YOPJ_YERPU
ID YOPJ_YERPU Reviewed; 288 AA.
AC A0A0N9NCU6;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 30.
DE RecName: Full=Serine/threonine-protein acetyltransferase YopJ {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:16728640};
DE AltName: Full=Virulence factor YopJ {ECO:0000305};
GN Name=yopJ {ECO:0000303|PubMed:10489373};
GN ORFNames=EGX47_00330 {ECO:0000312|EMBL:AYW89929.1},
GN EGX52_00040 {ECO:0000312|EMBL:AYX09385.1};
OS Yersinia pseudotuberculosis.
OG Plasmid pYV2666 {ECO:0000312|EMBL:ALG88417.1}.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Yersiniaceae; Yersinia.
OX NCBI_TaxID=633;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=IP2666; PLASMID=pYV2666;
RA Isberg R.R., Davis K.M., Kumamoto J.J.;
RT "Yersinia pseudotuberculosis virulence plasmid from strain IP2666.";
RL Submitted (JUL-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FDAARGOS_580 {ECO:0000312|Proteomes:UP000277634}, and FDAARGOS_581;
RA Bliska J., Tallon L., Sadzewicz L., Zhao X., Vavikolanu K., Mehta A.,
RA Aluvathingal J., Nadendla S., Yan Y., Sichtig H.;
RT "FDA dAtabase for Regulatory Grade micrObial Sequences (FDA-ARGOS):
RT Supporting development and validation of Infectious Disease Dx tests.";
RL Submitted (NOV-2018) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=10489373; DOI=10.1126/science.285.5435.1920;
RA Orth K., Palmer L.E., Bao Z.Q., Stewart S., Rudolph A.E., Bliska J.B.,
RA Dixon J.E.;
RT "Inhibition of the mitogen-activated protein kinase kinase superfamily by a
RT Yersinia effector.";
RL Science 285:1920-1923(1999).
RN [4]
RP MUTAGENESIS OF HIS-109 AND CYS-172, AND ACTIVE SITES.
RX PubMed=11090361; DOI=10.1126/science.290.5496.1594;
RA Orth K., Xu Z., Mudgett M.B., Bao Z.Q., Palmer L.E., Bliska J.B.,
RA Mangel W.F., Staskawicz B., Dixon J.E.;
RT "Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like
RT protein protease.";
RL Science 290:1594-1597(2000).
RN [5]
RP REVIEW.
RX PubMed=11834367; DOI=10.1016/s1369-5274(02)00283-7;
RA Orth K.;
RT "Function of the Yersinia effector YopJ.";
RL Curr. Opin. Microbiol. 5:38-43(2002).
RN [6]
RP FUNCTION.
RX PubMed=12433923; DOI=10.1074/jbc.m209905200;
RA Yoon S., Liu Z., Eyobo Y., Orth K.;
RT "Yersinia effector YopJ inhibits yeast MAPK signaling pathways by an
RT evolutionarily conserved mechanism.";
RL J. Biol. Chem. 278:2131-2135(2003).
RN [7]
RP CAUTION.
RX PubMed=16301742; DOI=10.1084/jem.20051194;
RA Zhou H., Monack D.M., Kayagaki N., Wertz I., Yin J., Wolf B., Dixit V.M.;
RT "Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-
RT kappa B activation.";
RL J. Exp. Med. 202:1327-1332(2005).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVE SITE.
RX PubMed=16728640; DOI=10.1126/science.1126867;
RA Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J.,
RA Orth K.;
RT "Yersinia YopJ acetylates and inhibits kinase activation by blocking
RT phosphorylation.";
RL Science 312:1211-1214(2006).
RN [9]
RP FUNCTION.
RA Orth K.;
RL Unpublished observations (JUL-2006).
RN [10]
RP FUNCTION.
RC STRAIN=IP2666; PLASMID=pYV2666;
RX PubMed=22563435; DOI=10.1371/journal.pone.0036019;
RA Zheng Y., Lilo S., Mena P., Bliska J.B.;
RT "YopJ-induced caspase-1 activation in Yersinia-infected macrophages:
RT independent of apoptosis, linked to necrosis, dispensable for innate host
RT defense.";
RL PLoS ONE 7:e36019-e36019(2012).
