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FLASH GENE
Symbol CNOT1 contributors: mct - updated : 12-06-2019
HGNC name CCR4-NOT transcription complex, subunit 1
HGNC id 7877
Corresponding disease
DDNFA developmental delay, neurological and facial abnormalities
HPEAP holoprosencephaly with pancreatic agenesis
Location 16q21      Physical location : 58.553.855 - 58.663.750
Synonym name
  • adrenal gland protein AD005
  • related to C elegans Cos F57B9
  • CCR4-associated factor 1
  • NOT1 (negative regulator of transcription 1, yeast) homolog
    • Synonym symbol(s) NOT1, CDC39, NOT1H, AD-005, KIAA1007, FLJ36492, FLJ90644, DKFZp686O168, DKFZp686E0722
    DNA
    TYPE functioning gene
    STRUCTURE 109.94 kb     49 Exon(s)
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    49 - 8476 - 2376 - 2013 24121232
    49 exons, isoform a
    31 - 5221 - 1551 - 2013 24121232
    31 exons, isoform b
    49 - 8461 - 2371 - 2013 24121232
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon lowly
     intestinesmall intestine   
     liver    
    Lymphoid/Immunespleen    
     thymus    
    Nervousbrain   highly
    Reproductivefemale systemplacenta  highly
    Respiratorylung    
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N-terminal HEAT domain
  • a CNOT1 domain interacting with CNOT9, which in turn interacts with the silencing domain of TNRC6 in a tryptophan motif-dependent manner
  • a domain of CNOT1 with an MIF4G fold recruits the DEAD-box ATPase DDX6, a known translational inhibitor
  • CNOT1-Cterminus provides a rigid scaffold consisting of two perpendicular stacks of HEAT-like repeats
    • HOMOLOGY
    interspecies ortholog to murine Cnot1
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    basic FUNCTION
  • may be a negative regulator of transcription
  • represses the ligand-dependent transcriptional activation function of oestrogen receptor (ESR1)
  • contains an intrinsic ability to mediate transcriptional repression
  • translational regulator through the binding of nuclear receptors and as a regulator of deadenylase activity
  • has an important role in exhibiting enzymatic activity of the CCR4-NOT complex, and thus is critical in control of mRNA deadenylation and mRNA decay
  • CNOT1, CNOT2, and CNOT3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in Embryonic stem cell (ESC)
  • CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity
  • CNOT1 facilitates recruitment of DDX6 to miRNA-targeted mRNAs, placing DDX6 as a downstream effector in the miRNA silencing pathway
  • CNOT1-LMNA-Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression
  • is associated with incomplete forebrain division
  • is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state
  • is a key factor in both pancreatic and neurological development
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CNOT1 can interact with the ligand-binding domain of ESR1 in a hormone-dependent fashion and is recruited with other Ccr4-Not subunits to endogenous oestrogen-regulated promoters dependent on the presence of ligand
  • CNOT1 interacts in a ligand-dependent manner with RXR and represses transcription mediated by several RXR heterodimers
  • interaction with ZFP36 (ZFP36 directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex)
  • DDX6 binds to a conserved CNOT1 subdomain in a manner resembling the interaction of the translation initiation factor EIF4A with EIF4G
  • DDX6 interacts with the CNOT1 complex and functions in concert with several post-transcriptional regulators, including EDC3, and EIF4ENIF1
  • YTHDF2 recruits the CCR4-NOT complex through a direct interaction between the YTHDF2 N-terminal region and the SH domain of the CNOT1 subunit, and this recruitment is essential for the deadenylation of m(6)A-containing RNAs by CAF1 and CCR4
  • CNOT1 interacted with LMNA (lamin A) and functioned as a positive regulator of this intermediate filament protein
  • CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTP&
    • 8209;mediated ICAM1 and IL8 mRNA decay
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HPEAP , DDNFA
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • genetic ablation of Atg7, but not Atg5, increased survival and partially restored cardiac function of Cnot1 or Cnot3 knockout mice