CIF_PHOLL
ID CIF_PHOLL Reviewed; 313 AA.
AC Q7N439;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Protein-glutamine deamidase Cif;
DE EC=3.5.1.44 {ECO:0000250|UniProtKB:Q63KH5};
DE AltName: Full=Cycle-inhibiting factor homolog {ECO:0000303|PubMed:19308257};
DE Short=CHPL {ECO:0000303|PubMed:19225106};
GN Name=cif {ECO:0000303|PubMed:19308257};
GN OrderedLocusNames=plu2515 {ECO:0000312|EMBL:CAE14889.1};
OS Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 /
OS TT01).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Morganellaceae; Photorhabdus.
OX NCBI_TaxID=243265;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 15139 / CIP 105565 / TT01 {ECO:0000312|Proteomes:UP000002514};
RX PubMed=14528314; DOI=10.1038/nbt886;
RA Duchaud E., Rusniok C., Frangeul L., Buchrieser C., Givaudan A.,
RA Taourit S., Bocs S., Boursaux-Eude C., Chandler M., Charles J.-F.,
RA Dassa E., Derose R., Derzelle S., Freyssinet G., Gaudriault S., Medigue C.,
RA Lanois A., Powell K., Siguier P., Vincent R., Wingate V., Zouine M.,
RA Glaser P., Boemare N., Danchin A., Kunst F.;
RT "The genome sequence of the entomopathogenic bacterium Photorhabdus
RT luminescens.";
RL Nat. Biotechnol. 21:1307-1313(2003).
RN [2]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-128.
RX PubMed=19308257; DOI=10.1371/journal.pone.0004855;
RA Jubelin G., Chavez C.V., Taieb F., Banfield M.J., Samba-Louaka A., Nobe R.,
RA Nougayrede J.P., Zumbihl R., Givaudan A., Escoubas J.M., Oswald E.;
RT "Cycle inhibiting factors (CIFs) are a growing family of functional
RT cyclomodulins present in invertebrate and mammal bacterial pathogens.";
RL PLoS ONE 4:e4855-e4855(2009).
RN [3]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-128.
RX PubMed=19225106; DOI=10.1073/pnas.0900212106;
RA Yao Q., Cui J., Zhu Y., Wang G., Hu L., Long C., Cao R., Liu X., Huang N.,
RA Chen S., Liu L., Shao F.;
RT "A bacterial type III effector family uses the papain-like hydrolytic
RT activity to arrest the host cell cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3716-3721(2009).
RN [4]
RP FUNCTION.
RX PubMed=20870031; DOI=10.1016/j.micinf.2010.09.006;
RA Chavez C.V., Jubelin G., Courties G., Gomard A., Ginibre N., Pages S.,
RA Taieb F., Girard P.A., Oswald E., Givaudan A., Zumbihl R., Escoubas J.M.;
RT "The cyclomodulin Cif of Photorhabdus luminescens inhibits insect cell
RT proliferation and triggers host cell death by apoptosis.";
RL Microbes Infect. 12:1208-1218(2010).
RN [5] {ECO:0007744|PDB:3GQJ}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 53-313, AND ACTIVE SITE.
RX PubMed=19440549; DOI=10.1371/journal.pone.0005582;
RA Crow A., Race P.R., Jubelin G., Varela Chavez C., Escoubas J.M., Oswald E.,
RA Banfield M.J.;
RT "Crystal structures of Cif from bacterial pathogens Photorhabdus
RT luminescens and Burkholderia pseudomallei.";
RL PLoS ONE 4:e5582-e5582(2009).
RN [6] {ECO:0007744|PDB:4FBJ}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 53-313 IN COMPLEX WITH HOST
RP NEDD8.
RX PubMed=22691497; DOI=10.1073/pnas.1112107109;
RA Crow A., Hughes R.K., Taieb F., Oswald E., Banfield M.J.;
RT "The molecular basis of ubiquitin-like protein NEDD8 deamidation by the
RT bacterial effector protein Cif.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E1830-E1838(2012).
