MED1

MED1
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, 5AWK, 5AWJ, 4YNK, 5B5B
Identifiers
Aliases	MED1 , CRSP1, CRSP200, DRIP205, DRIP230, PBP, PPARBP, PPARGBP, RB18A, TRAP220, TRIP2, mediator complex subunit 1
External IDs	OMIM: 604311; MGI: 1100846; HomoloGene: 21002; GeneCards: MED1; OMA:MED1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q12 Start 39,404,285 bp [1] End 39,451,272 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 D|11 61.75 cM Start 98,042,980 bp [2] End 98,084,119 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tendon of biceps brachii nipple visceral pleura lower lobe of lung mucosa of paranasal sinus superficial temporal artery parietal pleura trabecular bone human penis buccal mucosa cell Top expressed in Rostral migratory stream cumulus cell spermatocyte spermatid vestibular membrane of cochlear duct hair follicle tail of embryo otic placode internal carotid artery genital tubercle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-containing complex binding DNA-binding transcription factor activity, RNA polymerase II-specific estrogen receptor binding ubiquitin protein ligase activity transcription factor binding transcription coregulator activity thyroid hormone receptor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding retinoic acid receptor binding chromatin binding LBD domain binding protein binding nuclear receptor binding vitamin D receptor binding DNA binding mediator complex binding transcription coactivator activity peroxisome proliferator activated receptor binding nuclear receptor coactivator activity chromatin DNA binding RNA polymerase II core promoter sequence-specific DNA binding transcription corepressor activity signaling receptor activity Cellular component membrane nucleus mediator complex nucleolus chromatin ubiquitin ligase complex nucleoplasm protein-DNA complex Biological process regulation of RNA biosynthetic process thyroid hormone mediated signaling pathway negative regulation of neuron differentiation regulation of transcription by RNA polymerase II monocyte differentiation embryonic heart tube development androgen biosynthetic process epithelial cell proliferation involved in mammary gland duct elongation enucleate erythrocyte development animal organ regeneration angiogenesis animal organ morphogenesis regulation of transcription, DNA-templated negative regulation of keratinocyte proliferation positive regulation of erythrocyte differentiation regulation of transcription by RNA polymerase I ERK1 and ERK2 cascade in utero embryonic development mammary gland branching involved in pregnancy transcription, DNA-templated positive regulation of transcription, DNA-templated heart development protein ubiquitination camera-type eye development transcription initiation from RNA polymerase II promoter lactation cellular response to steroid hormone stimulus positive regulation of intracellular estrogen receptor signaling pathway peroxisome proliferator activated receptor signaling pathway cellular response to hepatocyte growth factor stimulus positive regulation of keratinocyte differentiation positive regulation of interferon-gamma-mediated signaling pathway positive regulation of G0 to G1 transition embryonic placenta development negative regulation of apoptotic process intracellular steroid hormone receptor signaling pathway negative regulation of transcription by RNA polymerase II retinal pigment epithelium development ventricular trabecula myocardium morphogenesis thyroid hormone generation fat cell differentiation positive regulation of hepatocyte proliferation megakaryocyte development androgen receptor signaling pathway positive regulation of mammary gland epithelial cell proliferation mammary gland epithelial cell proliferation mammary gland branching involved in thelarche regulation of vitamin D receptor signaling pathway mRNA transcription by RNA polymerase II keratinocyte differentiation regulation of cell cycle cellular response to epidermal growth factor stimulus multicellular organism development positive regulation of signaling receptor activity brain development positive regulation of gene expression lens development in camera-type eye cell morphogenesis embryonic hemopoiesis cellular response to thyroid hormone stimulus positive regulation of cell population proliferation liver development positive regulation of transcription by RNA polymerase II erythrocyte development embryonic hindlimb morphogenesis regulation of lipid metabolic process protein import into nucleus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5469 19014 Ensembl ENSG00000125686 ENSMUSG00000018160 UniProt Q15648 Q925J9 RefSeq (mRNA) NM_004774 NM_001080118 NM_013634 NM_134027 NM_001361950 NM_001361951 RefSeq (protein) NP_004765 NP_001073587 NP_038662 NP_598788 NP_001348879 NP_001348880 Location (UCSC) Chr 17: 39.4 – 39.45 Mb Chr 11: 98.04 – 98.08 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[5] [6] [7]} MED1 functions as a nuclear receptor coactivator.

Med1
Identifiers
Symbol	Med1
Pfam	PF10744
InterPro	IPR019680
Available protein structures: Pfam   structures / ECOD   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. ^[7]

Interactions

MED1 has been shown to interact with:

• Androgen receptor, ^[8]
• Calcitriol receptor, ^{[9] [10]}
• Cyclin-dependent kinase 8, ^{[9] [11]}
• Estrogen receptor alpha, ^{[10] [11]}
• Glucocorticoid receptor, ^{[12] [13]}
• Hepatocyte nuclear factor 4 alpha, ^{[14] [15]}
• P53, ^{[16] [17]}
• PPARGC1A, ^[18]
• TGS1, ^[19] and
• Thyroid hormone receptor alpha. ^[20]

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. ^[21]

References

1. GRCh38: Ensembl release 89: ENSG00000125686 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018160 – 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. 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.
6. 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. Bibcode:1999PNAS...9610848Z. doi: 10.1073/pnas.96.19.10848 . PMC   17971 . PMID   10485914.
7. "Entrez Gene: PPARBP PPAR binding protein".
8. 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.
9. 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.
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 (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.
11. 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. Bibcode:2002PNAS...99.2642K. doi: 10.1073/pnas.261715899 . PMC   122401 . PMID   11867769.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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. Bibcode:1998PNAS...95.7939Y. doi: 10.1073/pnas.95.14.7939 . PMC   20908 . PMID   9653119.
21. 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. S2CID   771362.

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/mend.9.2.7776974 . 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. Bibcode:1996PNAS...93.8329F. 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. Bibcode:1998PNAS...95.7939Y. 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. Bibcode:1999Natur.397..446R. doi:10.1038/17141. hdl: 11858/00-001M-0000-0019-A36A-8 . PMID   9989412. S2CID   4405569.
• 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. Bibcode:1999Natur.398..824R. doi:10.1038/19783. PMID   10235266. S2CID   204992765.
• 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. Bibcode:1999Natur.398..828N. doi:10.1038/19789. PMID   10235267. S2CID   23646963.
• 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/mend.13.9.0343 . 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. Bibcode:2002PNAS...99.2642K. 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. Bibcode:2002Natur.417..563G. doi:10.1038/417563a. PMID   12037571. S2CID   4432077.

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