MED8_YEAST
ID MED8_YEAST Reviewed; 223 AA.
AC P38304; D6VQI7;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 8;
DE AltName: Full=Mediator complex subunit 8;
GN Name=MED8; OrderedLocusNames=YBR193C; ORFNames=YBR1403;
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=ATCC 204508 / S288c;
RX PubMed=8346681; DOI=10.1002/yea.320090611;
RA Demolis N., Mallet L., Bussereau F., Jacquet M.;
RT "RIM2, MSI1 and PGI1 are located within an 8 kb segment of Saccharomyces
RT cerevisiae chromosome II, which also contains the putative ribosomal gene
RT L21 and a new putative essential gene with a leucine zipper motif.";
RL Yeast 9:645-659(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP PROTEIN SEQUENCE OF 2-11, AND FUNCTION.
RX PubMed=9918841; DOI=10.1006/bbrc.1998.9954;
RA Chaves R.S., Herrero P., Moreno F.;
RT "Med8, a subunit of the mediator CTD complex of RNA polymerase II, directly
RT binds to regulatory elements of SUC2 and HXK2 genes.";
RL Biochem. Biophys. Res. Commun. 254:345-350(1999).
RN [6]
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 [7]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=10526178; DOI=10.1016/s0014-5793(99)01289-2;
RA Moreno-Herrero F., Herrero P., Colchero J., Baro A.M., Moreno F.;
RT "Analysis by atomic force microscopy of Med8 binding to cis-acting
RT regulatory elements of the SUC2 and HXK2 genes of Saccharomyces
RT cerevisiae.";
RL FEBS Lett. 459:427-432(1999).
RN [8]
RP INTERACTION WITH SRB5, FUNCTION OF THE MEDIATOR COMPLEX, AND INTERACTION OF
RP 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 [9]
RP INTERACTION WITH HXK2.
RX PubMed=12054864; DOI=10.1016/s0022-2836(02)00377-7;
RA de la Cera T., Herrero P., Moreno-Herrero F., Chaves R.S., Moreno F.;
RT "Mediator factor Med8p interacts with the hexokinase 2: implication in the
RT glucose signalling pathway of Saccharomyces cerevisiae.";
RL J. Mol. Biol. 319:703-714(2002).
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 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 [12]
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 [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 INTERACTION WITH SRB4, FUNCTION OF THE MEDIATOR COMPLEX HEAD MODULE,
RP ELECTRON MICROSCOPY OF THE MEDIATOR COMPLEX HEAD MODULE, AND INTERACTION OF
RP THE MEDIATOR COMPLEX HEAD MODULE WITH RNA POLYMERASE II AND TFIIF.
RX PubMed=16885025; DOI=10.1016/j.molcel.2006.06.007;
RA Takagi Y., Calero G., Komori H., Brown J.A., Ehrensberger A.H., Hudmon A.,
RA Asturias F.J., Kornberg R.D.;
RT "Head module control of mediator interactions.";
RL Mol. Cell 23:355-364(2006).
RN [17]
RP INTERACTION WITH SRB5, CHARACTERIZATION OF THE MEDIATOR COMPLEX, AND
RP INTERACTION OF THE MEDIATOR 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 [18]
RP 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 [19]
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).
RN [20]
RP X-RAY STRUCTURE (2.7 ANGSTROMS) OF 190-210 IN COMPLEX WITH SRB2 AND SRB5,
RP AND INTERACTION WITH TBP1.
RX PubMed=16964259; DOI=10.1038/nsmb1143;
RA Lariviere L., Geiger S., Hoeppner S., Roether S., Straesser K., Cramer P.;
RT "Structure and TBP binding of the Mediator head subcomplex Med8-Med18-
RT Med20.";
RL Nat. Struct. Mol. Biol. 13:895-901(2006).
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. MED8 binds to the consensus sequence
CC 5'-[AC][AG]GAAAT-3' in both the UAS of SUC2 and the DRS2 of HXK2.
CC {ECO:0000269|PubMed:10526178, ECO:0000269|PubMed:11555651,
CC ECO:0000269|PubMed:16076843, ECO:0000269|PubMed:16263706,
CC ECO:0000269|PubMed:16885025, ECO:0000269|PubMed:9918841}.
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. MED8 interacts
CC directly with SRB5/MED18. Interacts also with Hexokinase B (HXK2).
CC Interacts with TBP1. {ECO:0000269|PubMed:11555651,
CC ECO:0000269|PubMed:12054864, ECO:0000269|PubMed:16885025,
CC ECO:0000269|PubMed:16964259, ECO:0000269|PubMed:17192271}.
