Q96G25 (MED8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

MED8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	268 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	mediator complex Inferred from direct assay PubMed 14638676. Source: MGI
Molecular_function	RNA polymerase II transcription cofactor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TCEB1	Q15369	3	EBI-394405,EBI-301231
TCEB2	Q15370	5	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 268	268	Mediator of RNA polymerase II transcription subunit 8		PRO_0000096394
Regions
	Region	142 – 151	10	Interaction with the Elongin BC complex
	Coiled coil	1 – 28	28	Potential
	Coiled coil	133 – 163	31	Potential
Amino acid modifications
	Modified residue	82	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 89	89	Missing in isoform 3.		VSP_035507
	Alternative sequence	268	1	R → RPSCLGFILAIPLRRKVKKL LGQEGKKNAHLQLW in isoform 2.		VSP_007524
Experimental info
	Mutagenesis	143	1	L → P: Impairs interaction with the Elongin BC complex; when associated with F-147. Ref.1
	Mutagenesis	147	1	C → F: Impairs interaction with the Elongin BC complex; when associated with P-143. Ref.1
	Sequence conflict	257	1	N → K in BG722466. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 23, 2003. Version 2. Checksum: 6C186A4CECD1AFB3	FASTA	268	29,080
	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
	Isoform 2 [UniParc]. Checksum: EE7EE86B0E9C3D4F	FASTA	301	32,819
	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 250 260 270 280 290 300 MAQAGQPGKM PSGIKTNIKS ASMHPYQRPS CLGFILAIPL RRKVKKLLGQ EGKKNAHLQL W
	Isoform 3 [UniParc]. Checksum: FA54BCD42B60EF7A	FASTA	179	19,002
	10 20 30 40 50 60 MRQTEGRVPV FSHEVVPDHL RTKPDPEVEE QEKQLTTDAA RIGADAAQKQ IQSLNKMCSN 70 80 90 100 110 120 LLEKISKEER ESESGGLRPN KQTFNPTDTN ALVAAVAFGK GLSNWRPSGS SGPGQAGQPG 130 140 150 160 170 AGTILAGTSG LQQVQMAGAP SQQQPMLSGV QMAQAGQPGK MPSGIKTNIK SASMHPYQR

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY.
[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.
IPI	IPI00300278. IPI00418130. IPI00419516.
RefSeq	NP_001001653.1. NM_001001653.2. NP_443109.2. NM_052877.4. NP_963836.2. NM_201542.4.
UniGene	Hs.301756.
3D structure databases
ProteinModelPortal	Q96G25.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96G25. 20 interactions.
MINT	MINT-275810.
STRING	9606.ENSP00000290663.
PTM databases
PhosphoSite	Q96G25.
Polymorphism databases
DMDM	31076772.
Proteomic databases
PaxDb	Q96G25.
PRIDE	Q96G25.
Protocols and materials databases
DNASU	112950.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290663; ENSP00000290663; ENSG00000159479. ENST00000372455; ENSP00000361533; ENSG00000159479. ENST00000372457; ENSP00000361535; ENSG00000159479.
GeneID	112950.
KEGG	hsa:112950.
UCSC	uc001cje.1. human. uc001cjf.4. human.
Organism-specific databases
CTD	112950.
GeneCards	GC01M043849.
HGNC	HGNC:19971. MED8.
HPA	HPA028377. HPA028438.
MIM	607956. gene.
neXtProt	NX_Q96G25.
PharmGKB	PA134893073.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG330005.
HOGENOM	HOG000231149.
HOVERGEN	HBG009716.
InParanoid	Q96G25.
KO	K15129.
OMA	NWPTFLD.
OrthoDB	EOG4CC427.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_71. Gene Expression.
UniPathway	UPA00143.
Gene expression databases
Bgee	Q96G25.
CleanEx	HS_MED8.
Genevestigator	Q96G25.
GermOnline	ENSG00000159479. Homo sapiens.
Family and domain databases
InterPro	IPR019364. Mediatior_Med8_fun/met. [Graphical view]
Pfam	PF10232. Med8. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	112950.
NextBio	78721.
SOURCE	Search...

Entry information

Entry name

MED8_HUMAN

Accession

Primary (citable) accession number: Q96G25
Secondary accession number(s): A9IZ91 , A9IZ92, Q5JUY8, Q96FQ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 23, 2003
Last sequence update:	May 23, 2003
Last modified:	April 3, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.