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Q9ULM6

- CNOT6_HUMAN

UniProt

Q9ULM6 - CNOT6_HUMAN

Protein

CCR4-NOT transcription complex subunit 6

Gene

CNOT6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 2 (13 Apr 2004)
      Previous versions | rss
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    Functioni

    Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in mRNA decay mediated by the major-protein-coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA. The increase of ligand-dependent ESR1-mediated transcription is much smaller, if any. Mediates cell proliferation and cell survival and prevents cellular senescence.4 Publications

    Catalytic activityi

    Exonucleolytic cleavage of poly(A) to 5'-AMP.1 Publication

    Cofactori

    Magnesium.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei240 – 2401By similarity
    Metal bindingi240 – 2401Magnesium 1By similarity
    Metal bindingi412 – 4121Magnesium 2By similarity
    Metal bindingi414 – 4141Magnesium 2By similarity
    Active sitei491 – 4911By similarity
    Active sitei531 – 5311By similarity
    Metal bindingi531 – 5311Magnesium 2By similarity

    GO - Molecular functioni

    1. exoribonuclease activity Source: UniProtKB
    2. metal ion binding Source: UniProtKB-KW
    3. poly(A)-specific ribonuclease activity Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Source: UniProtKB
    2. gene expression Source: Reactome
    3. gene silencing by miRNA Source: UniProtKB
    4. mRNA metabolic process Source: Reactome
    5. nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: Reactome
    6. nuclear-transcribed mRNA catabolic process, no-go decay Source: UniProtKB
    7. nuclear-transcribed mRNA poly(A) tail shortening Source: Reactome
    8. positive regulation of cell proliferation Source: UniProtKB
    9. positive regulation of cytoplasmic mRNA processing body assembly Source: UniProtKB
    10. positive regulation of ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
    11. regulation of transcription, DNA-templated Source: UniProtKB-KW
    12. regulation of translation Source: UniProtKB-KW
    13. RNA metabolic process Source: Reactome
    14. RNA phosphodiester bond hydrolysis, exonucleolytic Source: GOC
    15. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Exonuclease, Hydrolase, Nuclease

    Keywords - Biological processi

    RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

    Keywords - Ligandi

    Magnesium, Metal-binding, RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_20514. Deadenylation of mRNA.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    CCR4-NOT transcription complex subunit 6 (EC:3.1.13.4)
    Alternative name(s):
    CCR4 carbon catabolite repression 4-like
    Carbon catabolite repressor protein 4 homolog
    Cytoplasmic deadenylase
    Gene namesi
    Name:CNOT6
    Synonyms:CCR4, CCR4a, KIAA1194
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:14099. CNOT6.

    Subcellular locationi

    Cytoplasm Curated. Nucleus Curated

    GO - Cellular componenti

    1. CCR4-NOT complex Source: UniProtKB
    2. cytosol Source: Reactome
    3. membrane Source: UniProtKB
    4. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi240 – 2401E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA. 1 Publication

    Organism-specific databases

    PharmGKBiPA26677.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 557557CCR4-NOT transcription complex subunit 6PRO_0000218573Add
    BLAST

    Proteomic databases

    MaxQBiQ9ULM6.
    PaxDbiQ9ULM6.
    PRIDEiQ9ULM6.

    PTM databases

    PhosphoSiteiQ9ULM6.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9ULM6.
    BgeeiQ9ULM6.
    CleanExiHS_CCR4.
    HS_CNOT6.
    GenevestigatoriQ9ULM6.

    Organism-specific databases

    HPAiHPA044568.

    Interactioni

    Subunit structurei

    Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8. Interacts with UNR and ZNF335.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CNOT1A5YKK62EBI-2104530,EBI-1222758
    CNOT7Q9UIV12EBI-2104530,EBI-2105113
    CNOT8Q9UFF92EBI-2104530,EBI-742299
    TNRC6CQ9HCJ02EBI-2104530,EBI-6507625

    Protein-protein interaction databases

    BioGridi121542. 13 interactions.
    DIPiDIP-46838N.
    IntActiQ9ULM6. 15 interactions.
    STRINGi9606.ENSP00000261951.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9ULM6.
    SMRiQ9ULM6. Positions 31-540.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati52 – 7322LRR 1Add
    BLAST
    Repeati75 – 9622LRR 2Add
    BLAST
    Repeati98 – 12023LRR 3Add
    BLAST
    Repeati121 – 14323LRR 4Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni153 – 557405Nuclease domainBy similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the CCR4/nocturin family.Curated
    Contains 4 LRR (leucine-rich) repeats.Curated

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG4886.
    HOGENOMiHOG000294222.
    HOVERGENiHBG052641.
    InParanoidiQ9ULM6.
    KOiK12603.
    OMAiHLGMEKQ.
    OrthoDBiEOG7JX35D.
    PhylomeDBiQ9ULM6.
    TreeFamiTF323175.

    Family and domain databases

    Gene3Di3.60.10.10. 2 hits.
    InterProiIPR005135. Endo/exonuclease/phosphatase.
    IPR001611. Leu-rich_rpt.
    IPR003591. Leu-rich_rpt_typical-subtyp.
    [Graphical view]
    PfamiPF03372. Exo_endo_phos. 1 hit.
    PF13855. LRR_8. 1 hit.
    [Graphical view]
    SMARTiSM00369. LRR_TYP. 2 hits.
    [Graphical view]
    SUPFAMiSSF56219. SSF56219. 2 hits.
    PROSITEiPS51450. LRR. 4 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9ULM6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPKEKYEPPD PRRMYTIMSS EEAANGKKSH WAELEISGKV RSLSASLWSL    50
    THLTALHLSD NSLSRIPSDI AKLHNLVYLD LSSNKIRSLP AELGNMVSLR 100
    ELHLNNNLLR VLPFELGKLF QLQTLGLKGN PLTQDILNLY QEPDGTRRLL 150
    NYLLDNLSGT AKRITTEQPP PRSWIMLQEP DRTRPTALFS VMCYNVLCDK 200
    YATRQLYGYC PSWALNWDYR KKAIIQEILS CNADIVSLQE VETEQYYSFF 250
    LVELKERGYN GFFSPKSRAR TMSEQERKHV DGCAIFFKTE KFTLVQKHTV 300
    EFNQLAMANS EGSEAMLNRV MTKDNIGVAV LLELRKESIE MPSGKPHLGT 350
    EKQLILVANA HMHWDPEYSD VKLVQTMMFL SEVKNIIDKA SRNLKSSVLG 400
    EFGTIPLVLC ADLNSLPDSG VVEYLSTGGV ETNHKDFKEL RYNESLTNFS 450
    CHGKNGTTNG RITHGFKLQS AYESGLMPYT NYTFDFKGII DYIFYSKPQL 500
    NTLGILGPLD HHWLVENNIS GCPHPLIPSD HFSLFAQLEL LLPFLPQVNG 550
    IHLPGRR 557
    Length:557
    Mass (Da):63,307
    Last modified:April 13, 2004 - v2
    Checksum:iDA9FF7A059BFB583
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB033020 mRNA. Translation: BAA86508.1.
    CH471165 Genomic DNA. Translation: EAW53752.1.
    CH471165 Genomic DNA. Translation: EAW53753.1.
    BC152469 mRNA. Translation: AAI52470.1.
    CCDSiCCDS4455.1.
    RefSeqiNP_056270.2. NM_015455.3.
    XP_005266010.1. XM_005265953.1.
    XP_006714962.1. XM_006714899.1.
    UniGeneiHs.608380.

    Genome annotation databases

    EnsembliENST00000261951; ENSP00000261951; ENSG00000113300.
    ENST00000393356; ENSP00000377024; ENSG00000113300.
    GeneIDi57472.
    KEGGihsa:57472.
    UCSCiuc003mlx.3. human.

    Polymorphism databases

    DMDMi46396033.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB033020 mRNA. Translation: BAA86508.1 .
    CH471165 Genomic DNA. Translation: EAW53752.1 .
    CH471165 Genomic DNA. Translation: EAW53753.1 .
    BC152469 mRNA. Translation: AAI52470.1 .
    CCDSi CCDS4455.1.
    RefSeqi NP_056270.2. NM_015455.3.
    XP_005266010.1. XM_005265953.1.
    XP_006714962.1. XM_006714899.1.
    UniGenei Hs.608380.