RN [11]
RP FUNCTION.
RC STRAIN=32777 / IP2777 / Serotype O1:b;
RX PubMed=26810037; DOI=10.1128/iai.00843-15;
RA Schoberle T.J., Chung L.K., McPhee J.B., Bogin B., Bliska J.B.;
RT "Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in
RT Activated Macrophages and Promoting Yersinia pseudotuberculosis
RT Virulence.";
RL Infect. Immun. 84:1062-1072(2016).
RN [12]
RP FUNCTION.
RC STRAIN=IP2666; PLASMID=pYV2666;
RX PubMed=30381458; DOI=10.1073/pnas.1809548115;
RA Sarhan J., Liu B.C., Muendlein H.I., Li P., Nilson R., Tang A.Y.,
RA Rongvaux A., Bunnell S.C., Shao F., Green D.R., Poltorak A.;
RT "Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during
RT Yersinia infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E10888-E10897(2018).
RN [13]
RP FUNCTION.
RC STRAIN=32777 / IP2777 / Serotype O1:b;
RX PubMed=30361383; DOI=10.1126/science.aau2818;
RA Orning P., Weng D., Starheim K., Ratner D., Best Z., Lee B., Brooks A.,
RA Xia S., Wu H., Kelliher M.A., Berger S.B., Gough P.J., Bertin J.,
RA Proulx M.M., Goguen J.D., Kayagaki N., Fitzgerald K.A., Lien E.;
RT "Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of
RT gasdermin D and cell death.";
RL Science 362:1064-1069(2018).
CC -!- FUNCTION: Serine/threonine-protein acetyltransferase translocated into
CC infected cells, which inhibits the host immune response and induces
CC cell death by mediating acetylation of target proteins
CC (PubMed:10489373, PubMed:12433923, PubMed:16728640, PubMed:22563435,
CC PubMed:26810037). Inhibits the MAPK and NF-kappa-B signaling pathways
CC by acetylating protein-kinases such as MAP2K1, MAP2K6, MAP3K7/TAK1 and
CC I-kappa-B kinase (CHUK/IKKA and IKBKB) on serine and threonine residues
CC critical for their activation by phosphorylation, thereby preventing
CC protein-kinase activation (PubMed:16728640, Ref.9, PubMed:30361383).
CC Promotes pyroptosis, a programmed cell death, in host cells by
CC mediating acetylation of MAP3K7/TAK1: MAP3K7/TAK1 inactivation triggers
CC activation of caspase-8 (CASP8), followed by CASP8-dependent cleavage
CC of gasdermin-D (GSDMD) and induction of pyroptosis (PubMed:30381458,
CC PubMed:30361383). Also able to induce intestinal barrier dysfunction by
CC acetylating and inhibiting host protein-kinases RIPK2/RICK and
CC MAP3K7/TAK1, thereby promoting cell death (By similarity).
CC {ECO:0000250|UniProtKB:P0DUD0, ECO:0000269|PubMed:10489373,
CC ECO:0000269|PubMed:12433923, ECO:0000269|PubMed:16728640,
CC ECO:0000269|PubMed:22563435, ECO:0000269|PubMed:26810037,
CC ECO:0000269|PubMed:30361383, ECO:0000269|PubMed:30381458,
CC ECO:0000269|Ref.9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-threonyl-[protein] = CoA + O-acetyl-L-threonyl-
CC [protein]; Xref=Rhea:RHEA:65340, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:16780, ChEBI:CHEBI:30013, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:141025; Evidence={ECO:0000269|PubMed:16728640};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65341;
CC Evidence={ECO:0000269|PubMed:16728640};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-seryl-[protein] = CoA + O-acetyl-L-seryl-
CC [protein]; Xref=Rhea:RHEA:59392, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:15352, ChEBI:CHEBI:29999, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:141128; Evidence={ECO:0000269|PubMed:16728640};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59393;
CC Evidence={ECO:0000269|PubMed:16728640};
CC -!- COFACTOR:
CC Name=1D-myo-inositol hexakisphosphate; Xref=ChEBI:CHEBI:58130;
CC Evidence={ECO:0000250|UniProtKB:O68718};
CC -!- ACTIVITY REGULATION: 1D-myo-inositol hexakisphosphate activates
CC protein-acetyltransferase activity via an allosteric mechanism: 1D-myo-
CC inositol hexakisphosphate-binding induces a conformational
CC rearrangement that stimulates the interaction with acetyl-CoA.
