CCR4_YEAST
ID CCR4_YEAST Reviewed; 837 AA.
AC P31384; D6VPJ7;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=CCR4-Not complex 3'-5'-exoribonuclease subunit Ccr4 {ECO:0000305};
DE EC=3.1.13.4;
DE AltName: Full=Carbon catabolite repressor protein 4;
DE AltName: Full=Cytoplasmic deadenylase;
DE AltName: Full=Glucose-repressible alcohol dehydrogenase transcriptional effector;
GN Name=CCR4; OrderedLocusNames=YAL021C; ORFNames=FUN27;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1459446; DOI=10.1093/genetics/132.4.951;
RA Malvar T., Biron R.W., Kaback D.B., Denis C.L.;
RT "The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich
RT repeat region which is required for its control of ADH2 gene expression.";
RL Genetics 132:951-962(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8458570; DOI=10.1139/g93-005;
RA Ouellette B.F.F., Clark M.W., Keng T., Storms R.K., Zhong W.-W., Zeng B.,
RA Fortin N., Delaney S., Barton A.B., Kaback D.B., Bussey H.;
RT "Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32
RT kb region between the LTE1 and SPO7 genes.";
RL Genome 36:32-42(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8144453; DOI=10.1128/jb.176.7.1872-1880.1994;
RA Barton A.B., Kaback D.B.;
RT "Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae:
RT analysis of the genes in the FUN38-MAK16-SPO7 region.";
RL J. Bacteriol. 176:1872-1880(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7731988; DOI=10.1073/pnas.92.9.3809;
RA Bussey H., Kaback D.B., Zhong W.-W., Vo D.H., Clark M.W., Fortin N.,
RA Hall J., Ouellette B.F.F., Keng T., Barton A.B., Su Y., Davies C.J.,
RA Storms R.K.;
RT "The nucleotide sequence of chromosome I from Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3809-3813(1995).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX, AND FUNCTION OF THE CCR4-NOT
RP CORE COMPLEX IN TRANSCRIPTIONAL REGULATION.
RX PubMed=9463387; DOI=10.1093/emboj/17.4.1096;
RA Liu H.Y., Badarinarayana V., Audino D.C., Rappsilber J., Mann M.,
RA Denis C.L.;
RT "The NOT proteins are part of the CCR4 transcriptional complex and affect
RT gene expression both positively and negatively.";
RL EMBO J. 17:1096-1106(1998).
RN [7]
RP INTERACTION WITH NOT1.
RX PubMed=10490603; DOI=10.1128/mcb.19.10.6642;
RA Bai Y., Salvadore C., Chiang Y.C., Collart M.A., Liu H.Y., Denis C.L.;
RT "The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and
RT functionally separated from NOT2, NOT4, and NOT5.";
RL Mol. Cell. Biol. 19:6642-6651(1999).
RN [8]
RP FUNCTION IN MRNA DEADENYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=11239395; DOI=10.1016/s0092-8674(01)00225-2;
RA Tucker M., Valencia-Sanchez M.A., Staples R.R., Chen J., Denis C.L.,
RA Parker R.;
RT "The transcription factor associated Ccr4 and Caf1 proteins are components
RT of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae.";
RL Cell 104:377-386(2001).
RN [9]
RP IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX.
RX PubMed=11733989; DOI=10.1006/jmbi.2001.5162;
RA Chen J., Rappsilber J., Chiang Y.C., Russell P., Mann M., Denis C.L.;
RT "Purification and characterization of the 1.0 MDa CCR4-NOT complex
RT identifies two novel components of the complex.";
RL J. Mol. Biol. 314:683-694(2001).
RN [10]
RP FUNCTION IN MRNA DEADENYLATION, AND MUTAGENESIS OF GLU-556; ASP-713;
RP ASP-780 AND HIS-818.
RX PubMed=11889047; DOI=10.1093/emboj/21.6.1414;
RA Chen J., Chiang Y.-C., Denis C.L.;
RT "CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic
RT component of the cytoplasmic deadenylase.";
RL EMBO J. 21:1414-1426(2002).
RN [11]
RP FUNCTION IN MRNA DEADENYLATION.
RX PubMed=11889048; DOI=10.1093/emboj/21.6.1427;
RA Tucker M., Staples R.R., Valencia-Sanchez M.A., Muhlrad D., Parker R.;
RT "Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase
RT complex in Saccharomyces cerevisiae.";
RL EMBO J. 21:1427-1436(2002).
