ID GRAA_HUMAN STANDARD; PRT; 262 AA. AC P12544; DT 01-OCT-1989 (Rel. 12, Created) DT 01-OCT-1989 (Rel. 12, Last sequence update) DT 13-SEP-2005 (Rel. 48, Last annotation update) DE Granzyme A precursor (EC 3.4.21.78) (Cytotoxic T-lymphocyte proteinase DE 1) (Hanukkah factor) (H factor) (HF) (Granzyme-1) (CTL tryptase) DE (Fragmentin-1). GN Name=GZMA; Synonyms=CTLA3, HFSP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE. RC TISSUE=T-cell; RX MEDLINE=88125000; PubMed=3257574; 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- RT and 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]. RC TISSUE=Blood; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP NUCLEOTIDE SEQUENCE OF 1-23. RA Goralski T.J., Krensky A.M.; RT "The upstream region of the human granzyme A locus contains both RT positive and negative transcriptional regulatory elements."; RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases. RN [4] RP PROTEIN SEQUENCE OF 29-53. RX MEDLINE=88330824; PubMed=3047119; RA Poe M., Bennett C.D., Biddison W.E., Blake J.T., Norton G.P., RA Rodkey J.A., Sigal N.H., Turner R.V., Wu J.K., Zweerink H.J.; RT "Human cytotoxic lymphocyte tryptase. Its purification from granules RT and the characterization of inhibitor and substrate specificity."; RL J. Biol. Chem. 263:13215-13222(1988). RN [5] RP PROTEIN SEQUENCE OF 29-40, AND CHARACTERIZATION. RX MEDLINE=89009866; 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 [6] RP PROTEIN SEQUENCE OF 29-39, AND CHARACTERIZATION. RX MEDLINE=89035468; 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 RT cloned human cytotoxic T lymphocytes."; RL J. Immunol. 141:3471-3477(1988). RN [7] RP 3D-STRUCTURE MODELING. RX MEDLINE=89184501; PubMed=3237717; RA Murphy M.E.P., Moult J., Bleackley R.C., Gershenfeld H., RA Weissman I.L., 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 [8] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH A TRIPEPTIDE CMK RP INHIBITOR. RX MEDLINE=22708839; PubMed=12819769; DOI=10.1038/nsb944; RA Bell J.K., Goetz D.H., Mahrus S., Harris J.L., Fletterick R.J., RA 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 [9] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH SUBSTRATE. RX MEDLINE=22708840; PubMed=12819770; DOI=10.1038/nsb945; RA Hink-Schauer C., Estebanez-Perpina E., Kurschus F.C., Bode W., RA Jenne D.E.; RT "Crystal structure of the apoptosis-inducing human granzyme A dimer."; RL Nat. Struct. Biol. 10:535-540(2003). CC -!- FUNCTION: This enzyme is necessary for target cell lysis in cell- CC mediated immune responses. It cleaves after Lys or Arg. May be CC involved in apoptosis. CC -!- CATALYTIC ACTIVITY: Hydrolysis of proteins, including fibronectin, CC type IV collagen and nucleolin. Preferential cleavage: Arg-|-Xaa, CC Lys-|-Xaa >> Phe-|-Xaa in small molecule substrates. CC -!- SUBUNIT: Homodimer; disulfide-linked. CC -!- INTERACTION: CC Self; NbExp=1; IntAct=EBI-519800, EBI-519800; CC -!- SUBCELLULAR LOCATION: Secreted; cytoplasmic granules. CC -!- SIMILARITY: Belongs to the peptidase S1 family. Granzyme CC subfamily. CC -!- SIMILARITY: Contains 1 peptidase S1 domain. CC -------------------------------------------------------------------------- CC This Swiss-Prot entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use as long as its content is in no way modified and this statement is not CC removed. CC -------------------------------------------------------------------------- DR EMBL; M18737; AAA52647.1; -; mRNA. DR EMBL; BC015739; AAH15739.1; -; mRNA. DR EMBL; U40006; AAD00009.1; -; Genomic_DNA. DR PIR; A31372; A31372. DR PDB; 1HF1; Model; @=29-262. DR PDB; 1OP8; X-ray; A/B/C/D/E/F=29-262. DR PDB; 1ORF; X-ray; A=29-262. DR IntAct; P12544; -. DR MEROPS; S01.135; -. DR Ensembl; ENSG00000145649; Homo sapiens. DR HGNC; HGNC:4708; GZMA. DR H-InvDB; HIX0004862; -. DR MIM; 140050; -. DR GO; GO:0001772; C:immunological synapse; TAS. DR GO; GO:0005634; C:nucleus; TAS. DR GO; GO:0004277; F:granzyme A activity; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0042803; F:protein homodimerization activity; IDA. DR GO; GO:0006915; P:apoptosis; TAS. DR GO; GO:0006922; P:cleavage of lamin; IDA. DR GO; GO:0006955; P:immune response; TAS. DR InterPro; IPR001254; Peptidase_S1_S6. DR InterPro; IPR001314; Peptidase_S1A. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. KW 3D-structure; Apoptosis; Cytolysis; Direct protein sequencing; KW Glycoprotein; Hydrolase; Protease; Serine protease; Signal; T-cell; KW Zymogen. FT SIGNAL 1 26 FT PROPEP 27 28 Activation peptide. FT CHAIN 29 262 Granzyme A. FT DOMAIN 29 259 Peptidase S1. FT ACT_SITE 69 69 Charge relay system. FT ACT_SITE 114 114 Charge relay system. FT ACT_SITE 212 212 Charge relay system. FT CARBOHYD 170 170 N-linked (GlcNAc...) (Potential). FT DISULFID 54 70 FT DISULFID 148 218 FT DISULFID 179 197 FT DISULFID 208 234 FT STRAND 30 30 FT STRAND 33 34 FT TURN 37 38 FT TURN 41 42 FT STRAND 43 48 FT TURN 49 51 FT STRAND 52 60 FT TURN 61 62 FT STRAND 63 66 FT TURN 68 69 FT STRAND 76 80 FT STRAND 84 84 FT TURN 85 86 FT TURN 90 91 FT STRAND 93 102 FT TURN 104 105 FT HELIX 108 110 FT TURN 112 113 FT STRAND 116 120 FT STRAND 127 127 FT TURN 128 129 FT STRAND 130 130 FT STRAND 134 134 FT TURN 138 139 FT TURN 144 145 FT STRAND 147 152 FT STRAND 155 157 FT TURN 158 159 FT STRAND 160 162 FT STRAND 165 165 FT STRAND 167 173 FT HELIX 176 180 FT TURN 181 182 FT TURN 184 185 FT TURN 193 194 FT STRAND 195 199 FT TURN 201 202 FT STRAND 206 206 FT TURN 209 210 FT TURN 212 213 FT STRAND 215 218 FT TURN 219 220 FT STRAND 221 228 FT TURN 231 232 FT TURN 234 235 FT TURN 237 238 FT STRAND 241 245 FT TURN 246 249 FT HELIX 252 260 SQ SEQUENCE 262 AA; 28969 MW; DA87363A0D92BAF4 CRC64; MRNSYRFLAS SLSVVVSLLL IPEDVCEKII GGNEVTPHSR PYMVLLSLDR KTICAGALIA KDWVLTAAHC NLNKRSQVIL GAHSITREEP TKQIMLVKKE FPYPCYDPAT REGDLKLLQL TEKAKINKYV TILHLPKKGD DVKPGTMCQV AGWGRTHNSA SWSDTLREVN ITIIDRKVCN DRNHYNFNPV IGMNMVCAGS LRGGRDSCNG DSGSPLLCEG VFRGVTSFGL ENKCGDPRGP GVYILLSKKH LNWIIMTIKG AV //