MED8_HUMAN
ID MED8_HUMAN Reviewed; 268 AA.
AC Q96G25; A9IZ91; A9IZ92; Q5JUY8; Q96FQ4;
DT 23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 8;
DE AltName: Full=Activator-recruited cofactor 32 kDa component;
DE Short=ARC32;
DE AltName: Full=Mediator complex subunit 8;
GN Name=MED8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION IN AN E3 UBIQUITIN
RP LIGASE COMPLEX, INTERACTION WITH MED10, AND MUTAGENESIS OF LEU-143 AND
RP CYS-147.
RX PubMed=12149480; DOI=10.1073/pnas.162424199;
RA Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R.,
RA Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W.,
RA Conaway R.C.;
RT "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that
RT can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-259 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 5-268 (ISOFORM 2).
RC TISSUE=Cervix carcinoma, Melanoma, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION IN THE ARC COMPLEX, AND PROTEIN SEQUENCE OF 72-83 AND
RP 189-200.
RX PubMed=10235267; DOI=10.1038/19789;
RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.;
RT "Composite co-activator ARC mediates chromatin-directed transcriptional
RT activation.";
RL Nature 398:828-832(1999).
RN [5]
RP INTERACTION WITH MED10.
RX PubMed=12584197; DOI=10.1074/jbc.c300054200;
RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J.,
RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C.,
RA Conaway J.W.;
RT "Identification of mammalian Mediator subunits with similarities to yeast
RT Mediator subunits Srb5, Srb6, Med11, and Rox3.";
RL J. Biol. Chem. 278:15123-15127(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR
RP COMPLEX.
RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006;
RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B.,
RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W.,
RA Conaway R.C.;
RT "A set of consensus mammalian mediator subunits identified by
RT multidimensional protein identification technology.";
RL Mol. Cell 14:685-691(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR
RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015;
RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T.,
RA Roeder R.G.;
RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation
RT enriched in RNA polymerase II and is required for ER-mediated
RT transcription.";
RL Mol. Cell 19:89-100(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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. Mediator is recruited to promoters by direct
CC interactions with regulatory proteins and serves as a scaffold for the
CC assembly of a functional preinitiation complex with RNA polymerase II
CC and the general transcription factors. May play a role as a target
CC recruitment subunit in E3 ubiquitin-protein ligase complexes and thus
CC in ubiquitination and subsequent proteasomal degradation of target
CC proteins.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1,
CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L,
CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23,
CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and
CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct
CC module termed the CDK8 module. Mediator containing the CDK8 module is
CC less active than Mediator lacking this module in supporting
CC transcriptional activation. Individual preparations of the Mediator
CC complex lacking one or more distinct subunits have been variously
CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. May be part of a
CC multisubunit E3 ubiquitin-protein ligase complex with the elongin BC
CC complex (ELOB and ELOC), CUL2 and RBX1. {ECO:0000269|PubMed:10235267,
CC ECO:0000269|PubMed:12149480, ECO:0000269|PubMed:15175163,
CC ECO:0000269|PubMed:15989967}.
CC -!- INTERACTION:
CC Q96G25; Q15370: ELOB; NbExp=5; IntAct=EBI-394405, EBI-301238;
CC Q96G25; Q15369: ELOC; NbExp=3; IntAct=EBI-394405, EBI-301231;
CC Q96G25-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10286267, EBI-10171697;
CC Q96G25-2; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-10286267, EBI-302345;
CC Q96G25-2; P31321: PRKAR1B; NbExp=3; IntAct=EBI-10286267, EBI-2805516;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96G25-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G25-2; Sequence=VSP_007524;
CC Name=3;
CC IsoId=Q96G25-3; Sequence=VSP_035507;
CC -!- DOMAIN: The elongin BC complex binding domain is also known as BC-box
CC with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 8 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BG722466; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF521562; AAM76709.1; -; mRNA.
DR EMBL; AL139289; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010019; AAH10019.3; -; mRNA.
DR EMBL; BC010543; AAH10543.2; -; mRNA.
DR EMBL; BG722466; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS486.2; -. [Q96G25-2]
DR CCDS; CCDS487.2; -. [Q96G25-1]
DR CCDS; CCDS60108.1; -. [Q96G25-3]
DR RefSeq; NP_001001653.1; NM_001001653.2. [Q96G25-3]
DR RefSeq; NP_443109.2; NM_052877.4. [Q96G25-2]
DR RefSeq; NP_963836.2; NM_201542.4. [Q96G25-1]
DR PDB; 7EMF; EM; 3.50 A; H=1-268.
DR PDB; 7ENA; EM; 4.07 A; h=1-268.
DR PDB; 7ENC; EM; 4.13 A; h=1-268.
DR PDB; 7ENJ; EM; 4.40 A; H=1-268.
DR PDB; 7LBM; EM; 4.80 A; h=1-268.
DR PDB; 7NVR; EM; 4.50 A; b=1-268.
DR PDBsum; 7EMF; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7ENJ; -.
DR PDBsum; 7LBM; -.
DR PDBsum; 7NVR; -.
DR AlphaFoldDB; Q96G25; -.
DR SMR; Q96G25; -.
DR BioGRID; 125219; 110.
