Reviewed, UniProtKB/Swiss-Prot P24158 (PRTN3_HUMAN)

Names and origin

Protein names

Recommended name:
    Myeloblastin
    EC=3.4.21.76
Alternative name(s):
    Leukocyte proteinase 3
      Short name=PR-3
      Short name=PR3
    AGP7
    Wegener autoantigen
    P29
    C-ANCA antigen
    Neutrophil proteinase 4
      Short name=NP-4

Gene names

Name:	PRTN3
Synonyms:	MBN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	256 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Polymorphonuclear leukocyte serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) and causes emphysema when administered by tracheal insufflation to hamsters.
Catalytic activity	Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.
Sequence similarities	Belongs to the peptidase S1 family. Elastase subfamily. Contains 1 peptidase S1 domain.
Sequence caution	The sequence AAA36342.1 differs from that shown. Reason: Frameshift at positions 34 and 39.

Ontologies

Keywords
Biological process	Collagen degradation
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Ref.10 Traceable author statement. Source: ProtInc proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: IntAct serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD3	P84022	1	EBI-465028,EBI-347161

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Propeptide

26 – 27

2

Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.16 Ref.19

PRO_0000027707

Chain

28 – 248

221

Myeloblastin

PRO_0000027708

Propeptide

249 – 256

8

PRO_0000027709

Regions

Domain

28 – 248

221

Peptidase S1

Sites

Active site

71

1

Charge relay system

Active site

118

1

Charge relay system

Active site

203

1

Charge relay system

Amino acid modifications

Glycosylation

129

1

N-linked (GlcNAc...) Potential

Glycosylation

174

1

N-linked (GlcNAc...)

Disulfide bond

56 ↔ 72

Disulfide bond

152 ↔ 209

Disulfide bond

182 ↔ 188

Disulfide bond

199 ↔ 224

Natural variations

Natural variant

119

1

V → I: dbSNP rs351111. Ref.11 Ref.1 Ref.7 Ref.10

VAR_011691

Natural variant

135

1

A → T: dbSNP rs1042281. Ref.11 Ref.1 Ref.10

VAR_011713

Natural variant

136

1

T → S: dbSNP rs1042282. Ref.11 Ref.1 Ref.10

VAR_011714

Experimental info

Sequence conflict

2

1

A → R in CAA39203. Ref.9

Sequence conflict

38

1

S → I AA sequence Ref.19

Sequence conflict

40

1

P → PI AA sequence Ref.19

Sequence conflict

46

1

Q → E AA sequence Ref.13

Sequence conflict

46

1

Q → E AA sequence Ref.17

Sequence conflict

48

1

R → A AA sequence Ref.14

Sequence conflict

64

1

S → D AA sequence Ref.12

Sequence conflict

70

1

A → P in AAA59558. Ref.1

Sequence conflict

255

1

Missing in CAA39203. Ref.9

Secondary structure

1

.

.

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.

.

.

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.

.

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.

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256

Helix Strand Turn

Details...

