Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
1  structure 268  species 0  interactions 631  sequences 8  architectures

Family: Med15 (PF09606)

Summary: ARC105 or Med15 subunit of Mediator complex non-fungal

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "MED15". More...

MED15 Edit Wikipedia article

MED15
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases MED15, ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7, mediator complex subunit 15
External IDs GeneCards: MED15
Gene location (Human)
Chromosome 22 (human)
Chr. Chromosome 22 (human)[1]
Chromosome 22 (human)
Genomic location for MED15
Genomic location for MED15
Band 22q11.21 Start 20,495,913 bp[1]
End 20,587,632 bp[1]
RNA expression pattern
PBB GE PCQAP 222175 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC) Chr 22: 20.5 – 20.59 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

Mediator of RNA polymerase II transcription subunit 15, also known as Gal11,Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15 gene.[3]

Function

MED15 is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription, originally called Gal11 and Spt13 and found in yeast as an essential factor for Gal4 dependent transactivation by T.Fukasawa and F.Winston labs. Transcription factors Gcn4, Pho4, Msn2, Ino2, members of the Gal4 family - Gal4, Oaf1, Pdr1, and viral VP16 have been reported to interact with yeast MED15.[4]

Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15.[5]

Furthermore, human MED15 cooperates in mediator complex (previously known as PC2, ARC, or DRIP) with transcription factors like VP16 and SREBP. Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49.[3]

Gene

The MED15 gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge's syndrome. Two transcript variants encoding different isoforms have been found for this gene.[3]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000099917 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". 
  3. ^ a b c "Entrez Gene: PCQAP PC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated protein". 
  4. ^ Suzuki Y, Nogi Y, Abe A, Fukasawa T (Nov 1988). "GAL11 protein, an auxiliary transcription activator for genes encoding galactose-metabolizing enzymes in Saccharomyces cerevisiae". Molecular and Cellular Biology. 8 (11): 4991–9. doi:10.1128/mcb.8.11.4991. PMC 365593Freely accessible. PMID 3062377. ; Fassler JS, Winston F (Dec 1989). "The Saccharomyces cerevisiae SPT13/GAL11 gene has both positive and negative regulatory roles in transcription". Molecular and Cellular Biology. 9 (12): 5602–9. doi:10.1128/mcb.9.12.5602. PMC 363730Freely accessible. PMID 2685570. ; Swanson MJ, Qiu H, Sumibcay L, Krueger A, Kim SJ, Natarajan K, Yoon S, Hinnebusch AG (Apr 2003). "A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo". Molecular and Cellular Biology. 23 (8): 2800–20. doi:10.1128/MCB.23.8.2800-2820.2003. PMC 152555Freely accessible. PMID 12665580. ; Bryant GO, Ptashne M (May 2003). "Independent recruitment in vivo by Gal4 of two complexes required for transcription". Molecular Cell. 11 (5): 1301–9. doi:10.1016/S1097-2765(03)00144-8. PMID 12769853. ; Jedidi I, Zhang F, Qiu H, Stahl SJ, Palmer I, Kaufman JD, Nadaud PS, Mukherjee S, Wingfield PT, Jaroniec CP, Hinnebusch AG (Jan 2010). "Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo". The Journal of Biological Chemistry. 285 (4): 2438–55. doi:10.1074/jbc.M109.071589. PMC 2807301Freely accessible. PMID 19940160. ; Thakur JK, Arthanari H, Yang F, Chau KH, Wagner G, Näär AM (Feb 2009). "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". The Journal of Biological Chemistry. 284 (7): 4422–8. doi:10.1074/jbc.M808263200. PMC 3837390Freely accessible. PMID 19056732. 
  5. ^ Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (Jun 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953. ; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings. doi:10.1038/npre.2009.3488.2. ; Thakur JK, Arthanari H, Yang F, Chau KH, Wagner G, Näär AM (Feb 2009). "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". The Journal of Biological Chemistry. 284 (7): 4422–8. doi:10.1074/jbc.M808263200. PMC 3837390Freely accessible. PMID 19056732. ; Piskacek M (November 2009). "9aaTAD Prediction result (2006)". Nature Precedings. doi:10.1038/npre.2009.3984.1. ; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings. doi:10.1038/npre.2009.3488.2. ; Piskacek M (November 2009). "9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons)". Nature Precedings. doi:10.1038/npre.2009.3939.1. 

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Mediator (coactivator)". More...

Mediator (coactivator) Edit Wikipedia article

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

ARC105 or Med15 subunit of Mediator complex non-fungal Provide feedback

The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development [1].

Literature references

  1. Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Naar AM; , Nature. 2006;442:700-704.: An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. PUBMED:16799563 EPMC:16799563

  2. Lariviere L, Seizl M, van Wageningen S, Rother S, van de Pasch L, Feldmann H, Strasser K, Hahn S, Holstege FC, Cramer P; , Genes Dev. 2008;22:872-877.: Structure-system correlation identifies a gene regulatory Mediator submodule. PUBMED:18381891 EPMC:18381891

  3. Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, Bjorklund S, Blackwell TK, Borggrefe T, Carey M, Carlson M, Conaway JW, Conaway RC, Emmons SW, Fondell JD, Freedman LP, Fukasawa T, Gustafsson CM, Han M, He X, Herman PK, Hinnebusch AG, Holmberg S, , Mol Cell. 2004;14:553-557.: A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. PUBMED:15175151 EPMC:15175151


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR019087

The Mediator complex is 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. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: 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 subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation.

  • The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22.
  • The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4.
  • The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16.
  • The CDK8 module contains: MED12, MED13, CCNC and CDK8.

Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.

The proteins in this entry represent subunit Med15 of the Mediator complex. They contain a single copy of the approximately 70 residue ARC105 domain. The ARC105 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, ARC105 is a critical transducer of gene activation signals that control early metazoan development [PUBMED:16799563].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(5)
Full
(631)
Representative proteomes UniProt
(1052)
NCBI
(1717)
Meta
(0)
RP15
(125)
RP35
(215)
RP55
(369)
RP75
(426)
Jalview View  View  View  View  View  View  View  View   
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(5)
Full
(631)
Representative proteomes UniProt
(1052)
NCBI
(1717)
Meta
(0)
RP15
(125)
RP35
(215)
RP55
(369)
RP75
(426)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(5)
Full
(631)
Representative proteomes UniProt
(1052)
NCBI
(1717)
Meta
(0)
RP15
(125)
RP35
(215)
RP55
(369)
RP75
(426)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: pdb_2gut
Previous IDs: ARC105; ARC105_Med_act;
Type: Family
Sequence Ontology: SO:0100021
Author: Coggill P
Number in seed: 5
Number in full: 631
Average length of the domain: 379.90 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 88.92 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.5 27.5
Trusted cut-off 27.9 27.5
Noise cut-off 26.7 27.4
Model length: 780
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Med15 domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...