DB code: D00852

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. 3.4.21.78
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 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P12544 Granzyme A
EC 3.4.21.78
CTL tryptase
Cytotoxic T-lymphocyte proteinase 1
Fragmentin-1
Granzyme-1
Hanukkah factor
H factor
HF
NP_006135.1 (Protein)
NM_006144.3 (DNA/RNA sequence)
S01.135 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
Granzyme A
CTLA3
HuTPS
T-cell associated protease 1
Cytotoxic T lymphocyte serine protease
TSP-1
T-cell derived serine proteinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P12544 GRAA_HUMAN Hydrolysis of proteins, including fibronectin,type IV collagen and nucleolin. Preferential cleavage: -Arg-|-Xaa-, -Lys-|-Xaa- >> -Phe-|-Xaa- in small molecule substrates. Homodimer, disulfide-linked. Interacts with APEX1. Isoform alpha: Secreted. Cytoplasmic granule.

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
1op8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8E01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8F01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1orfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Transition-state-analogue:0G6
1op8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8E02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1op8F02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1orfA02 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] & Swiss-prot;P12544

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1op8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8E01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8F01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1orfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1op8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1op8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1op8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1op8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1op8E02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1op8F02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1orfA02 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
[1]
Figure 5, p.4505-4508

References
[1]
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
[2]
Resource
Comments
Medline ID
PubMed ID 14499264
Journal Curr Opin Immunol
Year 2003
Volume 15
Pages 553-9
Authors Lieberman J, Fan Z
Title Nuclear war: the granzyme A-bomb.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 29-262 IN COMPLEX WITH A TRIPEPTIDE CMK INHIBITOR.
Medline ID
PubMed ID 12819769
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 527-34
Authors Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS
Title The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity.
Related PDB 1orf
Related UniProtKB P12544
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 29-262 IN COMPLEX WITH SUBSTRATE.
Medline ID
PubMed ID 12819770
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 535-40
Authors Hink-Schauer C, Estebanez-Perpina E, Kurschus FC, Bode W, Jenne DE
Title Crystal structure of the apoptosis-inducing human granzyme A dimer.
Related PDB 1op8
Related UniProtKB P12544
[5]
Resource
Comments
Medline ID
PubMed ID 18304003
Journal Annu Rev Immunol
Year 2008
Volume 26
Pages 389-420
Authors Chowdhury D, Lieberman J
Title Death by a thousand cuts: granzyme pathways of programmed cell death.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 20536382
Journal Biol Chem
Year 2010
Volume 391
Pages 983-97
Authors Van Damme P, Maurer-Stroh S, Hao H, Colaert N, Timmerman E, Eisenhaber F, Vandekerckhove J, Gevaert K
Title The substrate specificity profile of human granzyme A.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 20536557
Journal Immunol Rev
Year 2010
Volume 235
Pages 93-104
Authors Lieberman J
Title Granzyme A activates another way to die.
Related PDB
Related UniProtKB

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]).

Created Updated
2011-05-27 2012-07-31