MED1

Mediator complex subunit 1
Rendering of MED1 from PDB 1RJK​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1RJK​, 1RK3​, 1RKG​, 1RKH​, 2O4J​, 2O4R​, 2ZFX​, 3A2H​, 3AUN​, 3VJS​, 3VJT​, 3VRT​, 3VRU​, 3VRV​, 3VRW​, 3W0G​, 3W0H​, 3W0I​, 3W0J​, 3W5P​, 3W5Q​, 3W5R​, 3W5T​, 3WT5​, 3WT6​, 3WT7​, 3WTQ​
Identifiers
Symbols	MED1 ; CRSP1; CRSP200; DRIP205; DRIP230; PBP; PPARBP; PPARGBP; RB18A; TRAP220; TRIP2
External IDs	OMIM: 604311 MGI: 1100846 HomoloGene: 21002 GeneCards: MED1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • core promoter binding • RNA polymerase II transcription cofactor activity • chromatin binding • transcription cofactor activity • transcription coactivator activity • receptor activity • protein binding • transcription factor binding • ligand-dependent nuclear receptor binding • estrogen receptor binding • ligand-dependent nuclear receptor transcription coactivator activity • thyroid hormone receptor coactivator activity • chromatin DNA binding • nuclear hormone receptor binding • mediator complex binding • vitamin D receptor binding • retinoic acid receptor binding • peroxisome proliferator activated receptor binding • thyroid hormone receptor binding • LBD domain binding • ubiquitin protein ligase activity Cellular component • ubiquitin ligase complex • chromatin • nucleus • nucleoplasm • nucleolus • membrane • mediator complex • protein-DNA complex Biological process • negative regulation of transcription from RNA polymerase II promoter • cell morphogenesis • angiogenesis • liver development • embryonic placenta development • lens development in camera-type eye • thyroid hormone mediated signaling pathway • ventricular trabecula myocardium morphogenesis • retinal pigment epithelium development • regulation of transcription from RNA polymerase I promoter • transcription initiation from RNA polymerase II promoter • thyroid hormone generation • androgen biosynthetic process • brain development • lactation • gene expression • positive regulation of gene expression • negative regulation of keratinocyte proliferation • protein ubiquitination • keratinocyte differentiation • monocyte differentiation • intracellular steroid hormone receptor signaling pathway • androgen receptor signaling pathway • organ regeneration • positive regulation of intracellular estrogen receptor signaling pathway • positive regulation of protein import into nucleus, translocation • positive regulation of mammary gland epithelial cell proliferation • embryonic heart tube development • embryonic hindlimb morphogenesis • embryonic hemopoiesis • peroxisome proliferator activated receptor signaling pathway • cellular response to hepatocyte growth factor stimulus • megakaryocyte development • mRNA transcription from RNA polymerase II promoter • negative regulation of apoptotic process • cellular lipid metabolic process • small molecule metabolic process • fat cell differentiation • positive regulation of keratinocyte differentiation • positive regulation of erythrocyte differentiation • negative regulation of neuron differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • erythrocyte development • enucleate erythrocyte development • regulation of cell cycle • positive regulation of interferon-gamma-mediated signaling pathway • mammary gland branching involved in thelarche • mammary gland branching involved in pregnancy • epithelial cell proliferation involved in mammary gland duct elongation • positive regulation of G0 to G1 transition • ERK1 and ERK2 cascade • regulation of vitamin D receptor signaling pathway • cellular response to epidermal growth factor stimulus • cellular response to steroid hormone stimulus • cellular response to thyroid hormone stimulus • positive regulation of receptor activity • positive regulation of hepatocyte proliferation • regulation of RNA biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5469	19014
Ensembl	ENSG00000125686	ENSMUSG00000018160
UniProt	Q15648	Q925J9
RefSeq (mRNA)	NM_004774	NM_001080118
RefSeq (protein)	NP_004765	NP_001073587
Location (UCSC)	Chr 17: 39.4 – 39.45 Mb	Chr 11: 98.15 – 98.19 Mb
PubMed search

Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the MED1 gene.^[1][2][3] MED1 functions as a nuclear receptor coactivator.

