MED4_YEAST
ID MED4_YEAST Reviewed; 284 AA.
AC Q12343; D6W2N0;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 4;
DE AltName: Full=Mediator complex subunit 4;
GN Name=MED4; OrderedLocusNames=YOR174W; ORFNames=O3630;
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].
RC STRAIN=S288c / FY1678;
RX PubMed=8972579;
RX DOI=10.1002/(sici)1097-0061(199612)12:15<1563::aid-yea44>3.0.co;2-m;
RA Madania A., Poch O., Tarassov I.A., Winsor B., Martin R.P.;
RT "Analysis of a 22,956 bp region on the right arm of Saccharomyces
RT cerevisiae chromosome XV.";
RL Yeast 12:1563-1573(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND COMPONENT OF MEDIATOR COMPLEX.
RX PubMed=9420330; DOI=10.1101/gad.12.1.45;
RA Myers L.C., Gustafsson C.M., Bushnell D.A., Lui M., Erdjument-Bromage H.,
RA Tempst P., Kornberg R.D.;
RT "The Med proteins of yeast and their function through the RNA polymerase II
RT carboxy-terminal domain.";
RL Genes Dev. 12:45-54(1998).
RN [5]
RP INTERACTION WITH MED1; MED7 AND CSE2, FUNCTION OF THE MEDIATOR COMPLEX, AND
RP INTERACTION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
RX PubMed=11555651; DOI=10.1074/jbc.m105961200;
RA Kang J.S., Kim S.H., Hwang M.S., Han S.J., Lee Y.C., Kim Y.-J.;
RT "The structural and functional organization of the yeast mediator
RT complex.";
RL J. Biol. Chem. 276:42003-42010(2001).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
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 [8]
RP PHOSPHORYLATION AT THR-237.
RX PubMed=15126497; DOI=10.1074/jbc.m404426200;
RA Guidi B.W., Bjornsdottir G., Hopkins D.C., Lacomis L.,
RA Erdjument-Bromage H., Tempst P., Myers L.C.;
RT "Mutual targeting of mediator and the TFIIH kinase Kin28.";
RL J. Biol. Chem. 279:29114-29120(2004).
RN [9]
RP NOMENCLATURE.
RX PubMed=15175151; DOI=10.1016/j.molcel.2004.05.011;
RA Bourbon H.-M., Aguilera A., Ansari A.Z., Asturias F.J., Berk A.J.,
RA Bjoerklund S., Blackwell T.K., Borggrefe T., Carey M., Carlson M.,
RA Conaway J.W., Conaway R.C., Emmons S.W., Fondell J.D., Freedman L.P.,
RA Fukasawa T., Gustafsson C.M., Han M., He X., Herman P.K., Hinnebusch A.G.,
RA Holmberg S., Holstege F.C.P., Jaehning J.A., Kim Y.-J., Kuras L., Leutz A.,
RA Lis J.T., Meisterernest M., Naeaer A.M., Nasmyth K., Parvin J.D.,
RA Ptashne M., Reinberg D., Ronne H., Sadowski I., Sakurai H., Sipiczki M.,
RA Sternberg P.W., Stillman D.J., Strich R., Struhl K., Svejstrup J.Q.,
RA Tuck S., Winston F., Roeder R.G., Kornberg R.D.;
RT "A unified nomenclature for protein subunits of mediator complexes linking
RT transcriptional regulators to RNA polymerase II.";
RL Mol. Cell 14:553-557(2004).
RN [10]
RP PHOSPHORYLATION BY KIN28.
RX PubMed=14749387; DOI=10.1128/mcb.24.4.1721-1735.2004;
RA Liu Y., Kung C., Fishburn J., Ansari A.Z., Shokat K.M., Hahn S.;
RT "Two cyclin-dependent kinases promote RNA polymerase II transcription and
RT formation of the scaffold complex.";
RL Mol. Cell. Biol. 24:1721-1735(2004).
RN [11]
RP TOPOLOGY OF THE MEDIATOR COMPLEX.
RX PubMed=15477388; DOI=10.1093/nar/gkh878;
RA Guglielmi B., van Berkum N.L., Klapholz B., Bijma T., Boube M.,
RA Boschiero C., Bourbon H.-M., Holstege F.C.P., Werner M.;
RT "A high resolution protein interaction map of the yeast Mediator complex.";
RL Nucleic Acids Res. 32:5379-5391(2004).
RN [12]
RP INTERACTION WITH SRB7.
RX PubMed=15710619; DOI=10.1074/jbc.m413466200;
RA Baumli S., Hoeppner S., Cramer P.;
RT "A conserved mediator hinge revealed in the structure of the MED7-MED21
RT (Med7-Srb7) heterodimer.";
RL J. Biol. Chem. 280:18171-18178(2005).
RN [13]
RP CHARACTERIZATION OF THE MEDIATOR COMPLEX.
RX PubMed=16002404; DOI=10.1074/jbc.c500150200;
RA Takagi Y., Chadick J.Z., Davis J.A., Asturias F.J.;
RT "Preponderance of free mediator in the yeast Saccharomyces cerevisiae.";
RL J. Biol. Chem. 280:31200-31207(2005).
RN [14]
RP FUNCTION OF THE MEDIATOR COMPLEX.
RX PubMed=16076843; DOI=10.1074/jbc.m506067200;
RA Nair D., Kim Y., Myers L.C.;
RT "Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription
RT in yeast extracts.";
RL J. Biol. Chem. 280:33739-33748(2005).
RN [15]
RP FUNCTION OF THE MEDIATOR COMPLEX.
RX PubMed=16263706; DOI=10.1074/jbc.m508253200;
RA Takagi Y., Kornberg R.D.;
RT "Mediator as a general transcription factor.";
RL J. Biol. Chem. 281:80-89(2006).
RN [16]
RP CHARACTERIZATION OF THE MEDIATOR COMPLEX, AND INTERACTION OF THE MEDIATOR
RP COMPLEX WITH RNA POLYMERASE II.
RX PubMed=17192271; DOI=10.1074/jbc.m609484200;
RA Baidoobonso S.M., Guidi B.W., Myers L.C.;
RT "Med19(Rox3) regulates intermodule interactions in the Saccharomyces
RT cerevisiae mediator complex.";
RL J. Biol. Chem. 282:5551-5559(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-237, AND IDENTIFICATION BY
RP 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-237 AND SER-242, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242, AND IDENTIFICATION BY
RP 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-237, AND IDENTIFICATION BY
RP 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 [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP ELECTRON MICROSCOPY OF MEDIATOR COMPLEX IN COMPLEX WITH RNA POLYMERASE II.
RX PubMed=12191485; DOI=10.1016/s1097-2765(02)00598-1;
RA Davis J.A., Takagi Y., Kornberg R.D., Asturias F.J.;
RT "Structure of the yeast RNA polymerase II holoenzyme: mediator conformation
RT and polymerase interaction.";
RL Mol. Cell 10:409-415(2002).
CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in
CC the regulated transcription of nearly all RNA polymerase II-dependent
CC genes. Mediator functions as a bridge to convey information from gene-
CC specific regulatory proteins to the basal RNA polymerase II
CC transcription machinery. The Mediator complex, having a compact
CC conformation in its free form, is recruited to promoters by direct
CC interactions with regulatory proteins and serves for the assembly of a
CC functional preinitiation complex with RNA polymerase II and the general
CC transcription factors. The Mediator complex unfolds to an extended
CC conformation and partially surrounds RNA polymerase II, specifically
CC interacting with the unphosphorylated form of the C-terminal domain
CC (CTD) of RNA polymerase II. The Mediator complex dissociates from the
CC RNA polymerase II holoenzyme and stays at the promoter when
CC transcriptional elongation begins. {ECO:0000269|PubMed:11555651,
CC ECO:0000269|PubMed:16076843, ECO:0000269|PubMed:16263706}.
