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Protein

Myeloblastin

Gene

PRTN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:3198760, PubMed:2033050, PubMed:28240246). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration (PubMed:23202369). May play a role in neutrophil transendothelial migration, probably when associated with CD177 (PubMed:22266279).5 Publications

Catalytic activityi

Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.6 Publications

Enzyme regulationi

Inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP).1 Publication

pH dependencei

Optimum pH is 7.4.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei71Charge relay systemPROSITE-ProRule annotation1
Active sitei118Charge relay systemPROSITE-ProRule annotation1
Active sitei203Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • antimicrobial humoral response Source: Reactome
  • blood coagulation Source: Reactome
  • cell-cell junction maintenance Source: UniProtKB
  • collagen catabolic process Source: UniProtKB-KW
  • cytokine-mediated signaling pathway Source: Reactome
  • mature conventional dendritic cell differentiation Source: UniProtKB
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • negative regulation of phagocytosis Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • neutrophil extravasation Source: UniProtKB
  • positive regulation of cell proliferation Source: ProtInc
  • positive regulation of GTPase activity Source: UniProtKB
  • proteolysis Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processCollagen degradation

Enzyme and pathway databases

BRENDAi3.4.21.76. 2681.
ReactomeiR-HSA-140875. Common Pathway of Fibrin Clot Formation.
R-HSA-449836. Other interleukin signaling.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6803157. Antimicrobial peptides.

Protein family/group databases

MEROPSiS01.134.

Names & Taxonomyi

Protein namesi
Recommended name:
Myeloblastin (EC:3.4.21.766 Publications)
Alternative name(s):
AGP7
C-ANCA antigen
Leukocyte proteinase 3
Short name:
PR-3
Short name:
PR3
Neutrophil proteinase 4
Short name:
NP-4
P29
Wegener autoantigen
Gene namesi
Name:PRTN3
Synonyms:MBN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000196415.9.
HGNCiHGNC:9495. PRTN3.
MIMi177020. gene.
neXtProtiNX_P24158.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Is the major autoantigen in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (Wegener's granulomatosis) (PubMed:2377228, PubMed:2679910). This complex, systemic disease is characterized by granulomatous inflammation with necrotizing lesions in the respiratory tract, glomerulonephritis, vasculitis, and anti-neutrophil cytoplasmatic autoantibodies detected in patient sera (PubMed:2377228, PubMed:2679910). PRTN3 causes emphysema when administered by tracheal insufflation to hamsters (PubMed:3198760).2 Publications1 Publication

Organism-specific databases

DisGeNETi5657.
MalaCardsiPRTN3.
OpenTargetsiENSG00000196415.
Orphaneti900. Granulomatosis with polyangiitis.
PharmGKBiPA33842.

Chemistry databases

ChEMBLiCHEMBL3900.
DrugBankiDB05161. Elafin.
GuidetoPHARMACOLOGYi2401.

Polymorphism and mutation databases

BioMutaiPRTN3.
DMDMi6174926.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Add BLAST25
PropeptideiPRO_000002770726 – 272
ChainiPRO_000002770828 – 248Myeloblastin4 PublicationsAdd BLAST221
PropeptideiPRO_0000027709249 – 2568

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi56 ↔ 72Combined sources1 Publication
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi152 ↔ 209Combined sources1 Publication
Glycosylationi174N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi182 ↔ 188Combined sources1 Publication
Disulfide bondi199 ↔ 224Combined sources1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP24158.
PaxDbiP24158.
PeptideAtlasiP24158.
PRIDEiP24158.

Expressioni

Tissue specificityi

Expressed in polymorphonuclear leukocytes (at protein level) (PubMed:2033050, PubMed:7897245, PubMed:3198760). Expressed in neutrophils (at protein level) (PubMed:28240246, PubMed:18462208, PubMed:21193407, PubMed:22266279, PubMed:17244676). Expressed in differentiating neutrophils (PubMed:18462208).8 Publications

Inductioni

Induced during CSF3/G-CSF-mediated neutrophil differentiation.1 Publication

Gene expression databases

BgeeiENSG00000196415.
CleanExiHS_PRTN3.
ExpressionAtlasiP24158. baseline and differential.
GenevisibleiP24158. HS.

Organism-specific databases

HPAiCAB017558.
HPA005938.

Interactioni

Subunit structurei

May form dimers (PubMed:28240246). Interacts with CD177; the interaction tethers PRTN3 to the cell surface; the interaction is direct (PubMed:17244676, PubMed:28240246).2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111638. 15 interactors.
DIPiDIP-31107N.
IntActiP24158. 4 interactors.
MINTiP24158.
STRINGi9606.ENSP00000234347.

Chemistry databases

BindingDBiP24158.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi42 – 47Combined sources6
Beta strandi56 – 62Combined sources7
Beta strandi65 – 68Combined sources4
Helixi70 – 73Combined sources4
Beta strandi74 – 76Combined sources3
Helixi78 – 80Combined sources3
Beta strandi81 – 86Combined sources6
Beta strandi98 – 107Combined sources10
Turni112 – 115Combined sources4
Beta strandi120 – 126Combined sources7
Beta strandi151 – 160Combined sources10
Beta strandi162 – 164Combined sources3
Beta strandi171 – 178Combined sources8
Beta strandi186 – 190Combined sources5
Beta strandi192 – 195Combined sources4
Beta strandi206 – 209Combined sources4
Beta strandi212 – 219Combined sources8
Beta strandi221 – 223Combined sources3
Beta strandi227 – 229Combined sources3
Beta strandi231 – 235Combined sources5
Helixi236 – 239Combined sources4
Helixi240 – 247Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FUJX-ray2.20A/B/C/D28-248[»]
ProteinModelPortaliP24158.
SMRiP24158.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24158.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 248Peptidase S1PROSITE-ProRule annotationAdd BLAST221

Sequence similaritiesi

Belongs to the peptidase S1 family. Elastase subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00910000144219.
HOVERGENiHBG013304.
InParanoidiP24158.
KOiK01350.
OMAiPGSHFCG.
OrthoDBiEOG091G0DF7.
PhylomeDBiP24158.
TreeFamiTF335284.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiView protein in InterPro
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
PfamiView protein in Pfam
PF00089. Trypsin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiView protein in SMART
SM00020. Tryp_SPc. 1 hit.
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiView protein in PROSITE
PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P24158-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHRPPSPAL ASVLLALLLS GAARAAEIVG GHEAQPHSRP YMASLQMRGN
60 70 80 90 100
PGSHFCGGTL IHPSFVLTAA HCLRDIPQRL VNVVLGAHNV RTQEPTQQHF
110 120 130 140 150
SVAQVFLNNY DAENKLNDVL LIQLSSPANL SASVATVQLP QQDQPVPHGT
160 170 180 190 200
QCLAMGWGRV GAHDPPAQVL QELNVTVVTF FCRPHNICTF VPRRKAGICF
210 220 230 240 250
GDSGGPLICD GIIQGIDSFV IWGCATRLFP DFFTRVALYV DWIRSTLRRV

EAKGRP
Length:256
Mass (Da):27,807
Last modified:December 15, 1998 - v3
Checksum:iCBECA36D8C4B2A40
GO

Sequence cautioni

The sequence AAA36342 differs from that shown. Reason: Frameshift at positions 34 and 39.Curated
The sequence CAA39598 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2A → R in CAA39203 (PubMed:2258701).Curated1
Sequence conflicti38S → I AA sequence (PubMed:1688612).Curated1
Sequence conflicti40P → PI AA sequence (PubMed:1688612).Curated1
Sequence conflicti46Q → E AA sequence (PubMed:2404977).Curated1
Sequence conflicti46Q → E AA sequence (PubMed:2501794).Curated1
Sequence conflicti48R → A AA sequence (PubMed:2121162).Curated1
Sequence conflicti64S → D AA sequence (PubMed:2033050).Curated1
Sequence conflicti70A → P in AAA59558 (PubMed:1681549).Curated1
Sequence conflicti255Missing in CAA39203 (PubMed:2258701).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011691119V → I7 PublicationsCorresponds to variant dbSNP:rs351111Ensembl.1
Natural variantiVAR_011713135A → T4 PublicationsCorresponds to variant dbSNP:rs1042281Ensembl.1
Natural variantiVAR_011714136T → S4 PublicationsCorresponds to variant dbSNP:rs1042282Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AH005293 Genomic DNA. Translation: AAB59493.1.
M97911 Genomic DNA. No translation available.
AH007523 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.
CCDSiCCDS32860.1.
PIRiA45080. PRHU3.
RefSeqiNP_002768.3. NM_002777.3.
UniGeneiHs.928.

Genome annotation databases

EnsembliENST00000234347; ENSP00000234347; ENSG00000196415.
ENST00000612112; ENSP00000478977; ENSG00000277804.
GeneIDi5657.
KEGGihsa:5657.
UCSCiuc002lqa.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPRTN3_HUMAN
AccessioniPrimary (citable) accession number: P24158
Secondary accession number(s): P15637
, P18078, Q4VB08, Q4VB09, Q6LBM7, Q6LBN2, Q9UD25, Q9UQD8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: December 15, 1998
Last modified: March 28, 2018
This is version 195 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome