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

Gene ID: 4850, updated on 17-May-2023

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
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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_2023_03 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (135361795..135510102, complement)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (136669704..136817325, complement)
105.20220307 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 H3K4me1 hESC enhancer GRCh37_chr7:135023371-135023872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:135023873-135024372 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 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: 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. 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
  2. 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
  3. 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
  4. 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
  5. 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

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Single nucleotide polymorphism in CNOT4 gene is associated with osteosarcoma susceptibility.
    Title: Polymorphisms in miRNA processing genes and their role in osteosarcoma risk.
Submit: New GeneRIF Correction See all GeneRIFs (14)

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

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
 PubMed 
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
 PubMed 
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
 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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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/Swiss-Prot
    O95628
    UniProtKB/TrEMBL
    A0A024R776
    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/Swiss-Prot
    O95628
    UniProtKB/TrEMBL
    A0A024R781
    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
    O95628, Q9NZN6
    UniProtKB/TrEMBL
    A0A024R785
    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
    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
    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/Swiss-Prot
    O95628
    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_2023_03

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
    A0A024R781

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

    UniProtKB/TrEMBL
    A0A024R776

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

    UniProtKB/Swiss-Prot
    Q9NZN6
    UniProtKB/TrEMBL
    A0A024R785
    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
    A0A024R781

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

    UniProtKB/TrEMBL
    A0A024R776

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

    UniProtKB/Swiss-Prot
    Q9NZN6
    UniProtKB/TrEMBL
    A0A024R785
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95628.3 GenPept UniProtKB/Swiss-Prot:O95628

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