CNOT2_HUMAN
ID CNOT2_HUMAN Reviewed; 540 AA.
AC Q9NZN8; Q9H3E0; Q9NSX5; Q9NWR6; Q9P028;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=CCR4-NOT transcription complex subunit 2;
DE AltName: Full=CCR4-associated factor 2;
GN Name=CNOT2; Synonyms=CDC36, NOT2; ORFNames=HSPC131, MSTP046;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CNOT1, AND TISSUE
RP SPECIFICITY.
RX PubMed=10637334; DOI=10.1093/nar/28.3.809;
RA Albert T.K., Lemaire M., van Berkum N.L., Gentz R., Collart M.A.,
RA Timmers H.T.M.;
RT "Isolation and characterization of human orthologs of yeast CCR4-NOT
RT complex subunits.";
RL Nucleic Acids Res. 28:809-817(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RA Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y.,
RA Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y.,
RA Liu L.S., Ding J.F., Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C.,
RA Zhao M.S., Hui R.T.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Fetal kidney, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph, and Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-377.
RA Bi A., Yu L., Zhang M., Fan Y., Zhang Q., Zhao Y., Gao J., Zhao S.;
RT "Separation and molecular cloning of a novel human cDNA fragment coding a
RT protein without homologs.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, AND DOMAIN.
RX PubMed=14707134; DOI=10.1074/jbc.m311747200;
RA Zwartjes C.G., Jayne S., van den Berg D.L., Timmers H.T.;
RT "Repression of promoter activity by CNOT2, a subunit of the transcription
RT regulatory Ccr4-not complex.";
RL J. Biol. Chem. 279:10848-10854(2004).
RN [9]
RP FUNCTION, AND INTERACTION WITH NCOR1; NCOR2; HDAC3 AND GPS2.
RX PubMed=16712523; DOI=10.1042/bj20060406;
RA Jayne S., Zwartjes C.G., van Schaik F.M., Timmers H.T.;
RT "Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression
RT by the CNOT2 subunit of the human Ccr4-Not complex.";
RL Biochem. J. 398:461-467(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93; SER-126 AND SER-165, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION IN THE CCR4-NOT COMPLEX, AND COMPOSITION OF THE CCR4-NOT
RP COMPLEX.
RX PubMed=19558367; DOI=10.1042/bj20090500;
RA Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W.,
RA Heck A.J., Timmers H.T.;
RT "Human Ccr4-Not complexes contain variable deadenylase subunits.";
RL Biochem. J. 422:443-453(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP FUNCTION, INTERACTION WITH CNOT3, AND SUBCELLULAR LOCATION.
RX PubMed=21299754; DOI=10.1111/j.1365-2443.2011.01492.x;
RA Ito K., Inoue T., Yokoyama K., Morita M., Suzuki T., Yamamoto T.;
RT "CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and
RT induces apoptotic cell death.";
RL Genes Cells 16:368-379(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-242, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165 AND SER-274, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP INVOLVEMENT IN IDNADFS.
RX PubMed=31145527; DOI=10.1002/ajmg.a.61217;
RA Alesi V., Loddo S., Cali F., Orlando V., Genovese S., Ferretti D.,
RA Calacci C., Calvieri G., Falasca R., Ulgheri L., Drago F., Dallapiccola B.,
RA Baban A., Novelli A.;
RT "A heterozygous, intragenic deletion of CNOT2 recapitulates the phenotype
RT of 12q15 deletion syndrome.";
RL Am. J. Med. Genet. A 179:1615-1621(2019).
RN [23]
RP VARIANT IDNADFS 316-LYS--PHE-540 DEL.
RX PubMed=31512373; DOI=10.1002/ajmg.a.61356;
RA Uehara T., Tsuchihashi T., Yamada M., Suzuki H., Takenouchi T., Kosaki K.;
RT "CNOT2 haploinsufficiency causes a neurodevelopmental disorder with
RT characteristic facial features.";
RL Am. J. Med. Genet. A 179:2506-2509(2019).
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. {ECO:0000269|PubMed:14707134,
CC ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754,
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.
CC {ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16712523,
CC ECO:0000269|PubMed:19558367, ECO:0000269|PubMed:21299754}.
