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Q96G25

- MED8_HUMAN

UniProt

Q96G25 - MED8_HUMAN

Protein

Mediator of RNA polymerase II transcription subunit 8

Gene

MED8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (23 May 2003)
      Previous versions | rss
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    Functioni

    Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins.

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. RNA polymerase II transcription cofactor activity Source: InterPro

    GO - Biological processi

    1. gene expression Source: Reactome
    2. protein ubiquitination Source: UniProtKB-UniPathway
    3. transcription initiation from RNA polymerase II promoter Source: Reactome

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_116145. PPARA activates gene expression.
    REACT_12627. Generic Transcription Pathway.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mediator of RNA polymerase II transcription subunit 8
    Alternative name(s):
    Activator-recruited cofactor 32 kDa component
    Short name:
    ARC32
    Mediator complex subunit 8
    Gene namesi
    Name:MED8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:19971. MED8.

    Subcellular locationi

    Nucleus Curated

    GO - Cellular componenti

    1. mediator complex Source: MGI
    2. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi143 – 1431L → P: Impairs interaction with the Elongin BC complex; when associated with F-147. 1 Publication
    Mutagenesisi147 – 1471C → F: Impairs interaction with the Elongin BC complex; when associated with P-143. 1 Publication

    Organism-specific databases

    PharmGKBiPA134893073.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 268268Mediator of RNA polymerase II transcription subunit 8PRO_0000096394Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei82 – 821Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ96G25.
    PaxDbiQ96G25.
    PRIDEiQ96G25.

    PTM databases

    PhosphoSiteiQ96G25.

    Expressioni

    Gene expression databases

    BgeeiQ96G25.
    CleanExiHS_MED8.
    GenevestigatoriQ96G25.

    Organism-specific databases

    HPAiHPA028377.
    HPA028438.

    Interactioni

    Subunit structurei

    Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. May be part of a multisubunit E3 ubiquitin-protein ligase complex with the elongin BC complex (TCEB1 and TCEB2), CUL2 and RBX1.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TCEB1Q153693EBI-394405,EBI-301231
    TCEB2Q153705EBI-394405,EBI-301238

    Protein-protein interaction databases

    BioGridi125219. 39 interactions.
    IntActiQ96G25. 22 interactions.
    MINTiMINT-275810.
    STRINGi9606.ENSP00000290663.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96G25.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni142 – 15110Interaction with the Elongin BC complex

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili1 – 2828Sequence AnalysisAdd
    BLAST
    Coiled coili133 – 16331Sequence AnalysisAdd
    BLAST

    Domaini

    The elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].

    Sequence similaritiesi

    Belongs to the Mediator complex subunit 8 family.Curated

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiNOG330005.
    HOGENOMiHOG000231149.
    HOVERGENiHBG009716.
    InParanoidiQ96G25.
    KOiK15129.
    OMAiDVAQKQI.
    OrthoDBiEOG7KSX9K.
    PhylomeDBiQ96G25.
    TreeFamiTF316778.

    Family and domain databases

    InterProiIPR019364. Mediatior_Med8_fun/met.
    [Graphical view]
    PfamiPF10232. Med8. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96G25-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MQREEKQLEA SLDALLSQVA DLKNSLGSFI CKLENEYGRL TWPSVLDSFA    50
    LLSGQLNTLN KVLKHEKTPL FRNQVIIPLV LSPDRDEDLM RQTEGRVPVF 100
    SHEVVPDHLR TKPDPEVEEQ EKQLTTDAAR IGADAAQKQI QSLNKMCSNL 150
    LEKISKEERE SESGGLRPNK QTFNPTDTNA LVAAVAFGKG LSNWRPSGSS 200
    GPGQAGQPGA GTILAGTSGL QQVQMAGAPS QQQPMLSGVQ MAQAGQPGKM 250
    PSGIKTNIKS ASMHPYQR 268
    Length:268
    Mass (Da):29,080
    Last modified:May 23, 2003 - v2
    Checksum:i6C186A4CECD1AFB3
    GO
    Isoform 2 (identifier: Q96G25-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         268-268: R → RPSCLGFILAIPLRRKVKKLLGQEGKKNAHLQLW

    Show »
    Length:301
    Mass (Da):32,819
    Checksum:iEE7EE86B0E9C3D4F
    GO
    Isoform 3 (identifier: Q96G25-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-89: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:179
    Mass (Da):19,002
    Checksum:iFA54BCD42B60EF7A
    GO

    Sequence cautioni

    The sequence BG722466 differs from that shown. Reason: Frameshift at position 258.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti257 – 2571N → K in BG722466. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 8989Missing in isoform 3. 1 PublicationVSP_035507Add
    BLAST
    Alternative sequencei268 – 2681R → RPSCLGFILAIPLRRKVKKL LGQEGKKNAHLQLW in isoform 2. 1 PublicationVSP_007524

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF521562 mRNA. Translation: AAM76709.1.
    AL139289 Genomic DNA. Translation: CAI23382.1.
    AL139289 Genomic DNA. Translation: CAP58853.1.
    AL139289 Genomic DNA. Translation: CAP58854.1.
    BC010019 mRNA. Translation: AAH10019.3.
    BC010543 mRNA. Translation: AAH10543.2.
    BG722466 mRNA. No translation available.
    CCDSiCCDS486.2. [Q96G25-2]
    CCDS487.2. [Q96G25-1]
    CCDS60108.1. [Q96G25-3]
    RefSeqiNP_001001653.1. NM_001001653.2. [Q96G25-3]
    NP_443109.2. NM_052877.4. [Q96G25-2]
    NP_963836.2. NM_201542.4. [Q96G25-1]
    UniGeneiHs.301756.

    Genome annotation databases

    EnsembliENST00000290663; ENSP00000290663; ENSG00000159479. [Q96G25-2]
    ENST00000372455; ENSP00000361533; ENSG00000159479. [Q96G25-3]
    ENST00000372457; ENSP00000361535; ENSG00000159479. [Q96G25-1]
    GeneIDi112950.
    KEGGihsa:112950.
    UCSCiuc001cje.2. human. [Q96G25-2]
    uc001cjf.5. human. [Q96G25-1]

    Polymorphism databases

    DMDMi31076772.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF521562 mRNA. Translation: AAM76709.1 .
    AL139289 Genomic DNA. Translation: CAI23382.1 .
    AL139289 Genomic DNA. Translation: CAP58853.1 .
    AL139289 Genomic DNA. Translation: CAP58854.1 .
    BC010019 mRNA. Translation: AAH10019.3 .
    BC010543 mRNA. Translation: AAH10543.2 .
    BG722466 mRNA. No translation available.
    CCDSi CCDS486.2. [Q96G25-2 ]
    CCDS487.2. [Q96G25-1 ]
    CCDS60108.1. [Q96G25-3 ]
    RefSeqi NP_001001653.1. NM_001001653.2. [Q96G25-3 ]
    NP_443109.2. NM_052877.4. [Q96G25-2 ]
    NP_963836.2. NM_201542.4. [Q96G25-1 ]
    UniGenei Hs.301756.

    3D structure databases

    ProteinModelPortali Q96G25.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 125219. 39 interactions.
    IntActi Q96G25. 22 interactions.
    MINTi MINT-275810.
    STRINGi 9606.ENSP00000290663.

    PTM databases

    PhosphoSitei Q96G25.

    Polymorphism databases

    DMDMi 31076772.

    Proteomic databases

    MaxQBi Q96G25.
    PaxDbi Q96G25.
    PRIDEi Q96G25.

    Protocols and materials databases

    DNASUi 112950.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000290663 ; ENSP00000290663 ; ENSG00000159479 . [Q96G25-2 ]
    ENST00000372455 ; ENSP00000361533 ; ENSG00000159479 . [Q96G25-3 ]
    ENST00000372457 ; ENSP00000361535 ; ENSG00000159479 . [Q96G25-1 ]
    GeneIDi 112950.
    KEGGi hsa:112950.
    UCSCi uc001cje.2. human. [Q96G25-2 ]
    uc001cjf.5. human. [Q96G25-1 ]

    Organism-specific databases

    CTDi 112950.
    GeneCardsi GC01M043849.
    HGNCi HGNC:19971. MED8.
    HPAi HPA028377.
    HPA028438.
    MIMi 607956. gene.
    neXtProti NX_Q96G25.
    PharmGKBi PA134893073.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG330005.
    HOGENOMi HOG000231149.
    HOVERGENi HBG009716.
    InParanoidi Q96G25.
    KOi K15129.
    OMAi DVAQKQI.
    OrthoDBi EOG7KSX9K.
    PhylomeDBi Q96G25.
    TreeFami TF316778.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_116145. PPARA activates gene expression.
    REACT_12627. Generic Transcription Pathway.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.

    Miscellaneous databases

    GeneWikii MED8.
    GenomeRNAii 112950.
    NextBioi 78721.
    PROi Q96G25.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q96G25.
    CleanExi HS_MED8.
    Genevestigatori Q96G25.

    Family and domain databases

    InterProi IPR019364. Mediatior_Med8_fun/met.
    [Graphical view ]
    Pfami PF10232. Med8. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase."
      Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R., Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W., Conaway R.C.
      Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION IN AN E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH MED10, MUTAGENESIS OF LEU-143 AND CYS-147.
    2. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-259 (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-268 (ISOFORM 2).
      Tissue: Cervix carcinoma, Melanoma and Testis.
    4. "Composite co-activator ARC mediates chromatin-directed transcriptional activation."
      Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.
      Nature 398:828-832(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE ARC COMPLEX, PROTEIN SEQUENCE OF 72-83 AND 189-200.
    5. "Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3."
      Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., Conaway J.W.
      J. Biol. Chem. 278:15123-15127(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MED10.
    6. "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology."
      Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., Conaway R.C.
      Mol. Cell 14:685-691(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX.
    7. "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription."
      Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., Roeder R.G.
      Mol. Cell 19:89-100(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiMED8_HUMAN
    AccessioniPrimary (citable) accession number: Q96G25
    Secondary accession number(s): A9IZ91
    , A9IZ92, Q5JUY8, Q96FQ4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 23, 2003
    Last sequence update: May 23, 2003
    Last modified: October 1, 2014
    This is version 120 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3