CNOT4_HUMAN
ID CNOT4_HUMAN Reviewed; 575 AA.
AC O95628; B7Z6I4; E7ET38; F8VQP3; O95339; O95627; Q8IYM7; Q8NCL0; Q9NPQ1;
AC Q9NZN6;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=CCR4-NOT transcription complex subunit 4;
DE EC=2.3.2.27 {ECO:0000269|PubMed:11823428, ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:29861391};
DE AltName: Full=CCR4-associated factor 4;
DE AltName: Full=E3 ubiquitin-protein ligase CNOT4;
DE AltName: Full=Potential transcriptional repressor NOT4Hp;
DE AltName: Full=RING-type E3 ubiquitin transferase CNOT4 {ECO:0000305};
GN Name=CNOT4; Synonyms=NOT4;
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] (ISOFORMS 1; 3 AND 4).
RA Chiang P.-W.;
RT "Isolation and characterization of human and murine homologues of yeast
RT NOT4 gene.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLY-7.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 149-575 (ISOFORM 6).
RC TISSUE=Mammary gland, and Placenta;
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 GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [LARGE SCALE MRNA] OF 294-575 (ISOFORM 7).
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, UBIQUITINATION, INTERACTION WITH CNOT1 AND
RP UBIQUITIN E2 LIGASES, MUTAGENESIS OF LEU-16; CYS-17; MET-18; CYS-33;
RP TRP-42; ARG-44; ILE-45; GLU-49; PRO-54 AND ARG-57, AND STRUCTURE BY NMR OF
RP 1-78.
RX PubMed=11823428; DOI=10.1093/emboj/21.3.355;
RA Albert T.K., Hanzawa H., Legtenberg Y.I.A., de Ruwe M.J.,
RA van den Heuvel F.A.J., Collart M.A., Boelens R., Timmers H.T.M.;
RT "Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT
RT transcription repressor complex.";
RL EMBO J. 21:355-364(2002).
RN [9]
RP INTERACTION WITH UBE2D2, AUTOUBIQUITINATION, AND MUTAGENESIS OF GLU-49.
RX PubMed=15001359; DOI=10.1016/j.jmb.2004.01.031;
RA Winkler G.S., Albert T.K., Dominguez C., Legtenberg Y.I., Boelens R.,
RA Timmers H.T.;
RT "An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein
RT ligase pair.";
RL J. Mol. Biol. 337:157-165(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, AND IDENTIFICATION BY
RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-432 AND SER-490, AND
RP IDENTIFICATION BY 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, 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 [14]
RP FUNCTION.
RX PubMed=22159038; DOI=10.1096/fj.11-195875;
RA Gronholm J., Kaustio M., Myllymaki H., Kallio J., Saarikettu J.,
RA Kronhamn J., Valanne S., Silvennoinen O., Ramet M.;
RT "Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and
RT in human cells.";
RL FASEB J. 26:1239-1250(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301 AND SER-432, 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 [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-475; ARG-483 AND ARG-497, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
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).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26575292; DOI=10.7554/elife.07938;
RA Zhang L., Tran N.T., Su H., Wang R., Lu Y., Tang H., Aoyagi S., Guo A.,
RA Khodadadi-Jamayran A., Zhou D., Qian K., Hricik T., Cote J., Han X.,
RA Zhou W., Laha S., Abdel-Wahab O., Levine R.L., Raffel G., Liu Y., Chen D.,
RA Li H., Townes T., Wang H., Deng H., Zheng Y.G., Leslie C., Luo M., Zhao X.;
RT "Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15
RT controls RNA splicing.";
RL Elife 4:0-0(2015).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ABCE1; PINK1 AND PELO.
RX PubMed=29861391; DOI=10.1016/j.cmet.2018.05.007;
RA Wu Z., Wang Y., Lim J., Liu B., Li Y., Vartak R., Stankiewicz T.,
RA Montgomery S., Lu B.;
RT "Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links
RT Co-translational Quality Control to PINK1-Directed Mitophagy.";
RL Cell Metab. 28:130-144.e7(2018).
