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CNOT2 CCR4-NOT transcription complex subunit 2 [ Homo sapiens (human) ]

Gene ID: 4848, updated on 3-Apr-2024

Summary

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Official Symbol
CNOT2provided by HGNC
Official Full Name
CCR4-NOT transcription complex subunit 2provided by HGNC
Primary source
HGNC:HGNC:7878
See related
Ensembl:ENSG00000111596 MIM:604909; AllianceGenome:HGNC:7878
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
NOT2; CDC36; NOT2H; HSPC131; IDNADFS
Summary
This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]
Expression
Ubiquitous expression in bone marrow (RPKM 13.7), skin (RPKM 12.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
12q15
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (70243018..70354993)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (70222411..70334463)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (70636798..70748773)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene histone PARylation factor 1 pseudogene Neighboring gene MPRA-validated peak1797 silencer Neighboring gene MPRA-validated peak1798 silencer Neighboring gene long intergenic non-protein coding RNA 2821 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:70636499-70637698 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6658 Neighboring gene progenitor renewal associated non-coding RNA Neighboring gene MPRA-validated peak1799 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:70650862-70651362 Neighboring gene NANOG hESC enhancer GRCh37_chr12:70652346-70652879 Neighboring gene MPRA-validated peak1802 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4656 Neighboring gene MPRA-validated peak1805 silencer Neighboring gene potassium calcium-activated channel subfamily M regulatory beta subunit 4 Neighboring gene MPRA-validated peak1806 silencer Neighboring gene RNA, U4 small nuclear 65, pseudogene

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. Delineation of the clinical profile of CNOT2 haploinsufficiency and overview of the IDNADFS phenotype. Niceta M, et al. Clin Genet, 2023 Feb. PMID 36224108, Free PMC Article
  2. CNOT2 haploinsufficiency in a 40-year-old man with intellectual disability, autism, and seizures. Royer-Bertrand B, et al. Am J Med Genet A, 2021 Aug. PMID 34018673
  3. CNOT2 haploinsufficiency causes a neurodevelopmental disorder with characteristic facial features. Uehara T, et al. Am J Med Genet A, 2019 Dec. PMID 31512373
  4. CNOT2 facilitates dengue virus infection via negatively modulating IFN-Independent Non-Canonical JAK/STAT pathway. Liu J, et al. Biochem Biophys Res Commun, 2019 Jul 30. PMID 31155293
  5. A heterozygous, intragenic deletion of CNOT2 recapitulates the phenotype of 12q15 deletion syndrome. Alesi V, et al. Am J Med Genet A, 2019 Aug. PMID 31145527

See all (79) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53.
    Title: Inhibition of CNOT2 Induces Apoptosis via MID1IP1 in Colorectal Cancer Cells by Activating p53.
  2. CNOT2 haploinsufficiency in a 40-year-old man with intellectual disability, autism, and seizures.
    Title: CNOT2 haploinsufficiency in a 40-year-old man with intellectual disability, autism, and seizures.
  3. CCR4NOT transcription complex subunit 2 regulates TRAIL sensitivity in nonsmallcell lung cancer cells via the STAT3 pathway.
    Title: CCR4‑NOT transcription complex subunit 2 regulates TRAIL sensitivity in non‑small‑cell lung cancer cells via the STAT3 pathway.
  4. CNOT2 is a novel negative regulator of the JAK-STAT pathway and supports dengue virus infection.
    Title: CNOT2 facilitates dengue virus infection via negatively modulating IFN-Independent Non-Canonical JAK/STAT pathway.
  5. Increased expression of MHC II genes after knock-down or knock-out of either CNOT1, CNOT2, or CNOT3 subunit was seen in a variety of cell systems and also in naive macrophages from CNOT3 conditional knock-out mice.
    Title: The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription.
  6. CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells.
    Title: CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells.
  7. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex.
    Title: The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.
  8. The CNOT2-CNOT3 heterodimer is stabilized and tightly anchored to the surface of CNOT1 through an unexpected intertwined arrangement of peptide regions lacking defined secondary structure.
    Title: Structure and assembly of the NOT module of the human CCR4-NOT complex.
  9. Cnot1, Cnot2, and Cnot3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in mouse and human ESCs.
    Title: Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation.
  10. human CNOT2 is important for maintaining the deadenylase activity and structural integrity of the CCR4-NOT complex, thereby affecting cell viability.
    Title: CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death.
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