Med1
Identifiers
Symbol	Med1
Pfam	PF10744
InterPro	IPR019680
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Function

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The mediator of RNA polymerase II transcription subunit 1 protein is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes [e.g., thyroid hormone receptor-(TR-) associated proteins that interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors]. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize.^[3]

Interactions

MED1 has been shown to interact with:

• Androgen receptor,^[4]
• BRCA1,^[5]
• Calcitriol receptor,^[6][7]
• Cyclin-dependent kinase 8,^[6][8]
• Estrogen receptor alpha,^[7][8]
• Glucocorticoid receptor,^[9][10]
• Hepatocyte nuclear factor 4 alpha,^[11][12]
• P53,^[13][14]
• PPARGC1A,^[15]
• PPARG,^[16]
• TGS1,^[17] and
• Thyroid hormone receptor alpha.^[18]

Protein family

This entry represents subunit Med1 of the Mediator complex. The Med1 forms part of the Med9 submodule of the Srb/Med complex. It is one of three subunits essential for viability of the whole organism via its role in environmentally-directed cell-fate decisions.^[19]

References

1. Zhu Y, Qi C, Jain S, Rao MS, Reddy JK (November 1997). "Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor". J Biol Chem 272 (41): 25500–6. doi:10.1074/jbc.272.41.25500. PMID 9325263.
2. Zhu Y, Qi C, Jain S, Le Beau MM, Espinosa R, Atkins GB, Lazar MA, Yeldandi AV, Rao MS, Reddy JK (October 1999). "Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer". Proc Natl Acad Sci U S A 96 (19): 10848–53. doi:10.1073/pnas.96.19.10848. PMC 17971. PMID 10485914.
3. "Entrez Gene: PPARBP PPAR binding protein".
4. Wang Q, Sharma D, Ren Y, Fondell JD (November 2002). "A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression". J. Biol. Chem. 277 (45): 42852–8. doi:10.1074/jbc.M206061200. PMID 12218053.
5. Wada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S (August 2004). "BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220". Oncogene 23 (35): 6000–5. doi:10.1038/sj.onc.1207786. PMID 15208681.
6. Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (March 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell 3 (3): 361–70. doi:10.1016/s1097-2765(00)80463-3. PMID 10198638.
7. 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 (June 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.
8. Kang YK, Guermah M, Yuan CX, Roeder RG (March 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". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
9. Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (April 2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. doi:10.1210/mend.15.4.0624. PMID 11266503.
10. Hittelman AB, Burakov D, Iñiguez-Lluhí JA, Freedman LP, Garabedian MJ (October 1999). "Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins". EMBO J. 18 (19): 5380–8. doi:10.1093/emboj/18.19.5380. PMC 1171607. PMID 10508170.
11. Maeda Y, Rachez C, Hawel L, Byus CV, Freedman LP, Sladek FM (July 2002). "Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205". Mol. Endocrinol. 16 (7): 1502–10. doi:10.1210/mend.16.7.0883. PMID 12089346.
12. Malik S, Wallberg AE, Kang YK, Roeder RG (August 2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4". Mol. Cell. Biol. 22 (15): 5626–37. doi:10.1128/mcb.22.15.5626-5637.2002. PMC 133960. PMID 12101254.
13. Frade R, Balbo M, Barel M (December 2000). "RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity". Cancer Res. 60 (23): 6585–9. PMID 11118038.
14. Drané P, Barel M, Balbo M, Frade R (December 1997). "Identification of RB18A, a 205 kDa new p53 regulatory protein which shares antigenic and functional properties with p53". Oncogene 15 (25): 3013–24. doi:10.1038/sj.onc.1201492. PMID 9444950.
15. Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (November 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell 12 (5): 1137–49. doi:10.1016/s1097-2765(03)00391-5. PMID 14636573.
16. Kodera Y, Takeyama K, Murayama A, Suzawa M, Masuhiro Y, Kato S (October 2000). "Ligand type-specific interactions of peroxisome proliferator-activated receptor gamma with transcriptional coactivators". J. Biol. Chem. 275 (43): 33201–4. doi:10.1074/jbc.C000517200. PMID 10944516.
17. Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK (May 2002). "Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation". J. Biol. Chem. 277 (22): 20011–9. doi:10.1074/jbc.M201739200. PMID 11912212.
18. Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG (July 1998). "The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 7939–44. doi:10.1073/pnas.95.14.7939. PMC 20908. PMID 9653119.
19. Boube M, Joulia L, Cribbs DL, Bourbon HM (July 2002). "Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man". Cell 110 (2): 143–51. doi:10.1016/s0092-8674(02)00830-9. PMID 12150923.

Further reading

• Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (1995). "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.". Mol. Endocrinol. 9 (2): 243–54. doi:10.1210/me.9.2.243. PMID 7776974.
• Fondell JD, Ge H, Roeder RG (1996). "Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex.". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8329–33. doi:10.1073/pnas.93.16.8329. PMC 38670. PMID 8710870.
• Drané P, Barel M, Balbo M, Frade R (1998). "Identification of RB18A, a 205 kDa new p53 regulatory protein that shares antigenic and functional properties with p53.". Oncogene 15 (25): 3013–24. doi:10.1038/sj.onc.1201492. PMID 9444950.
• Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG (1998). "The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion.". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 7939–44. doi:10.1073/pnas.95.14.7939. PMC 20908. PMID 9653119.
• Ryu S, Zhou S, Ladurner AG, Tjian R (1999). "The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1.". Nature 397 (6718): 446–50. doi:10.1038/17141. PMID 9989412.
• Gu W, Malik S, Ito M, Yuan CX, Fondell JD, Zhang X, Martinez E, Qin J, Roeder RG (1999). "A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation.". Mol. Cell 3 (1): 97–108. doi:10.1016/S1097-2765(00)80178-1. PMID 10024883.
• Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.". Mol. Cell 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638.
• Rachez C, Lemon BD, Suldan Z, Bromleigh V, Gamble M, Näär AM, Erdjument-Bromage H, Tempst P, Freedman LP (1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex.". Nature 398 (6730): 824–8. doi:10.1038/19783. PMID 10235266.
• Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R (1999). "Composite co-activator ARC mediates chromatin-directed transcriptional activation.". Nature 398 (6730): 828–32. doi:10.1038/19789. PMID 10235267.
• Atkins GB, Hu X, Guenther MG, Rachez C, Freedman LP, Lazar MA (1999). "Coactivators for the orphan nuclear receptor RORalpha.". Mol. Endocrinol. 13 (9): 1550–7. doi:10.1210/me.13.9.1550. PMID 10478845.
• Rachez C, Gamble M, Chang CP, Atkins GB, Lazar MA, Freedman LP (2000). "The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor-binding determinants but constitute functionally distinct complexes.". Mol. Cell. Biol. 20 (8): 2718–26. doi:10.1128/MCB.20.8.2718-2726.2000. PMC 85487. PMID 10733574.
• Frade R, Balbo M, Barel M (2001). "RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity.". Cancer Res. 60 (23): 6585–9. PMID 11118038.
• Zilliacus J, Holter E, Wakui H, Tazawa H, Treuter E, Gustafsson JA (2001). "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140.". Mol. Endocrinol. 15 (4): 501–11. doi:10.1210/mend.15.4.0624. PMID 11266503.
• Crawford SE, Qi C, Misra P, Stellmach V, Rao MS, Engel JD, Zhu Y, Reddy JK (2002). "Defects of the heart, eye, and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of transcription factors.". J. Biol. Chem. 277 (5): 3585–92. doi:10.1074/jbc.M107995200. PMID 11724781.
• Frade R, Balbo M, Barel M (2002). "RB18A regulates p53-dependent apoptosis.". Oncogene 21 (6): 861–6. doi:10.1038/sj.onc.1205177. PMID 11840331.
• Kang YK, Guermah M, Yuan CX, Roeder RG (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.". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
• Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK (2002). "Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation.". J. Biol. Chem. 277 (22): 20011–9. doi:10.1074/jbc.M201739200. PMID 11912212.
• Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG (2002). "Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis.". Nature 417 (6888): 563–7. doi:10.1038/417563a. PMID 12037571.

This article incorporates text from the public domain Pfam and InterPro IPR019680