Beta strand

42 – 47

6

Beta strand

56 – 62

7

Beta strand

65 – 68

4

Helix

70 – 73

4

Beta strand

74 – 76

3

Helix

78 – 80

3

Beta strand

81 – 86

6

Beta strand

98 – 107

10

Turn

112 – 115

4

Beta strand

120 – 126

7

Beta strand

151 – 160

10

Beta strand

162 – 164

3

Beta strand

171 – 178

8

Beta strand

186 – 190

5

Beta strand

192 – 195

4

Beta strand

206 – 209

4

Beta strand

212 – 219

8

Beta strand

221 – 223

3

Beta strand

227 – 229

3

Beta strand

231 – 235

5

Helix

236 – 239

4

Helix

240 – 247

8

Sequences

	Sequence		Length	Mass (Da)
	P24158-1 [UniParc]. Last modified December 15, 1998. Version 3. Checksum: CBECA36D8C4B2A40	FASTA	256	27,807
	10 20 30 40 50 60 MAHRPPSPAL ASVLLALLLS GAARAAEIVG GHEAQPHSRP YMASLQMRGN PGSHFCGGTL 70 80 90 100 110 120 IHPSFVLTAA HCLRDIPQRL VNVVLGAHNV RTQEPTQQHF SVAQVFLNNY DAENKLNDVL 130 140 150 160 170 180 LIQLSSPANL SASVATVQLP QQDQPVPHGT QCLAMGWGRV GAHDPPAQVL QELNVTVVTF 190 200 210 220 230 240 FCRPHNICTF VPRRKAGICF GDSGGPLICD GIIQGIDSFV IWGCATRLFP DFFTRVALYV 250 DWIRSTLRRV EAKGRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Wegener autoantigen and myeloblastin are encoded by a single mRNA." Labbaye C., Musette P., Cayre Y.E. Proc. Natl. Acad. Sci. U.S.A. 88:9253-9256(1991) [PubMed: 1681549] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ILE-119; THR-135 AND SER-136.
[2]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-119.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-119.
[5]	"Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter." Zimmer M., Medcalf R.L., Fink T.M., Mattmann C., Lichter P., Jenne D.E. Proc. Natl. Acad. Sci. U.S.A. 89:8215-8219(1992) [PubMed: 1518849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20 AND 22-256.
[6]	"Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen." Sturrock A.B., Franklin K.F., Rao G., Marshall B.C., Rebentisch M.B., Lemons R.S., Hoidal J.R. J. Biol. Chem. 267:21193-21199(1992) [PubMed: 1400430] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-254, VARIANTS THR-135 AND SER-136.
[7]	"Donor-recipient polymorphism of the proteinase 3 gene: a potential target for T-cell alloresponses to myeloid leukemia." Clave E., Molldrem J., Hensel N., Raptis A., Barrett A.J. J. Immunother. 22:1-6(1999) [PubMed: 9924693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200, VARIANT ILE-119.
[8]	"Wegener's autoantigen and leukemia." Musette P., Labbaye C., Dorner M.H., Cayre Y.E., Casanova J.-L., Kourilsky P. Blood 77:1398-1399(1991) [PubMed: 2001463] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-42.
[9]	"Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils." Campanelli D., Melchior M., Fu Y., Nakata M., Shuman H., Nathan C., Gabay J.E. J. Exp. Med. 172:1709-1715(1990) [PubMed: 2258701] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-256, PROTEIN SEQUENCE OF 28-71; 156-181 AND 196-219.
[10]	"Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells." Bories D., Raynal M.-C., Solomon D.H., Darzynkiewicz Z., Cayre Y.E. Cell 59:959-968(1989) [PubMed: 2598267] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-256, VARIANTS ILE-119; THR-135 AND SER-136.
[11]	"Wegener's autoantigen decoded." Jenne D.E., Tschopp J., Luedemann J., Utecht B., Gross W.L. Nature 346:520-520(1990) [PubMed: 2377228] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-256, PROTEIN SEQUENCE OF 28-48, VARIANTS ILE-119; THR-135 AND SER-136, IDENTITY OF WEGENER'S AUTOANTIGEN WITH PR-3.
[12]	"Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties." Rao N.V., Wehner N.G., Marshall B.C., Gray W.R., Gray B.H., Hoidal J.R. J. Biol. Chem. 266:9540-9548(1991) [PubMed: 2033050] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-67 AND 228-244.
[13]	"Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase." Wilde C.G., Snable J.L., Griffith J.E., Scott R.W. J. Biol. Chem. 265:2038-2041(1990) [PubMed: 2404977] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47 AND 196-219.
[14]	"Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme." Ohlsson K., Linder C., Rosengren M. Biol. Chem. Hoppe-Seyler 371:549-555(1990) [PubMed: 2121162] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-52.
[15]	"The relation of 29 kD C-ANCA antigen to proteinase 3." Goldschmeding R., Dolman K.M., van den Ende M.E., van der Meer-Gerritsen C.H., Sonnenberg A., von dem Borne A.E. APMIS Suppl. 19:26-27(1990) [PubMed: 2285532] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-48.
[16]	"Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase." Niles J.L., McCluskey R.T., Ahmad M.F., Arnaout M.A. Blood 74:1888-1893(1989) [PubMed: 2679910] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47.
[17]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed: 2501794] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47.
[18]	"Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis." Gaskin G., Kendal H., Coulthart A., Turner N., Pusey C.D. J. Immunol. Methods 180:25-33(1995) [PubMed: 7897245] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47, CATALYTIC ACTIVITY. Tissue: Neutrophil.
[19]	"Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme." Ludemann J., Utecht B., Gross W.L. J. Exp. Med. 171:357-362(1990) [PubMed: 1688612] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-43.
[20]	"A novel form of dipeptidylpeptidase IV found in human serum. Isolation, characterization, and comparison with T lymphocyte membrane dipeptidylpeptidase IV (CD26)." Duke-Cohan J.S., Morimoto C., Rocker J.A., Schlossman S.F. J. Biol. Chem. 270:14107-14114(1995) [PubMed: 7539799] [Abstract] Cited for: PROTEIN SEQUENCE OF 110-121, VARIANT ILE-119. Tissue: Serum.
[21]	"Identity of Wegener's autoantigen (p29) with proteinase 3 and myeloblastin." Gupta S.K., Niles J.L., McCluskey R.T., Arnaout M.A. Blood 76:2162-2162(1990) [PubMed: 2242436] [Abstract] Cited for: IDENTITY OF WEGENER'S AUTOANTIGEN WITH PROTEINASE 3.
[22]	"The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies." Fujinaga M., Charnaia M.M., Halenbeck R., Koths K., James M.N.G. J. Mol. Biol. 261:267-278(1996) [PubMed: 8757293] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Wikipedia

