ID   MED3_YEAST              Reviewed;         397 AA.
AC   P40356; D6VUB3; Q6B1W3;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2005, sequence version 2.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Mediator of RNA polymerase II transcription subunit 3;
DE   AltName: Full=Hyper-recombination suppressor protein 1;
DE   AltName: Full=Mediator complex subunit 3;
DE   AltName: Full=Poly-glutamine domain protein 1;
GN   Name=PGD1; Synonyms=HRS1, MED3; OrderedLocusNames=YGL025C;
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=SC167;
RX   PubMed=7975891; DOI=10.1002/yea.320100604;
RA   Broehl S., Lisowsky T., Riemen G., Michaelis G.;
RT   "A new nuclear suppressor system for a mitochondrial RNA polymerase mutant
RT   identifies an unusual zinc-finger protein and a polyglutamine domain
RT   protein in Saccharomyces cerevisiae.";
RL   Yeast 10:719-731(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=8849881; DOI=10.1093/genetics/142.3.705;
RA   Santos-Rosa H., Clever B., Heyer W.-D., Aguilera A.;
RT   "The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required
RT   for spontaneous and hpr1-induced deletions between direct repeats.";
RL   Genetics 142:705-716(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169869;
RA   Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA   Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA   Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA   Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA   Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA   Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA   Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA   Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA   Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA   Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA   Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA   Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA   Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA   Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA   Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA   Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA   Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA   Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA   Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA   Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA   Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA   Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL   Nature 387:81-84(1997).
RN   [4]
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   [5]
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   [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 INTERACTION WITH CYC8 AND TUP1.
RX   PubMed=10722672; DOI=10.1074/jbc.275.12.8397;
RA   Papamichos-Chronakis M., Conlan R.S., Gounalaki N., Copf T., Tzamarias D.;
RT   "Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II
RT   holoenzyme.";
RL   J. Biol. Chem. 275:8397-8403(2000).
RN   [8]
RP   IDENTIFICATION OF PROBABLE INITIATION SITE.
RX   PubMed=12748633; DOI=10.1038/nature01644;
RA   Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT   "Sequencing and comparison of yeast species to identify genes and
RT   regulatory elements.";
RL   Nature 423:241-254(2003).
RN   [9]
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   [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.
RX   PubMed=16109375; DOI=10.1016/j.molcel.2005.06.033;
RA   van de Peppel J., Kettelarij N., van Bakel H., Kockelkorn T.T.J.P.,
RA   van Leenen D., Holstege F.C.P.;
RT   "Mediator expression profiling epistasis reveals a signal transduction
RT   pathway with antagonistic submodules and highly specific downstream
RT   targets.";
RL   Mol. Cell 19:511-522(2005).
RN   [16]
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   [17]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16630888; DOI=10.1016/j.molcel.2006.03.023;
RA   Andrau J.-C., van de Pasch L., Lijnzaad P., Bijma T., Koerkamp M.G.,
RA   van de Peppel J., Werner M., Holstege F.C.P.;
RT   "Genome-wide location of the coactivator mediator: binding without
RT   activation and transient Cdk8 interaction on DNA.";
RL   Mol. Cell 22:179-192(2006).
RN   [18]
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   [19]
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   [20]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [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   [21]
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. PGD1/MED3 is also involved in direct
CC       repeat recombination. {ECO:0000269|PubMed:10722672,
CC       ECO:0000269|PubMed:16076843, ECO:0000269|PubMed:16109375,
CC       ECO:0000269|PubMed:16263706, ECO:0000269|PubMed:8849881}.
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. PGD1/MED3
CC       interacts directly with the CYC8-TUP1 corepressor proteins.
CC       {ECO:0000269|PubMed:10722672, ECO:0000269|PubMed:17192271}.
CC   -!- INTERACTION:
CC       P40356; P14922: CYC8; NbExp=3; IntAct=EBI-13268, EBI-18215;
CC       P40356; P16649: TUP1; NbExp=3; IntAct=EBI-13268, EBI-19654;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095,
CC       ECO:0000269|PubMed:16630888, ECO:0000269|PubMed:8849881}.
CC   -!- MISCELLANEOUS: Present with 556 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the mediator complex subunit 3 family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAT92986.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA57213.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA81213.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA96725.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X81457; CAA57213.1; ALT_INIT; Genomic_DNA.
DR   EMBL; Z26254; CAA81213.1; ALT_INIT; Genomic_DNA.
DR   EMBL; Z72547; CAA96725.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AY692967; AAT92986.1; ALT_INIT; Genomic_DNA.
DR   EMBL; BK006941; DAA08074.1; -; Genomic_DNA.
DR   PIR; S46594; S46594.
DR   RefSeq; NP_011490.2; NM_001180890.1.
DR   PDB; 7UIC; EM; 3.70 A; c=1-397.
DR   PDB; 7UIK; EM; 7.70 A; c=1-397.
DR   PDB; 7UIL; EM; 4.30 A; 2/c=1-397.
DR   PDB; 7UIO; EM; 3.30 A; Ac/Bc=1-397.
DR   PDBsum; 7UIC; -.
DR   PDBsum; 7UIK; -.
DR   PDBsum; 7UIL; -.
DR   PDBsum; 7UIO; -.
DR   AlphaFoldDB; P40356; -.
DR   EMDB; EMD-26543; -.
DR   EMDB; EMD-26547; -.
DR   EMDB; EMD-26551; -.
DR   SMR; P40356; -.
DR   BioGRID; 33222; 196.
DR   ComplexPortal; CPX-3226; Core mediator complex.
DR   DIP; DIP-1186N; -.
DR   IntAct; P40356; 15.
DR   MINT; P40356; -.
DR   STRING; 4932.YGL025C; -.
DR   GlyGen; P40356; 4 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; P40356; -.
DR   MaxQB; P40356; -.
DR   PaxDb; 4932-YGL025C; -.
DR   PeptideAtlas; P40356; -.
DR   EnsemblFungi; YGL025C_mRNA; YGL025C; YGL025C.
DR   GeneID; 852860; -.
DR   KEGG; sce:YGL025C; -.
DR   AGR; SGD:S000002993; -.
DR   SGD; S000002993; PGD1.
DR   VEuPathDB; FungiDB:YGL025C; -.
DR   eggNOG; ENOG502S3GT; Eukaryota.
DR   HOGENOM; CLU_049224_0_0_1; -.
DR   InParanoid; P40356; -.
DR   OMA; FIQIMAN; -.
DR   OrthoDB; 2037096at2759; -.
DR   BioCyc; YEAST:G3O-30543-MONOMER; -.
DR   BioGRID-ORCS; 852860; 2 hits in 10 CRISPR screens.
DR   PRO; PR:P40356; -.
DR   Proteomes; UP000002311; Chromosome VII.
DR   RNAct; P40356; 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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:SGD.
DR   GO; GO:0003713; F:transcription coactivator activity; IMP:SGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP: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 by RNA polymerase II; IDA:ComplexPortal.
DR   GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:ComplexPortal.
DR   GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; IDA:ComplexPortal.
DR   InterPro; IPR020998; Med3.
DR   Pfam; PF11593; Med3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Activator; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..397
FT                   /note="Mediator of RNA polymerase II transcription subunit
FT                   3"
FT                   /id="PRO_0000096382"
FT   REGION          147..227
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          288..327
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          346..370
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        147..179
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CONFLICT        158
FT                   /note="A -> T (in Ref. 5; AAT92986)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   397 AA;  43079 MW;  69D60CE55EA30F18 CRC64;
     MDSIIPAGVK LDDLQVILAK NENETRDKVC KQINEARDEI LPLRLQFNEF IQIMANIDQE
     GSKQADRMAK YLHIRDKILQ LNDRFQTLSS HLEALQPLFS TVPEYLKTAD NRDRSFQLLE
     PLSTYNKNGN AVCSTATVVS TNHSAAASTP TTTATPHANP ITHAHSLSNP NSTATMQHNP
     LAGKRGPKSG STMGTPTVHN STAAAPIAAP KKPRKPRQTK KAKAQAQAQA QAQAQVYAQQ
     STVQTPITAS MAAALPNPTP SMINSVSPTN VMGTPLTNMM SPMGNAYSMG AQNQGGQVSM
     SQFNGSGNGS NPNTNTNSNN TPLQSQLNLN NLTPANILNM SMNNDFQQQQ QQQQQQQQPQ
     PQYNMNMGMN NMNNGGKELD SLDLNNLELG GLNMDFL
//