EzCatDB: D00855
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DB codeD00855
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.3.4.21.79

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,D00852,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411

Enzyme Name
UniProtKBKEGG

P18291P10144
Protein nameGranzyme BGranzyme BGranzyme B
CTLA1
CCPII
Cytotoxic cell proteinase-1
Granzyme G
Granzyme H
CCP1 proteinase
SynonymsEC 3.4.21.79
Fragmentin
Natural killer cell protease 1
RNKP-1
EC 3.4.21.79
C11
CTLA-1
Cathepsin G-like 1
CTSGL1
Cytotoxic T-lymphocyte proteinase 2
Lymphocyte protease
Fragmentin-2
Granzyme-2
Human lymphocyte protein
HLP
SECT
T-cell serine protease 1-3E
RefSeqNP_612526.2 (Protein)
NM_138517.3 (DNA/RNA sequence)
XP_002728303.2 (Protein)
XM_002728257.2 (DNA/RNA sequence)
NP_004122.2 (Protein)
NM_004131.4 (DNA/RNA sequence)
MEROPSS01.091 (Serine)
S01.010 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP18291P10144
Entry nameNKP1_RATGRAB_HUMAN
ActivityPreferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-.Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-.
Subunit

Subcellular location
Cytoplasmic granule. Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells.
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





               
1fi8A01Unbound UnboundAnalogue:PRO 83-ASP 84(chain C)UnboundUnboundUnbound
1fi8B01Unbound UnboundAnalogue:PRO 83-ASP 84(chain E)UnboundUnboundUnbound
1fq3A01Unbound UnboundUnboundUnboundUnboundUnbound
1fq3B01Unbound UnboundUnboundUnboundUnboundUnbound
1iauA01Unbound UnboundUnboundUnboundUnboundTransition-state-analogue:ACE-ILE-GLU-PRO-ASA
1fi8A02Unbound UnboundUnboundUnboundUnboundUnbound
1fi8B02Unbound UnboundUnboundUnboundUnboundUnbound
1fq3A02Unbound UnboundUnboundUnboundUnboundUnbound
1fq3B02Unbound UnboundUnboundUnboundUnboundUnbound
1iauA02Unbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [3], [5] & Swiss-prot;P10144, P18291
pdbCatalytic residuesMain-chain involved in catalysis
          
1fi8A01SER 195
GLY 193;SER 195
1fi8B01SER 195
GLY 193;SER 195
1fq3A01SER 195
GLY 193;SER 195
1fq3B01SER 195
GLY 193;SER 195
1iauA01SER 195
GLY 193;SER 195
1fi8A02HIS 57;ASP 102
 
1fi8B02HIS 57;ASP 102
 
1fq3A02HIS 57;ASP 102
 
1fq3B02HIS 57;ASP 102
 
1iauA02HIS 57;ASP 102
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Figure 5

references
[1]
PubMed ID9218414
JournalJ Biol Chem
Year1997
Volume272
Pages17907-11
AuthorsThornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW
TitleA combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
[2]
PubMed ID9765264
JournalJ Biol Chem
Year1998
Volume273
Pages27364-73
AuthorsHarris JL, Peterson EP, Hudig D, Thornberry NA, Craik CS
TitleDefinition and redesign of the extended substrate specificity of granzyme B.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
PubMed ID11209755
JournalBiol Chem
Year2000
Volume381
Pages1203-14
AuthorsEstebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W
TitleCrystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
Related PDB1fq3
Related UniProtKBP10144
[4]
PubMed ID10966646
JournalNat Struct Biol
Year2000
Volume7
Pages762-5
AuthorsWaugh SM, Harris JL, Fletterick R, Craik CS
TitleThe structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.
Related PDB1fi8
Related UniProtKBP18291
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247.
PubMed ID11325591
JournalChem Biol
Year2001
Volume8
Pages357-68
AuthorsRotonda J, Garcia-Calvo M, Bull HG, Geissler WM, McKeever BM, Willoughby CA, Thornberry NA, Becker JW
TitleThe three-dimensional structure of human granzyme B compared to caspase-3, key mediators of cell death with cleavage specificity for aspartic acid in P1.
Related PDB1iau
Related UniProtKBP10144
[6]
PubMed ID12475199
JournalChem Rev
Year2002
Volume102
Pages4501-24
AuthorsHedstrom L
TitleSerine protease mechanism and specificity.
[7]
PubMed ID17975553
JournalCell Death Differ
Year2008
Volume15
Pages251-62
AuthorsCullen SP, Martin SJ
TitleMechanisms of granule-dependent killing.
[8]
PubMed ID18836177
JournalMol Cell Proteomics
Year2009
Volume8
Pages258-72
AuthorsVan Damme P, Maurer-Stroh S, Plasman K, Van Durme J, Colaert N, Timmerman E, De Bock PJ, Goethals M, Rousseau F, Schymkowitz J, Vandekerckhove J, Gevaert K
TitleAnalysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs.
[9]
PubMed ID20536558
JournalImmunol Rev
Year2010
Volume235
Pages105-16
AuthorsAfonina IS, Cullen SP, Martin SJ
TitleCytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B.
[10]
PubMed ID21042704
JournalInt J Oncol
Year2010
Volume37
Pages1361-78
AuthorsRousalova I, Krepela E
TitleGranzyme B-induced apoptosis in cancer cells and its regulation (review).

comments
This enzyme belongs to peptidase family-S1.
This enzyme seems to activate caspases, and is involved in apoptosis in cancer cells (see [7], [9], [10]).
Since this enzyme has got the same catalytic site as trypsin, it must catalyze the trypsin-like reaction.

createdupdated
2011-06-292012-08-01


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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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