RN [19]
RP STRUCTURE BY NMR OF 1-78 IN COMPLEX WITH ZINC IONS.
RX PubMed=11087754; DOI=10.1074/jbc.m009298200;
RA Hanzawa H., de Ruwe M.J., Albert T.K., van Der Vliet P.C., Timmers H.T.M.,
RA Boelens R.;
RT "The structure of the C4C4 ring finger of human NOT4 reveals features
RT distinct from those of C3HC4 RING fingers.";
RL J. Biol. Chem. 276:10185-10190(2001).
CC -!- FUNCTION: Has E3 ubiquitin ligase activity, promoting ubiquitination
CC and degradation of target proteins (PubMed:11823428, PubMed:22159038,
CC PubMed:26575292). Involved in activation of the JAK/STAT pathway
CC (PubMed:11823428, PubMed:22159038). Catalyzes ubiquitination of
CC methylated RBM15 (PubMed:26575292). Plays a role in quality control of
CC translation of mitochondrial outer membrane-localized mRNA
CC (PubMed:29861391). As part of the PINK1-regulated signaling, upon
CC mitochondria damage, ubiquitinates ABCE1 and thereby recruits autophagy
CC receptors to the mitochondrial outer membrane to initiate mitophagy
CC (PubMed:29861391). {ECO:0000269|PubMed:11823428,
CC ECO:0000269|PubMed:22159038, ECO:0000269|PubMed:26575292,
CC ECO:0000269|PubMed:29861391}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:11823428,
CC ECO:0000269|PubMed:26575292, ECO:0000269|PubMed:29861391};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:26575292}.
CC -!- SUBUNIT: Interacts with CNOT1 via its C-terminus but does not stably
CC associate with the CCR4-NOT complex (PubMed:11823428). Interacts (via
CC RING domain) with UBE2D2 (PubMed:15001359). Interacts with ABCE1, PINK1
CC and PELO (PubMed:29861391). {ECO:0000269|PubMed:11823428,
CC ECO:0000269|PubMed:15001359, ECO:0000269|PubMed:29861391}.
CC -!- INTERACTION:
CC O95628-2; Q9UBH0: IL36RN; NbExp=5; IntAct=EBI-12019444, EBI-465156;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=1;
CC IsoId=O95628-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95628-2; Sequence=VSP_009924;
CC Name=3;
CC IsoId=O95628-3; Sequence=VSP_009923;
CC Name=4;
CC IsoId=O95628-4; Sequence=VSP_009928;
CC Name=5;
CC IsoId=O95628-5; Sequence=VSP_009925, VSP_009926;
CC Name=6;
CC IsoId=O95628-6; Sequence=VSP_009927;
CC Name=7;
CC IsoId=O95628-7; Sequence=VSP_009929;
CC Name=8;
CC IsoId=O95628-8; Sequence=VSP_009924, VSP_009928;
CC Name=9;
CC IsoId=O95628-9; Sequence=VSP_009924, VSP_045469;
CC Name=10;
CC IsoId=O95628-10; Sequence=VSP_045469;
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:11823428,
CC ECO:0000269|PubMed:15001359}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72963.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAC72963.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
CC Sequence=AAD00180.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC11125.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U71267; AAD00179.1; ALT_FRAME; mRNA.
DR EMBL; U71268; AAD00180.1; ALT_FRAME; mRNA.
DR EMBL; AF180475; AAF29829.1; -; mRNA.
DR EMBL; AL389980; CAB97536.1; -; mRNA.
DR EMBL; AK074671; BAC11125.1; ALT_INIT; mRNA.
DR EMBL; AK300365; BAH13270.1; -; mRNA.
DR EMBL; AC083871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035590; AAH35590.1; -; mRNA.
DR EMBL; AF091094; AAC72963.1; ALT_SEQ; mRNA.
DR CCDS; CCDS43650.1; -. [O95628-8]
DR CCDS; CCDS47719.1; -. [O95628-2]
DR CCDS; CCDS55164.1; -. [O95628-4]
DR CCDS; CCDS55165.1; -. [O95628-10]
DR CCDS; CCDS55166.1; -. [O95628-1]
DR CCDS; CCDS55167.1; -. [O95628-9]
DR RefSeq; NP_001008226.1; NM_001008225.2. [O95628-2]
DR RefSeq; NP_001177776.1; NM_001190847.1. [O95628-4]
DR RefSeq; NP_001177777.1; NM_001190848.1. [O95628-1]
DR RefSeq; NP_001177778.1; NM_001190849.1. [O95628-9]
DR RefSeq; NP_001177779.1; NM_001190850.1. [O95628-10]
DR RefSeq; NP_037448.2; NM_013316.3. [O95628-8]
DR RefSeq; XP_016867724.1; XM_017012235.1. [O95628-10]
DR PDB; 1E4U; NMR; -; A=1-78.
DR PDB; 1UR6; NMR; -; B=12-63.
DR PDBsum; 1E4U; -.
DR PDBsum; 1UR6; -.
DR AlphaFoldDB; O95628; -.
DR BMRB; O95628; -.
DR SMR; O95628; -.
DR BioGRID; 110912; 53.
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 IntAct; O95628; 11.
DR STRING; 9606.ENSP00000445508; -.
DR ChEMBL; CHEMBL4105770; -.
DR GlyGen; O95628; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; O95628; -.
DR PhosphoSitePlus; O95628; -.
DR BioMuta; CNOT4; -.
DR EPD; O95628; -.
DR jPOST; O95628; -.
DR MassIVE; O95628; -.
DR MaxQB; O95628; -.
DR PaxDb; O95628; -.
DR PeptideAtlas; O95628; -.
DR PRIDE; O95628; -.
DR ProteomicsDB; 18118; -.
DR ProteomicsDB; 28333; -.
DR ProteomicsDB; 50958; -. [O95628-1]
DR ProteomicsDB; 50959; -. [O95628-2]
DR ProteomicsDB; 50960; -. [O95628-3]
DR ProteomicsDB; 50961; -. [O95628-4]
DR ProteomicsDB; 50962; -. [O95628-5]
DR ProteomicsDB; 50963; -. [O95628-6]
DR ProteomicsDB; 50964; -. [O95628-7]
DR ProteomicsDB; 50965; -. [O95628-8]
DR Antibodypedia; 1419; 634 antibodies from 38 providers.
DR DNASU; 4850; -.
DR Ensembl; ENST00000315544.6; ENSP00000326731.5; ENSG00000080802.20. [O95628-1]
DR Ensembl; ENST00000361528.8; ENSP00000354673.4; ENSG00000080802.20. [O95628-8]
DR Ensembl; ENST00000414802.5; ENSP00000416532.1; ENSG00000080802.20. [O95628-5]
DR Ensembl; ENST00000423368.6; ENSP00000406777.2; ENSG00000080802.20. [O95628-4]
DR Ensembl; ENST00000428680.6; ENSP00000399108.2; ENSG00000080802.20. [O95628-2]
DR Ensembl; ENST00000451834.5; ENSP00000388491.1; ENSG00000080802.20. [O95628-9]
DR Ensembl; ENST00000541284.6; ENSP00000445508.1; ENSG00000080802.20. [O95628-10]
DR GeneID; 4850; -.
DR KEGG; hsa:4850; -.
DR MANE-Select; ENST00000541284.6; ENSP00000445508.1; NM_001190850.2; NP_001177779.1. [O95628-10]
DR UCSC; uc003vss.4; human. [O95628-1]
DR CTD; 4850; -.
DR DisGeNET; 4850; -.
DR GeneCards; CNOT4; -.
DR HGNC; HGNC:7880; CNOT4.
DR HPA; ENSG00000080802; Low tissue specificity.
DR MIM; 604911; gene.
DR neXtProt; NX_O95628; -.
DR OpenTargets; ENSG00000080802; -.
DR PharmGKB; PA26675; -.
DR VEuPathDB; HostDB:ENSG00000080802; -.
DR eggNOG; KOG2068; Eukaryota.
DR GeneTree; ENSGT00390000000068; -.
DR HOGENOM; CLU_011836_0_0_1; -.
DR InParanoid; O95628; -.
DR OMA; AKPPQIY; -.
DR OrthoDB; 1200559at2759; -.
DR PhylomeDB; O95628; -.
DR TreeFam; TF106134; -.
DR PathwayCommons; O95628; -.
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; O95628; -.
DR SIGNOR; O95628; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 4850; 62 hits in 1135 CRISPR screens.
DR ChiTaRS; CNOT4; human.
DR EvolutionaryTrace; O95628; -.
DR GenomeRNAi; 4850; -.
DR Pharos; O95628; Tbio.
DR PRO; PR:O95628; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O95628; protein.
DR Bgee; ENSG00000080802; Expressed in buccal mucosa cell and 213 other tissues.
DR ExpressionAtlas; O95628; baseline and differential.
DR Genevisible; O95628; HS.
DR GO; GO:0030014; C:CCR4-NOT complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IC:ComplexPortal.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR CDD; cd16618; mRING-HC-C4C4_CNOT4; 1.
DR CDD; cd12438; RRM_CNOT4; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR034261; CNOT4_RRM.
DR InterPro; IPR039780; Mot2.
DR InterPro; IPR039515; NOT4_mRING-HC-C4C4.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR003954; RRM_dom_euk.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR12603; PTHR12603; 2.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00361; RRM_1; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..575
FT /note="CCR4-NOT transcription complex subunit 4"
FT /id="PRO_0000081679"
FT DOMAIN 109..189
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 14..57
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 190..217
FT /note="C3H1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 256..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 68..104
FT /evidence="ECO:0000255"
FT COMPBIAS 280..303
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..448
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 475
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 483
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 497
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_009923"
FT VAR_SEQ 271..274
FT /note="RYDT -> S (in isoform 2, isoform 8 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_009924"
FT VAR_SEQ 419..433
FT /note="IEKELSVQDQPSLSP -> TEPIERKRLAVLKRR (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10637334"
FT /id="VSP_009925"
FT VAR_SEQ 434..575
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10637334"
FT /id="VSP_009926"
FT VAR_SEQ 543..575
FT /note="GEEEVKVSTMPLSTSSHSLQQGQQPTSLHTTVA -> DNSSSIESLNMKEWQ
FT DGLRALLPNININFGGLPNSSSPSNANHSAPTSNTATTDSLSWDSPGSWTDPAIITGIP
FT ASSGNSLDSLQDDNPPHWLKSLQALTEMDGPSAAPSQTHHSAPFSTQIPLHRASWNPYP
FT PPSNPSSFHSPPPQIYYRVQHWTAIRQRGATIRKCRICPTLFSPSQPTTHSSLLISYVL
FT KNPVPDQFFFSLTPDAMRSQGHYHLFINCKNFC (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_009927"
FT VAR_SEQ 543..575
FT /note="GEEEVKVSTMPLSTSSHSLQQGQQPTSLHTTVA -> DNSSSVESLNMKEWQ
FT DGLRALLPNININFGGLPNSSSPSNANHSAPTSNTATTDSLSWDSPGSWTDPAIITGIP
FT ASSGNSLDSLQDDNPPHWLKSLQALTEMDGPSAAPSQTHHSAPFSTQIPLHRASWNPYP
FT PPSNPSSFHSPPPGFQTAFRPPSKTPTDLLQSSTLDRH (in isoform 9 and
FT isoform 10)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045469"
