ID CNOT6_HUMAN Reviewed; 557 AA. AC Q9ULM6; A7MD46; D3DWR0; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 2. DT 27-MAR-2024, entry version 190. DE RecName: Full=CCR4-NOT transcription complex subunit 6; DE EC=3.1.13.4 {ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:20065043}; DE AltName: Full=CCR4 carbon catabolite repression 4-like; DE AltName: Full=Carbon catabolite repressor protein 4 homolog; DE AltName: Full=Cytoplasmic deadenylase; GN Name=CNOT6; Synonyms=CCR4, CCR4a, KIAA1194; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=10574462; DOI=10.1093/dnares/6.5.337; RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:337-345(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH CNOT7 AND CNOT8. RX PubMed=11747467; DOI=10.1186/1471-2164-2-9; RA Dupressoir A., Morel A.-P., Barbot W., Loireau M.-P., Corbo L., RA Heidmann T.; RT "Identification of four families of yCCR4- and Mg2+-dependent endonuclease- RT related proteins in higher eukaryotes, and characterization of orthologs of RT yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 RT binding."; RL BMC Genomics 2:9-9(2001). RN [5] RP FUNCTION, AND CATALYTIC ACTIVITY. 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 [6] RP INTERACTION WITH UNR. RX PubMed=15314026; DOI=10.1101/gad.1219104; RA Chang T.-C., Yamashita A., Chen C.-Y.A., Yamashita Y., Zhu W., Durdan S., RA Kahvejian A., Sonenberg N., Shyu A.-B.; RT "UNR, a new partner of poly(A)-binding protein, plays a key role in RT translationally coupled mRNA turnover mediated by the c-fos major coding- RT region determinant."; RL Genes Dev. 18:2010-2023(2004). RN [7] RP INTERACTION WITH ZFP36L1. RX PubMed=15687258; DOI=10.1101/gad.1282305; RA Lykke-Andersen J., Wagner E.; RT "Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay RT activation domains in the proteins TTP and BRF-1."; RL Genes Dev. 19:351-361(2005). RN [8] RP FUNCTION, AND INTERACTION WITH ZNF335. RX PubMed=18180299; DOI=10.1074/jbc.m706986200; RA Garapaty S., Mahajan M.A., Samuels H.H.; RT "Components of the CCR4-NOT complex function as nuclear hormone receptor RT coactivators via association with the NRC-interacting Factor NIF-1."; RL J. Biol. Chem. 283:6806-6816(2008). RN [9] RP IDENTIFICATION IN THE CCR4-NOT COMPLEX, AND COMPOSITION OF THE CCR4-NOT RP COMPLEX. RX PubMed=19558367; DOI=10.1042/bj20090500; RA Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W., RA Heck A.J., Timmers H.T.; RT "Human Ccr4-Not complexes contain variable deadenylase subunits."; RL Biochem. J. 422:443-453(2009). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-240. RX PubMed=20065043; DOI=10.1128/mcb.01481-09; RA Piao X., Zhang X., Wu L., Belasco J.G.; RT "CCR4-NOT deadenylates mRNA associated with complexes in human cells."; RL Mol. Cell. Biol. 30:1486-1494(2010). RN [11] RP FUNCTION. RX PubMed=21233283; DOI=10.1091/mbc.e10-11-0898; RA Mittal S., Aslam A., Doidge R., Medica R., Winkler G.S.; RT "The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human RT Ccr4-Not complex contribute to the prevention of cell death and RT senescence."; RL Mol. Biol. Cell 22:748-758(2011). CC -!- FUNCTION: Poly(A) nuclease with 3'-5' RNase activity. Catalytic CC component of the CCR4-NOT complex which is one of the major cellular CC mRNA deadenylases and is linked to various cellular processes including CC bulk mRNA degradation, miRNA-mediated repression, translational CC repression during translational initiation and general transcription CC regulation. Additional complex functions may be a consequence of its CC influence on mRNA expression. Involved in mRNA decay mediated by the CC major-protein-coding determinant of instability (mCRD) of the FOS gene CC in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent CC transcriptional activity of nuclear hormone receptors, including RARA. CC The increase of ligand-dependent ESR1-mediated transcription is much CC smaller, if any. Mediates cell proliferation and cell survival and CC prevents cellular senescence. {ECO:0000269|PubMed:11889047, CC ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:20065043, CC ECO:0000269|PubMed:21233283}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4; CC Evidence={ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:20065043}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q96LI5}; CC Note=Binds 2 magnesium ions, but the ions interact each with only 1 or CC 2 residues. {ECO:0000250|UniProtKB:Q96LI5}; CC -!