CNOT4_MOUSE
ID CNOT4_MOUSE Reviewed; 575 AA.
AC Q8BT14; Q8CCR4; Q9CV74; Q9Z1D0;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=CCR4-NOT transcription complex subunit 4;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:O95628};
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 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 [MRNA] (ISOFORM 1).
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, and Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-296; SER-298 AND SER-304 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, 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 [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-475 AND ARG-497, AND
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).
RN [8]
RP STRUCTURE BY NMR OF 101-198.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RNA recognition motif of CNOT4.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Has E3 ubiquitin ligase activity, promoting ubiquitination
CC and degradation of target proteins. Involved in activation of the
CC JAK/STAT pathway. Catalyzes ubiquitination of methylated RBM15. Plays a
CC role in quality control of translation of mitochondrial outer membrane-
CC localized mRNA. 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 {ECO:0000250|UniProtKB:O95628}.
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:0000250|UniProtKB:O95628};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:O95628}.
CC -!- SUBUNIT: Interacts with CNOT1 via its C-terminus but does not stably
CC associate with the CCR4-NOT complex. Interacts (via RING domain) with
CC UBE2D2. Interacts with ABCE1, PINK1 and PELO.
CC {ECO:0000250|UniProtKB:O95628}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BT14-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BT14-2; Sequence=VSP_009930;
CC Name=3;
CC IsoId=Q8BT14-3; Sequence=VSP_009931;
CC -!- PTM: Autoubiquitinated. {ECO:0000250|UniProtKB:O95628}.
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DR EMBL; U71269; AAD00181.1; -; mRNA.
DR EMBL; AK009234; BAB26155.1; -; mRNA.
DR EMBL; AK028190; BAC25801.1; -; mRNA.
DR EMBL; AK032248; BAC27779.1; -; mRNA.
DR EMBL; BC058778; AAH58778.1; -; mRNA.
DR CCDS; CCDS19999.1; -. [Q8BT14-1]
DR CCDS; CCDS80520.1; -. [Q8BT14-2]
DR RefSeq; NP_001157883.1; NM_001164411.1. [Q8BT14-2]
DR RefSeq; NP_001157885.1; NM_001164413.1.
DR RefSeq; NP_058573.3; NM_016877.4. [Q8BT14-1]
DR RefSeq; XP_011239709.1; XM_011241407.1. [Q8BT14-3]
DR RefSeq; XP_011239710.1; XM_011241408.2. [Q8BT14-3]
DR PDB; 2CPI; NMR; -; A=101-198.
DR PDBsum; 2CPI; -.
DR AlphaFoldDB; Q8BT14; -.
DR BMRB; Q8BT14; -.
DR SMR; Q8BT14; -.
DR BioGRID; 207338; 1.
DR IntAct; Q8BT14; 2.
DR STRING; 10090.ENSMUSP00000110645; -.
DR iPTMnet; Q8BT14; -.
DR PhosphoSitePlus; Q8BT14; -.
DR EPD; Q8BT14; -.
DR jPOST; Q8BT14; -.
DR MaxQB; Q8BT14; -.
DR PaxDb; Q8BT14; -.
DR PRIDE; Q8BT14; -.
DR ProteomicsDB; 283651; -. [Q8BT14-1]
DR ProteomicsDB; 283652; -. [Q8BT14-2]
DR ProteomicsDB; 283653; -. [Q8BT14-3]
DR Antibodypedia; 1419; 634 antibodies from 38 providers.
DR DNASU; 53621; -.
DR Ensembl; ENSMUST00000044163; ENSMUSP00000044137; ENSMUSG00000038784. [Q8BT14-1]
DR Ensembl; ENSMUST00000202417; ENSMUSP00000144409; ENSMUSG00000038784. [Q8BT14-2]
DR GeneID; 53621; -.
DR KEGG; mmu:53621; -.
DR UCSC; uc009bid.2; mouse. [Q8BT14-3]
DR UCSC; uc009big.2; mouse. [Q8BT14-1]
DR CTD; 4850; -.
DR MGI; MGI:1859026; Cnot4.
DR VEuPathDB; HostDB:ENSMUSG00000038784; -.
DR eggNOG; KOG2068; Eukaryota.
DR GeneTree; ENSGT00390000000068; -.
DR InParanoid; Q8BT14; -.
DR OrthoDB; 1200559at2759; -.
DR PhylomeDB; Q8BT14; -.
DR TreeFam; TF106134; -.
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 UniPathway; UPA00143; -.
DR BioGRID-ORCS; 53621; 10 hits in 76 CRISPR screens.
DR ChiTaRS; Cnot4; mouse.
DR EvolutionaryTrace; Q8BT14; -.
DR PRO; PR:Q8BT14; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BT14; protein.
DR Bgee; ENSMUSG00000038784; Expressed in floor plate of midbrain and 255 other tissues.
DR ExpressionAtlas; Q8BT14; baseline and differential.
DR Genevisible; Q8BT14; MM.
DR GO; GO:0030014; C:CCR4-NOT complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS: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 Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..575
FT /note="CCR4-NOT transcription complex subunit 4"
FT /id="PRO_0000081680"
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..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..459
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 346..365
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..459
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:0000250|UniProtKB:O95628"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 432
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95628"
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:0000250|UniProtKB:O95628"
FT MOD_RES 497
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 271..274
FT /note="RYDT -> S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009930"
FT VAR_SEQ 543..575
FT /note="GEEEVKVSTMPLSASSHSLQQGQQPTSLHTTVA -> DNNSSVESLNMKEWQ
FT DGLRALLPNININFGGLPNSSSPSNANHSAPTSNTATTDSVSWDSPGSWTDPAIITGIP
FT ASSGNTLDSIQDDNPPHWLKSLQALTEMDGPSAASSQPHHSAPFSTQIPLHRASWNPYP
FT PPSNPSSFHSPPPGFQTAFRPPSKTPTDLLQSSTLDRH (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009931"
FT CONFLICT 167
FT /note="E -> Q (in Ref. 2; BAC25801)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="N -> H (in Ref. 2; BAC25801)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="K -> Q (in Ref. 2; BAC25801)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="D -> Y (in Ref. 2; BAC27779)"
FT /evidence="ECO:0000305"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:2CPI"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:2CPI"
FT HELIX 123..127
FT /evidence="ECO:0007829|PDB:2CPI"
FT TURN 129..135
FT /evidence="ECO:0007829|PDB:2CPI"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:2CPI"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2CPI"
FT STRAND 157..165
FT /evidence="ECO:0007829|PDB:2CPI"
FT HELIX 166..176
FT /evidence="ECO:0007829|PDB:2CPI"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:2CPI"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:2CPI"
FT MOD_RES Q8BT14-2:296
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES Q8BT14-2:298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES Q8BT14-2:304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 575 AA; 63474 MW; E0B763C8262D03CA 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
PSDWPTAPEP QSLFTSETIP VSSSTDWQAA FGFGSSKQPE DDLGFDPFDV TRKALADLIE
KELSVQDQPS LSPTSLQNAS SHTTTAKGPG SGFLHSAAPT NANSLNSTFS VLPQRFPQFQ
QHRAVYNSFG FPGQAARYPW MAFPRNSIMH LNHTANPTSN SNFLDLNLPP QHNTGLGGIP
IAGEEEVKVS TMPLSASSHS LQQGQQPTSL HTTVA