CC {ECO:0000250|UniProtKB:Q6VE93}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DUD0}.
CC Note=Secreted via type III secretion system (TTSS).
CC {ECO:0000250|UniProtKB:P0DUD0}.
CC -!- SIMILARITY: Belongs to the acetyltransferase YopJ family.
CC {ECO:0000305}.
CC -!- CAUTION: Was initially thought to be a protease involved in
CC deubiquitination because of its similarity with cysteine proteases
CC (PubMed:11090361, PubMed:16301742). However, it was later shown that
CC YopJ is an acetyltransferase that uses a dual substrate mechanism
CC similar to the one used by papain-like proteases (PubMed:16728640).
CC {ECO:0000269|PubMed:11090361, ECO:0000269|PubMed:16301742,
CC ECO:0000269|PubMed:16728640}.
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DR EMBL; KT307967; ALG88417.1; -; Genomic_DNA.
DR EMBL; CP033712; AYW89929.1; -; Genomic_DNA.
DR EMBL; CP033714; AYX09385.1; -; Genomic_DNA.
DR RefSeq; WP_002225474.1; NZ_SDWX01000048.1.
DR AlphaFoldDB; A0A0N9NCU6; -.
DR SMR; A0A0N9NCU6; -.
DR EnsemblBacteria; AYW89929; AYW89929; EGX47_00330.
DR EnsemblBacteria; AYX09385; AYX09385; EGX52_00040.
DR GeneID; 66841083; -.
DR OMA; FAMAEMD; -.
DR OrthoDB; 1119222at2; -.
DR Proteomes; UP000277634; Plasmid unnamed.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016413; F:O-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IEP:CACAO.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:1903753; P:negative regulation of p38MAPK cascade; IEP:CACAO.
DR GO; GO:0030919; P:peptidyl-serine O-acetylation; IDA:UniProtKB.
DR GO; GO:0120258; P:peptidyl-threonine O-acetylation; IDA:UniProtKB.
DR InterPro; IPR005083; Ser/Thr_AcTrfase.
DR Pfam; PF03421; Acetyltransf_14; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Allosteric enzyme; Plasmid; Secreted; Transferase;
KW Virulence.
FT CHAIN 1..288
FT /note="Serine/threonine-protein acetyltransferase YopJ"
FT /id="PRO_0000451624"
FT ACT_SITE 109
FT /evidence="ECO:0000305|PubMed:11090361"
FT ACT_SITE 128
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT ACT_SITE 172
FT /evidence="ECO:0000305|PubMed:11090361,
FT ECO:0000305|PubMed:16728640"
FT BINDING 109
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 167..168
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 182..185
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 224..225
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 227..230
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 257
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT BINDING 266..270
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:Q6VE93"
FT MUTAGEN 109
FT /note="H->A: Abolished ability to inhibit the MAP kinase
FT kinase (MAPKK) pathway and promote virulence."
FT /evidence="ECO:0000269|PubMed:11090361"
FT MUTAGEN 172
FT /note="C->A: Abolished ability to inhibit the MAP kinase
FT kinase (MAPKK) pathway and promote virulence."
FT /evidence="ECO:0000269|PubMed:11090361"
SQ SEQUENCE 288 AA; 32487 MW; 6CEC20F2A61C5010 CRC64;
MIGPISQINI SGGLSEKETS SLISNEELKN IITQLETDIS DGSWFHKNYS RMDVEVMPAL
VIQANNKYPE MNLNLVTSPL DLSIEIKNVI ENGVRSSRFI INMGEGGIHF SVIDYKHING
KTSLILFEPA NFNSMGPAML AIRTKTAIER YQLPDCHFSM VEMDIQRSSS ECGIFSFALA
KKLYIERDSL LKIHEDNIKG ILSDGENPLP HDKLDPYLPV TFYKHTQGKK RLNEYLNTNP
QGVGTVVNKK NETIVNRFDN NKSIVDGKEL SVSVHKKRIA EYKTLLKV
