DB code: D00431

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. 3.4.21.59
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 D00432 D00433 D00434 D00435 M00227 M00209 D00194 D00197 D00211 D00212 D00216 M00212 D00224 D00497 M00217 M00216 D00528 D00848 D00850 D00851 D00852 D00855 M00152 M00155 M00157 M00181 M00315 M00316 M00317 M00348 M00349 T00074 T00410 T00411

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P20231 Tryptase beta-2
Tryptase-2
EC 3.4.21.59
Tryptase II
NP_003285.2 (Protein)
NM_003294.3 (DNA/RNA sequence)
NP_077078.5 (Protein)
NM_024164.5 (DNA/RNA sequence)
S01.015 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
tryptase
mast cell tryptase
mast cell protease II
skin tryptase
lung tryptase
pituitary tryptase
mast cell neutral proteinase
mast cell tryptase
mast cell neutral proteinase
mast cell serine proteinase II
mast cell proteinase II
mast cell serine proteinase tryptase
rat mast cell protease II
tryptase M

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P20231 TRYB2_HUMAN Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa, but with more restricted specificity than trypsin. Homotetramer. Secreted. Note=Released from the secretory granules upon mast cell activation.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00017 C00001 C00012 C00017 I00087 I00085 I00086
E.C.
Compound Peptide Protein H2O Peptide Protein Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
PubChem 22247451
962
1a0lA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Intermediate-analogue:APA Unbound Unbound
1a0lB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Intermediate-analogue:APA Unbound Unbound
1a0lC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Intermediate-analogue:APA Unbound Unbound
1a0lD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Intermediate-analogue:APA Unbound Unbound
1a0lA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a0lB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a0lC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1a0lD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P20231

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a0lA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a0lB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a0lC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a0lD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 195 GLY 193;SER 195
1a0lA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1a0lB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1a0lC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 57;ASP 102
1a0lD02 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
[4]
p.17079
[6]
p.309

