CNOT2 (CCR4-NOT transcription complex subunit 2)

Gene

• Entrez ID: 4848
• Gene name: CCR4-NOT transcription complex subunit 2
• Gene symbol: CNOT2
• Synonyms: CDC36, HSPC131, IDNADFS, NOT2, NOT2H
• Chromosome: 12
• Chromosome location: 12q15
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1593269476	A>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, downstream transcript variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT036704	hsa-miR-301b-3p	CLASH	23622248
MIRT044094	hsa-miR-361-5p	CLASH	23622248
MIRT051943	hsa-let-7b-5p	CLASH	23622248
MIRT507697	hsa-miR-7703	PAR-CLIP	23446348
MIRT507697	hsa-miR-7703	PAR-CLIP	22012620
MIRT507697	hsa-miR-7703	PAR-CLIP	21572407
MIRT507697	hsa-miR-7703	PAR-CLIP	20371350
MIRT507698	hsa-miR-4325	PAR-CLIP	23446348
MIRT507698	hsa-miR-4325	PAR-CLIP	22012620
MIRT507698	hsa-miR-4325	PAR-CLIP	21572407
MIRT507698	hsa-miR-4325	PAR-CLIP	20371350
MIRT507699	hsa-miR-889-3p	PAR-CLIP	23446348
MIRT507699	hsa-miR-889-3p	PAR-CLIP	22012620
MIRT507699	hsa-miR-889-3p	PAR-CLIP	21572407
MIRT507699	hsa-miR-889-3p	PAR-CLIP	20371350
MIRT507700	hsa-miR-548au-3p	PAR-CLIP	23446348
MIRT507700	hsa-miR-548au-3p	PAR-CLIP	22012620
MIRT507700	hsa-miR-548au-3p	PAR-CLIP	21572407
MIRT507700	hsa-miR-548au-3p	PAR-CLIP	20371350
MIRT507701	hsa-miR-92b-3p	PAR-CLIP	23446348
MIRT507701	hsa-miR-92b-3p	PAR-CLIP	22012620
MIRT507701	hsa-miR-92b-3p	PAR-CLIP	21572407
MIRT507701	hsa-miR-92b-3p	PAR-CLIP	20371350
MIRT507702	hsa-miR-92a-3p	PAR-CLIP	23446348
MIRT507702	hsa-miR-92a-3p	PAR-CLIP	22012620
MIRT507702	hsa-miR-92a-3p	PAR-CLIP	21572407
MIRT507702	hsa-miR-92a-3p	PAR-CLIP	20371350
MIRT507703	hsa-miR-367-3p	PAR-CLIP	23446348
MIRT507703	hsa-miR-367-3p	PAR-CLIP	22012620
MIRT507703	hsa-miR-367-3p	PAR-CLIP	21572407
MIRT507703	hsa-miR-367-3p	PAR-CLIP	20371350
MIRT507704	hsa-miR-363-3p	PAR-CLIP	23446348
MIRT507704	hsa-miR-363-3p	PAR-CLIP	22012620
MIRT507704	hsa-miR-363-3p	PAR-CLIP	21572407
MIRT507704	hsa-miR-363-3p	PAR-CLIP	20371350
MIRT507705	hsa-miR-32-5p	PAR-CLIP	23446348
MIRT507705	hsa-miR-32-5p	PAR-CLIP	21572407
MIRT507705	hsa-miR-32-5p	PAR-CLIP	20371350
MIRT507706	hsa-miR-25-3p	PAR-CLIP	23446348
MIRT507706	hsa-miR-25-3p	PAR-CLIP	22012620
MIRT507706	hsa-miR-25-3p	PAR-CLIP	21572407
MIRT507706	hsa-miR-25-3p	PAR-CLIP	20371350
MIRT507707	hsa-miR-5003-3p	PAR-CLIP	23446348
MIRT507707	hsa-miR-5003-3p	PAR-CLIP	22012620
MIRT507707	hsa-miR-5003-3p	PAR-CLIP	21572407
MIRT507707	hsa-miR-5003-3p	PAR-CLIP	20371350
MIRT532408	hsa-miR-935	PAR-CLIP	22012620
MIRT532408	hsa-miR-935	PAR-CLIP	21572407
MIRT615076	hsa-miR-9500	HITS-CLIP	23824327
MIRT615077	hsa-miR-1264	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	14707134, 16712523
GO:0000289	Process	Nuclear-transcribed mRNA poly(A) tail shortening	IBA	21873635
GO:0000289	Process	Nuclear-transcribed mRNA poly(A) tail shortening	TAS
GO:0000932	Component	P-body	IBA	21873635
GO:0001226	Function	RNA polymerase II transcription corepressor binding	IDA	16712523
GO:0001829	Process	Trophectodermal cell differentiation	IEA
GO:0003712	Function	Transcription coregulator activity	TAS	10637334
GO:0004535	Function	Poly(A)-specific ribonuclease activity	IMP	21299754
GO:0005515	Function	Protein binding	IPI	10637334, 16189514, 16778766, 17452450, 21981923, 21984185, 26496610, 31515488, 32296183
GO:0005634	Component	Nucleus	NAS	10637334
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	21299754
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	NAS	10637334
GO:0006417	Process	Regulation of translation	IEA
GO:0006977	Process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	TAS
GO:0010606	Process	Positive regulation of cytoplasmic mRNA processing body assembly	IMP	21299754
GO:0016020	Component	Membrane	HDA	19946888
GO:0030014	Component	CCR4-NOT complex	IDA	19558367
GO:0030015	Component	CCR4-NOT core complex	IBA	21873635
GO:0031047	Process	Gene silencing by RNA	IEA
GO:0033147	Process	Negative regulation of intracellular estrogen receptor signaling pathway	IMP	16778766
GO:0090503	Process	RNA phosphodiester bond hydrolysis, exonucleolytic	IEA
GO:2000036	Process	Regulation of stem cell population maintenance	IBA	21873635
GO:2000036	Process	Regulation of stem cell population maintenance	IMP	22367759

Other IDs

• MIM: 604909
• HGNC: 7878
• e!Ensembl: ENSG00000111596

Protein

• UniProt ID: Q9NZN8
• Protein name: CCR4-NOT transcription complex subunit 2 (CCR4-associated factor 2)
• Protein function: 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. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity.
• PDB: 4C0D, 4C0F, 5FU6, 5FU7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04153	NOT2_3_5	396 → 521	NOT2 / NOT3 / NOT5 family	Family

• Sequence:

  MVRTDGHTLSEKRNYQVTNSMFGASRKKFVEGVDSDYHDENMYYSQSSMFPHRSEKDMLA
  SPSTSGQLSQFGASLYGQQSALGLPMRGMSNNTPQLNRSLSQGTQLPSHVTPTTGVPTMS
  LHTPPSPSRGILPMNPRNMMNHSQVGQGIGIPSRTNSMSSSGLGSPNRSSPSIICMPKQQ
  PSRQPFTVNSMSGFGMNRNQAFGMNNSLSSNIFNGTDGSENVTGLDLSDFPALADRNRRE
  GSGNPTPLINPLAGRAPYVGMVTKPANEQSQDFSIHNEDFPALPGSSYKDPTSSNDDSKS
  NLNTSGKTTSSTDGPKFPGDKSSTTQNNNQQKKGIQVLPDGRVTNIPQGMVTDQFGMIGL
  LTFIRAAETDPGMVHLALGSDLTTLGLNLNSPENLYPKFASPWASSPCRPQDIDFHVPSE
  YLTNIHIRDKLAAIKLGRYGEDLLFYLYYMNGGDVLQLLAAVELFNRDWRYHKEERVWIT
  RAPGMEPTMKTNTYERGTYYFFDCLNWRKVAKEFHLEYDKLEERPHLPSTFNYNPAQQAF
  

• Sequence length: 540

Pathways

KEGG:

RNA degradation

Reactome:

Deadenylation of mRNA
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain

Associated diseases

Disease name	Disease term	References
	12q15q21.1 microdeletion syndrome
	ovarian neoplasm	30557369