CC -!- INTERACTION:
CC Q9NZN8; Q96C12: ARMC5; NbExp=3; IntAct=EBI-743033, EBI-6425121;
CC Q9NZN8; P41182: BCL6; NbExp=3; IntAct=EBI-743033, EBI-765407;
CC Q9NZN8; Q9HBH7: BEX1; NbExp=3; IntAct=EBI-743033, EBI-7162175;
CC Q9NZN8; Q9H5F2: C11orf1; NbExp=3; IntAct=EBI-743033, EBI-718615;
CC Q9NZN8; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-743033, EBI-12155483;
CC Q9NZN8; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-743033, EBI-10175300;
CC Q9NZN8; A5YKK6: CNOT1; NbExp=5; IntAct=EBI-743033, EBI-1222758;
CC Q9NZN8; O75175: CNOT3; NbExp=10; IntAct=EBI-743033, EBI-743073;
CC Q9NZN8; Q96LI5: CNOT6L; NbExp=2; IntAct=EBI-743033, EBI-1046635;
CC Q9NZN8; Q9UFF9: CNOT8; NbExp=3; IntAct=EBI-743033, EBI-742299;
CC Q9NZN8; P33240: CSTF2; NbExp=3; IntAct=EBI-743033, EBI-711360;
CC Q9NZN8; F2Z2M7: GALNT10; NbExp=3; IntAct=EBI-743033, EBI-23893155;
CC Q9NZN8; Q8N6F7: GCSAM; NbExp=3; IntAct=EBI-743033, EBI-10267082;
CC Q9NZN8; Q13098-7: GPS1; NbExp=3; IntAct=EBI-743033, EBI-10983983;
CC Q9NZN8; O75031: HSF2BP; NbExp=3; IntAct=EBI-743033, EBI-7116203;
CC Q9NZN8; Q9H019: MTFR1L; NbExp=3; IntAct=EBI-743033, EBI-2824497;
CC Q9NZN8; P0CG20: PRR35; NbExp=3; IntAct=EBI-743033, EBI-11986293;
CC Q9NZN8; P28070: PSMB4; NbExp=3; IntAct=EBI-743033, EBI-603350;
CC Q9NZN8; P63244: RACK1; NbExp=3; IntAct=EBI-743033, EBI-296739;
CC Q9NZN8; Q13207: TBX2; NbExp=3; IntAct=EBI-743033, EBI-2853051;
CC Q9NZN8; Q9BXF9: TEKT3; NbExp=3; IntAct=EBI-743033, EBI-8644516;
CC Q9NZN8; Q9HCJ0: TNRC6C; NbExp=4; IntAct=EBI-743033, EBI-6507625;
CC Q9NZN8; Q15911-2: ZFHX3; NbExp=3; IntAct=EBI-743033, EBI-10237226;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21299754}. Nucleus
CC {ECO:0000305|PubMed:21299754}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9NZN8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZN8-2; Sequence=VSP_009912;
CC Name=3;
CC IsoId=Q9NZN8-3; Sequence=VSP_009913;
CC Name=4;
CC IsoId=Q9NZN8-4; Sequence=VSP_009915, VSP_009916;
CC Name=5;
CC IsoId=Q9NZN8-5; Sequence=VSP_009914;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in brain, heart,
CC thymus, spleen, kidney, liver, small intestine, placenta, lung and
CC peripheral blood leukocytes. {ECO:0000269|PubMed:10637334}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem (ES) cells.
CC {ECO:0000269|PubMed:22367759}.
CC -!- DISEASE: Intellectual developmental disorder with nasal speech,
CC dysmorphic facies, and variable skeletal anomalies (IDNADFS)
CC [MIM:618608]: An autosomal dominant disorder characterized by delayed
CC development, speech delay with nasal speech, and characteristic facial
CC features including upslanted palpebral fissures, anteverted nares, a
CC thin upper lip, and micrognathia. Some patients may have skeletal
CC anomalies, such as brachydactyly, toe syndactyly and flat feet.
CC {ECO:0000269|PubMed:31145527, ECO:0000269|PubMed:31512373}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CNOT2/3/5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF29095.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ13426.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF180473; AAF29827.1; -; mRNA.
DR EMBL; AF113226; AAG39297.1; -; mRNA.
DR EMBL; AF161480; AAF29095.1; ALT_FRAME; mRNA.
DR EMBL; AK000662; BAA91313.1; -; mRNA.
DR EMBL; AL137674; CAB70869.1; -; mRNA.
DR EMBL; BX641116; CAE46054.1; -; mRNA.
DR EMBL; BC002597; AAH02597.1; -; mRNA.
DR EMBL; BC011826; AAH11826.1; -; mRNA.
