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Protein

Mediator of RNA polymerase II transcription subunit 8

Gene

MED8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-212436. Generic Transcription Pathway.
R-HSA-381340. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19971. MED8.

Subcellular locationi

GO - Cellular componenti

  • mediator complex Source: MGI
  • nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi143L → P: Impairs interaction with the Elongin BC complex; when associated with F-147. 1 Publication1
Mutagenesisi147C → F: Impairs interaction with the Elongin BC complex; when associated with P-143. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000159479.
PharmGKBiPA134893073.

Polymorphism and mutation databases

DMDMi31076772.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000963941 – 268Mediator of RNA polymerase II transcription subunit 8Add BLAST268

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei82PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96G25.
MaxQBiQ96G25.
PaxDbiQ96G25.
PeptideAtlasiQ96G25.
PRIDEiQ96G25.

PTM databases

iPTMnetiQ96G25.
PhosphoSitePlusiQ96G25.

Expressioni

Gene expression databases

BgeeiENSG00000159479.
CleanExiHS_MED8.
GenevisibleiQ96G25. HS.

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
KRT40Q6A1623EBI-10286267,EBI-10171697
PNMA1Q8ND903EBI-10286267,EBI-302345
TCEB1Q153693EBI-394405,EBI-301231
TCEB2Q153705EBI-394405,EBI-301238

Protein-protein interaction databases

BioGridi125219. 57 interactors.
IntActiQ96G25. 28 interactors.
MINTiMINT-275810.
STRINGi9606.ENSP00000290663.

Structurei

3D structure databases

ProteinModelPortaliQ96G25.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni142 – 151Interaction with the Elongin BC complex10

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1 – 28Sequence analysisAdd BLAST28
Coiled coili133 – 163Sequence analysisAdd BLAST31

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

eggNOGiKOG3583. Eukaryota.
ENOG410XNQY. LUCA.
GeneTreeiENSGT00390000011838.
HOGENOMiHOG000231149.
HOVERGENiHBG009716.
InParanoidiQ96G25.
KOiK15129.
OMAiDVAQKQI.
OrthoDBiEOG091G0VMU.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti257N → K in BG722466 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0355071 – 89Missing in isoform 3. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_007524268R → RPSCLGFILAIPLRRKVKKL LGQEGKKNAHLQLW in isoform 2. 1 Publication1

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.3. human. [Q96G25-1]

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.
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.

3D structure databases

ProteinModelPortaliQ96G25.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125219. 57 interactors.
IntActiQ96G25. 28 interactors.
MINTiMINT-275810.
STRINGi9606.ENSP00000290663.

PTM databases

iPTMnetiQ96G25.
PhosphoSitePlusiQ96G25.

Polymorphism and mutation databases

DMDMi31076772.

Proteomic databases

EPDiQ96G25.
MaxQBiQ96G25.
PaxDbiQ96G25.
PeptideAtlasiQ96G25.
PRIDEiQ96G25.

Protocols and materials databases

DNASUi112950.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi112950.
GeneCardsiMED8.
HGNCiHGNC:19971. MED8.
HPAiHPA028377.
HPA028438.
MIMi607956. gene.
neXtProtiNX_Q96G25.
OpenTargetsiENSG00000159479.
PharmGKBiPA134893073.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3583. Eukaryota.
ENOG410XNQY. LUCA.
GeneTreeiENSGT00390000011838.
HOGENOMiHOG000231149.
HOVERGENiHBG009716.
InParanoidiQ96G25.
KOiK15129.
OMAiDVAQKQI.
OrthoDBiEOG091G0VMU.
PhylomeDBiQ96G25.
TreeFamiTF316778.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-1989781. PPARA activates gene expression.
R-HSA-212436. Generic Transcription Pathway.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.

Miscellaneous databases

GeneWikiiMED8.
GenomeRNAii112950.
PROiQ96G25.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159479.
CleanExiHS_MED8.
GenevisibleiQ96G25. HS.

Family and domain databases

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

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: November 2, 2016
This is version 140 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.