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 27-MAR-2024, entry version 219. 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 a 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=7; 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=9; 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}. 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; 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; 3175. 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; 4932-YAL021C; -. DR PeptideAtlas; P31384; -. DR TopDownProteomics; P31384; -. DR EnsemblFungi; YAL021C_mRNA; YAL021C; YAL021C. DR GeneID; 851212; -. DR KEGG; sce:YAL021C; -. DR AGR; SGD:S000000019; -. 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; EHRMVAP; -. DR OrthoDB; 37764at2759; -. DR BioCyc; YEAST:G3O-28833-MONOMER; -. DR BioGRID-ORCS; 851212; 10 hits in 10 CRISPR screens. 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'-RNA exonuclease 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 by RNA polymerase II; IDA:SGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IPI:SGD. DR GO; GO:0006368; P:transcription elongation by RNA polymerase II; IMP:SGD. DR GO; GO:0007089; P:traversing start control point of mitotic cell cycle; IMP:SGD. DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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 PANTHER; PTHR12121; CARBON CATABOLITE REPRESSOR PROTEIN 4; 1. DR PANTHER; PTHR12121:SF34; POLY(A)-SPECIFIC RIBONUCLEASE; 1. DR Pfam; PF03372; Exo_endo_phos; 1. DR Pfam; PF13855; LRR_8; 1. DR SMART; SM00369; LRR_TYP; 2. DR SUPFAM; SSF56219; DNase I-like; 1. DR SUPFAM; SSF52058; L domain-like; 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 //