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Q96G25 (MED8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MED8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length268 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.1 Ref.4 Ref.6 Ref.7

Subcellular location

Nucleus Probable.

Domain

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

Sequence similarities

Belongs to the Mediator complex subunit 8 family.

Sequence caution

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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TCEB1Q153693EBI-394405,EBI-301231
TCEB2Q153705EBI-394405,EBI-301238

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96G25-1)

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.
Isoform 2 (identifier: Q96G25-2)

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: R → RPSCLGFILAIPLRRKVKKLLGQEGKKNAHLQLW
Isoform 3 (identifier: Q96G25-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 268268Mediator of RNA polymerase II transcription subunit 8
PRO_0000096394

Regions

Region142 – 15110Interaction with the Elongin BC complex
Coiled coil1 – 2828 Potential
Coiled coil133 – 16331 Potential

Amino acid modifications

Modified residue821Phosphoserine Ref.8

Natural variations

Alternative sequence1 – 8989Missing in isoform 3.
VSP_035507
Alternative sequence2681R → RPSCLGFILAIPLRRKVKKL LGQEGKKNAHLQLW in isoform 2.
VSP_007524

Experimental info

Mutagenesis1431L → P: Impairs interaction with the Elongin BC complex; when associated with F-147. Ref.1
Mutagenesis1471C → F: Impairs interaction with the Elongin BC complex; when associated with P-143. Ref.1
Sequence conflict2571N → K in BG722466. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 23, 2003. Version 2.
Checksum: 6C186A4CECD1AFB3

FASTA26829,080
        10         20         30         40         50         60 
MQREEKQLEA SLDALLSQVA DLKNSLGSFI CKLENEYGRL TWPSVLDSFA LLSGQLNTLN 

        70         80         90        100        110        120 
KVLKHEKTPL FRNQVIIPLV LSPDRDEDLM RQTEGRVPVF SHEVVPDHLR TKPDPEVEEQ 

       130        140        150        160        170        180 
EKQLTTDAAR IGADAAQKQI QSLNKMCSNL LEKISKEERE SESGGLRPNK QTFNPTDTNA 

       190        200        210        220        230        240 
LVAAVAFGKG LSNWRPSGSS GPGQAGQPGA GTILAGTSGL QQVQMAGAPS QQQPMLSGVQ 

       250        260 
MAQAGQPGKM PSGIKTNIKS ASMHPYQR 

« Hide

Isoform 2 [UniParc].

Checksum: EE7EE86B0E9C3D4F
Show »

FASTA30132,819
Isoform 3 [UniParc].

Checksum: FA54BCD42B60EF7A
Show »

FASTA17919,002

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001001653.1. NM_001001653.2.
NP_443109.2. NM_052877.4.
NP_963836.2. NM_201542.4.
UniGeneHs.301756.

3D structure databases

ProteinModelPortalQ96G25.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125219. 39 interactions.
IntActQ96G25. 22 interactions.
MINTMINT-275810.
STRING9606.ENSP00000290663.

PTM databases

PhosphoSiteQ96G25.

Polymorphism databases

DMDM31076772.

Proteomic databases

PaxDbQ96G25.
PRIDEQ96G25.

Protocols and materials databases

DNASU112950.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290663; ENSP00000290663; ENSG00000159479. [Q96G25-2]
ENST00000372455; ENSP00000361533; ENSG00000159479. [Q96G25-3]
ENST00000372457; ENSP00000361535; ENSG00000159479. [Q96G25-1]
GeneID112950.
KEGGhsa:112950.
UCSCuc001cje.2. human. [Q96G25-2]
uc001cjf.5. human. [Q96G25-1]

Organism-specific databases

CTD112950.
GeneCardsGC01M043849.
HGNCHGNC:19971. MED8.
HPAHPA028377.
HPA028438.
MIM607956. gene.
neXtProtNX_Q96G25.
PharmGKBPA134893073.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG330005.
HOGENOMHOG000231149.
HOVERGENHBG009716.
InParanoidQ96G25.
KOK15129.
OMADVAQKQI.
OrthoDBEOG7KSX9K.
PhylomeDBQ96G25.
TreeFamTF316778.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_71. Gene Expression.
UniPathwayUPA00143.

Gene expression databases

BgeeQ96G25.
CleanExHS_MED8.
GenevestigatorQ96G25.

Family and domain databases

InterProIPR019364. Mediatior_Med8_fun/met.
[Graphical view]
PfamPF10232. Med8. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMED8.
GenomeRNAi112950.
NextBio78721.
PROQ96G25.
SOURCESearch...

Entry information

Entry nameMED8_HUMAN
AccessionPrimary (citable) accession number: Q96G25
Secondary accession number(s): A9IZ91 expand/collapse secondary AC list , A9IZ92, Q5JUY8, Q96FQ4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: April 16, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM