.,
RA   Gomez-Puertas P., Ko J.K., Sarrio D., Moreno-Bueno G.;
RT   "Distinct GSDMB protein isoforms and protease cleavage processes
RT   differentially control pyroptotic cell death and mitochondrial damage in
RT   cancer cells.";
RL   Cell Death Differ. 30:1366-1381(2023).
RN   [20]
RP   3D-STRUCTURE MODELING OF 29-262.
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).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-262 IN COMPLEX WITH A
RP   TRIPEPTIDE CMK INHIBITOR, AND DISULFIDE BONDS.
RX   PubMed=12819769; DOI=10.1038/nsb944;
RA   Bell J.K., Goetz D.H., Mahrus S., Harris J.L., Fletterick R.J., Craik C.S.;
RT   "The oligomeric structure of human granzyme A is a determinant of its
RT   extended substrate specificity.";
RL   Nat. Struct. Biol. 10:527-534(2003).
RN   [22]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 29-262 IN COMPLEX WITH SUBSTRATE,
RP   FUNCTION, CATALYTIC ACTIVITY, AND DISULFIDE BONDS.
RX   PubMed=12819770; DOI=10.1038/nsb945;
RA   Hink-Schauer C., Estebanez-Perpina E., Kurschus F.C., Bode W., Jenne D.E.;
RT   "Crystal structure of the apoptosis-inducing human granzyme A dimer.";
RL   Nat. Struct. Biol. 10:535-540(2003).
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:3257574, PubMed:3262682, PubMed:3263427, PubMed:32299851,
CC       PubMed:12819770). It cleaves after Lys or Arg (PubMed:32299851,
CC       PubMed:12819770). Once delivered into the target cell, acts by
CC       catalyzing cleavage of gasdermin-B (GSDMB), releasing the pore-forming
CC       moiety of GSDMB, thereby triggering pyroptosis and target cell death
CC       (PubMed:32299851, PubMed:34022140, PubMed:36157507, PubMed:36899106).
CC       Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity
CC       (PubMed:12524539). Cleaves the nucleosome assembly protein SET after
CC       'Lys-189', which disrupts its nucleosome assembly activity and allows
CC       the SET complex to translocate into the nucleus to nick and degrade the
CC       DNA (PubMed:11555662, PubMed:12628186, PubMed:16818237).
CC       {ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12524539,
CC       ECO:0000269|PubMed:12628186, ECO:0000269|PubMed:12819770,
CC       ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:32299851,
CC       ECO:0000269|PubMed:3257574, ECO:0000269|PubMed:3262682,
CC       ECO:0000269|PubMed:3263427, ECO:0000269|PubMed:34022140,
CC       ECO:0000269|PubMed:36157507, ECO:0000269|PubMed:36899106}.
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:0000269|PubMed:12819770, ECO:0000269|PubMed:32299851,
CC         ECO:0000269|PubMed:34022140, ECO:0000269|PubMed:36157507};
CC   -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:12819769,
CC       PubMed:12819770). Interacts with APEX1 (PubMed:12524539).
CC       {ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:12819769,
CC       ECO:0000269|PubMed:12819770}.
CC   -!- SUBCELLULAR LOCATION: [Isoform alpha]: Secreted
CC       {ECO:0000269|PubMed:3257574}. Cytoplasmic granule
CC       {ECO:0000269|PubMed:3257574}. Note=Delivered into the target cell by
CC       perforin. {ECO:0000269|PubMed:20038786, ECO:0000269|PubMed:32299851}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage; Named isoforms=2;
CC       Name=alpha {ECO:0000303|PubMed:17180578};
CC         IsoId=P12544-1; Sequence=Displayed;
CC       Name=beta {ECO:0000303|PubMed:17180578};
CC         IsoId=P12544-2; Sequence=VSP_038571, VSP_038572;
CC   -!- INDUCTION: Dexamethasone (DEX) induces expression of isoform beta and
CC       represses expression of isoform alpha. The alteration in expression is
CC       mediated by binding of glucocorticoid receptor to independent promoters
CC       adjacent to the alternative first exons of isoform alpha and isoform
CC       beta. {ECO:0000269|PubMed:17180578}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   -!- CAUTION: Exons 1a and 1b of the sequence reported in PubMed:17180578
CC       are of human origin, however exon 2 shows strong similarity to the rat
CC       sequence. {ECO:0000305|PubMed:17180578}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/51130/GZMA";
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DR   EMBL; M18737; AAA52647.1; -; mRNA.
DR   EMBL; CR456968; CAG33249.1; -; mRNA.
DR   EMBL; AC091977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC015739; AAH15739.1; -; mRNA.
DR   EMBL; AB284134; BAF56159.1; -; mRNA.
DR   EMBL; U40006; AAD00009.1; -; Genomic_DNA.
DR   CCDS; CCDS3965.1; -. [P12544-1]
DR   PIR; A31372; A31372.
DR   RefSeq; NP_006135.1; NM_006144.3. [P12544-1]
DR   PDB; 1OP8; X-ray; 2.50 A; A/B/C/D/E/F=29-262.
DR   PDB; 1ORF; X-ray; 2.40 A; A=29-262.
DR   PDBsum; 1OP8; -.
DR   PDBsum; 1ORF; -.
DR   AlphaFoldDB; P12544; -.
DR   SMR; P12544; -.
DR   BioGRID; 109256; 17.
DR   IntAct; P12544; 4.
DR   STRING; 9606.ENSP00000274306; -.
DR   ChEMBL; CHEMBL4307; -.
DR   MEROPS; S01.135; -.
DR   GlyCosmos; P12544; 1 site, No reported glycans.
DR   GlyGen; P12544; 1 site.
DR   iPTMnet; P12544; -.
DR   PhosphoSitePlus; P12544; -.
DR   BioMuta; GZMA; -.
DR   DMDM; 317373360; -.
DR   jPOST; P12544; -.
DR   MassIVE; P12544; -.
DR   MaxQB; P12544; -.
DR   PaxDb; 9606-ENSP00000274306; -.
DR   PeptideAtlas; P12544; -.
DR   ProteomicsDB; 52858; -. [P12544-1]
DR   ProteomicsDB; 52859; -. [P12544-2]
DR   Antibodypedia; 11050; 412 antibodies from 39 providers.
DR   CPTC; P12544; 1 antibody.
DR   DNASU; 3001; -.
DR   Ensembl; ENST00000274306.7; ENSP00000274306.6; ENSG00000145649.8. [P12544-1]
DR   GeneID; 3001; -.
DR   KEGG; hsa:3001; -.
DR   MANE-Select; ENST00000274306.7; ENSP00000274306.6; NM_006144.4; NP_006135.2.
DR   UCSC; uc003jpm.4; human. [P12544-1]
DR   AGR; HGNC:4708; -.
DR   CTD; 3001; -.
DR   DisGeNET; 3001; -.
DR   GeneCards; GZMA; -.
DR   HGNC; HGNC:4708; GZMA.
DR   HPA; ENSG00000145649; Tissue enhanced (lymphoid).
DR   MIM; 140050; gene.
DR   neXtProt; NX_P12544; -.
DR   OpenTargets; ENSG00000145649; -.
DR   PharmGKB; PA29086; -.
DR   VEuPathDB; HostDB:ENSG00000145649; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT00940000159928; -.
DR   HOGENOM; CLU_006842_1_0_1; -.
DR   InParanoid; P12544; -.
DR   OMA; YPCYDPA; -.
DR   OrthoDB; 2878201at2759; -.
DR   PhylomeDB; P12544; -.
DR   TreeFam; TF333630; -.
DR   BRENDA; 3.4.21.78; 2681.
DR   PathwayCommons; P12544; -.
DR   SignaLink; P12544; -.
DR   SIGNOR; P12544; -.
DR   BioGRID-ORCS; 3001; 15 hits in 1148 CRISPR screens.
DR   EvolutionaryTrace; P12544; -.
DR   GeneWiki; GZMA; -.
DR   GenomeRNAi; 3001; -.
DR   Pharos; P12544; Tbio.
DR   PRO; PR:P12544; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P12544; Protein.
DR   Bgee; ENSG00000145649; Expressed in granulocyte and 140 other cell types or tissues.