References
[1]
Resource
Comments
Medline ID
PubMed ID 8896442
Journal EMBO J
Year 1996
Volume 15
Pages 5481-91
Authors Hof P, Mayr I, Huber R, Korzus E, Potempa J, Travis J, Powers JC, Bode W
Title The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9242660
Journal J Biol Chem
Year 1997
Volume 272
Pages 19931-7
Authors Stubbs MT, Morenweiser R, Sturzebecher J, Bauer M, Bode W, Huber R, Piechottka GP, Matschiner G, Sommerhoff CP, Fritz H, Auerswald EA
Title The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. Implications for the structure of human mast cell tryptase and its inhibition.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9317153
Journal J Immunol
Year 1997
Volume 159
Pages 3540-8
Authors Ren S, Lawson AE, Carr M, Baumgarten CM, Schwartz LB
Title Human tryptase fibrinogenolysis is optimal at acidic pH and generates anticoagulant fragments in the presence of the anti-tryptase monoclonal antibody B12.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9836602
Journal Biochemistry
Year 1998
Volume 37
Pages 17068-81
Authors Presnell SR, Patil GS, Mura C, Jude KM, Conley JM, Bertrand JA, Kam CM, Powers JC, Williams LD
Title Oxyanion-mediated inhibition of serine proteases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10197050
Journal Curr Pharm Des
Year 1998
Volume 4
Pages 381-96
Authors Rice KD, Tanaka RD, Katz BA, Numerof RP, Moore WR
Title Inhibitors of tryptase for the treatment of mast cell-mediated diseases.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID 98180625
PubMed ID 9521329
Journal Nature
Year 1998
Volume 392
Pages 306-11
Authors Pereira PJ, Bergner A, Macedo-Ribeiro S, Huber R, Matschiner G, Fritz H, Sommerhoff CP, Bode W
Title Human beta-tryptase is a ring-like tetramer with active sites facing a central pore.
Related PDB 1a0l
Related UniProtKB P20231
[7]
Resource
Comments
Medline ID
PubMed ID 9533631
Journal Peptides
Year 1998
Volume 19
Pages 437-43
Authors Erba F, Fiorucci L, Coletta M, Ascoli F
Title Bovine mast cell tryptase inactivation: effect of temperature.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10480954
Journal J Biol Chem
Year 1999
Volume 274
Pages 27331-7
Authors Wilharm E, Parry MA, Friebel R, Tschesche H, Matschiner G, Sommerhoff CP, Jenne DE
Title Generation of catalytically active granzyme K from Escherichia coli inclusion bodies and identification of efficient granzyme K inhibitors in human plasma.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS).
Medline ID 99432168
PubMed ID 10500112
Journal Proc Natl Acad Sci U S A
Year 1999
Volume 96
Pages 10984-91
Authors Sommerhoff CP, Bode W, Pereira PJ, Stubbs MT, Sturzebecher J, Piechottka GP, Matschiner G, Bergner A
Title The structure of the human betaII-tryptase tetramer: fo(u)r better or worse.
Related PDB
Related UniProtKB P20231
[10]
Resource
Comments
Medline ID
PubMed ID 10944445
Journal Biochem Biophys Res Commun
Year 2000
Volume 275
Pages 77-83
Authors Alm AK, Gagnemo-Persson R, Sorsa T, Sundelin J
Title Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10708866
Journal Biochim Biophys Acta
Year 2000
Volume 1477
Pages 307-23
Authors Kam CM, Hudig D, Powers JC
Title Granzymes (lymphocyte serine proteases): characterization with natural and synthetic substrates and inhibitors.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10708850
Journal Biochim Biophys Acta
Year 2000
Volume 1477
Pages 75-89
Authors Sommerhoff CP, Bode W, Matschiner G, Bergner A, Fritz H
Title The human mast cell tryptase tetramer: a fascinating riddle solved by structure.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 10617625
Journal J Biol Chem
Year 2000
Volume 275
Pages 351-8
Authors Huang C, Morales G, Vagi A, Chanasyk K, Ferrazzi M, Burklow C, Qiu WT, Feyfant E, Sali A, Stevens RL
Title Formation of enzymatically active, homotypic, and heterotypic tetramers of mouse mast cell tryptases. Dependence on a conserved Trp-rich domain on the surface.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11734467
Journal Am J Respir Crit Care Med
Year 2001
Volume 164
Pages S52-8
Authors Sommerhoff CP
Title Mast cell tryptases and airway remodeling.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 11172730
Journal Biochem Pharmacol
Year 2001
Volume 61
Pages 271-6
Authors Erba F, Fiorucci L, Pascarella S, Menegatti E, Ascenzi P, Ascoli F
Title Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11325588
Journal Chem Biol
Year 2001
Volume 8
Pages 313-27
Authors Schaschke N, Matschiner G, Zettl F, Marquardt U, Bergner A, Bode W, Sommerhoff CP, Moroder L
Title Bivalent inhibition of human beta-tryptase.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11602603
Journal J Biol Chem
Year 2001
Volume 276
Pages 49169-82
Authors Wong GW, Yasuda S, Madhusudhan MS, Li L, Yang Y, Krilis SA, Sali A, Stevens RL
Title Human tryptase epsilon (PRSS22), a new member of the chromosome 16p13.3 family of human serine proteases expressed in airway epithelial cells.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11060286
Journal J Biol Chem
Year 2001
Volume 276
Pages 3683-90
Authors Zhang D, Pasternack MS, Beresford PJ, Wagner L, Greenberg AH, Lieberman J
Title Induction of rapid histone degradation by the cytotoxic T lymphocyte protease Granzyme A.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11876641
Journal Biochemistry
Year 2002
Volume 41
Pages 3329-40
Authors Selwood T, Wang ZM, McCaslin DR, Schechter NM
Title Diverse stability and catalytic properties of human tryptase alpha and beta isoforms are mediated by residue differences at the S1 pocket.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12162961
Journal J Mol Biol
Year 2002
Volume 321
Pages 491-502
Authors Marquardt U, Zettl F, Huber R, Bode W, Sommerhoff C
Title The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11908961
Journal J Nat Prod
Year 2002
Volume 65
Pages 259-61
Authors Murakami Y, Takei M, Shindo K, Kitazume C, Tanaka J, Higa T, Fukamachi H
Title Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1.
According to the literature [6], this enzyme has got a similar catalytic triad (Ser/His/Asp) to that of trypsin, suggesting a similar mechanism.

Created Updated
2003-10-07 2011-02-18