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Q96G25

- MED8_HUMAN

UniProt

Q96G25 - MED8_HUMAN

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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

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. 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
Complete GO annotation...

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
Complete GO annotation...

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. 42 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.
GeneTreeiENSGT00390000011838.
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

        10         20         30         40         50
MQREEKQLEA SLDALLSQVA DLKNSLGSFI CKLENEYGRL TWPSVLDSFA
60 70 80 90 100
LLSGQLNTLN KVLKHEKTPL FRNQVIIPLV LSPDRDEDLM RQTEGRVPVF
110 120 130 140 150
SHEVVPDHLR TKPDPEVEEQ EKQLTTDAAR IGADAAQKQI QSLNKMCSNL
160 170 180 190 200
LEKISKEERE SESGGLRPNK QTFNPTDTNA LVAAVAFGKG LSNWRPSGSS
210 220 230 240 250
GPGQAGQPGA GTILAGTSGL QQVQMAGAPS QQQPMLSGVQ MAQAGQPGKM
260
PSGIKTNIKS ASMHPYQR
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. Curated

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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. 42 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.
GeneTreei ENSGT00390000011838.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 121 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