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    CNOT4 CCR4-NOT transcription complex subunit 4 [ Homo sapiens (human) ]

    Gene ID: 4850, updated on 10-Dec-2024

    Summary

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    Official Symbol
    CNOT4provided by HGNC
    Official Full Name
    CCR4-NOT transcription complex subunit 4provided by HGNC
    Primary source
    HGNC:HGNC:7880
    See related
    Ensembl:ENSG00000080802 MIM:604911; AllianceGenome:HGNC:7880
    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
    NOT4; NOT4H; CLONE243
    Summary
    The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]
    Expression
    Ubiquitous expression in testis (RPKM 8.1), brain (RPKM 5.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CNOT4 in Genome Data Viewer
    Location:
    7q33
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (135361795..135510102, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (136669704..136817325, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (135046547..135194850, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26713 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:134935285-134935435 Neighboring gene uncharacterized LOC107984123 Neighboring gene stimulated by retinoic acid 8 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26714 Neighboring gene solute carrier family 23 member 4, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr7:134998844-134999016 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:135023371-135023872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:135023873-135024372 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:135032494-135032998 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:135065068-135065648 Neighboring gene succinate dehydrogenase complex subunit D pseudogene 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:135193920-135194825 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:135194826-135195730 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26719 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26720 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26721 Neighboring gene nucleoporin 205 Neighboring gene Sharpr-MPRA regulatory region 5720 Neighboring gene protein max-like

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. CNOT4-Mediated Ubiquitination of Influenza A Virus Nucleoprotein Promotes Viral RNA Replication. Lin YC, et al. mBio, 2017 May 23. PMID 28536288, Free PMC Article
    2. RING domains functioning as E3 ligases reveal distinct structural features: a molecular dynamics simulation study. Zhao JH, et al. J Biomol Struct Dyn, 2008 Aug. PMID 18533727
    3. CNOT4 enhances the efficacy of anti-PD-1 immunotherapy in a model of non-small cell lung cancer. Zhang B, et al. FEBS Open Bio, 2020 Dec. PMID 33034149, Free PMC Article
    4. The structure of the C4C4 ring finger of human NOT4 reveals features distinct from those of C3HC4 RING fingers. Hanzawa H, et al. J Biol Chem, 2001 Mar 30. PMID 11087754
    5. CNOT4 suppresses non-small cell lung cancer progression and is required for effector cytolytic T lymphocytes cell responses to lung cancer cells. Zhang B, et al. Mol Immunol, 2021 Apr. PMID 33592572

    See all (60) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CNOT4 suppresses nonsmall cell lung cancer progression by promoting the degradation of PAF1.
      Title: CNOT4 suppresses nonsmall cell lung cancer progression by promoting the degradation of PAF1.
    2. Aberrant expression of MYD88 via RNA-controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer.
      Title: Aberrant expression of MYD88 via RNA-controlling CNOT4 and EXOSC3 in colonic mucosa impacts generation of colonic cancer.
    3. CNOT4 enhances the efficacy of anti-PD-1 immunotherapy in a model of non-small cell lung cancer.
      Title: CNOT4 enhances the efficacy of anti-PD-1 immunotherapy in a model of non-small cell lung cancer.
    4. CNOT4 suppresses non-small cell lung cancer progression and is required for effector cytolytic T lymphocytes cell responses to lung cancer cells.
      Title: CNOT4 suppresses non-small cell lung cancer progression and is required for effector cytolytic T lymphocytes cell responses to lung cancer cells.
    5. The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma.
      Title: The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma.
    6. conserved RNA recognition motif and C3H1 domain of the Not4
      Title: The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function.
    7. Damage-induced ubiquitination of ABCE1 protein by NOT4 generates poly-ubiquitin signals that attract autophagy receptors to mitochondrial outer membrane to initiate mitophagy.
      Title: Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy.
    8. the C-terminal regions of human and D. melanogaster NOT4 contain a conserved sequence motif that directly binds the CAF40 subunit of the CCR4-NOT complex (CAF40-binding motif [CBM]).
      Title: A conserved CAF40-binding motif in metazoan NOT4 mediates association with the CCR4-NOT complex.
    9. These results indicate that CNOT4 is a ubiquitin ligase of influenza A virus nucleoprotein, and ubiquitination of the nucleoprotein plays a positive role in viral RNA replication.
      Title: CNOT4-Mediated Ubiquitination of Influenza A Virus Nucleoprotein Promotes Viral RNA Replication.
    10. CNOT4 controls the degradation of chromatin-unbound PAF1 via the 26S proteasome.
      Title: Protein Degradation of RNA Polymerase II-Association Factor 1(PAF1) Is Controlled by CNOT4 and 26S Proteasome.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in nuclear-transcribed mRNA poly(A) tail shortening NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protein autoubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of megakaryocyte differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    CCR4-NOT transcription complex subunit 4
    Names
    CCR4-associated factor 4
    E3 ubiquitin-protein ligase CNOT4
    NOT4 (negative regulator of transcription 4, yeast) homolog
    RING-type E3 ubiquitin transferase CNOT4
    potential transcriptional repressor NOT4Hp
    NP_001008226.1
    NP_001177776.1
    NP_001177777.1
    NP_001177778.1
    NP_001177779.1
    NP_001380299.1
    NP_001380300.1
    NP_001380301.1
    NP_001380302.1
    NP_001380303.1
    NP_001380304.1
    NP_037448.2
    XP_047276368.1
    XP_047276369.1
    XP_047276370.1
    XP_047276371.1
    XP_054214243.1
    XP_054214244.1
    XP_054214245.1
    XP_054214246.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001008225.3 → NP_001008226.1  CCR4-NOT transcription complex subunit 4 isoform b