DR ComplexPortal; CPX-3227; Core mediator complex.
DR CORUM; Q96G25; -.
DR IntAct; Q96G25; 60.
DR MINT; Q96G25; -.
DR STRING; 9606.ENSP00000290663; -.
DR iPTMnet; Q96G25; -.
DR PhosphoSitePlus; Q96G25; -.
DR BioMuta; MED8; -.
DR DMDM; 31076772; -.
DR EPD; Q96G25; -.
DR jPOST; Q96G25; -.
DR MassIVE; Q96G25; -.
DR MaxQB; Q96G25; -.
DR PaxDb; Q96G25; -.
DR PeptideAtlas; Q96G25; -.
DR PRIDE; Q96G25; -.
DR ProteomicsDB; 76585; -. [Q96G25-1]
DR ProteomicsDB; 76586; -. [Q96G25-2]
DR ProteomicsDB; 76587; -. [Q96G25-3]
DR Antibodypedia; 32328; 180 antibodies from 28 providers.
DR DNASU; 112950; -.
DR Ensembl; ENST00000290663.10; ENSP00000290663.6; ENSG00000159479.17. [Q96G25-2]
DR Ensembl; ENST00000372455.4; ENSP00000361533.4; ENSG00000159479.17. [Q96G25-3]
DR Ensembl; ENST00000372457.9; ENSP00000361535.4; ENSG00000159479.17. [Q96G25-1]
DR GeneID; 112950; -.
DR KEGG; hsa:112950; -.
DR MANE-Select; ENST00000372457.9; ENSP00000361535.4; NM_201542.5; NP_963836.2.
DR UCSC; uc001cje.3; human. [Q96G25-1]
DR CTD; 112950; -.
DR DisGeNET; 112950; -.
DR GeneCards; MED8; -.
DR HGNC; HGNC:19971; MED8.
DR HPA; ENSG00000159479; Low tissue specificity.
DR MIM; 607956; gene.
DR neXtProt; NX_Q96G25; -.
DR OpenTargets; ENSG00000159479; -.
DR PharmGKB; PA134893073; -.
DR VEuPathDB; HostDB:ENSG00000159479; -.
DR eggNOG; KOG3583; Eukaryota.
DR GeneTree; ENSGT00390000011838; -.
DR HOGENOM; CLU_085476_0_0_1; -.
DR InParanoid; Q96G25; -.
DR OMA; IIMRVND; -.
DR OrthoDB; 1392867at2759; -.
DR PhylomeDB; Q96G25; -.
DR TreeFam; TF316778; -.
DR PathwayCommons; Q96G25; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR SignaLink; Q96G25; -.
DR SIGNOR; Q96G25; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 112950; 549 hits in 1110 CRISPR screens.
DR ChiTaRS; MED8; human.
DR GeneWiki; MED8; -.
DR GenomeRNAi; 112950; -.
DR Pharos; Q96G25; Tbio.
DR PRO; PR:Q96G25; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96G25; protein.
DR Bgee; ENSG00000159479; Expressed in oocyte and 201 other tissues.
DR Genevisible; Q96G25; HS.
DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal.
DR GO; GO:0016592; C:mediator complex; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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; IC:ComplexPortal.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
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; IC: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; Alternative splicing; Coiled coil;
KW Direct protein sequencing; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1..268
FT /note="Mediator of RNA polymerase II transcription subunit
FT 8"
FT /id="PRO_0000096394"
FT REGION 142..151
FT /note="Interaction with the Elongin BC complex"
FT REGION 156..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1..28
FT /evidence="ECO:0000255"
FT COILED 133..163
FT /evidence="ECO:0000255"
FT COMPBIAS 214..240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 253..268
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035507"
FT VAR_SEQ 268
FT /note="R -> RPSCLGFILAIPLRRKVKKLLGQEGKKNAHLQLW (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007524"
FT MUTAGEN 143
FT /note="L->P: Impairs interaction with the Elongin BC
FT complex; when associated with F-147."
FT /evidence="ECO:0000269|PubMed:12149480"
FT MUTAGEN 147
FT /note="C->F: Impairs interaction with the Elongin BC
FT complex; when associated with P-143."
FT /evidence="ECO:0000269|PubMed:12149480"
FT CONFLICT 257
FT /note="N -> K (in Ref. 3; BG722466)"
FT /evidence="ECO:0000305"
FT HELIX 4..35
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 42..65
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 115..128
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 135..157
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 175..186
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:7EMF"
SQ SEQUENCE 268 AA; 29080 MW; 6C186A4CECD1AFB3 CRC64;
MQREEKQLEA SLDALLSQVA DLKNSLGSFI CKLENEYGRL TWPSVLDSFA LLSGQLNTLN
KVLKHEKTPL FRNQVIIPLV LSPDRDEDLM RQTEGRVPVF SHEVVPDHLR TKPDPEVEEQ
EKQLTTDAAR IGADAAQKQI QSLNKMCSNL LEKISKEERE SESGGLRPNK QTFNPTDTNA
LVAAVAFGKG LSNWRPSGSS GPGQAGQPGA GTILAGTSGL QQVQMAGAPS QQQPMLSGVQ
MAQAGQPGKM PSGIKTNIKS ASMHPYQR
