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MED6_YEAST
ID   MED6_YEAST              Reviewed;         295 AA.
AC   P38782; D3DL07;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   03-AUG-2022, entry version 164.
DE   RecName: Full=Mediator of RNA polymerase II transcription subunit 6;
DE   AltName: Full=Mediator complex subunit 6;
GN   Name=MED6; Synonyms=MTR32; OrderedLocusNames=YHR058C;
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 [MRNA], AND FUNCTION.
RX   PubMed=9234719; DOI=10.1128/mcb.17.8.4622;
RA   Lee Y.C., Min S., Gim B.S., Kim Y.-J.;
RT   "A transcriptional mediator protein that is required for activation of many
RT   RNA polymerase II promoters and is conserved from yeast to humans.";
RL   Mol. Cell. Biol. 17:4622-4632(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8091229; DOI=10.1126/science.8091229;
RA   Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA   Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA   Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA   Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA   St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA   Waterston R., Wilson R., Vaudin M.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT   VIII.";
RL   Science 265:2077-2082(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   COMPONENT OF MEDIATOR COMPLEX.
RX   PubMed=7479899; DOI=10.1073/pnas.92.24.10864;
RA   Li Y., Bjoerklund S., Jiang Y.W., Kim Y.-J., Lane W.S., Stillman D.J.,
RA   Kornberg R.D.;
RT   "Yeast global transcriptional regulators Sin4 and Rgr1 are components of
RT   mediator complex/RNA polymerase II holoenzyme.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:10864-10868(1995).
RN   [5]
RP   FUNCTION.
RX   PubMed=9845373; DOI=10.1016/s0092-8674(00)81641-4;
RA   Holstege F.C.P., Jennings E.G., Wyrick J.J., Lee T.I., Hengartner C.J.,
RA   Green M.R., Golub T.R., Lander E.S., Young R.A.;
RT   "Dissecting the regulatory circuitry of a eukaryotic genome.";
RL   Cell 95:717-728(1998).
RN   [6]
RP   INTERACTION WITH SRB4.
RX   PubMed=9671455; DOI=10.1128/mcb.18.8.4455;
RA   Lee T.I., Wyrick J.J., Koh S.S., Jennings E.G., Gadbois E.L., Young R.A.;
RT   "Interplay of positive and negative regulators in transcription initiation
RT   by RNA polymerase II holoenzyme.";
RL   Mol. Cell. Biol. 18:4455-4462(1998).
RN   [7]
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   [8]
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   [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   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   [11]
RP   INTERACTION WITH SRB4 AND 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   [12]
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   [13]
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   [14]
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   [15]
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   [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   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   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, 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   [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).
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:16076843,
CC       ECO:0000269|PubMed:16263706, ECO:0000269|PubMed:16885025,
CC       ECO:0000269|PubMed:9234719, ECO:0000269|PubMed:9845373}.
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. MED6 interacts
CC       directly with SRB4/MED17 and SRB7/MED21. {ECO:0000269|PubMed:15710619,
CC       ECO:0000269|PubMed:16885025, ECO:0000269|PubMed:17192271,
CC       ECO:0000269|PubMed:9671455}.
CC   -!- INTERACTION:
CC       P38782; P32569: SRB4; NbExp=7; IntAct=EBI-10667, EBI-18025;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 4824 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the Mediator complex subunit 6 family.
CC       {ECO:0000305}.
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DR   EMBL; U78080; AAB57643.1; -; mRNA.
DR   EMBL; U00061; AAB68387.1; -; Genomic_DNA.
DR   EMBL; BK006934; DAA06751.1; -; Genomic_DNA.
DR   PIR; S46708; S46708.
DR   RefSeq; NP_011925.1; NM_001179188.1.
DR   PDB; 3J1O; EM; 16.00 A; N=166-190.
DR   PDB; 3RJ1; X-ray; 4.30 A; G/N/U=1-295.
DR   PDB; 4GWP; X-ray; 4.20 A; G=1-295.
DR   PDB; 4GWQ; X-ray; 4.50 A; G=1-295.
DR   PDB; 4V1O; EM; 9.70 A; S=1-295.
DR   PDB; 5OQM; EM; 5.80 A; a=1-295.
DR   PDB; 5SVA; EM; 15.30 A; M=1-295.
DR   PDBsum; 3J1O; -.
DR   PDBsum; 3RJ1; -.
DR   PDBsum; 4GWP; -.
DR   PDBsum; 4GWQ; -.
DR   PDBsum; 4V1O; -.
DR   PDBsum; 5OQM; -.
DR   PDBsum; 5SVA; -.
DR   AlphaFoldDB; P38782; -.
DR   SMR; P38782; -.
DR   BioGRID; 36490; 663.
DR   ComplexPortal; CPX-3226; Core mediator complex.
DR   DIP; DIP-2093N; -.
DR   IntAct; P38782; 23.
DR   MINT; P38782; -.
DR   STRING; 4932.YHR058C; -.
DR   iPTMnet; P38782; -.
DR   MaxQB; P38782; -.
DR   PaxDb; P38782; -.
DR   PRIDE; P38782; -.
DR   EnsemblFungi; YHR058C_mRNA; YHR058C; YHR058C.
DR   GeneID; 856455; -.
DR   KEGG; sce:YHR058C; -.
DR   SGD; S000001100; MED6.
DR   VEuPathDB; FungiDB:YHR058C; -.
DR   eggNOG; KOG3169; Eukaryota.
DR   GeneTree; ENSGT00390000017666; -.
DR   HOGENOM; CLU_077754_0_0_1; -.
DR   InParanoid; P38782; -.
DR   OMA; MQRQFSQ; -.
DR   BioCyc; YEAST:G3O-31111-MON; -.
DR   PRO; PR:P38782; -.
DR   Proteomes; UP000002311; Chromosome VIII.
DR   RNAct; P38782; 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:0003713; F:transcription coactivator activity; IDA:SGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA: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:SGD.
DR   Gene3D; 3.10.450.580; -; 1.
DR   InterPro; IPR007018; Mediator_Med6.
DR   InterPro; IPR016612; Mediator_Med6_fun.
DR   InterPro; IPR038566; Mediator_Med6_sf.
DR   PANTHER; PTHR13104; PTHR13104; 1.
DR   Pfam; PF04934; Med6; 1.
DR   PIRSF; PIRSF013286; MED6_fungi; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Nucleus; Phosphoprotein; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..295
FT                   /note="Mediator of RNA polymerase II transcription subunit
FT                   6"
FT                   /id="PRO_0000096391"
FT   REGION          211..243
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         225
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
SQ   SEQUENCE   295 AA;  32819 MW;  B84E87DCC2737849 CRC64;
     MNVTPLDELQ WKSPEWIQVF GLRTENVLDY FAESPFFDKT SNNQVIKMQR QFSQLNDPNA
     AVNMTQNIMT LPDGKNGNLE EEFAYVDPAR RQILFKYPMY MQLEEELMKL DGTEYVLSSV
     REPDFWVIRK QRRTNNSGVG SAKGPEIIPL QDYYIIGANI YQSPTIFKIV QSRLMSTSYH
     LNSTLESLYD LIEFQPSQGV HYKVPTDTST TATAATNGNN AGGGSNKSSV RPTGGANMAT
     VPSTTNVNMT VNTMGTGGQT IDNGTGRTGN GNMGITTEML DKLMVTSIRS TPNYI
 
 
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