SIDE_LEGPH
ID SIDE_LEGPH Reviewed; 1495 AA.
AC Q5ZYX7;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 2.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Ubiquitinating enzyme SidE;
DE Includes:
DE RecName: Full=Deubiquitinase {ECO:0000250|UniProtKB:Q5ZTK4};
DE Short=DUB {ECO:0000250|UniProtKB:Q5ZTK4};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q5ZTK4};
DE AltName: Full=Deubiquitinating enzyme {ECO:0000250|UniProtKB:Q5ZTK4};
DE Includes:
DE RecName: Full=Ubiquitin transferase;
DE EC=2.3.2.- {ECO:0000305|PubMed:27049943};
DE Includes:
DE RecName: Full=Mono-ADP-ribosyltransferase {ECO:0000305|PubMed:27049943};
DE Short=mART;
DE EC=2.4.2.31 {ECO:0000305|PubMed:27049943};
GN Name=sidE; OrderedLocusNames=lpg0234;
OS Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC
OS 33152 / DSM 7513).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales;
OC Legionellaceae; Legionella.
OX NCBI_TaxID=272624;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Philadelphia 1 / ATCC 33152 / DSM 7513;
RX PubMed=15448271; DOI=10.1126/science.1099776;
RA Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S.M., Asamani G.,
RA Hill K., Nuara J., Feder M., Rineer J., Greenberg J.J., Steshenko V.,
RA Park S.H., Zhao B., Teplitskaya E., Edwards J.R., Pampou S., Georghiou A.,
RA Chou I.-C., Iannuccilli W., Ulz M.E., Kim D.H., Geringer-Sameth A.,
RA Goldsberry C., Morozov P., Fischer S.G., Segal G., Qu X., Rzhetsky A.,
RA Zhang P., Cayanis E., De Jong P.J., Ju J., Kalachikov S., Shuman H.A.,
RA Russo J.J.;
RT "The genomic sequence of the accidental pathogen Legionella pneumophila.";
RL Science 305:1966-1968(2004).
RN [2]
RP FUNCTION.
RX PubMed=27912065; DOI=10.1016/j.cell.2016.11.019;
RA Bhogaraju S., Kalayil S., Liu Y., Bonn F., Colby T., Matic I., Dikic I.;
RT "Phosphoribosylation of ubiquitin promotes serine ubiquitination and
RT impairs conventional ubiquitination.";
RL Cell 167:1636-1649(2016).
RN [3]
RP FUNCTION AS AN UBIQUITINATING ENZYME, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, AND DOMAIN.
RC STRAIN=Philadelphia 1 / Lp02;
RX PubMed=27049943; DOI=10.1038/nature17657;
RA Qiu J., Sheedlo M.J., Yu K., Tan Y., Nakayasu E.S., Das C., Liu X.,
RA Luo Z.Q.;
RT "Ubiquitination independent of E1 and E2 enzymes by bacterial effectors.";
RL Nature 533:120-124(2016).
RN [4]
RP FUNCTION, AND SUBUNIT.
RX PubMed=29731171; DOI=10.1016/j.cell.2018.04.023;
RA Wang Y., Shi M., Feng H., Zhu Y., Liu S., Gao A., Gao P.;
RT "Structural Insights into non-canonical ubiquitination catalyzed by SidE.";
RL Cell 173:1231-1243.E16(2018).
CC -!- FUNCTION: Effector that interferes with the host cell ubiquitin pathway
CC and is required for intracellular bacterial replication. Catalyzes the
CC ubiquitination of several host Rab small GTPases associated with the
CC endoplasmic reticulum during L.pneumophila infection, without engaging
CC the standard cellular enzyme cascade (E1 and E2) (PubMed:27049943).
CC Transfers an ADP-ribose moiety from NAD to the 'Arg-42' residue of
CC ubiquitin in a reaction that releases nicotinamide (PubMed:27049943,
CC PubMed:29731171). The modified ubiquitin is subsequently transferred to
CC serine residues of the substrate protein via a phosphoribose linker
CC that results in the release of AMP (PubMed:27912065).
CC {ECO:0000269|PubMed:27049943, ECO:0000269|PubMed:27912065,
CC ECO:0000269|PubMed:29731171}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-
CC ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149,
CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:142554; EC=2.4.2.31;
CC Evidence={ECO:0000269|PubMed:27049943};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:29731171}.
CC -!- PTM: Glutamylated by SidJ; glutamylation inhibits sidE activity to
CC catalyze the production of ADP-ribosylated ubiquitin.
CC {ECO:0000250|UniProtKB:Q5ZTK4}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking all four members of the SidE family
CC (SdeA, SdeB, SdeC and SidE) show no intracellular growth defect in
CC mouse bone marrow macrophages (BMM), but display attenuated growth
CC inside the protozoan hosts A.castellanii and D.discoideum. This mutant
CC no longer recruits the endoplasmic reticulum (ER) marker GFP-HDEL to
CC its vacuoles, even at 10 hours post infection, and is unable to induce
CC RAB33B ubiquitination during infection. {ECO:0000269|PubMed:27049943}.
CC -!- SIMILARITY: Belongs to the SidE family. {ECO:0000305|PubMed:27049943}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAU26341.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305|PubMed:29731171};
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DR EMBL; AE017354; AAU26341.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_015444908.1; NC_002942.5.
DR RefSeq; YP_094288.1; NC_002942.5.
DR AlphaFoldDB; Q5ZYX7; -.
DR SMR; Q5ZYX7; -.
DR STRING; 272624.lpg0234; -.
DR PaxDb; Q5ZYX7; -.
