CNOT2_MOUSE
ID CNOT2_MOUSE Reviewed; 540 AA.
AC Q8C5L3; Q3UE39; Q80YA5; Q9D0P1;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=CCR4-NOT transcription complex subunit 2;
DE AltName: Full=CCR4-associated factor 2;
GN Name=Cnot2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Embryo, and Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157; SER-165 AND SER-169, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=22367759; DOI=10.1002/stem.1070;
RA Zheng X., Dumitru R., Lackford B.L., Freudenberg J.M., Singh A.P.,
RA Archer T.K., Jothi R., Hu G.;
RT "Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit
RT extraembryonic differentiation.";
RL Stem Cells 30:910-922(2012).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Component of the CCR4-NOT complex which is one of the major
CC cellular mRNA deadenylases and is linked to various cellular processes
CC including bulk mRNA degradation, miRNA-mediated repression,
CC translational repression during translational initiation and general
CC transcription regulation. Additional complex functions may be a
CC consequence of its influence on mRNA expression. Required for the CCR4-
CC NOT complex structural integrity. Can repress transcription and may
CC link the CCR4-NOT complex to transcriptional regulation; the repressive
CC function may specifically involve the N-Cor repressor complex
CC containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of
CC embryonic stem (ES) cell identity; prevents their differentiation
CC towards extraembryonic trophectoderm lineages.
CC {ECO:0000269|PubMed:22367759}.
CC -!- SUBUNIT: Component of the CCR4-NOT complex; distinct complexes seem to
CC exist that differ in the participation of probably mutually exclusive
CC catalytic subunits. In the complex interacts directly with CNOT3.
CC Interacts with NCOR1, NCOR2. HDAC3 and GPS2 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZN8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8C5L3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C5L3-2; Sequence=VSP_009918;
CC Name=3;
CC IsoId=Q8C5L3-3; Sequence=VSP_009917;
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem (ES) cells and in
CC inner cell mass (ICM) of the blastocyst. {ECO:0000269|PubMed:22367759}.
CC -!- SIMILARITY: Belongs to the CNOT2/3/5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH43133.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK011231; BAB27481.1; -; mRNA.
DR EMBL; AK078121; BAC37134.1; -; mRNA.
DR EMBL; AK149767; BAE29072.1; -; mRNA.
DR EMBL; BC043133; AAH43133.1; ALT_FRAME; mRNA.
DR EMBL; BC063105; AAH63105.1; -; mRNA.
DR EMBL; BC065171; AAH65171.1; -; mRNA.
DR CCDS; CCDS36064.1; -. [Q8C5L3-1]
DR CCDS; CCDS88089.1; -. [Q8C5L3-3]
DR RefSeq; NP_001032935.2; NM_001037846.3. [Q8C5L3-1]
DR RefSeq; NP_001032936.2; NM_001037847.2.
DR RefSeq; NP_001032937.1; NM_001037848.3.
DR RefSeq; NP_082358.2; NM_028082.2.
DR RefSeq; XP_006514238.1; XM_006514175.3. [Q8C5L3-1]
DR RefSeq; XP_006514240.1; XM_006514177.3.
DR RefSeq; XP_006514242.1; XM_006514179.3.
DR RefSeq; XP_006514243.1; XM_006514180.1.
DR RefSeq; XP_006514244.1; XM_006514181.1. [Q8C5L3-2]
DR RefSeq; XP_006514246.1; XM_006514183.3. [Q8C5L3-3]
DR RefSeq; XP_006514247.1; XM_006514184.3. [Q8C5L3-3]
DR RefSeq; XP_017169595.1; XM_017314106.1.
DR RefSeq; XP_017169596.1; XM_017314107.1. [Q8C5L3-2]
DR RefSeq; XP_017169597.1; XM_017314108.1.
DR RefSeq; XP_017169598.1; XM_017314109.1.
DR AlphaFoldDB; Q8C5L3; -.
DR BioGRID; 215128; 20.
DR IntAct; Q8C5L3; 19.
DR STRING; 10090.ENSMUSP00000100902; -.
DR iPTMnet; Q8C5L3; -.
DR PhosphoSitePlus; Q8C5L3; -.
DR EPD; Q8C5L3; -.
DR jPOST; Q8C5L3; -.
DR MaxQB; Q8C5L3; -.
DR PaxDb; Q8C5L3; -.
DR PRIDE; Q8C5L3; -.
DR ProteomicsDB; 283464; -. [Q8C5L3-1]
DR ProteomicsDB; 283465; -. [Q8C5L3-2]
DR ProteomicsDB; 283466; -. [Q8C5L3-3]
DR Antibodypedia; 17029; 454 antibodies from 33 providers.
DR DNASU; 72068; -.
DR Ensembl; ENSMUST00000105265; ENSMUSP00000100900; ENSMUSG00000020166. [Q8C5L3-3]
DR Ensembl; ENSMUST00000105267; ENSMUSP00000100902; ENSMUSG00000020166. [Q8C5L3-1]
DR Ensembl; ENSMUST00000169921; ENSMUSP00000132152; ENSMUSG00000020166. [Q8C5L3-1]
DR GeneID; 72068; -.
DR KEGG; mmu:72068; -.
DR UCSC; uc007hcb.2; mouse. [Q8C5L3-1]
DR CTD; 4848; -.
DR MGI; MGI:1919318; Cnot2.
DR VEuPathDB; HostDB:ENSMUSG00000020166; -.
DR eggNOG; KOG2151; Eukaryota.
DR GeneTree; ENSGT00390000001285; -.
DR HOGENOM; CLU_033275_1_0_1; -.
DR InParanoid; Q8C5L3; -.
DR OMA; GMNRNQV; -.
DR OrthoDB; 1790973at2759; -.
DR PhylomeDB; Q8C5L3; -.
DR TreeFam; TF313102; -.
DR Reactome; R-MMU-429947; Deadenylation of mRNA.
DR Reactome; R-MMU-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR BioGRID-ORCS; 72068; 13 hits in 72 CRISPR screens.
DR ChiTaRS; Cnot2; mouse.
DR PRO; PR:Q8C5L3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8C5L3; protein.
DR Bgee; ENSMUSG00000020166; Expressed in indifferent gonad and 263 other tissues.
DR ExpressionAtlas; Q8C5L3; baseline and differential.
DR Genevisible; Q8C5L3; MM.
DR GO; GO:0030014; C:CCR4-NOT complex; ISS:UniProtKB.
DR GO; GO:0030015; C:CCR4-NOT core complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISS:UniProtKB.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IBA:GO_Central.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; ISS:UniProtKB.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IMP:UniProtKB.
DR Gene3D; 2.30.30.1020; -; 1.
DR InterPro; IPR038635; CCR4-NOT_su2/3/5_N_sf.
DR InterPro; IPR040168; Not2/3/5.
DR InterPro; IPR007282; NOT2/3/5_C.
DR PANTHER; PTHR23326; PTHR23326; 1.
DR Pfam; PF04153; NOT2_3_5; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; RNA-mediated gene silencing;
KW Transcription; Transcription regulation; Translation regulation.
FT CHAIN 1..540
FT /note="CCR4-NOT transcription complex subunit 2"
FT /id="PRO_0000198332"
FT REGION 96..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..125
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 287..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 93
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN8"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN8"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN8"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZN8"
FT VAR_SEQ 1..85
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009917"
FT VAR_SEQ 1..15
FT /note="MVRTDGHTLSEKRNY -> MLKEVA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009918"
FT CONFLICT 148
FT /note="G -> S (in Ref. 1; BAC37134)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="H -> Y (in Ref. 2; AAH43133)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 540 AA; 59711 MW; C5185262B5E3C78C CRC64;
MVRTDGHTLS EKRNYQVTNS MFGASRKKFV EGVDSDYHDE NMYYSQSSMF PHRSEKDMLA
SPSTSGQLSQ FGASLYGQQS ALGLPMRGMS NNTPQLNRSL SQGTQLPSHV TPTTGVPTMS
LHTPPSPSRG ILPMNPRNMM NHSQVGQGIG IPSRTNSMSS SGLGSPNRSS PSIICMPKQQ
PSRQPFTVNS MSGFGMNRNQ AFGMNNSLSS NIFNGTDGSE NVTGLDLSDF PALADRNRRE
GSGNPTPLIN PLAGRAPYVG MVTKPANEQS QDFSIHNEDF PALPGSSYKD PTSSNDDSKS
NLSTSGKTTS STDGPKFPGD KSSTTQNNNQ QKKGIQVLPD GRVTNIPQGM VTDQFGMIGL
LTFIRAAETD PGMVHLALGS DLTTLGLNLN SPENLYPKFA SPWASSPCRP QDIDFHVPSE
YLTNIHIRDK LAAIKLGRYG EDLLFYLYYM NGGDVLQLLA AVELFNRDWR YHKEERVWIT
RAPGMEPTMK TNTYERGTYY FFDCLNWRKV AKEFHLEYDK LEERPHLPST FNYNPAQQAF