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 15377
PubChem							22247451 962 22247451 962
1op8A01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8B01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8C01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8D01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8E01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8F01						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1orfA01						Unbound		Unbound	Unbound	Unbound	Unbound	Transition-state-analogue:0G6
1op8A02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8B02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8C02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8D02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8E02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1op8F02						Unbound		Unbound	Unbound	Unbound	Unbound	Unbound
1orfA02						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						SER 195			GLY 193;SER 195
1op8B01						SER 195			GLY 193;SER 195
1op8C01						SER 195			GLY 193;SER 195
1op8D01						SER 195			GLY 193;SER 195
1op8E01						SER 195			GLY 193;SER 195
1op8F01						SER 195			GLY 193;SER 195
1orfA01						SER 195			GLY 193;SER 195
1op8A02						HIS 57;ASP 102
1op8B02						HIS 57;ASP 102
1op8C02						HIS 57;ASP 102
1op8D02						HIS 57;ASP 102
1op8E02						HIS 57;ASP 102
1op8F02						HIS 57;ASP 102
1orfA02						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