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2022-11-08)

ClinGen Genome Curation Page
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2022-11-08)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
EBI GWAS Catalog

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

Clone Names

  • FLJ26456

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to poly(A)-specific ribonuclease activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transcription coregulator activity TAS
Traceable Author Statement
more info
 PubMed 
enables transcription corepressor binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of intracellular estrogen receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
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 NAS
Non-traceable Author Statement
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 stem cell population maintenance IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of stem cell population maintenance IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of translation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulatory ncRNA-mediated gene silencing IEA
Inferred from Electronic Annotation
more info
  
involved_in trophectodermal cell differentiation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
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 
part_of CCR4-NOT core complex IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in P-body IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
CCR4-NOT transcription complex subunit 2
Names
CC chemokine receptor 4-negative regulator of transcription 2
CCR4-associated factor 2
negative regulator of transcription 2

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_001199302.2 → NP_001186231.1  CCR4-NOT transcription complex subunit 2 isoform a

    See identical proteins and their annotated locations for NP_001186231.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-3 and 5 all encode the same isoform (a).
    Source sequence(s)
    AA234384, AC025569, AC092881, AK315715, BC002597
    Consensus CDS
    CCDS31857.1
    UniProtKB/Swiss-Prot
    Q9H3E0, Q9NSX5, Q9NWR6, Q9NZN8, Q9P028
    UniProtKB/TrEMBL
    B3KTL6
    Related
    ENSP00000412091.3, ENST00000418359.7
    Conserved Domains (1) summary
    pfam04153
    Location:396 → 519
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

  2. NM_001199303.2 → NP_001186232.1  CCR4-NOT transcription complex subunit 2 isoform a

    See identical proteins and their annotated locations for NP_001186232.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1-3 and 5 all encode the same isoform (a).
    Source sequence(s)
    AA234384, AC025569, AK095789, AK307479, BC002597
    Consensus CDS
    CCDS31857.1
    UniProtKB/Swiss-Prot
    Q9H3E0, Q9NSX5, Q9NWR6, Q9NZN8, Q9P028
    UniProtKB/TrEMBL
    B3KTL6
    Related
    ENSP00000449260.1, ENST00000551043.5
    Conserved Domains (1) summary
    pfam04153
    Location:396 → 519
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

  3. NM_001414651.1 → NP_001401580.1  CCR4-NOT transcription complex subunit 2 isoform a

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/Swiss-Prot
    Q9H3E0, Q9NSX5, Q9NWR6, Q9NZN8, Q9P028

  4. NM_001414652.1 → NP_001401581.1  CCR4-NOT transcription complex subunit 2 isoform b

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881

  5. NM_001414653.1 → NP_001401582.1  CCR4-NOT transcription complex subunit 2 isoform c

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VV52
    Related
    ENSP00000449659.1, ENST00000548159.5

  6. NM_001414654.1 → NP_001401583.1  CCR4-NOT transcription complex subunit 2 isoform c

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VV52

  7. NM_001414655.1 → NP_001401584.1  CCR4-NOT transcription complex subunit 2 isoform c

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VV52

  8. NM_001414656.1 → NP_001401585.1  CCR4-NOT transcription complex subunit 2 isoform d

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881

  9. NM_001414657.1 → NP_001401586.1  CCR4-NOT transcription complex subunit 2 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VUB4

  10. NM_001414658.1 → NP_001401587.1  CCR4-NOT transcription complex subunit 2 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VUB4

  11. NM_001414659.1 → NP_001401588.1  CCR4-NOT transcription complex subunit 2 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VUB4

