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CNOT6 CCR4-NOT transcription complex subunit 6 [ Homo sapiens (human) ]

Gene ID: 57472, updated on 11-Apr-2024

Summary

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Official Symbol
CNOT6provided by HGNC
Official Full Name
CCR4-NOT transcription complex subunit 6provided by HGNC
Primary source
HGNC:HGNC:14099
See related
Ensembl:ENSG00000113300 MIM:608951; AllianceGenome:HGNC:14099
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CCR4; Ccr4a
Summary
This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]
Expression
Ubiquitous expression in testis (RPKM 8.0), urinary bladder (RPKM 6.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
5q35.3
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (180494379..180578358)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (181050244..181134238)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (179921379..180005358)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901153 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:179894063-179895262 Neighboring gene uncharacterized LOC102725231 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23768 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:179901825-179902356 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:179912532-179913731 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16766 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16767 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16769 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16768 Neighboring gene NANOG hESC enhancer GRCh37_chr5:179954464-179954965 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:179958359-179959013 Neighboring gene proteolipid protein 2 (colonic epithelium-enriched) pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23769 Neighboring gene Sharpr-MPRA regulatory region 4663 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:180016691-180017360 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:180017361-180018030 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:180018031-180018700 Neighboring gene uncharacterized LOC124901154 Neighboring gene secretoglobin family 3A member 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs. Zhou F, et al. Mol Carcinog, 2017 Apr. PMID 27805284, Free PMC Article
  2. hCCR4/cNOT6 targets DNA-damage response proteins. Sanchez-Perez I, et al. Cancer Lett, 2009 Jan 18. PMID 18818012
  3. Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex. Chen Y, et al. Nucleic Acids Res, 2021 Jun 21. PMID 34038562, Free PMC Article
  4. miR-29c-3p promotes senescence of human mesenchymal stem cells by targeting CNOT6 through p53-p21 and p16-pRB pathways. Shang J, et al. Biochim Biophys Acta, 2016 Apr. PMID 26792405
  5. The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module. Maryati M, et al. Biochem J, 2015 Jul 1. PMID 25944446, Free PMC Article

See all (54) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex.
    Title: Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex.
  2. Studied hepatic role in metabolic homeostasis of fibroblast growth factor 21(FGF21) and the "CCR4-NOT complex" (a multisubunit protein complex composed of "CCR4-NOT transcription complex subunit 6 like" (CNOT6L) and "CCR4-NOT transcription complex subunit 6" (CNOT6). Results show CNOT6L plays a major role in regulation FGF21 levels.
    Title: Hepatic posttranscriptional network comprised of CCR4-NOT deadenylase and FGF21 maintains systemic metabolic homeostasis.
  3. The CNOT6 rs2453176 Single Nucleotide Polymorphism may be a new functional susceptible locus for lung cancer risk.
    Title: Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs.
  4. miR-29c-3p promotes the senescence of Mesenchymal stem cells by targeting CNOT6 through p53-p21 and p16-pRB pathways.
    Title: miR-29c-3p promotes senescence of human mesenchymal stem cells by targeting CNOT6 through p53-p21 and p16-pRB pathways.
  5. These results indicate that Caf1 and Ccr4 cooperate in mRNA deadenylation and suggest that the enzyme activities of Caf1 and Ccr4 are regulated via allosteric interactions within the nuclease module.
    Title: The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the human Ccr4-Not nuclease module.
  6. Results identified CNOT6/CNOT6L as a key regulator of insulin-like growth factor-binding protein 5, which mediates cell cycle arrest and senescence via a p53-dependent pathway.
    Title: The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human Ccr4-Not complex contribute to the prevention of cell death and senescence.
  7. Data show that Ccr4-Not function in RNA splicing and nuclear export, and that CNOT6 binds CNOT8 in yeast two-hybrid assays.
    Title: Human Ccr4-Not complexes contain variable deadenylase subunits.
  8. hCCR4/cNOT6 targets DNA-damage response proteins
    Title: hCCR4/cNOT6 targets DNA-damage response proteins.
  9. CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and RCD1 and CCR4 might mediate their function through their interaction with NIF-1
    Title: Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.
  10. CCR4 and BTG2 interact and have a role in cell-cycle regulation
    Title: BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA1194

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA exonuclease activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables nuclear receptor coactivator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables poly(A)-specific ribonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables poly(A)-specific ribonuclease activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables poly(A)-specific ribonuclease activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in miRNA-mediated post-transcriptional gene silencing TAS
Traceable Author Statement
more info
 PubMed 
involved_in nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in nuclear-transcribed mRNA catabolic process, no-go decay IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nuclear-transcribed mRNA poly(A) tail shortening IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nuclear-transcribed mRNA poly(A) tail shortening IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nuclear-transcribed mRNA poly(A) tail shortening NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in nuclear-transcribed mRNA poly(A) tail shortening TAS
Traceable Author Statement
more info
  
involved_in positive regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cytoplasmic mRNA processing body assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of translation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of CCR4-NOT complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of CCR4-NOT complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of CCR4-NOT complex NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
CCR4-NOT transcription complex subunit 6
Names
carbon catabolite repression 4 protein
carbon catabolite repressor protein 4 homolog
cytoplasmic deadenylase
NP_001357401.1
NP_001357402.1
NP_001357403.1
XP_016865160.1
XP_016865161.1
XP_024301904.1
XP_047273392.1
XP_047273393.1
XP_047273394.1
XP_047273395.1
XP_047273396.1
XP_047273397.1
XP_047273398.1
XP_054208966.1
XP_054208967.1
XP_054208968.1
XP_054208969.1
XP_054208970.1
XP_054208971.1
XP_054208972.1
XP_054208973.1
XP_054208974.1
XP_054208975.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001370472.1 → NP_001357401.1  CCR4-NOT transcription complex subunit 6 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC034213, AC122714
    Consensus CDS
    CCDS4455.1
    UniProtKB/Swiss-Prot
    A7MD46, D3DWR0, Q9ULM6
    Related
    ENSP00000261951.4, ENST00000261951.9
    Conserved Domains (3) summary
    cd10313
    Location:191 → 540
    Deadenylase_CCR4a; C-terminal deadenylase domain of CCR4a, also known as CCR4-NOT transcription complex subunit 6
    COG4886
    Location:52 → 159
    LRR; Leucine-rich repeat (LRR) protein [Transcription]
    sd00031
    Location:33 → 52
    LRR_1; leucine-rich repeat [structural motif]

  2. NM_001370473.1 → NP_001357402.1  CCR4-NOT transcription complex subunit 6 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC034213, AC122714
    Conserved Domains (3) summary
    cd10313
    Location:186 → 535
    Deadenylase_CCR4a; C-terminal deadenylase domain of CCR4a, also known as CCR4-NOT transcription complex subunit 6
    COG4886
    Location:52 → 158
    LRR; Leucine-rich repeat (LRR) protein [Transcription]
    sd00031
    Location:33 → 52
    LRR_1; leucine-rich repeat [structural motif]

  3. NM_001370474.1 → NP_001357403.1  CCR4-NOT transcription complex subunit 6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC122714
    Conserved Domains (3) summary
    cd10313
    Location:96 → 445
    Deadenylase_CCR4a; C-terminal deadenylase domain of CCR4a, also known as CCR4-NOT transcription complex subunit 6
    sd00033
    Location:4 → 26
    LRR_RI; leucine-rich repeat [structural motif]
    pfam12799
    Location:3 → 44
    LRR_4; Leucine Rich repeats (2 copies)

RNA

  1. NR_163437.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC034213, AC122714

  2. NR_163438.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC034213, AC122714

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    180494379..180578358
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047417436.1 → XP_047273392.1  CCR4-NOT transcription complex subunit 6 isoform X1

