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 27-MAR-2024, entry version 202. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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; 69. 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; 16. DR STRING; 9606.ENSP00000445508; -. DR ChEMBL; CHEMBL4105770; -. DR GlyCosmos; O95628; 7 sites, 2 glycans. DR GlyGen; O95628; 11 sites, 2 O-linked glycans (11 sites). DR iPTMnet; O95628; -. DR PhosphoSitePlus; O95628; -. DR BioMuta; CNOT4; -. DR EPD; O95628; -. DR jPOST; O95628; -. DR MassIVE; O95628; -. DR MaxQB; O95628; -. DR PaxDb; 9606-ENSP00000445508; -. DR PeptideAtlas; 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 Pumba; O95628; -. DR Antibodypedia; 1419; 707 antibodies from 38 providers. DR DNASU; 4850; -. DR Ensembl; ENST00000315544.6; ENSP00000326731.5; ENSG00000080802.21. [O95628-1] DR Ensembl; ENST00000361528.8; ENSP00000354673.4; ENSG00000080802.21. [O95628-8] DR Ensembl; ENST00000414802.5; ENSP00000416532.1; ENSG00000080802.21. [O95628-5] DR Ensembl; ENST00000423368.6; ENSP00000406777.2; ENSG00000080802.21. [O95628-4] DR Ensembl; ENST00000428680.6; ENSP00000399108.2; ENSG00000080802.21. [O95628-2] DR Ensembl; ENST00000451834.5; ENSP00000388491.1; ENSG00000080802.21. [O95628-9] DR Ensembl; ENST00000541284.6; ENSP00000445508.1; ENSG00000080802.21. [O95628-10] DR Ensembl; ENST00000707064.1; ENSP00000516715.1; ENSG00000080802.21. [O95628-1] 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 AGR; HGNC:7880; -. 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; QGHYHLF; -. DR OrthoDB; 1748at2759; -. 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 Reactome; R-HSA-9820841; M-decay: degradation of maternal mRNAs by maternally stored factors. DR SignaLink; O95628; -. DR SIGNOR; O95628; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 4850; 72 hits in 1227 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 215 other cell types or tissues. DR ExpressionAtlas; O95628; baseline and differential. 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; NAS: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; 3.30.70.330; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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; CCR4-NOT TRANSCRIPTION COMPLEX RELATED; 1. DR PANTHER; PTHR12603:SF0; CCR4-NOT TRANSCRIPTION COMPLEX SUBUNIT 4; 1. DR Pfam; PF00076; RRM_1; 1. DR Pfam; PF14570; zf-RING_4; 1. DR SMART; SM00361; RRM_1; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS50102; RRM; 1. DR PROSITE; PS50103; ZF_C3H1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; O95628; HS. 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 //