  12. NM_001414660.1 → NP_001401589.1  CCR4-NOT transcription complex subunit 2 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881
    UniProtKB/TrEMBL
    F8VUB4
    Related
    ENSP00000448024.2, ENST00000550641.6

  13. NM_001414661.1 → NP_001401590.1  CCR4-NOT transcription complex subunit 2 isoform f

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881

  14. NM_001414662.1 → NP_001401591.1  CCR4-NOT transcription complex subunit 2 isoform g

    Status: REVIEWED

    Source sequence(s)
    AC025569, AC092881

  15. NM_014515.7 → NP_055330.1  CCR4-NOT transcription complex subunit 2 isoform a

    See identical proteins and their annotated locations for NP_055330.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-3 and 5 all encode the same isoform (a).
    Source sequence(s)
    AC025569, AC092881
    Consensus CDS
    CCDS31857.1
    UniProtKB/Swiss-Prot
    Q9H3E0, Q9NSX5, Q9NWR6, Q9NZN8, Q9P028
    UniProtKB/TrEMBL
    B3KTL6
    Related
    ENSP00000229195.3, ENST00000229195.8
    Conserved Domains (1) summary
    pfam04153
    Location:396 → 519
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

RNA

  1. NR_037615.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) includes an alternate internal exon compared to variant 1. This variant is represented as non-coding because use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AA234384, AC025569, AK307479, BC002597

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    70243018..70354993
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047428882.1 → XP_047284838.1  CCR4-NOT transcription complex subunit 2 isoform X2

    UniProtKB/TrEMBL
    F8VUB4

  2. XM_017019348.2 → XP_016874837.1  CCR4-NOT transcription complex subunit 2 isoform X1

    UniProtKB/TrEMBL
    B3KTL6, F8VV52
    Conserved Domains (1) summary
    pfam04153
    Location:387 → 510
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

  3. XM_024448986.2 → XP_024304754.1  CCR4-NOT transcription complex subunit 2 isoform X5

    Conserved Domains (1) summary
    pfam04153
    Location:250 → 373
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

  4. XM_006719433.5 → XP_006719496.1  CCR4-NOT transcription complex subunit 2 isoform X4

    See identical proteins and their annotated locations for XP_006719496.1

    Conserved Domains (1) summary
    pfam04153
    Location:259 → 382
    NOT2_3_5; NOT2 / NOT3 / NOT5 family

  5. XM_047428885.1 → XP_047284841.1  CCR4-NOT transcription complex subunit 2 isoform X3

  6. XM_024448988.2 → XP_024304756.1  CCR4-NOT transcription complex subunit 2 isoform X6

  7. XM_047428886.1 → XP_047284842.1  CCR4-NOT transcription complex subunit 2 isoform X4

  8. XM_047428884.1 → XP_047284840.1  CCR4-NOT transcription complex subunit 2 isoform X2

    UniProtKB/TrEMBL
    F8VUB4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    70222411..70334463
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372116.1 → XP_054228091.1  CCR4-NOT transcription complex subunit 2 isoform X2

    UniProtKB/TrEMBL
    F8VUB4

  2. XM_054372115.1 → XP_054228090.1  CCR4-NOT transcription complex subunit 2 isoform X1

    UniProtKB/TrEMBL
    F8VV52

  3. XM_054372121.1 → XP_054228096.1  CCR4-NOT transcription complex subunit 2 isoform X8

  4. XM_054372119.1 → XP_054228094.1  CCR4-NOT transcription complex subunit 2 isoform X7

  5. XM_054372118.1 → XP_054228093.1  CCR4-NOT transcription complex subunit 2 isoform X3

  6. XM_054372122.1 → XP_054228097.1  CCR4-NOT transcription complex subunit 2 isoform X6

  7. XM_054372120.1 → XP_054228095.1  CCR4-NOT transcription complex subunit 2 isoform X7

  8. XM_054372117.1 → XP_054228092.1  CCR4-NOT transcription complex subunit 2 isoform X2

    UniProtKB/TrEMBL
    F8VUB4
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NZN8.1 GenPept UniProtKB/Swiss-Prot:Q9NZN8

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