CIF_YERPY
ID CIF_YERPY Reviewed; 290 AA.
AC A0A0H3B1Q8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Protein-glutamine deamidase Cif;
DE EC=3.5.1.44 {ECO:0000269|PubMed:22691497};
DE AltName: Full=Cycle-inhibiting factor homolog {ECO:0000303|PubMed:19308257};
DE Short=CHYP {ECO:0000303|PubMed:19225106};
GN Name=cif {ECO:0000303|PubMed:19308257};
GN OrderedLocusNames=YPK_1971 {ECO:0000312|EMBL:ACA68260.1};
OS Yersinia pseudotuberculosis serotype O:3 (strain YPIII).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Yersiniaceae; Yersinia.
OX NCBI_TaxID=502800;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=YPIII;
RG US DOE Joint Genome Institute;
RA Copeland A., Lucas S., Lapidus A., Glavina del Rio T., Dalin E., Tice H.,
RA Bruce D., Goodwin L., Pitluck S., Munk A.C., Brettin T., Detter J.C.,
RA Han C., Tapia R., Schmutz J., Larimer F., Land M., Hauser L.,
RA Challacombe J.F., Green L., Lindler L.E., Nikolich M.P., Richardson P.;
RT "Complete sequence of Yersinia pseudotuberculosis YPIII.";
RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-117.
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 IDENTIFICATION.
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] {ECO:0007744|PDB:4F8C}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 33-288 IN COMPLEX WITH HOST
RP NEDD8, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF
RP ASP-66; VAL-104; LEU-106; VAL-116; CYS-117; GLY-118 AND ASP-195.
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:22691497). Acts by
CC mediating the side chain deamidation of 'Gln-40' of host NEDD8,
CC converting it to glutamate, thereby abolishing the activity of cullin-
CC RING-based E3 ubiquitin-protein ligase complexes (CRL complexes)
CC (PubMed:22691497). 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). Also able to catalyze
CC deamidation of 'Gln-40' of host ubiquitin in vitro; however, NEDD8
CC constitutes the preferred substrate in vivo (By similarity).
CC {ECO:0000250|UniProtKB:Q63KH5, ECO:0000269|PubMed:19308257,
CC ECO:0000269|PubMed:22691497}.
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:0000269|PubMed:22691497};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442;
CC Evidence={ECO:0000269|PubMed:22691497};
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP000950; ACA68260.1; -; Genomic_DNA.
DR RefSeq; WP_012304060.1; NZ_CP009792.1.
DR PDB; 4F8C; X-ray; 1.95 A; A/C=33-288.
DR PDBsum; 4F8C; -.
DR SMR; A0A0H3B1Q8; -.
DR EnsemblBacteria; ACA68260; ACA68260; YPK_1971.
DR KEGG; ypy:YPK_1971; -.
DR PATRIC; fig|502800.11.peg.2643; -.
DR OMA; RFEDWMT; -.
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; Secreted; Toxin; Virulence.
FT CHAIN 1..290
FT /note="Protein-glutamine deamidase Cif"
FT /id="PRO_0000453904"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 117
FT /evidence="ECO:0000305|PubMed:19308257,
FT ECO:0000305|PubMed:22691497"
FT ACT_SITE 173
FT /evidence="ECO:0000250|UniProtKB:Q63KH5"
FT ACT_SITE 193
FT /evidence="ECO:0000250|UniProtKB:Q63KH5"
FT MUTAGEN 66
FT /note="D->R: Slightly decreased interaction with host
FT NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT MUTAGEN 104
FT /note="V->A: Does not affect interaction with host NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT MUTAGEN 106
FT /note="L->E: Decreased interaction with host NEDD8, leading
FT to reduced ability to mediate deamidation of host NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT MUTAGEN 116
FT /note="V->D: Decreased interaction with host NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT MUTAGEN 117
FT /note="C->A,S: Impaired ability to mediate deamidation of
FT host NEDD8, leading to decreased ability to inhibit the
FT host cell cycle. Abolished accumulation of the cyclin-
FT dependent kinase inhibitors CDKN1A/p21 and CDKN1B/p27."
FT /evidence="ECO:0000269|PubMed:19308257,
FT ECO:0000269|PubMed:22691497"
FT MUTAGEN 118
FT /note="G->T: Decreased interaction with host NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT MUTAGEN 195
FT /note="D->N: Does not strongly affect ability to mediate
FT deamidation of host NEDD8."
FT /evidence="ECO:0000269|PubMed:22691497"
FT HELIX 41..53
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 57..63
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 77..95
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 99..106
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 117..129
FT /evidence="ECO:0007829|PDB:4F8C"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 146..154
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 160..168
FT /evidence="ECO:0007829|PDB:4F8C"
FT TURN 169..172
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 173..179
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 206..212
FT /evidence="ECO:0007829|PDB:4F8C"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:4F8C"
FT STRAND 266..273
FT /evidence="ECO:0007829|PDB:4F8C"
FT HELIX 275..285
FT /evidence="ECO:0007829|PDB:4F8C"
SQ SEQUENCE 290 AA; 32280 MW; A7B10B3B30B67BBB CRC64;
MKISPNTISP SQSDPRMSTN VSQRSRVSGI GVPVSHSINN PSIQHVQDFA TLSARSLRAN
VLLNSDDHSV PIHAKNPSEL LEAIDNNISQ TAQDWGVSIQ EVEVILGSSK RIIEPVCGVT
ANTIMKLFLD NDIFSYSFEK GQSLSLSQLQ ERLASLPAHK NFILRVNDGG LGHAYVIDFP
ATTNPSRDAF LYQSDLGEGV TREVRFEDWM TQKASHPISL DDINTHFIGI AQDQIDLAHI
AKLFDVDGNV KMLRADHLIS HKTSEFNFQL FEYDLKNLEN NMSIIKTHCN