CC -!- SUBUNIT: Component of the Mediator complex, which is composed of at
CC least 21 subunits that form three structurally distinct submodules. The
CC Mediator head module contains MED6, MED8, MED11, SRB4/MED17,
CC SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22, the middle module
CC contains MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21
CC and SOH1/MED31, and the tail module contains MED2, PGD1/MED3,
CC RGR1/MED14, GAL11/MED15 and SIN4/MED16. The head and the middle modules
CC interact directly with RNA polymerase II, whereas the elongated tail
CC module interacts with gene-specific regulatory proteins. MED4 interacts
CC directly with MED1, MED7 and SRB7/MED21. {ECO:0000269|PubMed:11555651,
CC ECO:0000269|PubMed:15710619, ECO:0000269|PubMed:17192271}.
CC -!- INTERACTION:
CC Q12343; Q08278: MED7; NbExp=4; IntAct=EBI-31503, EBI-10674;
CC Q12343; P47822: SRB7; NbExp=4; IntAct=EBI-31503, EBI-18046;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 1617 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 4 family.
CC {ECO:0000305}.
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DR EMBL; U55021; AAB47419.1; -; Genomic_DNA.
DR EMBL; Z75082; CAA99383.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10946.1; -; Genomic_DNA.
DR PIR; S67062; S67062.
DR RefSeq; NP_014817.3; NM_001183593.3.
DR PDB; 5OQM; EM; 5.80 A; h=1-284.
DR PDB; 5SVA; EM; 15.30 A; T=1-284.
DR PDBsum; 5OQM; -.
DR PDBsum; 5SVA; -.
DR AlphaFoldDB; Q12343; -.
DR SMR; Q12343; -.
DR BioGRID; 34568; 570.
DR ComplexPortal; CPX-3226; Core mediator complex.
DR DIP; DIP-1178N; -.
DR IntAct; Q12343; 43.
DR MINT; Q12343; -.
DR STRING; 4932.YOR174W; -.
DR iPTMnet; Q12343; -.
DR MaxQB; Q12343; -.
DR PaxDb; Q12343; -.
DR PRIDE; Q12343; -.
DR EnsemblFungi; YOR174W_mRNA; YOR174W; YOR174W.
DR GeneID; 854345; -.
DR KEGG; sce:YOR174W; -.
DR SGD; S000005700; MED4.
DR VEuPathDB; FungiDB:YOR174W; -.
DR eggNOG; ENOG502RXM0; Eukaryota.
DR HOGENOM; CLU_071875_0_0_1; -.
DR InParanoid; Q12343; -.
DR OMA; MKLAKFT; -.
DR BioCyc; YEAST:G3O-33687-MON; -.
DR PRO; PR:Q12343; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q12343; protein.
DR GO; GO:0070847; C:core mediator complex; IDA:SGD.
DR GO; GO:0016592; C:mediator complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; IDA:ComplexPortal.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:SGD.
DR InterPro; IPR019258; Mediator_Med4.
DR PANTHER; PTHR13208; PTHR13208; 1.
DR Pfam; PF10018; Med4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..284
FT /note="Mediator of RNA polymerase II transcription subunit
FT 4"
FT /id="PRO_0000096386"
FT REGION 205..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..269
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..284
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 237
FT /note="Phosphothreonine; by KIN28"
FT /evidence="ECO:0000269|PubMed:15126497,
FT ECO:0007744|PubMed:17287358, ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:18407956"
SQ SEQUENCE 284 AA; 32205 MW; D42A3C62D465DDAD CRC64;
MSVQDTKAVE FSMGHIRSSS VSLVAEATSN TNSEDKLSKV QLYEDLCRYE DTLSKLVESV
DRFKPNLDIA KDLIRTDEAL FENVKLLAEY DNIYRNLQKI DKDSEELDSK TRKILEILNE
CHDELKALPM LEQVEFEKNT ILQQRSKINS TELLDYATKL SKFTKIPPTF DKGAVGPNNF
IWPAEDALRR GMLAMASLHS KELTRIPGEE VEETEVPTVP PSQSEEQKGQ MAKKEGTPKT
DSFIFDGTAK EVGDEADNTK DKEKEENNDD ALDLDLDLFD PDDF