Proteinase 3 entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M75154 mRNA. Translation: AAA59558.1.
AC004799 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69591.1.
BC096183 mRNA. Translation: AAH96183.1.
BC096184 mRNA. Translation: AAH96184.1.
BC096185 mRNA. Translation: AAH96185.1.
BC096186 mRNA. Translation: AAH96186.1.
M96628 Genomic DNA. Translation: AAB59364.1.
M96839, M96838, M96837 Genomic DNA. Translation: AAB59493.1.
M97911 Genomic DNA. No translation available.
AF015449 , AF015446, AF015447, AF015448 Genomic DNA. Translation: AAD21524.1.
X56606 mRNA. Translation: CAA39943.1.
X55668 mRNA. Translation: CAA39203.1.
M29142 mRNA. Translation: AAA36342.1. Frameshift.
X56132 mRNA. Translation: CAA39597.1.
X56132 mRNA. Translation: CAA39598.1. Different initiation.

IPI

IPI00027409.

PIR

PRHU3. A45080.

RefSeq

NP_002768.3.

UniGene

Hs.928

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FUJ	X-ray	2.20	A/B/C/D	28-248	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P24158. 1 interaction.

Protein family/group databases

MEROPS

S01.134.

Proteomic databases

PeptideAtlas

P24158.

PRIDE

P24158.

Genome annotation databases

Ensembl

ENSG00000196415. Homo sapiens. [Contig view]

GeneID

5657.

KEGG

hsa:5657.

Organism-specific databases

GeneCards

GC19P000794.

H-InvDB

HIX0040155.

HGNC

HGNC:9495. PRTN3.

HPA

CAB017558.
HPA005938.

MIM

177020. gene.

Orphanet

900. Wegener granulomatosis.

PharmGKB

PA33842.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P24158.

HOVERGEN

P24158.

OMA

P24158. QGTQCLA.

Enzyme and pathway databases

BRENDA

3.4.21.76. 247.

Gene expression databases

ArrayExpress

P24158.

Bgee

P24158.

CleanEx

HS_PRTN3.

GermOnline

ENSG00000196415. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

21988.

SOURCE

Search...

Entry information

Entry name

PRTN3_HUMAN

Accession

Primary (citable) accession number: P24158
Secondary accession number(s): P15637 , P18078, Q4VB08, Q4VB09, Q6LBM7, Q6LBN2, Q9UD25, Q9UQD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	December 15, 1998
Last modified:	June 16, 2009
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)