Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

CNOT1

contributors: mct - updated : 12-06-2019

HGNC name	CCR4-NOT transcription complex, subunit 1
HGNC id	7877

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine large intestine colon   lowly   intestine small intestine         liver         Lymphoid/Immune spleen           thymus         Nervous brain       highly Reproductive female system placenta     highly Respiratory lung         Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

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