EzCatDB: D00433
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DB codeD00433
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.3.4.21.76

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,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

Enzyme Name
UniProtKBKEGG

P24158
Protein nameMyeloblastinmyeloblastin
leukocyte proteinase 3
leukocyte proteinase 4
Wegener's granulomatosis autoantigen
proteinase PR-3
proteinase-3
PMNL proteinase
SynonymsEC 3.4.21.76
Leukocyte proteinase 3
PR-3
PR3
AGP7
Wegener autoantigen
P29
C-ANCA antigen
Neutrophil proteinase 4
NP-4
RefSeqNP_002768.3 (Protein)
NM_002777.3 (DNA/RNA sequence)
MEROPSS01.134 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP24158
Entry namePRTN3_HUMAN
ActivityHydrolysis of proteins, including elastin, by preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.
Subunit
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00012C00017C00001C00012C00017I00087I00085I00086
CompoundPeptideProteinH2OPeptideProteinPeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein


ChEBI

15377





PubChem

962
22247451





                
1fujA01UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujB01UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujC01UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujD01UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujA02UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujB02UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujC02UnboundUnbound UnboundUnboundUnboundUnboundUnbound
1fujD02UnboundUnbound UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P24158
pdbCatalytic residuesMain-chain involved in catalysis
          
1fujA01SER 195
GLY 193;SER 195
1fujB01SER 195
GLY 193;SER 195
1fujC01SER 195
GLY 193;SER 195
1fujD01SER 195
GLY 193;SER 195
1fujA02HIS 57;ASP 102
 
1fujB02HIS 57;ASP 102
 
1fujC02HIS 57;ASP 102
 
1fujD02HIS 57;ASP 102
 


references
[1]
CommentsIDENTITY OF WEGENER'S AUTOANTIGEN WITH PROTEINASE 3.
Medline ID91055123
PubMed ID2242436
JournalBlood
Year1990
Volume76
Pages2162
AuthorsGupta SK, Niles JL, McCluskey RT, Arnaout MA
TitleIdentity of Wegener's autoantigen (p29) with proteinase 3 and myeloblastin.
Related UniProtKBP24158
[2]
PubMed ID2258701
JournalJ Exp Med
Year1990
Volume172
Pages1709-15
AuthorsCampanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE
TitleCloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils.
[3]
PubMed ID1459241
JournalFEBS Lett
Year1992
Volume314
Pages117-21
AuthorsDolman KM, van de Wiel BA, Kam CM, Abbink JJ, Hack CE, Sonnenberg A, Powers JC, von dem Borne AE, Goldschmeding R
TitleDetermination of proteinase 3-alpha 1-antitrypsin complexes in inflammatory fluids.
[4]
PubMed ID1380042
JournalJ Immunol
Year1992
Volume149
Pages1409-15
AuthorsBini P, Gabay JE, Teitel A, Melchior M, Zhou JL, Elkon KB
TitleAntineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis recognize conformational epitope(s) on proteinase 3.
[5]
PubMed ID7925979
JournalFEBS Lett
Year1994
Volume352
Pages231-5
AuthorsPadrines M, Wolf M, Walz A, Baggiolini M
TitleInterleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3.
[6]
PubMed ID8157982
JournalJ Immunol
Year1994
Volume152
Pages4722-37
AuthorsWilliams RC Jr, Staud R, Malone CC, Payabyab J, Byres L, Underwood D
TitleEpitopes on proteinase-3 recognized by antibodies from patients with Wegener's granulomatosis.
[7]
PubMed ID8581420
JournalBioorg Med Chem
Year1995
Volume3
Pages375-81
AuthorsGroutas WC, Brubaker MJ, Chong LS, Venkataraman R, Huang H, Epp JB, Kuang R, Hoidal JR
TitleDesign, synthesis and biological evaluation of succinimide derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.
[8]
PubMed ID7796053
JournalBioorg Med Chem
Year1995
Volume3
Pages187-93
AuthorsGroutas WC, Chong LS, Venkataraman R, Epp JB, Kuang R, Houser-Archield N, Hoidal JR
TitleThe Gabriel-Colman rearrangement in biological systems: design, synthesis and biological evaluation of phthalimide and saccharin derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.
[9]
PubMed ID7796046
JournalBioorg Med Chem
Year1995
Volume3
Pages125-8
AuthorsGroutas WC, Venkataraman R, Chong LS, Yoder JE, Epp JB, Stanga MA, Kim EH
TitleIsoxazoline derivatives as potential inhibitors of the proteolytic enzymes human leukocyte elastase, cathepsin G and proteinase 3: a structure-activity relationship study.
[10]
PubMed ID8806743
JournalArch Biochem Biophys
Year1996
Volume332
Pages335-40
AuthorsGroutas WC, Chong LS, Venkataraman R, Kuang R, Epp JB, Houser-Archield N, Huang H, Hoidal JR
TitleAmino acid-derived phthalimide and saccharin derivatives as inhibitors of human leukocyte elastase, cathepsin G, and proteinase 3.
[11]
PubMed ID8894097
JournalBioorg Med Chem
Year1996
Volume4
Pages1393-400
AuthorsGroutas WC, Epp JB, Venkataraman R, Kuang R, Truong TM, McClenahan JJ, Prakash O
TitleDesign, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID96346178
PubMed ID8757293
JournalJ Mol Biol
Year1996
Volume261
Pages267-78
AuthorsFujinaga M, Chernaia MM, Halenbeck R, Koths K, James MN
TitleThe crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies.
Related PDB1fuj
Related UniProtKBP24158
[13]
PubMed ID9125494
JournalBiochemistry
Year1997
Volume36
Pages4739-50
AuthorsGroutas WC, Kuang R, Venkataraman R, Epp JB, Ruan S, Prakash O
TitleStructure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold.
[14]
PubMed ID9058715
JournalBlood
Year1997
Volume89
Pages1944-53
AuthorsRenesto P, Si-Tahar M, Moniatte M, Balloy V, Van Dorsselaer A, Pidard D, Chignard M
TitleSpecific inhibition of thrombin-induced cell activation by the neutrophil proteinases elastase, cathepsin G, and proteinase 3: evidence for distinct cleavage sites within the aminoterminal domain of the thrombin receptor.
[15]
PubMed ID9092534
JournalJ Biol Chem
Year1997
Volume272
Pages9950-5
AuthorsCadene M, Duranton J, North A, Si-Tahar M, Chignard M, Bieth JG
TitleInhibition of neutrophil serine proteinases by suramin.
[16]
PubMed ID9681132
JournalBioorg Med Chem
Year1998
Volume6
Pages661-71
AuthorsGroutas WC, Kuang R, Ruan S, Epp JB, Venkataraman R, Truong TM
TitlePotent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
[17]
PubMed ID9756722
JournalClin Immunol Immunopathol
Year1998
Volume89
Pages35-43
AuthorsDavis JA, Peen E, Williams RC, Perkins S, Malone CC, McCormack WT, Csernok E, Gross WL, Kolaskar AS, Kulkarni-Kale U
TitleDetermination of primary amino acid sequence and unique three-dimensional structure of WGH1, a monoclonal human IgM antibody with anti-PR3 specificity.
[18]
PubMed ID10103046
JournalEur J Biochem
Year1999
Volume261
Pages155-62
AuthorsGoldmann WH, Niles JL, Arnaout MA
TitleInteraction of purified human proteinase 3 (PR3) with reconstituted lipid bilayers.
[19]
PubMed ID11094439
JournalArthritis Res
Year2000
Volume2
Pages263-7
AuthorsSpecks U
TitleWhat you should know about PR3-ANCA. Conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA.
[20]
PubMed ID10976518
JournalBioorg Med Chem
Year2000
Volume8
Pages1713-7
AuthorsHe S, Kuang R, Venkataraman R, Tu J, Truong TM, Chan HK, Groutas WC
TitlePotent inhibition of serine proteases by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1 dioxide.
[21]
PubMed ID10975855
JournalJ Immunol
Year2000
Volume165
Pages3366-74
AuthorsCampbell EJ, Campbell MA, Owen CA
TitleBioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition.
[22]
PubMed ID11159195
JournalAm J Pathol
Year2001
Volume158
Pages581-92
AuthorsYang JJ, Preston GA, Pendergraft WF, Segelmark M, Heeringa P, Hogan SL, Jennette JC, Falk RJ
TitleInternalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants.
[23]
PubMed ID11747453
JournalBiochemistry
Year2001
Volume40
Pages15762-70
AuthorsCooley J, Takayama TK, Shapiro SD, Schechter NM, Remold-O'Donnell E
TitleThe serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites.
[24]
PubMed ID11408173
JournalBioorg Med Chem
Year2001
Volume9
Pages1543-8
AuthorsGroutas WC, He S, Kuang R, Ruan S, Tu J, Chan HK
TitleInhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
[25]
PubMed ID11168015
JournalClin Exp Immunol
Year2001
Volume123
Pages170-7
AuthorsGriffith ME, Coulthart A, Pemberton S, George AJ, Pusey CD
TitleAnti-neutrophil cytoplasmic antibodies (ANCA) from patients with systemic vasculitis recognize restricted epitopes of proteinase 3 involving the catalytic site.
[26]
PubMed ID12135665
JournalExp Hematol
Year2002
Volume30
Pages689-96
AuthorsSkold S, Zeberg L, Gullberg U, Olofsson T
TitleFunctional dissociation between proforms and mature forms of proteinase 3, azurocidin, and granzyme B in regulation of granulopoiesis.

comments
This enzyme belongs to the peptidase family-S1.
This enzyme has got a classical catalytic triad, composed of Ser/His/Asp, which is the same as that of trypsin (D00197 in EzCatDB). It suggests that it may have a similar catalytic mechanism to that of trypsin.

createdupdated
2004-10-292011-02-21


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
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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