- SUBUNIT: Component of the CCR4-NOT complex; distinct complexes seem to CC exist that differ in the participation of probably mutually exclusive CC catalytic subunits; the complex contains two deadenylase subunits, CC CNOT6 or CNOT6L, and CNOT7 or CNOT8 (PubMed:19558367). Interacts with CC CNOT7 and CNOT8 (PubMed:11747467). Interacts with UNR CC (PubMed:15314026). Interacts with ZFP36L1 (via N-terminus) CC (PubMed:15687258). Interacts with ZNF335 (PubMed:18180299). CC {ECO:0000269|PubMed:11747467, ECO:0000269|PubMed:15314026, CC ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:18180299, CC ECO:0000269|PubMed:19558367}. CC -!- INTERACTION: CC Q9ULM6; A5YKK6: CNOT1; NbExp=3; IntAct=EBI-2104530, EBI-1222758; CC Q9ULM6; Q9UIV1: CNOT7; NbExp=2; IntAct=EBI-2104530, EBI-2105113; CC Q9ULM6; Q9UFF9: CNOT8; NbExp=2; IntAct=EBI-2104530, EBI-742299; CC Q9ULM6; Q86TB9: PATL1; NbExp=3; IntAct=EBI-2104530, EBI-2562092; CC Q9ULM6; Q9HCJ0: TNRC6C; NbExp=2; IntAct=EBI-2104530, EBI-6507625; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96LI5}. Nucleus CC {ECO:0000250|UniProtKB:Q96LI5}. Note=Predominantly cytoplasmic. CC {ECO:0000250|UniProtKB:Q96LI5}. 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; AB033020; BAA86508.1; -; mRNA. DR EMBL; CH471165; EAW53752.1; -; Genomic_DNA. DR EMBL; CH471165; EAW53753.1; -; Genomic_DNA. DR EMBL; BC152469; AAI52470.1; -; mRNA. DR CCDS; CCDS4455.1; -. DR RefSeq; NP_001290170.1; NM_001303241.1. DR RefSeq; XP_005266010.1; XM_005265953.1. DR RefSeq; XP_011532908.1; XM_011534606.1. DR RefSeq; XP_011532909.1; XM_011534607.1. DR PDB; 7AX1; X-ray; 3.30 A; A=1-557. DR PDBsum; 7AX1; -. DR AlphaFoldDB; Q9ULM6; -. DR SMR; Q9ULM6; -. DR BioGRID; 121542; 59. DR ComplexPortal; CPX-2849; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT8 variant. DR ComplexPortal; CPX-707; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT7 variant. DR CORUM; Q9ULM6; -. DR DIP; DIP-46838N; -. DR IntAct; Q9ULM6; 21. DR STRING; 9606.ENSP00000481893; -. DR ChEMBL; CHEMBL3616363; -. DR GlyGen; Q9ULM6; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9ULM6; -. DR PhosphoSitePlus; Q9ULM6; -. DR BioMuta; CNOT6; -. DR DMDM; 46396033; -. DR EPD; Q9ULM6; -. DR jPOST; Q9ULM6; -. DR MassIVE; Q9ULM6; -. DR MaxQB; Q9ULM6; -. DR PaxDb; 9606-ENSP00000377024; -. DR PeptideAtlas; Q9ULM6; -. DR ProteomicsDB; 85079; -. DR Pumba; Q9ULM6; -. DR Antibodypedia; 29603; 184 antibodies from 23 providers. DR DNASU; 57472; -. DR Ensembl; ENST00000261951.9; ENSP00000261951.4; ENSG00000113300.13. DR Ensembl; ENST00000393356.7; ENSP00000377024.1; ENSG00000113300.13. DR Ensembl; ENST00000618123.4; ENSP00000481893.1; ENSG00000113300.13. DR MANE-Select; ENST00000261951.9; ENSP00000261951.4; NM_001370472.1; NP_001357401.1. DR UCSC; uc003mlx.3; human. DR AGR; HGNC:14099; -. DR GeneCards; CNOT6; -. DR HGNC; HGNC:14099; CNOT6. DR HPA; ENSG00000113300; Low tissue specificity. DR MIM; 608951; gene. DR neXtProt; NX_Q9ULM6; -. DR OpenTargets; ENSG00000113300; -. DR PharmGKB; PA26677; -. DR VEuPathDB; HostDB:ENSG00000113300; -. DR eggNOG; KOG0620; Eukaryota. DR GeneTree; ENSGT00940000158978; -. DR HOGENOM; CLU_016428_4_2_1; -. DR InParanoid; Q9ULM6; -. DR OMA; EHRMVAP; -. DR OrthoDB; 37764at2759; -. DR PhylomeDB; Q9ULM6; -. DR TreeFam; TF323175; -. DR PathwayCommons; Q9ULM6; -. DR Reactome; R-HSA-429947; Deadenylation of mRNA. DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis. DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain. DR Reactome; R-HSA-9820841; M-decay: degradation of maternal mRNAs by maternally stored factors. DR SignaLink; Q9ULM6; -. DR SIGNOR; Q9ULM6; -. DR BioGRID-ORCS; 57472; 21 hits in 1159 CRISPR screens. DR ChiTaRS; CNOT6; human. DR GeneWiki; CNOT6; -. DR GenomeRNAi; 57472; -. DR Pharos; Q9ULM6; Tbio. DR PRO; PR:Q9ULM6; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9ULM6; Protein. DR Bgee; ENSG00000113300; Expressed in secondary oocyte and 202 other cell types or tissues. DR ExpressionAtlas; Q9ULM6; baseline and differential. DR GO; GO:0030014; C:CCR4-NOT complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:GO_Central. DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0004532; F:RNA exonuclease activity; IDA:UniProtKB. DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; IDA:UniProtKB. DR GO; GO:0035195; P:miRNA-mediated post-transcriptional gene silencing; TAS:UniProtKB. DR GO; GO:0070966; P:nuclear-transcribed mRNA catabolic process, no-go decay; IMP:UniProtKB. DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IMP:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR CDD; cd10313; Deadenylase_CCR4a; 1. DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR034966; Cnot6. 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:SF33; CCR4-NOT TRANSCRIPTION COMPLEX SUBUNIT 6; 1. DR Pfam; PF03372; Exo_endo_phos; 1. DR Pfam; PF13855; LRR_8; 1. DR SMART; SM00369; LRR_TYP; 3. DR SUPFAM; SSF56219; DNase I-like; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR PROSITE; PS51450; LRR; 4. DR Genevisible; Q9ULM6; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Cytoplasm; Exonuclease; Hydrolase; KW Leucine-rich repeat; Magnesium; Metal-binding; Nuclease; Nucleus; KW Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing; KW Transcription; Transcription regulation; Translation regulation. FT CHAIN 1..557 FT /note="CCR4-NOT transcription complex subunit 6" FT /id="PRO_0000218573" FT REPEAT 52..73 FT /note="LRR 1" FT REPEAT 75..96 FT /note="LRR 2" FT REPEAT 98..120 FT /note="LRR 3" FT REPEAT 121..143 FT /note="LRR 4" FT REGION 153..557 FT /note="Nuclease domain" FT /evidence="ECO:0000250" FT ACT_SITE 412 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 240 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 240 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 276 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 361 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 366 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 412 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 414 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 481 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT BINDING 486 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96LI5" FT MUTAGEN 240 FT /note="E->A: Impairs deadenylation and decay of FT mRNAi-targeted mRNA." FT /evidence="ECO:0000269|PubMed:20065043" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 33..36 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 68..72 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 101..103 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 114..118 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 134..141 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 145..160 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 186..195 FT /evidence="ECO:0007829|PDB:7AX1" FT TURN 204..206 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 212..215 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 217..231 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 234..240 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 243..248 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 250..255 FT /evidence="ECO:0007829|PDB:7AX1" FT TURN 256..258 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 274..278 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 284..288 FT /evidence="ECO:0007829|PDB:7AX1" FT TURN 289..291 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 296..299 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 311..320 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 327..334 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 354..361 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 366..368 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 369..393 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 407..412 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 420..426 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 427..431 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 435..440 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 446..449 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 461..463 FT /evidence="ECO:0007829|PDB:7AX1" FT TURN 471..475 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 480..482 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 491..496 FT /evidence="ECO:0007829|PDB:7AX1" FT TURN 497..499 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 500..506 FT /evidence="ECO:0007829|PDB:7AX1" FT HELIX 511..516 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 521..524 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 529..531 FT /evidence="ECO:0007829|PDB:7AX1" FT STRAND 536..541 FT /evidence="ECO:0007829|PDB:7AX1" SQ SEQUENCE 557 AA; 63307 MW; DA9FF7A059BFB583 CRC64; MPKEKYEPPD PRRMYTIMSS EEAANGKKSH WAELEISGKV RSLSASLWSL THLTALHLSD NSLSRIPSDI AKLHNLVYLD LSSNKIRSLP AELGNMVSLR ELHLNNNLLR VLPFELGKLF QLQTLGLKGN PLTQDILNLY QEPDGTRRLL NYLLDNLSGT AKRITTEQPP PRSWIMLQEP DRTRPTALFS VMCYNVLCDK YATRQLYGYC PSWALNWDYR KKAIIQEILS CNADIVSLQE VETEQYYSFF LVELKERGYN GFFSPKSRAR TMSEQERKHV DGCAIFFKTE KFTLVQKHTV EFNQLAMANS EGSEAMLNRV MTKDNIGVAV LLELRKESIE MPSGKPHLGT EKQLILVANA HMHWDPEYSD VKLVQTMMFL SEVKNIIDKA SRNLKSSVLG EFGTIPLVLC ADLNSLPDSG VVEYLSTGGV ETNHKDFKEL RYNESLTNFS CHGKNGTTNG RITHGFKLQS AYESGLMPYT NYTFDFKGII DYIFYSKPQL NTLGILGPLD HHWLVENNIS GCPHPLIPSD HFSLFAQLEL LLPFLPQVNG IHLPGRR //