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

    Gene ID: 4848, updated on 10-Dec-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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    See CNOT2 in Genome Data Viewer
    Location:
    12q15
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (70243018..70354993)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (70222411..70334463)
    RS_2024_09 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: 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. CNOT2 haploinsufficiency causes a neurodevelopmental disorder with characteristic facial features. Uehara T, et al. Am J Med Genet A, 2019 Dec. PMID 31512373
    2. 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
    3. 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
    4. The CCR4-NOT complex plays diverse roles in mRNA metabolism. Denis CL, et al. Prog Nucleic Acid Res Mol Biol, 2003. PMID 12882519
    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 (85) 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)

    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
      UniProtKB/TrEMBL
      B3KTL6

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

      Status: REVIEWED

      Source sequence(s)
      AC025569, AC092881
      UniProtKB/TrEMBL
      B3KTL6

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

      Status: REVIEWED

      Source sequence(s)
      AC025569, AC092881
      UniProtKB/TrEMBL
      B3KTL6, 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
      B3KTL6, 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
      B3KTL6, F8VV52

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

      Status: REVIEWED

      Source sequence(s)
      AC025569, AC092881
      UniProtKB/TrEMBL
      B3KTL6

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

      Status: REVIEWED

      Source sequence(s)
      AC025569, AC092881
      UniProtKB/TrEMBL
      B3KTL6, 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
      B3KTL6, 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
      B3KTL6, 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
      B3KTL6, 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
      UniProtKB/TrEMBL
      B3KTL6

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

      Status: REVIEWED

      Source sequence(s)
      AC025569, AC092881
      UniProtKB/TrEMBL
      B2RDX7, B3KTL6

    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_2024_08

    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
      B3KTL6, 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
      B3KTL6, 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
      B3KTL6, F8VUB4

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

      UniProtKB/TrEMBL
      B3KTL6, 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
      B3KTL6, 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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