DR EnsemblBacteria; AAU26341; AAU26341; lpg0234.
DR GeneID; 66489436; -.
DR KEGG; lpn:lpg0234; -.
DR PATRIC; fig|272624.6.peg.248; -.
DR eggNOG; COG1196; Bacteria.
DR HOGENOM; CLU_002024_0_0_6; -.
DR Proteomes; UP000000609; Chromosome.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR InterPro; IPR043934; SidE_DUB.
DR InterPro; IPR043935; SidE_mART.
DR InterPro; IPR021014; SidE_PDE.
DR Pfam; PF19049; SidE_DUB; 1.
DR Pfam; PF19048; SidE_mART; 1.
DR Pfam; PF12252; SidE_PDE; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Hydrolase; Isopeptide bond; Multifunctional enzyme;
KW NAD; Nucleotide-binding; Nucleotidyltransferase; Protease;
KW Reference proteome; Thiol protease; Transferase; Ubl conjugation pathway;
KW Virulence.
FT CHAIN 1..1495
FT /note="Ubiquitinating enzyme SidE"
FT /id="PRO_0000448402"
FT REGION 1..192
FT /note="Deubiquitinase"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
FT REGION 476..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION ?755..?995
FT /note="Mono-ADP-ribosyltransferase"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
FT ACT_SITE 64
FT /note="For deubiquitinase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
FT ACT_SITE 80
FT /note="For deubiquitinase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
FT ACT_SITE 117
FT /note="Nucleophile; for deubiquitinase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
FT BINDING 761..767
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21454,
FT ECO:0000250|UniProtKB:Q5ZTK4"
FT BINDING 857
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P21454,
FT ECO:0000250|UniProtKB:Q5ZTK4"
FT MOD_RES 855
FT /note="5-glutamyl glutamate"
FT /evidence="ECO:0000250|UniProtKB:Q5ZTK4"
SQ SEQUENCE 1495 AA; 169413 MW; 9C0844457989CA71 CRC64;
MPKYVEGIEL TQEGMHAIFE RMGHPNITSG TIYNGEPTID KGALDRQGFM PVLTGVSPRQ
DSGHWIMLIK GQGNQYFLFD PLGESSGKYY QNILAKKLPG ATLSVIPNNA GLNMGLCGYW
VASVGLRAHA ALTQPIPPSL RNLGQTITQE MRDELTQDGS EKITQWLRAV GNEFPDGDIQ
PDATALRRAT EKNVRIDEFQ PVLTGTSPKE ISINPTAPQE VSVPTWNGFS LYTDETVRNA
ARYAYDNYLG KPYTGTVEAT PVNFGGQMVY RQHHGLAHTL RTMAYAEIIV EEARKAKLRG
ESLKTFADGR TLADVTPEEL RKIMIAQAFF VTGRDDEESS KNYEKYHEQS RDAFLKYVEE
NKSTLIPDVF KDEKDVKFYA DVIEDKDHKW ADSPAHVLVN QGHMVDLVRV KQPPESYLEY
YFSQLQPWIG STATEAVFAT QRQFFHATYE AVAGFDSENK EPHLVVDGLG RYVIGQDGNP
IREESDDEDE EESGELKFFS QKKKLEENQR YMRVDEYLKL DEVQKRFPGA GKKLDGGLPG
LKEYQYLQRL NSINRARCEN DVDFCLGQLQ TAHHQTKITP IKRAFQSSSE KARRQPNMDE
IAAARIVQQI MANPDCIHDD HVFLNGQKLE EKFFRDLLAK CDMAIVGSLL NDTDIRNIDT
LMQHERNTEF HSTDAKAKPV KLGETWEKTI RSGGGVTQIK HDLIFLMQND AWYHTRVNAI
AQNRDKDSTF KEVLITALMT PLTNKSLMDT SRSPAPKTLF RGLDLSEEFK NKLINQAETI
IANTTEHLFT DLSTEAFKQI KLNDFSQVSA RTCASTSTNI EVPRTIFGSN TIFEILDPDG
LLHPKQVGTH VSGSESEYSI YLPEDVALVP IKVSFDGKTG KGKDRHIFTL VAVKSPDFTP
RHESGYAVGP LLKMQTPKLE EIQRLVEQAR EEPDLERVFN LQSRVARQAK FSTESGYKTF
LNEKVAPVLE QSLNGLLDNN VTILGKVLSA FPSDGQWSAF NSVEARQMKI QMDAIKQMVE
KKAVLEGQIL PALAQCQNAL EKQNIAGALQ ALRNIPSEKE MQTMLSISGG LRGQIQRAKQ
DLTETLEPLQ RAITAKLVSD QEKVKVRYEK LIAGIPQQIA DLEKAELADL AKVKKVVSRF
NHLQEELKLL RNEKIRMHTG SEKVDFSDIA QLEAQLQKIH TKLYDAYLVE LTKEISALVK
EKPKNLADVK RMVSNFYAMS ADIEQLRQEK IKEHGESKDP IDMSDIDKLK EELQKINQFL
VKAMGTNIRV SLNQMEVKTF DAQEKEAQQN LKQLDALINK LESSDAVQKQ KEELEKLNQL
LVEKRKAYPA MVQLQFRSEA LIIHLRELCE AHQAQMAKTR NVRAQEITNG RWKVQWLTDW
VGLTTDERVT LANKEKELAK FKEDLNNDEY DLQELISNLA EKNPSELEEA IGISKESAQK
LHKLLTHLNH STTFMSKIEQ RLQSIDELLN EFGKQAPRTE MIKTVEEKQG TLLRL
