MEP72_PSEAE
ID MEP72_PSEAE Reviewed; 599 AA.
AC Q9I060;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Peptidyl-Asp metalloendopeptidase {ECO:0000305};
DE EC=3.4.24.33 {ECO:0000250|UniProtKB:Q9R4J4};
DE AltName: Full=Biofilm-associated metzincin protease {ECO:0000303|PubMed:25488299};
DE AltName: Full=Metalloendopeptidase Mep72 {ECO:0000303|PubMed:24279383};
DE Flags: Precursor;
GN Name=mep72 {ECO:0000303|PubMed:24279383};
GN OrderedLocusNames=PA2783 {ECO:0000312|EMBL:AAG06171.1};
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, COFACTOR, INDUCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=24279383; DOI=10.1186/1471-2180-13-269;
RA Balyimez A., Colmer-Hamood J.A., San Francisco M., Hamood A.N.;
RT "Characterization of the Pseudomonas aeruginosa metalloendopeptidase,
RT Mep72, a member of the Vfr regulon.";
RL BMC Microbiol. 13:269-269(2013).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, DOMAIN, IDENTIFICATION BY MASS
RP SPECTROMETRY, PROCESSING, INTERACTION WITH BAMI, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=25488299; DOI=10.1128/jb.02404-14;
RA Passmore I.J., Nishikawa K., Lilley K.S., Bowden S.D., Chung J.C.,
RA Welch M.;
RT "Mep72, a metzincin protease that is preferentially secreted by biofilms of
RT Pseudomonas aeruginosa.";
RL J. Bacteriol. 197:762-773(2015).
CC -!- FUNCTION: Metalloprotease with endopeptidase activity
CC (PubMed:24279383). Specifically cleaves on the N-terminal side of
CC aspartyl, glutamyl and cysteic acid residues (By similarity). Mep72
CC appears to be a secreted biofilm-specific regulator that affects the
CC processing of a very specific subset of virulence factors exported by
CC the type III secretion machinery as well as flagellar proteins. Binds
CC directly to ExoS and PcrV and affects the processing of these proteins
CC in the biofilm secretome, but contrary to expectation, Mep72 seems to
CC protect these targets against proteolytic processing/degradation
CC (PubMed:25488299). {ECO:0000250|UniProtKB:Q9R4J4,
CC ECO:0000269|PubMed:24279383, ECO:0000269|PubMed:25488299}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of Xaa-|-Asp, Xaa-|-Glu and Xaa-|-cysteic acid
CC bonds.; EC=3.4.24.33; Evidence={ECO:0000250|UniProtKB:Q9R4J4};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:24279383};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000305|PubMed:24279383};
CC -!- ACTIVITY REGULATION: Is inhibited by BamI, the product of its
CC coregulated adjacent gene. {ECO:0000269|PubMed:25488299}.
CC -!- SUBUNIT: Interacts with BamI, the product of its coregulated adjacent
CC gene, which inhibits its protease activity.
CC {ECO:0000269|PubMed:25488299}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24279383,
CC ECO:0000269|PubMed:25488299}. Note=Is secreted through the type II
CC general secretory pathway (Xcp system) and undergoes processing during
CC export. {ECO:0000269|PubMed:25488299}.
CC -!- INDUCTION: Its transcription is positively regulated by Vfr, the
CC virulence factor regulator, in a cAMP-dependent manner
CC (PubMed:24279383). Constitutes an operon together with PA2782
CC (PubMed:24279383, PubMed:25488299). Is expressed only during biofilm
CC growth (PubMed:25488299). {ECO:0000269|PubMed:24279383,
CC ECO:0000269|PubMed:25488299}.
CC -!- DOMAIN: Has a tridomain structure comprised of an N-terminal metzincin
CC protease-like domain and two tandem C-terminal carbohydrate-binding
CC domains. {ECO:0000269|PubMed:24279383, ECO:0000269|PubMed:25488299}.
CC -!- PTM: Made as a membrane-associated pre-pro-protein, which is exported
CC to the periplasm with removal of the signal peptide, leading to a
CC protein with a molecular mass of 65 kDa, that likely contains the
CC metzincin domain plus tandem carbohydrate-binding domains. Undergoes
CC processing during export to the extracellular milieu, probably by
CC autocatalysis, yielding a (mature length) 25 kDa protein that most
CC likely corresponds to the metzincin domain only.
CC {ECO:0000269|PubMed:25488299}.
CC -!- SIMILARITY: Belongs to the peptidase M72 family. {ECO:0000305}.
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DR EMBL; AE004091; AAG06171.1; -; Genomic_DNA.
DR PIR; G83296; G83296.
DR RefSeq; NP_251473.1; NC_002516.2.
DR RefSeq; WP_003114786.1; NZ_QZGE01000011.1.
DR AlphaFoldDB; Q9I060; -.
DR SMR; Q9I060; -.
DR STRING; 287.DR97_5164; -.
DR CAZy; CBM22; Carbohydrate-Binding Module Family 22.
DR MEROPS; M72.001; -.
DR PaxDb; Q9I060; -.
DR PRIDE; Q9I060; -.
DR EnsemblBacteria; AAG06171; AAG06171; PA2783.
DR GeneID; 878794; -.
DR KEGG; pae:PA2783; -.
DR PATRIC; fig|208964.12.peg.2922; -.
DR PseudoCAP; PA2783; -.
DR HOGENOM; CLU_451179_0_0_6; -.
DR OMA; VDIMVLY; -.
DR BioCyc; PAER208964:G1FZ6-2831-MON; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0009279; C:cell outer membrane; IDA:PseudoCAP.
DR GO; GO:0005615; C:extracellular space; IDA:PseudoCAP.
DR GO; GO:0019867; C:outer membrane; IDA:PseudoCAP.
DR GO; GO:0004175; F:endopeptidase activity; IDA:PseudoCAP.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0097264; P:self proteolysis; IDA:PseudoCAP.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR003305; CenC_carb-bd.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR Pfam; PF02018; CBM_4_9; 1.
DR SUPFAM; SSF49785; SSF49785; 2.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..?
FT /note="Peptidyl-Asp metalloendopeptidase"
FT /id="PRO_5004326926"
FT PROPEP ?..599
FT /evidence="ECO:0000305|PubMed:25488299"
FT /id="PRO_0000452832"
FT DOMAIN 458..583
FT /note="CBM-cenC"
FT /evidence="ECO:0000255"
FT REGION 265..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 165
FT /evidence="ECO:0000305|PubMed:24279383"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24279383"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24279383"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24279383"
SQ SEQUENCE 599 AA; 64960 MW; D90F21AF743D3B94 CRC64;
MKKSLLCSTL ALAVASAAQA APKTVDIMVL YTPAATQTAN GRDIDARIAS YIEFANTAYE
KSGVNLRLRL VHKQRLDWAD YPTVTGANLD RFMRDPQVQR LREQYGADLV SLVNRSQNSG
NGYITCGIGY MGSGDKNSGR FHGNAKDIAY NLTGVDCGLN TFAHEAGHNM GLRHSYEQDL
ESSYYDPRYA HSGTYEWSRG YGVQGRFATV MAYPHAFGTN KQAPFFANPR LVNAECANQP
CGREEHADAV RALNSMATQI ADFRPTKVPG TVNPGSGGDT PTPPDLPWCT KAKLGGLLGD
GEFASMEGWR AWSGNAQLSL VNVAKGCRDN ALLVDVRGFD LLVRPIAPLR AGSGYRLSGK
VMLKAANTRE TVRMALLSER ADGALAYNPA QSVELSVSGN EFSRLEKTFD YRPAADQRNL
YVAVWSDSGA SLLVDEMNLQ EAQAAPPSVP PAPKRIAYDF ESGIGGWSGV HASARATRVA
SAGRLALEAY QRRYAGTGAS TSLLGNLEAG RTYAFSADVR VGDGRGSQAM TYAYLYLESQ
GRPGEYLPLG YKVVENGRWA SLRGQVQLPK GPIKRAELMI LSGNQQESMF IDNVQLLQK