CC -!- FUNCTION: Protein-glutamine deamidase effector that inhibits the host
CC cell cycle and other key cellular processes such as the actin network
CC and programmed-cell death (PubMed:19308257, PubMed:19225106,
CC PubMed:20870031). Acts by mediating the side chain deamidation of 'Gln-
CC 40' of host NEDD8, converting it to glutamate, thereby abolishing the
CC activity of cullin-RING-based E3 ubiquitin-protein ligase complexes
CC (CRL complexes) (By similarity). Inactivation of CRL complexes prevents
CC ubiquitination and subsequent degradation of the cyclin-dependent
CC kinase inhibitors CDKN1A/p21 and CDKN1B/p27, leading to G1 and G2 cell
CC cycle arrests in host cells (PubMed:19308257). Deamidation of 'Gln-40'
CC of host NEDD8 also triggers macrophage-specific programmed cell death
CC (By similarity). Also able to catalyze deamidation of 'Gln-40' of host
CC ubiquitin in vitro; however, NEDD8 constitutes the preferred substrate
CC in vivo (By similarity). {ECO:0000250|UniProtKB:Q63KH5,
CC ECO:0000269|PubMed:19225106, ECO:0000269|PubMed:19308257,
CC ECO:0000269|PubMed:20870031}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutaminyl-[protein] = L-glutamyl-[protein] + NH4(+);
CC Xref=Rhea:RHEA:16441, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:10208,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29973,
CC ChEBI:CHEBI:30011; EC=3.5.1.44;
CC Evidence={ECO:0000250|UniProtKB:Q63KH5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442;
CC Evidence={ECO:0000250|UniProtKB:Q63KH5};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0DUW5}. Host
CC nucleus {ECO:0000250|UniProtKB:P0DUW5}. Note=Secreted via the type III
CC secretion system (TTSS). {ECO:0000250|UniProtKB:P0DUW5}.
CC -!- SIMILARITY: Belongs to the Cif family. {ECO:0000305}.
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DR EMBL; BX571867; CAE14889.1; -; Genomic_DNA.
DR PDB; 3GQJ; X-ray; 1.85 A; A=53-313.
DR PDB; 4FBJ; X-ray; 1.60 A; A=53-313.
DR PDBsum; 3GQJ; -.
DR PDBsum; 4FBJ; -.
DR SMR; Q7N439; -.
DR STRING; 243265.plu2515; -.
DR EnsemblBacteria; CAE14889; CAE14889; plu2515.
DR KEGG; plu:plu2515; -.
DR eggNOG; ENOG5032RCC; Bacteria.
DR HOGENOM; CLU_077138_0_0_6; -.
DR OMA; RFEDWMT; -.
DR OrthoDB; 1404593at2; -.
DR BioCyc; PLUM243265:PLU_RS12475-MON; -.
DR EvolutionaryTrace; Q7N439; -.
DR Proteomes; UP000002514; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0044071; P:modulation by symbiont of host cell cycle; IDA:UniProtKB.
DR InterPro; IPR032278; Cif.
DR Pfam; PF16374; CIF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host nucleus; Hydrolase; Reference proteome; Secreted; Toxin;
KW Virulence.
FT CHAIN 1..313
FT /note="Protein-glutamine deamidase Cif"
FT /id="PRO_0000453903"
FT ACT_SITE 128
FT /evidence="ECO:0000305|PubMed:19225106,
FT ECO:0000305|PubMed:19308257, ECO:0000305|PubMed:19440549"
FT ACT_SITE 186
FT /evidence="ECO:0000305|PubMed:19440549"
FT ACT_SITE 205
FT /evidence="ECO:0000305|PubMed:19440549"
FT MUTAGEN 128
FT /note="C->S: Abolished ability to inhibit the host cell
FT cycle. Abolished accumulation of the cyclin-dependent
FT kinase inhibitors CDKN1A/p21 and CDKN1B/p27."
FT /evidence="ECO:0000269|PubMed:19225106,
FT ECO:0000269|PubMed:19308257"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 72..78
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 128..140
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 148..154
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 174..181
FT /evidence="ECO:0007829|PDB:4FBJ"
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 218..223
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 241..245
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 248..259
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:4FBJ"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:4FBJ"
FT HELIX 288..303
FT /evidence="ECO:0007829|PDB:4FBJ"
SQ SEQUENCE 313 AA; 35319 MW; 8B37A7EE2173FC95 CRC64;
MGDDIMPISN LAKESEVRAV KDIPCKNIET DNHLEIGLSS GLSRSKDTSK FKKNSINTIK
LIDDIIALHN DPKGNKLLWN DNWQDKIINR DLANIFEKID ESVSELGGLE MYQEMVGVNP
YDPTEPVCGL SAQNIFKLMT EGEHAVDPVE MAQTGKIDGN EFAESVDQLS SAKNYVALVN
DRRLGHMFLI DIPSNDQETV GYIYQSDLGQ GALPPLKIAD WLNSRGKDAV SLNKLKKLLS
REFNLLSDDE KRALISETLD IHKDVSNVEL DRIKRDRGVD IYLTEYDVNN FYENIETLKS
KLSNYDKKLS KPK
