EzCatDB: D00852
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DB codeD00852
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 22.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.78

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411

Enzyme Name
UniProtKBKEGG

P12544
Protein nameGranzyme AGranzyme A
CTLA3
HuTPS
T-cell associated protease 1
Cytotoxic T lymphocyte serine protease
TSP-1
T-cell derived serine proteinase
SynonymsEC 3.4.21.78
CTL tryptase
Cytotoxic T-lymphocyte proteinase 1
Fragmentin-1
Granzyme-1
Hanukkah factor
H factor
HF
RefSeqNP_006135.1 (Protein)
NM_006144.3 (DNA/RNA sequence)
MEROPSS01.135 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP12544
Entry nameGRAA_HUMAN
ActivityHydrolysis of proteins, including fibronectin,type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates.
SubunitHomodimer, disulfide-linked. Interacts with APEX1.
Subcellular locationIsoform alpha: Secreted. Cytoplasmic granule.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00017C00001C00017C00012I00087I00085I00086
CompoundProteinH2OProteinPeptidePeptidyl-Ser-tetrahedral-intermediate (with previous peptide)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typepeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI
15377





PubChem
962
22247451





               
1op8A01Unbound UnboundUnboundUnboundUnboundUnbound
1op8B01Unbound UnboundUnboundUnboundUnboundUnbound
1op8C01Unbound UnboundUnboundUnboundUnboundUnbound
1op8D01Unbound UnboundUnboundUnboundUnboundUnbound
1op8E01Unbound UnboundUnboundUnboundUnboundUnbound
1op8F01Unbound UnboundUnboundUnboundUnboundUnbound
1orfA01Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:0G6
1op8A02Unbound UnboundUnboundUnboundUnboundUnbound
1op8B02Unbound UnboundUnboundUnboundUnboundUnbound
1op8C02Unbound UnboundUnboundUnboundUnboundUnbound
1op8D02Unbound UnboundUnboundUnboundUnboundUnbound
1op8E02Unbound UnboundUnboundUnboundUnboundUnbound
1op8F02Unbound UnboundUnboundUnboundUnboundUnbound
1orfA02Unbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [3] & Swiss-prot;P12544
pdbCatalytic residuesMain-chain involved in catalysis
          
1op8A01SER 195
GLY 193;SER 195
1op8B01SER 195
GLY 193;SER 195
1op8C01SER 195
GLY 193;SER 195
1op8D01SER 195
GLY 193;SER 195
1op8E01SER 195
GLY 193;SER 195
1op8F01SER 195
GLY 193;SER 195
1orfA01SER 195
GLY 193;SER 195
1op8A02HIS 57;ASP 102
 
1op8B02HIS 57;ASP 102
 
1op8C02HIS 57;ASP 102
 
1op8D02HIS 57;ASP 102
 
1op8E02HIS 57;ASP 102
 
1op8F02HIS 57;ASP 102
 
1orfA02HIS 57;ASP 102
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Figure 5, p.4505-4508

references
[1]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[2]
PubMed ID14499264
JournalCurr Opin Immunol
Year2003
Volume15
Pages553-9
AuthorsLieberman J, Fan Z
TitleNuclear war: the granzyme A-bomb.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-262 IN COMPLEX WITH A TRIPEPTIDE CMK INHIBITOR.
PubMed ID12819769
JournalNat Struct Biol
Year2003
Volume10
Pages527-34
AuthorsBell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS
TitleThe oligomeric structure of human granzyme A is a determinant of its extended substrate specificity.
Related PDB1orf
Related UniProtKBP12544
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 29-262 IN COMPLEX WITH SUBSTRATE.
PubMed ID12819770
JournalNat Struct Biol
Year2003
Volume10
Pages535-40
AuthorsHink-Schauer C, Estebanez-Perpina E, Kurschus FC, Bode W, Jenne DE
TitleCrystal structure of the apoptosis-inducing human granzyme A dimer.
Related PDB1op8
Related UniProtKBP12544
[5]
PubMed ID18304003
JournalAnnu Rev Immunol
Year2008
Volume26
Pages389-420
AuthorsChowdhury D, Lieberman J
TitleDeath by a thousand cuts: granzyme pathways of programmed cell death.
[6]
PubMed ID20536382
JournalBiol Chem
Year2010
Volume391
Pages983-97
AuthorsVan Damme P, Maurer-Stroh S, Hao H, Colaert N, Timmerman E, Eisenhaber F, Vandekerckhove J, Gevaert K
TitleThe substrate specificity profile of human granzyme A.
[7]
PubMed ID20536557
JournalImmunol Rev
Year2010
Volume235
Pages93-104
AuthorsLieberman J
TitleGranzyme A activates another way to die.

comments
This enzyme belongs to peptidase family-S1.
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.
This enzyme is stored in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, and induces cell death (see [2], [5] and [7]).

createdupdated
2011-05-272012-07-31


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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