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0  structures 1008  species 0  interactions 1427  sequences 20  architectures

Family: Med12 (PF09497)

Summary: Transcription mediator complex subunit Med12

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 "MED12". More...

MED12 Edit Wikipedia article

MED12
Identifiers
AliasesMED12, ARC240, CAGH45, FGS1, HOPA, MED12S, OHDOX, OKS, OPA1, TNRC11, TRAP230, mediator complex subunit 12, Kto
External IDsOMIM: 300188 MGI: 1926212 HomoloGene: 68441 GeneCards: MED12
Gene location (Human)
X chromosome (human)
Chr.X chromosome (human)[1]
X chromosome (human)
Genomic location for MED12
Genomic location for MED12
BandXq13.1Start71,118,556 bp[1]
End71,142,454 bp[1]
RNA expression pattern
PBB GE MED12 216071 x at fs.png

PBB GE MED12 203506 s at fs.png

PBB GE MED12 211342 x at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005120

NM_021521

RefSeq (protein)

NP_005111

NP_067496

Location (UCSC)Chr X: 71.12 – 71.14 MbChr X: 101.27 – 101.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome.[5]

Clinical significance

Mutations in MED12 are responsible for at least two different forms of X-linked dominant mental retardation, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer.[6]

Mutations in MED12 are associated with uterine leiomyomas [7] and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors).[8]

Interactions

MED12 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000184634 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000079487 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: MED12 mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae)".
  6. ^ Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae SS, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JM, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA (Jun 2012). "Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer" (PDF). Nature Genetics. 44 (6): 685–9. doi:10.1038/ng.2279. PMC 3673022. PMID 22610119.
  7. ^ Kämpjärvi K, Park MJ, Mehine M, Kim NH, Clark AD, Bützow R, Böhling T, Böhm J, Mecklin JP, Järvinen H, Tomlinson IP, van der Spuy ZM, Sjöberg J, Boyer TG, Vahteristo P (Sep 2014). "Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas". Human Mutation. 35 (9): 1136–41. doi:10.1002/humu.22612. PMID 24980722.
  8. ^ Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS (Nov 2015). "MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast". Histopathology. 67 (5): 719–29. doi:10.1111/his.12712. PMC 4996373. PMID 25855048.
  9. ^ a b c Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell. 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638.
  10. ^ Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S (Jun 2003). "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome". Cell. 113 (7): 905–17. doi:10.1016/S0092-8674(03)00436-7. PMID 12837248.
  11. ^ a b Kang YK, Guermah M, Yuan CX, Roeder RG (Mar 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proceedings of the National Academy of Sciences of the United States of America. 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
  12. ^ Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (Nov 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Molecular Cell. 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573.
  13. ^ Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway JW, Conaway RC (Jun 2004). "A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology". Molecular Cell. 14 (5): 685–91. doi:10.1016/j.molcel.2004.05.006. PMID 15175163.
  14. ^ Zhou R, Bonneaud N, Yuan CX, de Santa Barbara P, Boizet B, Schomber T, Scherer G, Roeder RG, Poulat F, Berta P, Tibor S (Jul 2002). "SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex". Nucleic Acids Research. 30 (14): 3245–52. doi:10.1093/nar/gkf443. PMC 135763. PMID 12136106.

Further reading

External links

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.

Transcription mediator complex subunit Med12 Provide feedback

Med12 is a negative regulator of the Gli3-dependent sonic hedgehog signalling pathway via its interaction with Gli3 within the RNA polymerase II transcriptional Mediator. A complex is formed between Med12, Med13, CDK8 and CycC which is responsible for suppression of transcription. This subunit forms part of the Kinase section of Mediator [2].

Literature references

  1. Zhou H, Kim S, Ishii S, Boyer TG; , Mol Cell Biol. 2006;26:8667-8682.: Mediator modulates Gli3-dependent Sonic hedgehog signaling. PUBMED:17000779 EPMC:17000779

  2. 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


This tab holds annotation information from the InterPro database.

InterPro entry IPR019035

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.

Med12 is a component of the evolutionarily conserved Mediator complex [PUBMED:17088561]. The Med12 subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. Med12 is a negative regulator of the Gli3-dependent sonic hedgehog signaling pathway via its interaction with Gli3 within the Mediator. A complex is formed between Med12, Med13, CDK8 and CycC which is responsible for suppression of transcription [PUBMED:18394596].

Gene Ontology

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Domain organisation

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Alignments

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(77)
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(3537)
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(183)
RP35
(556)
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(954)
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  Seed
(77)
Full
(1427)
Representative proteomes UniProt
(2364)
NCBI
(3537)
Meta
(0)
RP15
(183)
RP35
(556)
RP55
(954)
RP75
(1421)
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  Seed
(77)
Full
(1427)
Representative proteomes UniProt
(2364)
NCBI
(3537)
Meta
(0)
RP15
(183)
RP35
(556)
RP55
(954)
RP75
(1421)
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Curation and family details

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Seed source: Wood V
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Wood V , Coggill P
Number in seed: 77
Number in full: 1427
Average length of the domain: 61.60 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 3.42 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.1 25.1
Noise cut-off 24.7 24.3
Model length: 63
Family (HMM) version: 11
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