FT VAR_SEQ 544..575
FT /note="EEEVKVSTMPLSTSSHSLQQGQQPTSLHTTVA -> IPASSGNSLDSLQDDN
FT PPHWLKSLQALTEMDGPSAAPSQTHHSAPFSTQIPLHRASWNPYPPPSNPSSFHSPPPG
FT FQTAFRPPSKTPTDLLQSSTLDRH (in isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_009928"
FT VAR_SEQ 544..575
FT /note="EEEVKVSTMPLSTSSHSLQQGQQPTSLHTTVA -> IPASSGNSLDSLQDDN
FT PPHWLKSLQALTEMDGQRCSITDPPQRPLQHTDPAAQSQLESLPSSFKPFQLPLPTPRL
FT SDGLQTPQQNPHRFTTEFNTGPPLGKEEQPLENAGFVPLCFLPLSPPPTAPFSSLMF
FT (in isoform 7)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_009929"
FT VARIANT 7
FT /note="A -> G (in dbSNP:rs17480616)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_027833"
FT MUTAGEN 16
FT /note="L->A,E: Abolishes interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 17
FT /note="C->A: Abolishes interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 18
FT /note="M->A: Strongly reduces interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 33
FT /note="C->R: Abolishes interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 42
FT /note="W->A: Strongly reduces interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 44
FT /note="R->A,E: Strongly reduces interaction with E2
FT ubiquitin ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 45
FT /note="I->A,W: Strongly reduces interaction with E2
FT ubiquitin ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 49
FT /note="E->A: Strongly reduces interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428,
FT ECO:0000269|PubMed:15001359"
FT MUTAGEN 49
FT /note="E->K: Strongly reduced interaction with UBE2D2."
FT /evidence="ECO:0000269|PubMed:11823428,
FT ECO:0000269|PubMed:15001359"
FT MUTAGEN 54
FT /note="P->A: Strongly reduces interaction with E2 ubiquitin
FT ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT MUTAGEN 57
FT /note="R->A,E: Strongly reduces interaction with E2
FT ubiquitin ligases."
FT /evidence="ECO:0000269|PubMed:11823428"
FT CONFLICT 178
FT /note="N -> D (in Ref. 4; BAH13270)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="K -> R (in Ref. 4; BAH13270)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="N -> I (in Ref. 6; AAH35590)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="L -> F (in Ref. 1; AAD00179/AAD00180)"
FT /evidence="ECO:0000305"
FT TURN 15..17
FT /evidence="ECO:0007829|PDB:1E4U"
FT TURN 23..27
FT /evidence="ECO:0007829|PDB:1E4U"
FT HELIX 39..45
FT /evidence="ECO:0007829|PDB:1E4U"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:1E4U"
FT CONFLICT O95628-9:545
FT /note="V -> I (in Ref. 4; BAH13270)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 575 AA; 63510 MW; C41762D4EC4222BC CRC64;
MSRSPDAKED PVECPLCMEP LEIDDINFFP CTCGYQICRF CWHRIRTDEN GLCPACRKPY
PEDPAVYKPL SQEELQRIKN EKKQKQNERK QKISENRKHL ASVRVVQKNL VFVVGLSQRL
ADPEVLKRPE YFGKFGKIHK VVINNSTSYA GSQGPSASAY VTYIRSEDAL RAIQCVNNVV
VDGRTLKASL GTTKYCSYFL KNMQCPKPDC MYLHELGDEA ASFTKEEMQA GKHQEYEQKL
LQELYKLNPN FLQLSTGSVD KNKNKVTPLQ RYDTPIDKPS DSLSIGNGDN SQQISNSDTP
SPPPGLSKSN PVIPISSSNH SARSPFEGAV TESQSLFSDN FRHPNPIPSG LPPFPSSPQT
SSDWPTAPEP QSLFTSETIP VSSSTDWQAA FGFGSSKQPE DDLGFDPFDV TRKALADLIE
KELSVQDQPS LSPTSLQNSS SHTTTAKGPG SGFLHPAAAT NANSLNSTFS VLPQRFPQFQ
QHRAVYNSFS FPGQAARYPW MAFPRNSIMH LNHTANPTSN SNFLDLNLPP QHNTGLGGIP
VAGEEEVKVS TMPLSTSSHS LQQGQQPTSL HTTVA
