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Protein

CCR4-NOT transcription complex subunit 6

Gene

CNOT6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei240By similarity1
Metal bindingi240Magnesium 1By similarity1
Metal bindingi412Magnesium 2By similarity1
Metal bindingi414Magnesium 2By similarity1
Active sitei491By similarity1
Active sitei531By similarity1
Metal bindingi531Magnesium 2By similarity1

GO - Molecular functioni

  • exoribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • poly(A)-specific ribonuclease activity Source: UniProtKB
  • RNA binding Source: UniProtKB-KW

GO - Biological processi

  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Source: UniProtKB
  • gene silencing by miRNA Source: UniProtKB
  • nuclear-transcribed mRNA catabolic process, no-go decay Source: UniProtKB
  • nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cytoplasmic mRNA processing body assembly Source: UniProtKB
  • positive regulation of ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • 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

BioCyciZFISH:ENSG00000113300-MONOMER.
ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:14099. CNOT6.

Subcellular locationi

GO - Cellular componenti

  • CCR4-NOT complex Source: UniProtKB
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi240E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA. 1 Publication1

Organism-specific databases

DisGeNETi57472.
OpenTargetsiENSG00000113300.
PharmGKBiPA26677.

Chemistry databases

ChEMBLiCHEMBL3616363.

Polymorphism and mutation databases

BioMutaiCNOT6.
DMDMi46396033.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002185731 – 557CCR4-NOT transcription complex subunit 6Add BLAST557

Proteomic databases

EPDiQ9ULM6.
MaxQBiQ9ULM6.
PaxDbiQ9ULM6.
PeptideAtlasiQ9ULM6.
PRIDEiQ9ULM6.

PTM databases

iPTMnetiQ9ULM6.
PhosphoSitePlusiQ9ULM6.

Expressioni

Gene expression databases

BgeeiENSG00000113300.
CleanExiHS_CCR4.
HS_CNOT6.
ExpressionAtlasiQ9ULM6. baseline and differential.
GenevisibleiQ9ULM6. HS.

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 (PubMed:19558367). Interacts with CNOT7 and CNOT8 (PubMed:11747467). Interacts with UNR (PubMed:15314026). Interacts with ZFP36L1 (via N-terminus) (PubMed:15687258). Interacts with ZNF335 (PubMed:18180299).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CNOT1A5YKK63EBI-2104530,EBI-1222758
CNOT7Q9UIV12EBI-2104530,EBI-2105113
CNOT8Q9UFF92EBI-2104530,EBI-742299
TNRC6CQ9HCJ02EBI-2104530,EBI-6507625

Protein-protein interaction databases

BioGridi121542. 29 interactors.
DIPiDIP-46838N.
IntActiQ9ULM6. 18 interactors.
STRINGi9606.ENSP00000261951.

Structurei

3D structure databases

ProteinModelPortaliQ9ULM6.
SMRiQ9ULM6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati52 – 73LRR 1Add BLAST22
Repeati75 – 96LRR 2Add BLAST22
Repeati98 – 120LRR 3Add BLAST23
Repeati121 – 143LRR 4Add BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni153 – 557Nuclease domainBy similarityAdd BLAST405

Sequence similaritiesi

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

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG4886. LUCA.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000294222.
HOVERGENiHBG052641.
InParanoidiQ9ULM6.
KOiK12603.
OMAiHLGMEKQ.
OrthoDBiEOG091G05MA.
PhylomeDBiQ9ULM6.
TreeFamiTF323175.

Family and domain databases

Gene3Di3.60.10.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR032675. L_dom-like.
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. 3 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF56219. 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:
EMBLi
GenBanki
DDBJi
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_001290170.1. NM_001303241.1.
XP_005266010.1. XM_005265953.1.
XP_011532908.1. XM_011534606.1.
XP_011532909.1. XM_011534607.1.
UniGeneiHs.608380.

Genome annotation databases

EnsembliENST00000261951; ENSP00000261951; ENSG00000113300.
ENST00000393356; ENSP00000377024; ENSG00000113300.
ENST00000618123; ENSP00000481893; ENSG00000113300.
GeneIDi57472.
KEGGihsa:57472.
UCSCiuc003mlx.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001290170.1. NM_001303241.1.
XP_005266010.1. XM_005265953.1.
XP_011532908.1. XM_011534606.1.
XP_011532909.1. XM_011534607.1.
UniGeneiHs.608380.

3D structure databases

ProteinModelPortaliQ9ULM6.
SMRiQ9ULM6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121542. 29 interactors.
DIPiDIP-46838N.
IntActiQ9ULM6. 18 interactors.
STRINGi9606.ENSP00000261951.

Chemistry databases

ChEMBLiCHEMBL3616363.

PTM databases

iPTMnetiQ9ULM6.
PhosphoSitePlusiQ9ULM6.

Polymorphism and mutation databases

BioMutaiCNOT6.
DMDMi46396033.

Proteomic databases

EPDiQ9ULM6.
MaxQBiQ9ULM6.
PaxDbiQ9ULM6.
PeptideAtlasiQ9ULM6.
PRIDEiQ9ULM6.

Protocols and materials databases

DNASUi57472.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261951; ENSP00000261951; ENSG00000113300.
ENST00000393356; ENSP00000377024; ENSG00000113300.
ENST00000618123; ENSP00000481893; ENSG00000113300.
GeneIDi57472.
KEGGihsa:57472.
UCSCiuc003mlx.3. human.

Organism-specific databases

CTDi57472.
DisGeNETi57472.
GeneCardsiCNOT6.
HGNCiHGNC:14099. CNOT6.
HPAiHPA044568.
MIMi608951. gene.
neXtProtiNX_Q9ULM6.
OpenTargetsiENSG00000113300.
PharmGKBiPA26677.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG4886. LUCA.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000294222.
HOVERGENiHBG052641.
InParanoidiQ9ULM6.
KOiK12603.
OMAiHLGMEKQ.
OrthoDBiEOG091G05MA.
PhylomeDBiQ9ULM6.
TreeFamiTF323175.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113300-MONOMER.
ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-5617472. Activation of anterior HOX genes in hindbrain development during early embryogenesis.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

Miscellaneous databases

GeneWikiiCNOT6.
GenomeRNAii57472.
PROiQ9ULM6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113300.
CleanExiHS_CCR4.
HS_CNOT6.
ExpressionAtlasiQ9ULM6. baseline and differential.
GenevisibleiQ9ULM6. HS.

Family and domain databases

Gene3Di3.60.10.10. 2 hits.
3.80.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR032675. L_dom-like.
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. 3 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF56219. SSF56219. 2 hits.
PROSITEiPS51450. LRR. 4 hits.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 143 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.