DR EMBL; AF044215; AAQ13426.1; ALT_FRAME; mRNA.
DR CCDS; CCDS31857.1; -. [Q9NZN8-1]
DR PIR; T46494; T46494.
DR RefSeq; NP_001186231.1; NM_001199302.1. [Q9NZN8-1]
DR RefSeq; NP_001186232.1; NM_001199303.1. [Q9NZN8-1]
DR RefSeq; NP_055330.1; NM_014515.5. [Q9NZN8-1]
DR RefSeq; XP_011536701.1; XM_011538399.1. [Q9NZN8-1]
DR PDB; 4C0D; X-ray; 3.20 A; B=344-540.
DR PDB; 4C0F; X-ray; 2.40 A; A/B/C/D=429-540.
DR PDB; 5FU6; X-ray; 2.90 A; B/E=350-540.
DR PDB; 5FU7; X-ray; 3.10 A; B/F=350-540.
DR PDBsum; 4C0D; -.
DR PDBsum; 4C0F; -.
DR PDBsum; 5FU6; -.
DR PDBsum; 5FU7; -.
DR AlphaFoldDB; Q9NZN8; -.
DR SMR; Q9NZN8; -.
DR BioGRID; 110910; 165.
DR ComplexPortal; CPX-2522; CCR4-NOT mRNA deadenylase complex, CNOT6L-CNOT7 variant.
DR ComplexPortal; CPX-2535; CCR4-NOT mRNA deadenylase complex, CNOT6L-CNOT8 variant.
DR ComplexPortal; CPX-2849; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT8 variant.
DR ComplexPortal; CPX-707; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT7 variant.
DR CORUM; Q9NZN8; -.
DR DIP; DIP-42656N; -.
DR IntAct; Q9NZN8; 88.
DR MINT; Q9NZN8; -.
DR STRING; 9606.ENSP00000229195; -.
DR ChEMBL; CHEMBL4105920; -.
DR GlyGen; Q9NZN8; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9NZN8; -.
DR MetOSite; Q9NZN8; -.
DR PhosphoSitePlus; Q9NZN8; -.
DR BioMuta; CNOT2; -.
DR DMDM; 46396017; -.
DR EPD; Q9NZN8; -.
DR jPOST; Q9NZN8; -.
DR MassIVE; Q9NZN8; -.
DR MaxQB; Q9NZN8; -.
DR PaxDb; Q9NZN8; -.
DR PeptideAtlas; Q9NZN8; -.
DR PRIDE; Q9NZN8; -.
DR ProteomicsDB; 83462; -. [Q9NZN8-1]
DR ProteomicsDB; 83463; -. [Q9NZN8-2]
DR ProteomicsDB; 83464; -. [Q9NZN8-3]
DR ProteomicsDB; 83465; -. [Q9NZN8-4]
DR ProteomicsDB; 83466; -. [Q9NZN8-5]
DR Antibodypedia; 17029; 454 antibodies from 33 providers.
DR DNASU; 4848; -.
DR Ensembl; ENST00000229195.8; ENSP00000229195.3; ENSG00000111596.14. [Q9NZN8-1]
DR Ensembl; ENST00000418359.7; ENSP00000412091.3; ENSG00000111596.14. [Q9NZN8-1]
DR Ensembl; ENST00000551043.5; ENSP00000449260.1; ENSG00000111596.14. [Q9NZN8-1]
DR Ensembl; ENST00000551483.5; ENSP00000448883.1; ENSG00000111596.14. [Q9NZN8-3]
DR GeneID; 4848; -.
DR KEGG; hsa:4848; -.
DR MANE-Select; ENST00000229195.8; ENSP00000229195.3; NM_014515.7; NP_055330.1.
DR UCSC; uc001svv.4; human. [Q9NZN8-1]
DR CTD; 4848; -.
DR DisGeNET; 4848; -.
DR GeneCards; CNOT2; -.
DR HGNC; HGNC:7878; CNOT2.
DR HPA; ENSG00000111596; Low tissue specificity.
DR MalaCards; CNOT2; -.
DR MIM; 604909; gene.
DR MIM; 618608; phenotype.
DR neXtProt; NX_Q9NZN8; -.
DR OpenTargets; ENSG00000111596; -.
DR Orphanet; 289513; 12q15q21.1 microdeletion syndrome.
DR PharmGKB; PA26673; -.
DR VEuPathDB; HostDB:ENSG00000111596; -.