    3D structure databases

    ProteinModelPortali Q9ULM6.
    SMRi Q9ULM6. Positions 31-540.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121542. 13 interactions.
    DIPi DIP-46838N.
    IntActi Q9ULM6. 15 interactions.
    STRINGi 9606.ENSP00000261951.

    PTM databases

    PhosphoSitei Q9ULM6.

    Polymorphism databases

    DMDMi 46396033.

    Proteomic databases

    MaxQBi Q9ULM6.
    PaxDbi Q9ULM6.
    PRIDEi Q9ULM6.

    Protocols and materials databases

    DNASUi 57472.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000261951 ; ENSP00000261951 ; ENSG00000113300 .
    ENST00000393356 ; ENSP00000377024 ; ENSG00000113300 .
    GeneIDi 57472.
    KEGGi hsa:57472.
    UCSCi uc003mlx.3. human.

    Organism-specific databases

    CTDi 57472.
    GeneCardsi GC05P179921.
    HGNCi HGNC:14099. CNOT6.
    HPAi HPA044568.
    MIMi 608951. gene.
    neXtProti NX_Q9ULM6.
    PharmGKBi PA26677.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG4886.
    HOGENOMi HOG000294222.
    HOVERGENi HBG052641.
    InParanoidi Q9ULM6.
    KOi K12603.
    OMAi HLGMEKQ.
    OrthoDBi EOG7JX35D.
    PhylomeDBi Q9ULM6.
    TreeFami TF323175.

    Enzyme and pathway databases

    Reactomei REACT_20514. Deadenylation of mRNA.

    Miscellaneous databases

    GeneWikii CNOT6.
    GenomeRNAii 57472.
    NextBioi 63703.
    PROi Q9ULM6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9ULM6.
    Bgeei Q9ULM6.
    CleanExi HS_CCR4.
    HS_CNOT6.
    Genevestigatori Q9ULM6.

    Family and domain databases

    Gene3Di 3.60.10.10. 2 hits.
    InterProi IPR005135. Endo/exonuclease/phosphatase.
    IPR001611. Leu-rich_rpt.
    IPR003591. Leu-rich_rpt_typical-subtyp.
    [Graphical view ]
    Pfami PF03372. Exo_endo_phos. 1 hit.
    PF13855. LRR_8. 1 hit.
    [Graphical view ]
    SMARTi SM00369. LRR_TYP. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56219. SSF56219. 2 hits.
    PROSITEi PS51450. LRR. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.
      DNA Res. 6:337-345(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding."
      Dupressoir A., Morel A.-P., Barbot W., Loireau M.-P., Corbo L., Heidmann T.
      BMC Genomics 2:9-9(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CNOT7 AND CNOT8.
    5. "CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase."
      Chen J., Chiang Y.-C., Denis C.L.
      EMBO J. 21:1414-1426(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY.
    6. "UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant."
      Chang T.-C., Yamashita A., Chen C.-Y.A., Yamashita Y., Zhu W., Durdan S., Kahvejian A., Sonenberg N., Shyu A.-B.
      Genes Dev. 18:2010-2023(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UNR.
    7. "Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1."
      Garapaty S., Mahajan M.A., Samuels H.H.
      J. Biol. Chem. 283:6806-6816(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ZNF335.
    8. Cited for: IDENTIFICATION IN THE CCR4-NOT COMPLEX, COMPOSITION OF THE CCR4-NOT COMPLEX.
    9. "CCR4-NOT deadenylates mRNA associated with complexes in human cells."
      Piao X., Zhang X., Wu L., Belasco J.G.
      Mol. Cell. Biol. 30:1486-1494(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF GLU-240.
    10. "The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human Ccr4-Not complex contribute to the prevention of cell death and senescence."
      Mittal S., Aslam A., Doidge R., Medica R., Winkler G.S.
      Mol. Biol. Cell 22:748-758(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiCNOT6_HUMAN
    AccessioniPrimary (citable) accession number: Q9ULM6
    Secondary accession number(s): A7MD46, D3DWR0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 13, 2004
    Last sequence update: April 13, 2004
    Last modified: October 1, 2014
    This is version 121 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3