CC -!- INTERACTION:
CC P38304; P13393: SPT15; NbExp=3; IntAct=EBI-20932, EBI-19129;
CC P38304; P32569: SRB4; NbExp=9; IntAct=EBI-20932, EBI-18025;
CC P38304; P32585: SRB5; NbExp=8; IntAct=EBI-20932, EBI-18032;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- MISCELLANEOUS: Present with 937 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 8 family.
CC {ECO:0000305}.
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DR EMBL; Z21487; CAA79680.1; -; Genomic_DNA.
DR EMBL; Z36062; CAA85155.1; -; Genomic_DNA.
DR EMBL; AY557711; AAS56037.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07307.1; -; Genomic_DNA.
DR PIR; S34018; S34018.
DR RefSeq; NP_009752.3; NM_001178541.3.
DR PDB; 2HZS; X-ray; 2.70 A; I/J/K/L=190-210.
DR PDB; 3J1O; EM; 16.00 A; J=1-223.
DR PDB; 3RJ1; X-ray; 4.30 A; C/J/Q=1-223.
DR PDB; 4GWP; X-ray; 4.20 A; C=1-223.
DR PDB; 4GWQ; X-ray; 4.50 A; C=1-223.
DR PDB; 4V1O; EM; 9.70 A; U=2-223.
DR PDB; 5OQM; EM; 5.80 A; b=1-223.
DR PDB; 5SVA; EM; 15.30 A; N=1-223.
DR PDBsum; 2HZS; -.
DR PDBsum; 3J1O; -.
DR PDBsum; 3RJ1; -.
DR PDBsum; 4GWP; -.
DR PDBsum; 4GWQ; -.
DR PDBsum; 4V1O; -.
DR PDBsum; 5OQM; -.
DR PDBsum; 5SVA; -.
DR AlphaFoldDB; P38304; -.
DR SMR; P38304; -.
DR BioGRID; 32890; 620.
DR ComplexPortal; CPX-3226; Core mediator complex.
DR DIP; DIP-1659N; -.
DR IntAct; P38304; 18.
DR MINT; P38304; -.
DR STRING; 4932.YBR193C; -.
DR iPTMnet; P38304; -.
DR MaxQB; P38304; -.
DR PaxDb; P38304; -.
DR PRIDE; P38304; -.
DR TopDownProteomics; P38304; -.
DR EnsemblFungi; YBR193C_mRNA; YBR193C; YBR193C.
DR GeneID; 852492; -.
DR KEGG; sce:YBR193C; -.
DR SGD; S000000397; MED8.
DR VEuPathDB; FungiDB:YBR193C; -.
DR eggNOG; ENOG502S8U1; Eukaryota.
DR HOGENOM; CLU_108151_0_0_1; -.
DR InParanoid; P38304; -.
DR OMA; PQWYSLQ; -.
DR BioCyc; YEAST:G3O-29135-MON; -.
DR EvolutionaryTrace; P38304; -.
DR PRO; PR:P38304; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38304; protein.
DR GO; GO:0070847; C:core mediator complex; IDA:SGD.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:SGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0017025; F:TBP-class protein binding; IDA:SGD.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IPI:SGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:SGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:SGD.
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 InterPro; IPR019364; Mediatior_Med8_fun/met.
DR PANTHER; PTHR13074; PTHR13074; 1.
DR Pfam; PF10232; Med8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Coiled coil; Direct protein sequencing;
KW DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9918841"
FT CHAIN 2..223
FT /note="Mediator of RNA polymerase II transcription subunit
FT 8"
FT /id="PRO_0000096397"
FT REGION 2..138
FT /note="Interaction with TBP1"
FT /evidence="ECO:0000269|PubMed:16964259"
FT COILED 33..59
FT /evidence="ECO:0000255"
FT HELIX 198..207
FT /evidence="ECO:0007829|PDB:2HZS"
SQ SEQUENCE 223 AA; 25268 MW; 86B2A064293C6B61 CRC64;
MSQSTASLVP EGNQGSLQED VSFDFNGVPG QALDAVRMRL AQLTHSLRRI RDEMSKAELP
QWYTLQSQLN VTLSQLVSVT STLQHFQETL DSTVVYPLPK FPTTSHESLV TTLLRKKNIP
EVDEWMKYVR ETSGVTTALL KDEEIEKLLQ QDREITNWAR TTFRNEYGKH DFKNEESLSE
EHASLLVRDS KPSKPFNVDD VLKFTFTGEK PIITGSTSTS SSN