DR eggNOG; KOG2151; Eukaryota.
DR GeneTree; ENSGT00390000001285; -.
DR HOGENOM; CLU_033275_1_0_1; -.
DR InParanoid; Q9NZN8; -.
DR OMA; GMNRNQV; -.
DR PhylomeDB; Q9NZN8; -.
DR TreeFam; TF313102; -.
DR PathwayCommons; Q9NZN8; -.
DR Reactome; R-HSA-429947; Deadenylation of mRNA.
DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR SignaLink; Q9NZN8; -.
DR SIGNOR; Q9NZN8; -.
DR BioGRID-ORCS; 4848; 295 hits in 1086 CRISPR screens.
DR ChiTaRS; CNOT2; human.
DR GeneWiki; CNOT2; -.
DR GenomeRNAi; 4848; -.
DR Pharos; Q9NZN8; Tbio.
DR PRO; PR:Q9NZN8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NZN8; protein.
DR Bgee; ENSG00000111596; Expressed in oocyte and 213 other tissues.
DR ExpressionAtlas; Q9NZN8; baseline and differential.
DR Genevisible; Q9NZN8; HS.
DR GO; GO:0030014; C:CCR4-NOT complex; IDA:UniProtKB.
DR GO; GO:0030015; C:CCR4-NOT core complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0003712; F:transcription coregulator activity; TAS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IDA: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; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA: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; IMP:UniProtKB.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; NAS:UniProtKB.
DR GO; GO:0090503; P:RNA phosphodiester bond hydrolysis, exonucleolytic; IEA:GOC.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
DR Gene3D; 2.30.30.1020; -; 1.
DR IDEAL; IID00503; -.
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 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW Disease variant; Intellectual disability; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; RNA-mediated gene silencing; Transcription;
KW Transcription regulation; Translation regulation.
FT CHAIN 1..540
FT /note="CCR4-NOT transcription complex subunit 2"
FT /id="PRO_0000198331"
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 REGION 437..540
FT /note="Repressor domain"
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:0007744|PubMed:18669648"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C5L3"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 169
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C5L3"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..349
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_009913"
FT VAR_SEQ 1..175
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_009912"
FT VAR_SEQ 229..278
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_009914"
FT VAR_SEQ 465..475
FT /note="FNRDWRYHKEE -> YVQSILITFVL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_009915"
FT VAR_SEQ 476..540
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_009916"
FT VARIANT 316..540
FT /note="Missing (in IDNADFS)"
FT /evidence="ECO:0000269|PubMed:31512373"
FT /id="VAR_083417"
FT VARIANT 460
FT /note="A -> T (in dbSNP:rs11178192)"
FT /id="VAR_048750"
FT HELIX 357..366
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 371..373
FT /evidence="ECO:0007829|PDB:4C0D"
FT TURN 376..378
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:5FU6"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 424..427
FT /evidence="ECO:0007829|PDB:5FU6"
FT HELIX 429..432
FT /evidence="ECO:0007829|PDB:4C0F"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:4C0F"
FT HELIX 441..449
FT /evidence="ECO:0007829|PDB:4C0F"
FT HELIX 453..466
FT /evidence="ECO:0007829|PDB:4C0F"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4C0F"
FT TURN 473..476
FT /evidence="ECO:0007829|PDB:4C0F"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:4C0F"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:4C0F"
FT STRAND 492..503
FT /evidence="ECO:0007829|PDB:4C0F"
FT TURN 504..507
FT /evidence="ECO:0007829|PDB:4C0F"
FT STRAND 508..517
FT /evidence="ECO:0007829|PDB:4C0F"
FT HELIX 518..520
FT /evidence="ECO:0007829|PDB:4C0F"
FT HELIX 537..539
FT /evidence="ECO:0007829|PDB:4C0F"
SQ SEQUENCE 540 AA; 59738 MW; 7183890F033E3B83 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
NLNTSGKTTS STDGPKFPGD KSSTTQNNNQ QKKGIQVLPD GRVTNIPQGM VTDQFGMIGL
LTFIRAAETD PGMVHLALGS DLTTLGLNLN SPENLYPKFA SPWASSPCRP QDIDFHVPSE
YLTNIHIRDK LAAIKLGRYG EDLLFYLYYM NGGDVLQLLA AVELFNRDWR YHKEERVWIT
RAPGMEPTMK TNTYERGTYY FFDCLNWRKV AKEFHLEYDK LEERPHLPST FNYNPAQQAF
