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FLASH GENE

Symbol

CNOT3

contributors: mct/npt - updated : 17-01-2018

HGNC name	CCR4-NOT transcription complex, subunit 3
HGNC id	7879

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.42      Physical location : 54.641.435 - 54.659.445
Synonym name	NOT3 (negative regulator of transcription3, yeast) homolog
	cDNA sequence, expressed in brain, >100kDa, related to S Pombe cos C1B3
	CCR4-associated factor 3
	leukocyte receptor cluster member 2
Synonym symbol(s)	KIAA0691, NOT3, LENG2, NOT3H

DNA

TYPE	functioning gene
STRUCTURE	17.98 kb     18 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

regionally located

in the region of the leukocyte receptor cluster

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NOT3L - - - - 897 - 2002 12207886 has an extra 144 amino acids (AAs) at the C-terminus of a classical NOT3 associated with CAND2 but not with CAND1 NM_014516 18 - 2908 NP_055331 - 753 - 2002 12207886 NOT3

EXPRESSION

Type	ubiquitous

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       highly Homo sapiens Digestive intestine small intestine     moderately Endocrine neuroendocrine pituitary     moderately Lymphoid/Immune thymus       moderately Nervous brain           nerve cranial nerve     highly Reproductive female system ovary     highly Respiratory respiratory tract larynx     predominantly Skin/Tegument skin       moderately Urinary bladder       moderately   kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Muscular striatum cardiac   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Muscular myocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a putative N terminal coiled-coil domain of the spectrin repeat type
	a C ternimus rich in proline and serine residues with a specific C terminal region of interaction with TIP120B

mono polymer

complex

HOMOLOGY

interspecies	homolog to rattus Cnot3 (95.7 pc)
	homolog to murine Cnot3 (95.5 pc)

Homologene

FAMILY

CNOT2/3/5 family

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	involved in the control of gene expression
	constituent of CCR4-NOT complex, and may be involved in global gene regulation via interaction with TBP (Aoki 2002)
	global regulator of RNA polymerase II transcription (Albert 2000)
	responds to feeding conditions to regulate deadenylation-specific mRNAs and energy metabolism
	involved in the regulation of the spindle assembly checkpoint
	CNOT3 regulation of MAD1L1 represents a novel type of post-transcriptional regulation of the spindle assembly checkpoint
	involved in the regulation of the spindle assembly checkpoint through two different mechanisms, namely at the levels of mRNA expression and protein–protein interaction
	involved in regulation of mitotic progression through mRNA destabilization-mediated inhibition of MAD1L1 expression
	CNOT1, CNOT2, and CNOT3 represent a novel component of the core self-renewal and pluripotency circuitry conserved in Embryonic stem cell (ESC)
	is a critical regulator of bone mass acting on bone resorption through posttranscriptional down-regulation of RANK mRNA stability, at least in part, even in aging-induced osteoporosis
	maintains likely the pluripotent state by promoting differentiation gene mRNA deadenylation and degradation
	is a critical regulator in cardiomyocyte proliferation at the late stage of cardiac differentiation from human ESCs
	CNOT3 enhances cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation
	CNOT3 bound to and shortened the poly(A) tail of the mRNA encoding the key autophagy regulator ATG7

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

component of the CCR4-NOT (CAF1) core complex containing CHAF1A, CHAF1B, CNOT1, CNOT2, CNOT3, CNOT4, CNOT6 and CNOT8

INTERACTION

DNA

RNA	CNOT3 targets specific mRNAs to prevent cells from being disposed to necroptotic death

small molecule

protein	CNOT8 and other CNOTs subunits
	binding to TBP-interacting protein TIP120B
	interacting with CREBBP
	negatively regulates the expression of MAD1L1, which is evidenced by the stabilization of MAD1L1 mRNA upon CNOT3 depletion
	CNOT3 is the main modifier gene determining penetrance of PRPF31 mutations, via a mechanism of transcriptional repression
	a fraction of all HIPK family members associates with the CCR4-NOT components CNOT2 and CNOT3
	interaction of CNOT3 with EBF1 diversifies the function of EBF1 in a context-dependent manner and may coordinate transcriptional and post-transcriptional gene regulation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in 8p100 of adult T-cell acute lymphoblastic leukemias constitutional   deletion     results in increases in the poly(A) tail lengths, half-lives, and steady-state levels of differentiation gene mRNAs constitutional       loss of function causes an enhancement in bone resorption in association with an elevation in bone formation, resulting in high-turnover type bone loss

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	is a new biomarker for molecular and prognostic classification of early-stage colorectal cancer
Therapy target

ANIMAL & CELL MODELS

	adipocyte-specific disruption of mouse Cnot3 causes lipodystrophy
	Cnot3-depleted mouse embryonic fibroblasts (MEFs) undergo cell death
	mice lacking the CNOT3 subunit of this complex, specifically in B cells, have a developmental block at the pro- to pre-B cell transition