ID NOT4_YEAST Reviewed; 587 AA.
AC P34909; D3DLX3;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 27-MAR-2024, entry version 218.
DE RecName: Full=General negative regulator of transcription subunit 4;
DE EC=2.3.2.27 {ECO:0000269|PubMed:30609991};
DE AltName: Full=Modulator of transcription 2;
GN Name=MOT2; Synonyms=CCL1, NOT4 {ECO:0000303|PubMed:30609991}, SIG1, SSF1;
GN OrderedLocusNames=YER068W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8039500; DOI=10.1002/j.1460-2075.1994.tb06604.x;
RA Leberer E., Dignard D., Harcus D., Whiteway M., Thomas D.Y.;
RT "Molecular characterization of SIG1, a Saccharomyces cerevisiae gene
RT involved in negative regulation of G-protein-mediated signal
RT transduction.";
RL EMBO J. 13:3050-3064(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8164669; DOI=10.1128/mcb.14.5.3139-3149.1994;
RA Cade R.M., Errede B.;
RT "MOT2 encodes a negative regulator of gene expression that affects basal
RT expression of pheromone-responsive genes in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 14:3139-3149(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=8164670; DOI=10.1128/mcb.14.5.3150-3157.1994;
RA Irie K., Yamaguchi K., Kawase K., Matsumoto K.;
RT "The yeast MOT2 gene encodes a putative zinc finger protein that serves as
RT a global negative regulator affecting expression of several categories of
RT genes, including mating-pheromone-responsive genes.";
RL Mol. Cell. Biol. 14:3150-3157(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP CHARACTERIZATION.
RX PubMed=7926748; DOI=10.1101/gad.8.5.525;
RA Collart M.A., Struhl K.;
RT "NOT1(CDC39), NOT2(CDC36), NOT3, and NOT4 encode a global-negative
RT regulator of transcription that differentially affects TATA-element
RT utilization.";
RL Genes Dev. 8:525-537(1994).
RN [7]
RP IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX, AND FUNCTION OF THE CCR4-NOT
RP CORE COMPLEX IN TRANSCRIPTIONAL REGULATION.
RX PubMed=9463387; DOI=10.1093/emboj/17.4.1096;
RA Liu H.Y., Badarinarayana V., Audino D.C., Rappsilber J., Mann M.,
RA Denis C.L.;
RT "The NOT proteins are part of the CCR4 transcriptional complex and affect
RT gene expression both positively and negatively.";
RL EMBO J. 17:1096-1106(1998).
RN [8]
RP INTERACTION WITH NOT1.
RX PubMed=10490603; DOI=10.1128/mcb.19.10.6642;
RA Bai Y., Salvadore C., Chiang Y.C., Collart M.A., Liu H.Y., Denis C.L.;
RT "The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and
RT functionally separated from NOT2, NOT4, and NOT5.";
RL Mol. Cell. Biol. 19:6642-6651(1999).
RN [9]
RP IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX.
RX PubMed=11733989; DOI=10.1006/jmbi.2001.5162;
RA Chen J., Rappsilber J., Chiang Y.C., Russell P., Mann M., Denis C.L.;
RT "Purification and characterization of the 1.0 MDa CCR4-NOT complex
RT identifies two novel components of the complex.";
RL J. Mol. Biol. 314:683-694(2001).
RN [10]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-310 AND SER-312, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-310; SER-312; THR-326 AND
RP SER-360, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [14]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-270, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=30609991; DOI=10.15252/embj.2018100276;
RA Ikeuchi K., Tesina P., Matsuo Y., Sugiyama T., Cheng J., Saeki Y.,
RA Tanaka K., Becker T., Beckmann R., Inada T.;
RT "Collided ribosomes form a unique structural interface to induce Hel2-
RT driven quality control pathways.";
RL EMBO J. 38:0-0(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase component of the CCR4-NOT core
CC complex, which in the nucleus seems to be a general transcription
CC factor, and in the cytoplasm the major mRNA deadenylase involved in
CC mRNA turnover (PubMed:9463387, PubMed:30609991). The NOT protein
CC subcomplex negatively regulates the basal and activated transcription
CC of many genes (PubMed:9463387). Preferentially affects TC-type TATA
CC element-dependent transcription. Could directly or indirectly inhibit
CC component(s) of the general transcription machinery (PubMed:9463387).
CC In the cytoplasm, catalyzes monoubiquitination of RPS7/es7 in response
CC to stalled ribosomes, initiating a HEL2-dependent response that
CC activates the No-Go Decay (NGD) pathway (PubMed:30609991).
CC {ECO:0000269|PubMed:30609991, ECO:0000269|PubMed:9463387}.
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:30609991};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:30609991}.
CC -!- SUBUNIT: Forms a NOT protein complex that comprises NOT1, NOT2, NOT3,
CC NOT4 and NOT5. Subunit of the 1.0 MDa CCR4-NOT core complex that
CC contains CCR4, CAF1, NOT1, NOT2, NOT3, NOT4, NOT5, CAF40 and CAF130. In
CC the complex interacts with NOT1. The core complex probably is part of a
CC less characterized 1.9 MDa CCR4-NOT complex.
CC {ECO:0000269|PubMed:10490603, ECO:0000269|PubMed:11733989,
CC ECO:0000269|PubMed:9463387}.
CC -!- INTERACTION:
CC P34909; P53829: CAF40; NbExp=5; IntAct=EBI-12174, EBI-28306;
CC P34909; P31384: CCR4; NbExp=3; IntAct=EBI-12174, EBI-4396;
CC P34909; P06100: CDC36; NbExp=3; IntAct=EBI-12174, EBI-12153;
CC P34909; P25655: CDC39; NbExp=8; IntAct=EBI-12174, EBI-12139;
CC P34909; Q12514: NOT5; NbExp=3; IntAct=EBI-12174, EBI-12184;
CC P34909; P39008: POP2; NbExp=3; IntAct=EBI-12174, EBI-13629;
CC P34909; Q01939: RPT6; NbExp=2; IntAct=EBI-12174, EBI-13914;
CC P34909; P15731: UBC4; NbExp=2; IntAct=EBI-12174, EBI-19735;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus.
CC -!- MISCELLANEOUS: Present with 4280 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; M96736; AAC37413.1; -; Genomic_DNA.
DR EMBL; L26309; AAB00326.1; -; Unassigned_DNA.
DR EMBL; U18813; AAB64604.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07727.1; -; Genomic_DNA.
DR PIR; A56015; A56015.
DR RefSeq; NP_010991.3; NM_001178959.3.
DR PDB; 5AIE; X-ray; 2.80 A; A=30-83.
DR PDB; 5AJD; X-ray; 3.62 A; B/D/F/H/J/L=418-477.
DR PDBsum; 5AIE; -.
DR PDBsum; 5AJD; -.
DR AlphaFoldDB; P34909; -.
DR SMR; P34909; -.
DR BioGRID; 36811; 208.
DR ComplexPortal; CPX-1800; CCR4-NOT mRNA deadenylase complex.
DR DIP; DIP-2255N; -.
DR IntAct; P34909; 25.
DR MINT; P34909; -.
DR STRING; 4932.YER068W; -.
DR GlyGen; P34909; 7 sites, 1 O-linked glycan (7 sites).
DR iPTMnet; P34909; -.
DR MaxQB; P34909; -.
DR PaxDb; 4932-YER068W; -.
DR PeptideAtlas; P34909; -.
DR EnsemblFungi; YER068W_mRNA; YER068W; YER068W.
DR GeneID; 856799; -.
DR KEGG; sce:YER068W; -.
DR AGR; SGD:S000000870; -.
DR SGD; S000000870; MOT2.
DR VEuPathDB; FungiDB:YER068W; -.
DR eggNOG; KOG2068; Eukaryota.
DR GeneTree; ENSGT00940000174608; -.
DR HOGENOM; CLU_028046_0_0_1; -.
DR InParanoid; P34909; -.
DR OMA; DGTYMDG; -.
DR OrthoDB; 1748at2759; -.
DR BioCyc; YEAST:G3O-30242-MONOMER; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 856799; 5 hits in 13 CRISPR screens.
DR PRO; PR:P34909; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P34909; Protein.
DR GO; GO:0030014; C:CCR4-NOT complex; IBA:GO_Central.
DR GO; GO:0030015; C:CCR4-NOT core complex; IPI:SGD.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt.
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:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0031087; P:deadenylation-independent decapping of nuclear-transcribed mRNA; IMP:SGD.
DR GO; GO:0070966; P:nuclear-transcribed mRNA catabolic process, no-go decay; IDA:UniProt.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; NAS:ComplexPortal.
DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IDA:SGD.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IGI:SGD.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProt.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:SGD.
DR GO; GO:0016567; P:protein ubiquitination; IDA:SGD.
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; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Coiled coil; Cytoplasm; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW RNA-binding; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..587
FT /note="General negative regulator of transcription subunit
FT 4"
FT /id="PRO_0000081681"
FT DOMAIN 137..228
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 33..78
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 229..256
FT /note="C3H1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 370..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 94..128
FT /evidence="ECO:0000255"
FT COMPBIAS 370..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 310
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 326
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:5AIE"
FT TURN 42..46
FT /evidence="ECO:0007829|PDB:5AIE"
FT HELIX 58..66
FT /evidence="ECO:0007829|PDB:5AIE"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:5AIE"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:5AIE"
SQ SEQUENCE 587 AA; 65354 MW; 8847084BD9BF48B7 CRC64;
MMNPHVQENL QAIHNALSNF DTSFLSEDEE DYCPLCIEPM DITDKNFFPC PCGYQICQFC
YNNIRQNPEL NGRCPACRRK YDDENVRYVT LSPEELKMER AKLARKEKER KHREKERKEN
EYTNRKHLSG TRVIQKNLVY VVGINPPVPY EEVAPTLKSE KYFGQYGKIN KIVVNRKTPH
SNNTTSEHYH HHSPGYGVYI TFGSKDDAAR CIAQVDGTYM DGRLIKAAYG TTKYCSSYLR
GLPCPNPNCM FLHEPGEEAD SFNKRELHNK QQAQQQSGGT AFTRSGIHNN ISTSTAGSNT
NLLSENFTGT PSPAAMRAQL HHDSHTNAGT PVLTPAPVPA GSNPWGVTQS ATPVTSINLS
KNSSSINLPT LNDSLGHHTT PTTENTITST TTTTNTNATS HSHGSKKKQS LAAEEYKDPY
DALGNAVDFL DARLHSLSNY QKRPISIKSN IIDEETYKKY PSLFSWDKIE ASKKSDNTLA
NKLVEILAIK PIDYTASVVQ FLQSVNVGVN DNITITDNTK TPTQPIRLQT VSQQIQPPLN
VSTPPPGIFG PQHKVPIQQQ QMGDTSSRNS SDLLNQLING RKIIAGN
//