RN [12]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33; SER-278 AND THR-285, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Acts as catalytic component of the CCR4-NOT core complex,
CC which in the nucleus seems to be a general transcription factor, and in
CC the cytoplasm the major mRNA deadenylase involved in mRNA turnover.
CC CCR4 has 3'-5' RNase activity with a strong preference for
CC polyadenylated substrates and also low exonuclease activity towards
CC single-stranded DNA. Discovered because of its role in the control of
CC ADH2 gene expression. It is required for the expression of genes
CC involved in non-fermentative growth and it mediates or is required for
CC the action of the SPT6 and SPT10 genes. {ECO:0000269|PubMed:11239395,
CC ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:11889048,
CC ECO:0000269|PubMed:9463387}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Subunit of the 1.0 MDa CCR4-NOT core complex that contains
CC CCR4, CAF1, NOT1, NOT2, NOT3, NOT4, NOT5, CAF40 and CAF130. In the
CC complex interacts with NOT1. The core complex probably is part of a
CC less characterized 1.9 MDa CCR4-NOT complex.
CC {ECO:0000269|PubMed:10490603, ECO:0000269|PubMed:11733989,
CC ECO:0000269|PubMed:9463387}.
CC -!- INTERACTION:
CC P31384; P53829: CAF40; NbExp=8; IntAct=EBI-4396, EBI-28306;
CC P31384; P25655: CDC39; NbExp=8; IntAct=EBI-4396, EBI-12139;
CC P31384; P34909: MOT2; NbExp=3; IntAct=EBI-4396, EBI-12174;
CC P31384; P39016: MPT5; NbExp=2; IntAct=EBI-4396, EBI-2052996;
CC P31384; P39008: POP2; NbExp=10; IntAct=EBI-4396, EBI-13629;
CC P31384; Q01939: RPT6; NbExp=3; IntAct=EBI-4396, EBI-13914;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11239395}. Nucleus
CC {ECO:0000269|PubMed:11239395}.
CC -!- DOMAIN: The 169 C-terminal residues are important for deadenylase
CC activity.
CC -!- MISCELLANEOUS: Present with 2780 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. {ECO:0000305}.
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DR EMBL; S50459; AAB24455.1; -; Genomic_DNA.
DR EMBL; L05146; AAC04936.1; -; Genomic_DNA.
DR EMBL; BK006935; DAA06967.1; -; Genomic_DNA.
DR PIR; S36713; S36713.
DR RefSeq; NP_009381.1; NM_001178166.1.
DR PDB; 4B8C; X-ray; 3.41 A; D/J/K/L=111-837.
DR PDBsum; 4B8C; -.
DR AlphaFoldDB; P31384; -.
DR SMR; P31384; -.
DR BioGRID; 31745; 3169.
DR ComplexPortal; CPX-1800; CCR4-NOT mRNA deadenylase complex.
DR DIP; DIP-2522N; -.
DR IntAct; P31384; 55.
DR MINT; P31384; -.
DR STRING; 4932.YAL021C; -.
DR CarbonylDB; P31384; -.
DR iPTMnet; P31384; -.
DR MaxQB; P31384; -.
DR PaxDb; P31384; -.
DR PRIDE; P31384; -.
DR TopDownProteomics; P31384; -.
DR EnsemblFungi; YAL021C_mRNA; YAL021C; YAL021C.
DR GeneID; 851212; -.
DR KEGG; sce:YAL021C; -.
DR SGD; S000000019; CCR4.
DR VEuPathDB; FungiDB:YAL021C; -.
DR eggNOG; KOG0620; Eukaryota.
DR GeneTree; ENSGT00940000169297; -.
DR HOGENOM; CLU_016428_4_1_1; -.
DR InParanoid; P31384; -.
DR OMA; YHFPSDH; -.
DR BioCyc; YEAST:G3O-28833-MON; -.
DR PRO; PR:P31384; -.
DR Proteomes; UP000002311; Chromosome I.
DR RNAct; P31384; protein.
DR GO; GO:0030014; C:CCR4-NOT complex; IBA:GO_Central.
DR GO; GO:0030015; C:CCR4-NOT core complex; IDA:SGD.
DR GO; GO:0016593; C:Cdc73/Paf1 complex; IPI:SGD.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; IDA:SGD.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IGI:SGD.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IGI:SGD.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:SGD.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IDA:SGD.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IDA:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IPI:SGD.
DR GO; GO:0048478; P:replication fork protection; IGI:SGD.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IMP:SGD.
DR GO; GO:0007089; P:traversing start control point of mitotic cell cycle; IMP:SGD.
DR Gene3D; 3.60.10.10; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 2.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS51450; LRR; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Exonuclease; Hydrolase;
KW Leucine-rich repeat; Magnesium; Metal-binding; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Repressor; RNA-binding;
KW Transcription; Transcription regulation.
FT CHAIN 1..837
FT /note="CCR4-Not complex 3'-5'-exoribonuclease subunit Ccr4"
FT /id="PRO_0000218577"
FT REPEAT 334..356
FT /note="LRR 1"
FT REPEAT 358..379
FT /note="LRR 2"
FT REPEAT 381..402
FT /note="LRR 3"
FT REPEAT 404..426
FT /note="LRR 4"
FT REPEAT 427..447
FT /note="LRR 5"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 254..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..281
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 556
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 285
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 556
FT /note="E->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11889047"
FT MUTAGEN 713
FT /note="D->A: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:11889047"
FT MUTAGEN 780
FT /note="D->A: Reduces activity."
FT /evidence="ECO:0000269|PubMed:11889047"
FT MUTAGEN 818
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11889047"
FT CONFLICT 544
FT /note="I -> L (in Ref. 1; AAB24455)"
FT /evidence="ECO:0000305"
FT CONFLICT 803
FT /note="V -> E (in Ref. 1; AAB24455)"
FT /evidence="ECO:0000305"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 155..169
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 245..258
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 351..355
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 374..379
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 441..460
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:4B8C"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 533..546
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 550..554
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 559..563
FT /evidence="ECO:0007829|PDB:4B8C"
FT TURN 564..566
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 600..602
FT /evidence="ECO:0007829|PDB:4B8C"
FT HELIX 800..803
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 807..811
FT /evidence="ECO:0007829|PDB:4B8C"
FT STRAND 816..818
FT /evidence="ECO:0007829|PDB:4B8C"
SQ SEQUENCE 837 AA; 94670 MW; 5CDB2E8FEDDBEF6F CRC64;
MNDPSLLGYP NVGPQQQQQQ QQQQHAGLLG KGTPNALQQQ LHMNQLTGIP PPGLMNNSDV
HTSSNNNSRQ LLDQLANGNA NMLNMNMDNN NNNNNNNNNN NNNGGGSGVM MNASTAAVNS
IGMVPTVGTP VNINVNASNP LLHPHLDDPS LLNNPIWKLQ LHLAAVSAQS LGQPNIYARQ
NAMKKYLATQ QAQQAQQQAQ QQAQQQVPGP FGPGPQAAPP ALQPTDFQQS HIAEASKSLV
DCTKQALMEM ADTLTDSKTA KKQQPTGDST PSGTATNSAV STPLTPKIEL FANGKDEANQ
ALLQHKKLSQ YSIDEDDDIE NRMVMPKDSK YDDQLWHALD LSNLQIFNIS ANIFKYDFLT
RLYLNGNSLT ELPAEIKNLS NLRVLDLSHN RLTSLPAELG SCFQLKYFYF FDNMVTTLPW
EFGNLCNLQF LGVEGNPLEK QFLKILTEKS VTGLIFYLRD NRPEIPLPHE RRFIEINTDG
EPQREYDSLQ QSTEHLATDL AKRTFTVLSY NTLCQHYATP KMYRYTPSWA LSWDYRRNKL
KEQILSYDSD LLCLQEVESK TFEEYWVPLL DKHGYTGIFH AKARAKTMHS KDSKKVDGCC
IFFKRDQFKL ITKDAMDFSG AWMKHKKFQR TEDYLNRAMN KDNVALFLKL QHIPSGDTIW
AVTTHLHWDP KFNDVKTFQV GVLLDHLETL LKEETSHNFR QDIKKFPVLI CGDFNSYINS
AVYELINTGR VQIHQEGNGR DFGYMSEKNF SHNLALKSSY NCIGELPFTN FTPSFTDVID
YIWFSTHALR VRGLLGEVDP EYVSKFIGFP NDKFPSDHIP LLARFEFMKT NTGSKKV