DR   Genevisible; P12544; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0001772; C:immunological synapse; TAS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR   GO; GO:1902483; P:cytotoxic T cell pyroptotic process; IDA:UniProtKB.
DR   GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; IDA:UniProtKB.
DR   GO; GO:0006955; P:immune response; TAS:UniProtKB.
DR   GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR   GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
DR   GO; GO:0032078; P:negative regulation of endodeoxyribonuclease activity; IDA:UniProtKB.
DR   GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR   GO; GO:0051604; P:protein maturation; IDA:UniProt.
DR   GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:UniProtKB.
DR   GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR   GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
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: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   3D-structure; Alternative promoter usage; Cytolysis;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW   Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..28
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:3047119,
FT                   ECO:0000269|PubMed:3262682, ECO:0000269|PubMed:3263427"
FT                   /id="PRO_0000027393"
FT   CHAIN           29..262
FT                   /note="Granzyme A"
FT                   /id="PRO_0000027394"
FT   DOMAIN          29..259
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        69
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770"
FT   ACT_SITE        114
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770"
FT   ACT_SITE        212
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770, ECO:0000305|PubMed:32299851"
FT   CARBOHYD        170
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   DISULFID        54..70
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770, ECO:0007744|PDB:1OP8,
FT                   ECO:0007744|PDB:1ORF"
FT   DISULFID        148..218
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770, ECO:0007744|PDB:1OP8,
FT                   ECO:0007744|PDB:1ORF"
FT   DISULFID        179..197
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770, ECO:0007744|PDB:1OP8,
FT                   ECO:0007744|PDB:1ORF"
FT   DISULFID        208..234
FT                   /evidence="ECO:0000269|PubMed:12819769,
FT                   ECO:0000269|PubMed:12819770, ECO:0007744|PDB:1OP8,
FT                   ECO:0007744|PDB:1ORF"
FT   VAR_SEQ         1..17
FT                   /note="Missing (in isoform beta)"
FT                   /evidence="ECO:0000303|PubMed:17180578"
FT                   /id="VSP_038571"
FT   VAR_SEQ         18..23
FT                   /note="LLLIPE -> MTKGLR (in isoform beta)"
FT                   /evidence="ECO:0000303|PubMed:17180578"
FT                   /id="VSP_038572"
FT   VARIANT         121
FT                   /note="M -> T (in dbSNP:rs3104233)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:3257574, ECO:0000269|Ref.2"
FT                   /id="VAR_024291"
FT   MUTAGEN         212
FT                   /note="S->A: Abolished protease activity."
FT                   /evidence="ECO:0000269|PubMed:32299851"
FT   CONFLICT        33..34
FT                   /note="NE -> DT (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        36
FT                   /note="T -> V (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        47
FT                   /note="S -> K (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        49..52
FT                   /note="DRKT -> KPDS (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        62
FT                   /note="D -> N (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        71..72
FT                   /note="NL -> IP (in Ref. 5; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   STRAND          43..47
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          49..51
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          53..60
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          63..66
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          77..81
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          83..87
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          93..95
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          97..102
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   TURN            108..110
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          116..122
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          127..130
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          147..154
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          156..160
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          167..174
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   HELIX           176..179
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   TURN            182..189
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          195..199
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          215..218
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          221..228
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   STRAND          241..245
FT                   /evidence="ECO:0007829|PDB:1ORF"
FT   HELIX           248..258
FT                   /evidence="ECO:0007829|PDB:1ORF"
SQ   SEQUENCE   262 AA;  28999 MW;  FD773628BA6F301B CRC64;
     MRNSYRFLAS SLSVVVSLLL IPEDVCEKII GGNEVTPHSR PYMVLLSLDR KTICAGALIA
     KDWVLTAAHC NLNKRSQVIL GAHSITREEP TKQIMLVKKE FPYPCYDPAT REGDLKLLQL
     MEKAKINKYV TILHLPKKGD DVKPGTMCQV AGWGRTHNSA SWSDTLREVN ITIIDRKVCN
     DRNHYNFNPV IGMNMVCAGS LRGGRDSCNG DSGSPLLCEG VFRGVTSFGL ENKCGDPRGP
     GVYILLSKKH LNWIIMTIKG AV
//
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