DB code: D00855

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.79
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P18291 Granzyme B
EC 3.4.21.79
Fragmentin
Natural killer cell protease 1
RNKP-1
NP_612526.2 (Protein)
NM_138517.3 (DNA/RNA sequence)
XP_002728303.2 (Protein)
XM_002728257.2 (DNA/RNA sequence)
S01.091 (Serine)
PF00089 (Trypsin)
[Graphical View]
P10144 Granzyme B
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
NP_004122.2 (Protein)
NM_004131.4 (DNA/RNA sequence)
S01.010 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Granzyme B
CTLA1
CCPII
Cytotoxic cell proteinase-1
Granzyme G
Granzyme H
CCP1 proteinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10144 GRAB_HUMAN Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-. Cytoplasmic granule. Cytoplasmic granules of cytolytic T-lymphocytes and natural killer cells.
P18291 NKP1_RAT Preferential cleavage: -Asp-|-Xaa- >> -Asn-|-Xaa- > -Met-|-Xaa-, -Ser-|-Xaa-.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00017 C00001 C00017 C00012 I00087 I00085 I00086
E.C.
Compound Protein H2O Protein Peptide Peptidyl-Ser-tetrahedral-intermediate (with previous peptide) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1fi8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:PRO_83-ASP_84(chain C) Unbound Unbound Unbound
1fi8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:PRO_83-ASP_84(chain E) Unbound Unbound Unbound
1fq3A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1fq3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1iauA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:ACE-ILE-GLU-PRO-ASA
1fi8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1fi8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1fq3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1fq3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1iauA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [3], [5] & Swiss-prot;P10144, P18291

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fi8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1fi8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1fq3A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1fq3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1iauA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1fi8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fi8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fq3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1fq3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1iauA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[6]
Figure 5

References
[1]
Resource
Comments
Medline ID
PubMed ID 9218414
Journal J Biol Chem
Year 1997
Volume 272
Pages 17907-11
Authors Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, Nicholson DW
Title A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9765264
Journal J Biol Chem
Year 1998
Volume 273
Pages 27364-73
Authors Harris JL, Peterson EP, Hudig D, Thornberry NA, Craik CS
Title Definition and redesign of the extended substrate specificity of granzyme B.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 21-247.
Medline ID
PubMed ID 11209755
Journal Biol Chem
Year 2000
Volume 381
Pages 1203-14
Authors Estebanez-Perpina E, Fuentes-Prior P, Belorgey D, Braun M, Kiefersauer R, Maskos K, Huber R, Rubin H, Bode W
Title Crystal structure of the caspase activator human granzyme B, a proteinase highly specific for an Asp-P1 residue.
Related PDB 1fq3
Related UniProtKB P10144
[4]
Resource
Comments
Medline ID
PubMed ID 10966646
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 762-5
Authors Waugh SM, Harris JL, Fletterick R, Craik CS
Title The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity.
Related PDB 1fi8
Related UniProtKB P18291
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 21-247.
Medline ID
PubMed ID 11325591
Journal Chem Biol
Year 2001
Volume 8
Pages 357-68
Authors Rotonda J, Garcia-Calvo M, Bull HG, Geissler WM, McKeever BM, Willoughby CA, Thornberry NA, Becker JW
Title The 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 PDB 1iau
Related UniProtKB P10144
[6]
Resource
Comments
Medline ID
PubMed ID 12475199
Journal Chem Rev
Year 2002
Volume 102
Pages 4501-24
Authors Hedstrom L
Title Serine protease mechanism and specificity.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 17975553
Journal Cell Death Differ
Year 2008
Volume 15
Pages 251-62
Authors Cullen SP, Martin SJ
Title Mechanisms of granule-dependent killing.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 18836177
Journal Mol Cell Proteomics
Year 2009
Volume 8
Pages 258-72
Authors Van 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
Title Analysis of protein processing by N-terminal proteomics reveals novel species-specific substrate determinants of granzyme B orthologs.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 20536558
Journal Immunol Rev
Year 2010
Volume 235
Pages 105-16
Authors Afonina IS, Cullen SP, Martin SJ
Title Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 21042704
Journal Int J Oncol
Year 2010
Volume 37
Pages 1361-78
Authors Rousalova I, Krepela E
Title Granzyme B-induced apoptosis in cancer cells and its regulation (review).
Related PDB
Related UniProtKB

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.

Created Updated
2011-06-29 2012-08-01