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Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of embryonic stem (ES) cell identity.
our findings implicate CNOT3 in the coordination of colonic epithelial cell self-renewal, suggesting this factor as a new biomarker for molecular and prognostic classification of early-stage colorectal cancer PMID: 27899379
A mutation in PRPF31 is hypostatic to a trait acting on CNOT3, with the RP11 phenotype only being observed when there is homozygous (recessive) inheritance of the higher expressivity CNOT3 ("symptomatic" or risk) allele. PMID: 24116917
In asymptomatic carriers CNOT3 is expressed at low levels, allowing higher amounts of wild-type PRPF31 transcripts to be produced and preventing manifestation of retinal degeneration. PMID: 23144630
CNOT3 is a tumor suppressor mutated in 7 of 89 (7.9%) adult T-cell acute lymphoblastic leukemias, and its knockdown causes tumors in a sensitized Drosophila melanogaster model. PMID: 23263491
A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis. PMID: 22294640
CNOT3 depletion stabilizes the MAD1 mRNA, and MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. PMID: 22342980
TBP-interacting protein 120B binds to NOT3 PMID: 12207886
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Subcellular Location
Cytoplasm. Nucleus. Cytoplasm, P-body.
Protein Families
CNOT2/3/5 family
Tissue Specificity
Ubiquitous. Highly expressed in brain, heart, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes.