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Q9ULM6

- CNOT6_HUMAN

UniProt

Q9ULM6 - CNOT6_HUMAN

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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

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. 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
Complete GO annotation...

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-KW
Complete GO annotation...

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

BgeeiQ9ULM6.
CleanExiHS_CCR4.
HS_CNOT6.
ExpressionAtlasiQ9ULM6. baseline and differential.
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. 15 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.
GeneTreeiENSGT00550000074364.
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

        10         20         30         40         50
MPKEKYEPPD PRRMYTIMSS EEAANGKKSH WAELEISGKV RSLSASLWSL
60 70 80 90 100
THLTALHLSD NSLSRIPSDI AKLHNLVYLD LSSNKIRSLP AELGNMVSLR
110 120 130 140 150
ELHLNNNLLR VLPFELGKLF QLQTLGLKGN PLTQDILNLY QEPDGTRRLL
160 170 180 190 200
NYLLDNLSGT AKRITTEQPP PRSWIMLQEP DRTRPTALFS VMCYNVLCDK
210 220 230 240 250
YATRQLYGYC PSWALNWDYR KKAIIQEILS CNADIVSLQE VETEQYYSFF
260 270 280 290 300
LVELKERGYN GFFSPKSRAR TMSEQERKHV DGCAIFFKTE KFTLVQKHTV
310 320 330 340 350
EFNQLAMANS EGSEAMLNRV MTKDNIGVAV LLELRKESIE MPSGKPHLGT
360 370 380 390 400
EKQLILVANA HMHWDPEYSD VKLVQTMMFL SEVKNIIDKA SRNLKSSVLG
410 420 430 440 450
EFGTIPLVLC ADLNSLPDSG VVEYLSTGGV ETNHKDFKEL RYNESLTNFS
460 470 480 490 500
CHGKNGTTNG RITHGFKLQS AYESGLMPYT NYTFDFKGII DYIFYSKPQL
510 520 530 540 550
NTLGILGPLD HHWLVENNIS GCPHPLIPSD HFSLFAQLEL LLPFLPQVNG

IHLPGRR
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.
ENST00000618123; ENSP00000481893; 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. 15 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 .
ENST00000618123 ; ENSP00000481893 ; 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.
GeneTreei ENSGT00550000074364.
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

Bgeei Q9ULM6.
CleanExi HS_CCR4.
HS_CNOT6.
ExpressionAtlasi Q9ULM6. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 122 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