      See identical proteins and their annotated locations for NP_001008226.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 3' end of an exon and differs in the 3' UTR and coding sequence compared to variant 6. The resulting isoform (b) lacks an internal 3 aa segment and has a shorter and distinct C-terminus compared to isoform f.
      Source sequence(s)
      AC009331, AC083871, AL389980, DA247976
      Consensus CDS
      CCDS47719.1
      UniProtKB/TrEMBL
      A0A9L9PY48
      Related
      ENSP00000399108.2, ENST00000428680.6
      Conserved Domains (1) summary
      COG5175
      Location:14 → 319
      MOT2; Transcriptional repressor [Transcription]

    2. NM_001190847.2 → NP_001177776.1  CCR4-NOT transcription complex subunit 4 isoform c

      See identical proteins and their annotated locations for NP_001177776.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 6. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform f.
      Source sequence(s)
      AC009331, AC083871, AK314540, DA247976, U71267
      Consensus CDS
      CCDS55164.1
      UniProtKB/TrEMBL
      A0A9L9PY48
      Related
      ENSP00000406777.2, ENST00000423368.6
      Conserved Domains (1) summary
      COG5175
      Location:14 → 322
      MOT2; Transcriptional repressor [Transcription]

    3. NM_001190848.2 → NP_001177777.1  CCR4-NOT transcription complex subunit 4 isoform d

      See identical proteins and their annotated locations for NP_001177777.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' UTR and coding sequence compared to variant 6. The resulting isoform (d) has a shorter and distinct C-terminus compared to isoform f.
      Source sequence(s)
      AC009331, AC083871, AL389980, DA247976, U71268
      Consensus CDS
      CCDS55166.1
      UniProtKB/Swiss-Prot
      B7Z6I4, E7ET38, F8VQP3, O95339, O95627, O95628, Q8IYM7, Q8NCL0, Q9NPQ1, Q9NZN6
      UniProtKB/TrEMBL
      A0A9L9PY48
      Related
      ENSP00000326731.5, ENST00000315544.6
      Conserved Domains (1) summary
      COG5175
      Location:14 → 322
      MOT2; Transcriptional repressor [Transcription]

    4. NM_001190849.2 → NP_001177778.1  CCR4-NOT transcription complex subunit 4 isoform e

      See identical proteins and their annotated locations for NP_001177778.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 6. The resulting isoform (e) has the same N- and C-termini but is 3 aa shorter compared to isoform f.
      Source sequence(s)
      AC009331, AC083871, AK314540, CA396599, DA247976
      Consensus CDS
      CCDS55167.1
      UniProtKB/Swiss-Prot
      O95628
      Related
      ENSP00000388491.1, ENST00000451834.5
      Conserved Domains (1) summary
      COG5175
      Location:14 → 319
      MOT2; Transcriptional repressor [Transcription]

    5. NM_001190850.2 → NP_001177779.1  CCR4-NOT transcription complex subunit 4 isoform f

      See identical proteins and their annotated locations for NP_001177779.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) encodes the longest isoform (f).
      Source sequence(s)
      AC009331, AC083871, AK314540, CA396599, DA247976, U71267
      Consensus CDS
      CCDS55165.1
      UniProtKB/Swiss-Prot
      O95628
      Related
      ENSP00000445508.1, ENST00000541284.6
      Conserved Domains (1) summary
      COG5175
      Location:14 → 322
      MOT2; Transcriptional repressor [Transcription]

    6. NM_001393370.1 → NP_001380299.1  CCR4-NOT transcription complex subunit 4 isoform f

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      Consensus CDS
      CCDS55165.1
      Conserved Domains (1) summary
      COG5175
      Location:14 → 322
      MOT2; Transcriptional repressor [Transcription]

    7. NM_001393371.1 → NP_001380300.1  CCR4-NOT transcription complex subunit 4 isoform g

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      Conserved Domains (1) summary
      COG5175
      Location:14 → 297
      MOT2; Transcriptional repressor [Transcription]

    8. NM_001393372.1 → NP_001380301.1  CCR4-NOT transcription complex subunit 4 isoform h

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      Conserved Domains (1) summary
      COG5175
      Location:14 → 285
      MOT2; Transcriptional repressor [Transcription]

    9. NM_001393373.1 → NP_001380302.1  CCR4-NOT transcription complex subunit 4 isoform i

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      Conserved Domains (1) summary
      COG5175
      Location:14 → 256
      MOT2; Transcriptional repressor [Transcription]

    10. NM_001393374.1 → NP_001380303.1  CCR4-NOT transcription complex subunit 4 isoform a

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      Consensus CDS
      CCDS43650.1
      UniProtKB/TrEMBL
      A0A9L9PY48
      Conserved Domains (1) summary
      COG5175
      Location:14 → 319
      MOT2; Transcriptional repressor [Transcription]

    11. NM_001393375.1 → NP_001380304.1  CCR4-NOT transcription complex subunit 4 isoform k

      Status: REVIEWED

      Source sequence(s)
      AC009331, AC083871, KF458610
      UniProtKB/TrEMBL
      A0A9L9PY48
      Conserved Domains (1) summary
      COG5175
      Location:14 → 285
      MOT2; Transcriptional repressor [Transcription]

    12. NM_013316.4 → NP_037448.2  CCR4-NOT transcription complex subunit 4 isoform a

      See identical proteins and their annotated locations for NP_037448.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) uses an alternate in-frame splice junction at the 3' end of an exon and lacks an alternate in-frame exon compared to variant 6. The resulting isoform (a) has the same N- and C-termini but is shorter compared to isoform f.
      Source sequence(s)
      AC009331, AC083871, AK314540, DA247976
      Consensus CDS
      CCDS43650.1
      UniProtKB/TrEMBL
      A0A9L9PY48
      Related
      ENSP00000354673.4, ENST00000361528.8
      Conserved Domains (1) summary
      COG5175
      Location:14 → 319
      MOT2; Transcriptional repressor [Transcription]

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      135361795..135510102 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420412.1 → XP_047276368.1  CCR4-NOT transcription complex subunit 4 isoform X1

    2. XM_047420413.1 → XP_047276369.1  CCR4-NOT transcription complex subunit 4 isoform X2

      UniProtKB/TrEMBL
      A0A9L9PY48

    3. XM_047420415.1 → XP_047276371.1  CCR4-NOT transcription complex subunit 4 isoform X4

      UniProtKB/TrEMBL
      A0A9L9PY48

    4. XM_047420414.1 → XP_047276370.1  CCR4-NOT transcription complex subunit 4 isoform X3

      UniProtKB/Swiss-Prot
      B7Z6I4, E7ET38, F8VQP3, O95339, O95627, O95628, Q8IYM7, Q8NCL0, Q9NPQ1, Q9NZN6
      UniProtKB/TrEMBL
      A0A9L9PY48
      Related
      ENSP00000516715.1, ENST00000707064.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      136669704..136817325 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358268.1 → XP_054214243.1  CCR4-NOT transcription complex subunit 4 isoform X1

    2. XM_054358269.1 → XP_054214244.1  CCR4-NOT transcription complex subunit 4 isoform X2

      UniProtKB/TrEMBL
      A0A9L9PY48

    3. XM_054358271.1 → XP_054214246.1  CCR4-NOT transcription complex subunit 4 isoform X4

      UniProtKB/TrEMBL
      A0A9L9PY48

    4. XM_054358270.1 → XP_054214245.1  CCR4-NOT transcription complex subunit 4 isoform X3

      UniProtKB/Swiss-Prot
      B7Z6I4, E7ET38, F8VQP3, O95339, O95627, O95628, Q8IYM7, Q8NCL0, Q9NPQ1, Q9NZN6
      UniProtKB/TrEMBL
      A0A9L9PY48
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95628.3 GenPept UniProtKB/Swiss-Prot:O95628

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