    UniProtKB/Swiss-Prot
    A7MD46, D3DWR0, Q9ULM6
    Related
    ENSP00000481893.1, ENST00000618123.4

  2. XM_047417440.1 → XP_047273396.1  CCR4-NOT transcription complex subunit 6 isoform X4

  3. XM_047417438.1 → XP_047273394.1  CCR4-NOT transcription complex subunit 6 isoform X2

  4. XM_047417437.1 → XP_047273393.1  CCR4-NOT transcription complex subunit 6 isoform X2

  5. XM_017009672.2 → XP_016865161.1  CCR4-NOT transcription complex subunit 6 isoform X4

    Conserved Domains (4) summary
    sd00031
    Location:33 → 52
    LRR_1; leucine-rich repeat [structural motif]
    pfam12799
    Location:51 → 91
    LRR_4; Leucine Rich repeats (2 copies)
    pfam13855
    Location:51 → 109
    LRR_8; Leucine rich repeat
    cl00490
    Location:191 → 420
    EEP; Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily

  6. XM_047417439.1 → XP_047273395.1  CCR4-NOT transcription complex subunit 6 isoform X5

  7. XM_047417442.1 → XP_047273398.1  CCR4-NOT transcription complex subunit 6 isoform X7

  8. XM_017009671.3 → XP_016865160.1  CCR4-NOT transcription complex subunit 6 isoform X3

    Conserved Domains (3) summary
    cd10313
    Location:96 → 445
    Deadenylase_CCR4a; C-terminal deadenylase domain of CCR4a, also known as CCR4-NOT transcription complex subunit 6
    sd00033
    Location:4 → 26
    LRR_RI; leucine-rich repeat [structural motif]
    pfam12799
    Location:3 → 44
    LRR_4; Leucine Rich repeats (2 copies)

  9. XM_047417441.1 → XP_047273397.1  CCR4-NOT transcription complex subunit 6 isoform X6

  10. XM_024446136.2 → XP_024301904.1  CCR4-NOT transcription complex subunit 6 isoform X6

    Conserved Domains (1) summary
    cd10313
    Location:16 → 365
    Deadenylase_CCR4a; C-terminal deadenylase domain of CCR4a, also known as CCR4-NOT transcription complex subunit 6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    181050244..181134238
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352991.1 → XP_054208966.1  CCR4-NOT transcription complex subunit 6 isoform X1

    UniProtKB/Swiss-Prot
    A7MD46, D3DWR0, Q9ULM6

  2. XM_054352997.1 → XP_054208972.1  CCR4-NOT transcription complex subunit 6 isoform X4

  3. XM_054352993.1 → XP_054208968.1  CCR4-NOT transcription complex subunit 6 isoform X2

  4. XM_054352992.1 → XP_054208967.1  CCR4-NOT transcription complex subunit 6 isoform X2

  5. XM_054352995.1 → XP_054208970.1  CCR4-NOT transcription complex subunit 6 isoform X4

  6. XM_054352996.1 → XP_054208971.1  CCR4-NOT transcription complex subunit 6 isoform X5

  7. XM_054353000.1 → XP_054208975.1  CCR4-NOT transcription complex subunit 6 isoform X7

  8. XM_054352994.1 → XP_054208969.1  CCR4-NOT transcription complex subunit 6 isoform X3

  9. XM_054352998.1 → XP_054208973.1  CCR4-NOT transcription complex subunit 6 isoform X6

  10. XM_054352999.1 → XP_054208974.1  CCR4-NOT transcription complex subunit 6 isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001303241.2: Suppressed sequence

    Description
    NM_001303241.2: This RefSeq was removed because currently there is insufficient support for the transcript. Intron1 is not supported by transcript data and likely represented repeat copy number variation.

  2. NM_015455.3: Suppressed sequence

    Description
    NM_015455.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9ULM6.2 GenPept UniProtKB/Swiss-Prot:Q9ULM6

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