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

    Gene ID: 57472, updated on 2-Nov-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
    mouse all
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    Genomic context

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    See CNOT6 in Genome Data Viewer
    Location:
    5q35.3
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (180494379..180578358)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (181050244..181134238)
    RS_2024_09 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 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. hCCR4/cNOT6 targets DNA-damage response proteins. Sanchez-Perez I, et al. Cancer Lett, 2009 Jan 18. PMID 18818012
    2. 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
    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. CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase. Chen J, et al. EMBO J, 2002 Mar 15. PMID 11889047, Free PMC Article

    See all (57) 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 gene silencing by mRNA destabilization 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_2024_08

    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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