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Q9ULM6 (CNOT6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CNOT6
Synonyms:CCR4, CCR4a, KIAA1194
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length557 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.7 Ref.9 Ref.10

Catalytic activity

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

Cofactor

Magnesium.

Subunit structure

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. Ref.4 Ref.6 Ref.7 Ref.8

Subcellular location

Cytoplasm Probable. Nucleus Probable.

Sequence similarities

Belongs to the CCR4/nocturin family.

Contains 4 LRR (leucine-rich) repeats.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
Nucleus
   DomainLeucine-rich repeat
Repeat
   LigandMagnesium
Metal-binding
RNA-binding
   Molecular functionActivator
Exonuclease
Hydrolase
Nuclease
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA metabolic process

Traceable author statement. Source: Reactome

RNA phosphodiester bond hydrolysis, exonucleolytic

Inferred from direct assay Ref.5PubMed 18377426. Source: GOC

exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay

Inferred from direct assay Ref.9. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

gene silencing by miRNA

Traceable author statement Ref.9. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA catabolic process, no-go decay

Inferred from mutant phenotype Ref.6. Source: UniProtKB

nuclear-transcribed mRNA poly(A) tail shortening

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of cytoplasmic mRNA processing body assembly

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of ligand-dependent nuclear receptor transcription coactivator activity

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCCR4-NOT complex

Inferred from direct assay Ref.8. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

exoribonuclease activity

Inferred from direct assay Ref.5. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

poly(A)-specific ribonuclease activity

Inferred from direct assay Ref.5PubMed 18377426. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 557557CCR4-NOT transcription complex subunit 6
PRO_0000218573

Regions

Repeat52 – 7322LRR 1
Repeat75 – 9622LRR 2
Repeat98 – 12023LRR 3
Repeat121 – 14323LRR 4
Region153 – 557405Nuclease domain By similarity

Sites

Active site2401 By similarity
Active site4911 By similarity
Active site5311 By similarity
Metal binding2401Magnesium 1 By similarity
Metal binding4121Magnesium 2 By similarity
Metal binding4141Magnesium 2 By similarity
Metal binding5311Magnesium 2 By similarity

Experimental info

Mutagenesis2401E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q9ULM6 [UniParc].

Last modified April 13, 2004. Version 2.
Checksum: DA9FF7A059BFB583

FASTA55763,307
        10         20         30         40         50         60 
MPKEKYEPPD PRRMYTIMSS EEAANGKKSH WAELEISGKV RSLSASLWSL THLTALHLSD 

        70         80         90        100        110        120 
NSLSRIPSDI AKLHNLVYLD LSSNKIRSLP AELGNMVSLR ELHLNNNLLR VLPFELGKLF 

       130        140        150        160        170        180 
QLQTLGLKGN PLTQDILNLY QEPDGTRRLL NYLLDNLSGT AKRITTEQPP PRSWIMLQEP 

       190        200        210        220        230        240 
DRTRPTALFS VMCYNVLCDK YATRQLYGYC PSWALNWDYR KKAIIQEILS CNADIVSLQE 

       250        260        270        280        290        300 
VETEQYYSFF LVELKERGYN GFFSPKSRAR TMSEQERKHV DGCAIFFKTE KFTLVQKHTV 

       310        320        330        340        350        360 
EFNQLAMANS EGSEAMLNRV MTKDNIGVAV LLELRKESIE MPSGKPHLGT EKQLILVANA 

       370        380        390        400        410        420 
HMHWDPEYSD VKLVQTMMFL SEVKNIIDKA SRNLKSSVLG EFGTIPLVLC ADLNSLPDSG 

       430        440        450        460        470        480 
VVEYLSTGGV ETNHKDFKEL RYNESLTNFS CHGKNGTTNG RITHGFKLQS AYESGLMPYT 

       490        500        510        520        530        540 
NYTFDFKGII DYIFYSKPQL NTLGILGPLD HHWLVENNIS GCPHPLIPSD HFSLFAQLEL 

       550 
LLPFLPQVNG IHLPGRR 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Human Ccr4-Not complexes contain variable deadenylase subunits."
Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W., Heck A.J., Timmers H.T.
Biochem. J. 422:443-453(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB033020 mRNA. Translation: BAA86508.1.
CH471165 Genomic DNA. Translation: EAW53752.1.
CH471165 Genomic DNA. Translation: EAW53753.1.
BC152469 mRNA. Translation: AAI52470.1.
RefSeqNP_056270.2. NM_015455.3.
XP_005266010.1. XM_005265953.1.
UniGeneHs.608380.

3D structure databases

ProteinModelPortalQ9ULM6.
SMRQ9ULM6. Positions 31-540.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121542. 13 interactions.
DIPDIP-46838N.
IntActQ9ULM6. 15 interactions.
STRING9606.ENSP00000261951.

PTM databases

PhosphoSiteQ9ULM6.

Polymorphism databases

DMDM46396033.

Proteomic databases

PaxDbQ9ULM6.
PRIDEQ9ULM6.

Protocols and materials databases

DNASU57472.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261951; ENSP00000261951; ENSG00000113300.
ENST00000393356; ENSP00000377024; ENSG00000113300.
GeneID57472.
KEGGhsa:57472.
UCSCuc003mlx.3. human.

Organism-specific databases

CTD57472.
GeneCardsGC05P179921.
HGNCHGNC:14099. CNOT6.
HPAHPA044568.
MIM608951. gene.
neXtProtNX_Q9ULM6.
PharmGKBPA26677.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4886.
HOGENOMHOG000294222.
HOVERGENHBG052641.
InParanoidQ9ULM6.
KOK12603.
OMAFMRYKWY.
OrthoDBEOG7JX35D.
PhylomeDBQ9ULM6.
TreeFamTF323175.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9ULM6.
BgeeQ9ULM6.
CleanExHS_CCR4.
HS_CNOT6.
GenevestigatorQ9ULM6.

Family and domain databases

Gene3D3.60.10.10. 2 hits.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SMARTSM00369. LRR_TYP. 2 hits.
[Graphical view]
SUPFAMSSF56219. SSF56219. 2 hits.
PROSITEPS51450. LRR. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCNOT6.
GenomeRNAi57472.
NextBio63703.
PROQ9ULM6.
SOURCESearch...

Entry information

Entry nameCNOT6_HUMAN
AccessionPrimary (citable) accession number: Q9ULM6
Secondary accession number(s): A7MD46, D3DWR0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: April 16, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM