MED25_HUMAN
ID MED25_HUMAN Reviewed; 747 AA.
AC Q71SY5; A8K095; B9TX30; O95783; Q6P143; Q6QMH5; Q707U4; Q8TB55; Q9H0L5;
AC Q9HB34;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 25;
DE AltName: Full=Activator interaction domain-containing protein 1;
DE AltName: Full=Activator-recruited cofactor 92 kDa component;
DE Short=ARC92;
DE AltName: Full=Mediator complex subunit 25;
DE AltName: Full=p78;
GN Name=MED25; Synonyms=ACID1, ARC92, PTOV2; ORFNames=TCBAP0758;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12163014; DOI=10.1016/s0006-291x(02)00872-0;
RA Wang C., McCarty I.M., Balazs L., Li Y., Steiner M.S.;
RT "A prostate-derived cDNA that is mapped to human chromosome 19 encodes a
RT novel protein.";
RL Biochem. Biophys. Res. Commun. 296:281-287(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP IDENTIFICATION IN THE MEDIATOR COMPLEX, INTERACTION WITH VP16, ASSOCIATION
RP WITH PROMOTER REGIONS, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=14657022; DOI=10.1093/emboj/cdg619;
RA Mittler G., Stuehler T., Santolin L., Uhlmann T., Kremmer E.,
RA Lottspeich F., Berti L., Meisterernst M.;
RT "A novel docking site on Mediator is critical for activation by VP16 in
RT mammalian cells.";
RL EMBO J. 22:6494-6504(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-11; 197-207; 241-254;
RP 398-446 AND 520-530, FUNCTION, IDENTIFICATION IN THE MEDIATOR COMPLEX,
RP INTERACTION WITH VP16, AND TISSUE SPECIFICITY.
RX PubMed=14983011; DOI=10.1073/pnas.0308676100;
RA Yang F., DeBeaumont R., Zhou S., Naeaer A.M.;
RT "The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a
RT functionally important target of the VP16 transcriptional activator.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2339-2344(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND ALTERNATIVE SPLICING.
RA Kivil A., Kazantseva A., Vinkel K.J.M., Sadam H., Neuman T., Palm K.;
RT "Alternative splicing as a prevalent mechanism in regulating mammalian
RT mediator tail subcomplex activity.";
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 159-747 (ISOFORM 5).
RC TISSUE=Eye, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 178-747 (ISOFORM 4).
RC TISSUE=Leukocyte;
RA Villalon D.K., Luna R.A., Margolin J.K., Tsang Y.T.M., Hale S.M., Mei G.,
RA Bouck J., Gibbs R.A.;
RT "Pediatric leukemia cDNA sequencing project.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR
RP COMPLEX.
RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006;
RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B.,
RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W.,
RA Conaway R.C.;
RT "A set of consensus mammalian mediator subunits identified by
RT multidimensional protein identification technology.";
RL Mol. Cell 14:685-691(2004).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR
RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015;
RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T.,
RA Roeder R.G.;
RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation
RT enriched in RNA polymerase II and is required for ER-mediated
RT transcription.";
RL Mol. Cell 19:89-100(2005).
RN [13]
RP FUNCTION, ASSOCIATION WITH PROMOTER REGIONS, INTERACTION WITH CREBBP; ESR1;
RP GR; MED1; MED6; RARA; RXRA AND THRB, AND MUTAGENESIS OF LEU-646 AND
RP 649-LEU-LEU-650.
RX PubMed=17641689; DOI=10.1038/sj.emboj.7601797;
RA Lee H.-K., Park U.-H., Kim E.-J., Um S.-J.;
RT "MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid
RT receptor activation.";
RL EMBO J. 26:3545-3557(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP STRUCTURE BY NMR OF 391-548.
RX PubMed=20974256; DOI=10.1016/j.jsb.2010.10.011;
RA Bontems F., Verger A., Dewitte F., Lens Z., Baert J.L., Ferreira E.,
RA Launoit Y.D., Sizun C., Guittet E., Villeret V., Monte D.;
RT "NMR structure of the human Mediator MED25 ACID domain.";
RL J. Struct. Biol. 174:245-251(2011).
RN [16]
RP VARIANT CMT2B2 VAL-335.
RX PubMed=19290556; DOI=10.1007/s10048-009-0183-3;
RA Leal A., Huehne K., Bauer F., Sticht H., Berger P., Suter U., Morera B.,
RA Del Valle G., Lupski J.R., Ekici A., Pasutto F., Endele S., Barrantes R.,
RA Berghoff C., Berghoff M., Neundoerfer B., Heuss D., Dorn T., Young P.,
RA Santolin L., Uhlmann T., Meisterernst M., Sereda M.W., Sereda M.,
RA Stassart R.M., Zu Horste G.M., Nave K.A., Reis A., Rautenstrauss B.;
RT "Identification of the variant Ala335Val of MED25 as responsible for
RT CMT2B2: molecular data, functional studies of the SH3 recognition motif and
RT correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal
RT models.";
RL Neurogenetics 10:275-287(2009).
RN [17]
RP ERRATUM OF PUBMED:19290556.
RA Leal A., Huehne K., Bauer F., Sticht H., Berger P., Suter U., Morera B.,
RA Del Valle G., Lupski J.R., Ekici A., Pasutto F., Endele S., Barrantes R.,
RA Berghoff C., Berghoff M., Neundoerfer B., Heuss D., Dorn T., Young P.,
RA Santolin L., Uhlmann T., Meisterernst M., Sereda M.W., Sereda M.,
RA Stassart R.M., Zu Horste G.M., Nave K.A., Reis A., Rautenstrauss B.;
RL Neurogenetics 10:375-376(2009).
RN [18]
RP INVOLVEMENT IN BVSYS, VARIANT BVSYS CYS-39, AND CHARACTERIZATION OF VARIANT
RP BVSYS CYS-39.
RX PubMed=25792360; DOI=10.1007/s00439-015-1541-x;
RA Basel-Vanagaite L., Smirin-Yosef P., Essakow J.L., Tzur S., Lagovsky I.,
RA Maya I., Pasmanik-Chor M., Yeheskel A., Konen O., Orenstein N.,
RA Weisz Hubshman M., Drasinover V., Magal N., Peretz Amit G., Zalzstein Y.,
RA Zeharia A., Shohat M., Straussberg R., Monte D., Salmon-Divon M.,
RA Behar D.M.;
RT "Homozygous MED25 mutation implicated in eye-intellectual disability
RT syndrome.";
RL Hum. Genet. 134:577-587(2015).
RN [19]
RP VARIANT TRP-140.
RX PubMed=25527630; DOI=10.1136/jmedgenet-2014-102793;
RA Figueiredo T., Melo U.S., Pessoa A.L., Nobrega P.R., Kitajima J.P.,
RA Correa I., Zatz M., Kok F., Santos S.;
RT "Homozygous missense mutation in MED25 segregates with syndromic
RT intellectual disability in a large consanguineous family.";
RL J. Med. Genet. 52:123-127(2015).
CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in
CC the regulated transcription of nearly all RNA polymerase II-dependent
CC genes. Mediator functions as a bridge to convey information from gene-
CC specific regulatory proteins to the basal RNA polymerase II
CC transcription machinery. Mediator is recruited to promoters by direct
CC interactions with regulatory proteins and serves as a scaffold for the
CC assembly of a functional preinitiation complex with RNA polymerase II
CC and the general transcription factors. Required for RARA/RXRA-mediated
CC transcription. {ECO:0000269|PubMed:14657022,
CC ECO:0000269|PubMed:14983011, ECO:0000269|PubMed:17641689}.
CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1,
CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L,
CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23,
CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and
CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct
CC module termed the CDK8 module. Mediator containing the CDK8 module is
CC less active than Mediator lacking this module in supporting
CC transcriptional activation. Individual preparations of the Mediator
CC complex lacking one or more distinct subunits have been variously
CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CREBBP.
CC Interacts with ESR1, GR, RARA, RXRA and THRB in a ligand-dependent
CC fashion. Binds the Herpes simplex virus activator VP16.
CC {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011,
CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967,
CC ECO:0000269|PubMed:17641689}.
CC -!- INTERACTION:
CC Q71SY5; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-394558, EBI-3867333;
CC Q71SY5; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-394558, EBI-10213520;
CC Q71SY5; O00167-2: EYA2; NbExp=3; IntAct=EBI-394558, EBI-12807776;
CC Q71SY5; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-394558, EBI-12193763;
CC Q71SY5; O14964: HGS; NbExp=3; IntAct=EBI-394558, EBI-740220;
CC Q71SY5; Q53G59: KLHL12; NbExp=3; IntAct=EBI-394558, EBI-740929;
CC Q71SY5; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-394558, EBI-12111050;
CC Q71SY5; Q14847-2: LASP1; NbExp=3; IntAct=EBI-394558, EBI-9088686;
CC Q71SY5; O60244: MED14; NbExp=2; IntAct=EBI-394558, EBI-394489;
CC Q71SY5; Q96RN5: MED15; NbExp=2; IntAct=EBI-394558, EBI-394506;
CC Q71SY5; Q9Y2X0: MED16; NbExp=3; IntAct=EBI-394558, EBI-394541;
CC Q71SY5; Q9ULK4: MED23; NbExp=4; IntAct=EBI-394558, EBI-311161;
CC Q71SY5; O75448: MED24; NbExp=2; IntAct=EBI-394558, EBI-394523;
CC Q71SY5; Q9NZQ3-3: NCKIPSD; NbExp=3; IntAct=EBI-394558, EBI-10963850;
CC Q71SY5; A1E959: ODAM; NbExp=3; IntAct=EBI-394558, EBI-5774125;
CC Q71SY5; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-394558, EBI-12813389;
CC Q71SY5; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-394558, EBI-724639;
CC Q71SY5; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-394558, EBI-373552;
CC Q71SY5; P10276: RARA; NbExp=10; IntAct=EBI-394558, EBI-413374;
CC Q71SY5; Q92753-1: RORB; NbExp=3; IntAct=EBI-394558, EBI-18560266;
CC Q71SY5; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-394558, EBI-6257312;
CC Q71SY5; P19793: RXRA; NbExp=4; IntAct=EBI-394558, EBI-78598;
CC Q71SY5; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-394558, EBI-748621;
CC Q71SY5; P51692: STAT5B; NbExp=3; IntAct=EBI-394558, EBI-1186119;
CC Q71SY5; Q92734: TFG; NbExp=3; IntAct=EBI-394558, EBI-357061;
CC Q71SY5; Q08117-2: TLE5; NbExp=3; IntAct=EBI-394558, EBI-11741437;
CC Q71SY5; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-394558, EBI-11975223;
CC Q71SY5; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-394558, EBI-12040603;
CC Q71SY5; O00308: WWP2; NbExp=3; IntAct=EBI-394558, EBI-743923;
CC Q71SY5; P28700: Rxra; Xeno; NbExp=3; IntAct=EBI-394558, EBI-346715;
CC Q71SY5; G8HBG2: UL48; Xeno; NbExp=5; IntAct=EBI-394558, EBI-15844956;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14657022}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q71SY5-1; Sequence=Displayed;
CC Name=4;
CC IsoId=Q71SY5-4; Sequence=VSP_028146;
CC Name=5;
CC IsoId=Q71SY5-5; Sequence=VSP_028143;
CC Name=6;
CC IsoId=Q71SY5-6; Sequence=VSP_047570;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highest levels in brain,
CC heart, kidney, peripheral leukocytes, placenta, skeletal muscle and
CC spleen. {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011}.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2B2 (CMT2B2) [MIM:605589]: A
CC recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness and
CC atrophy, initially of the peroneal muscles and later of the distal
CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two
CC main groups on the basis of electrophysiologic properties and
CC histopathology: primary peripheral demyelinating neuropathies
CC (designated CMT1 when they are dominantly inherited) and primary
CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group
CC are characterized by signs of axonal degeneration in the absence of
CC obvious myelin alterations, normal or slightly reduced nerve conduction
CC velocities, and progressive distal muscle weakness and atrophy.
CC {ECO:0000269|PubMed:19290556}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) [MIM:616449]: An
CC autosomal recessive syndrome characterized by eye, brain, cardiac and
CC palatal abnormalities as well as growth retardation, microcephaly and
CC severe intellectual disability. {ECO:0000269|PubMed:25792360}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 25 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG15589.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAS45401.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAB66680.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB66680.1; Type=Miscellaneous discrepancy; Note=Non-canonical splice intron-exon junction.; Evidence={ECO:0000305};
CC Sequence=CAE84581.1; Type=Miscellaneous discrepancy; Note=Non-canonical splice intron-exon junction.; Evidence={ECO:0000305};
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DR EMBL; AF261072; AAM20739.1; -; mRNA.
DR EMBL; AJ617479; CAE84581.1; ALT_SEQ; mRNA.
DR EMBL; AY533507; AAS45401.1; ALT_SEQ; mRNA.
DR EMBL; AL136746; CAB66680.1; ALT_SEQ; mRNA.
DR EMBL; EU392500; ACB88862.1; -; mRNA.
DR EMBL; AK289460; BAF82149.1; -; mRNA.
DR EMBL; AC006942; AAD15565.1; -; Genomic_DNA.
DR EMBL; AC018766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471177; EAW52546.1; -; Genomic_DNA.
DR EMBL; BC024312; AAH24312.2; -; mRNA.
DR EMBL; BC065297; AAH65297.1; -; mRNA.
DR EMBL; AF283769; AAG15589.1; ALT_INIT; mRNA.
DR CCDS; CCDS33075.1; -. [Q71SY5-1]
DR RefSeq; NP_112235.2; NM_030973.3. [Q71SY5-1]
DR PDB; 2KY6; NMR; -; A=391-553.
DR PDB; 2L23; NMR; -; A=391-548.
DR PDB; 2L6U; NMR; -; A=391-543.
DR PDB; 2XNF; NMR; -; A=394-543.
DR PDB; 7EMF; EM; 3.50 A; Y=1-747.
DR PDB; 7LBM; EM; 4.80 A; 3=1-747.
DR PDBsum; 2KY6; -.
DR PDBsum; 2L23; -.
DR PDBsum; 2L6U; -.
DR PDBsum; 2XNF; -.
DR PDBsum; 7EMF; -.
DR PDBsum; 7LBM; -.
DR AlphaFoldDB; Q71SY5; -.
DR BMRB; Q71SY5; -.
DR SMR; Q71SY5; -.
DR BioGRID; 123607; 80.
DR ComplexPortal; CPX-3227; Core mediator complex.
DR CORUM; Q71SY5; -.
DR DIP; DIP-31454N; -.
DR IntAct; Q71SY5; 59.
DR MINT; Q71SY5; -.
DR STRING; 9606.ENSP00000326767; -.
DR iPTMnet; Q71SY5; -.
DR PhosphoSitePlus; Q71SY5; -.
DR BioMuta; MED25; -.
DR DMDM; 158706143; -.
DR EPD; Q71SY5; -.
DR jPOST; Q71SY5; -.
DR MassIVE; Q71SY5; -.
DR MaxQB; Q71SY5; -.
DR PaxDb; Q71SY5; -.
DR PeptideAtlas; Q71SY5; -.
DR PRIDE; Q71SY5; -.
DR ProteomicsDB; 68625; -. [Q71SY5-1]
DR ProteomicsDB; 68628; -. [Q71SY5-4]
DR ProteomicsDB; 68629; -. [Q71SY5-5]
DR ProteomicsDB; 7538; -.
DR Antibodypedia; 45928; 123 antibodies from 20 providers.
DR DNASU; 81857; -.
DR Ensembl; ENST00000312865.10; ENSP00000326767.5; ENSG00000104973.19. [Q71SY5-1]
DR Ensembl; ENST00000538643.5; ENSP00000437496.1; ENSG00000104973.19. [Q71SY5-6]
DR GeneID; 81857; -.
DR KEGG; hsa:81857; -.
DR MANE-Select; ENST00000312865.10; ENSP00000326767.5; NM_030973.4; NP_112235.2.
DR UCSC; uc002ppw.3; human. [Q71SY5-1]
DR CTD; 81857; -.
DR DisGeNET; 81857; -.
DR GeneCards; MED25; -.
DR GeneReviews; MED25; -.
DR HGNC; HGNC:28845; MED25.
DR HPA; ENSG00000104973; Low tissue specificity.
DR MalaCards; MED25; -.
DR MIM; 605589; phenotype.
DR MIM; 610197; gene.
DR MIM; 616449; phenotype.
DR neXtProt; NX_Q71SY5; -.
DR OpenTargets; ENSG00000104973; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR Orphanet; 464738; Basel-Vanagaite-Smirin-Yosef syndrome.
DR Orphanet; 101101; Charcot-Marie-Tooth disease type 2B2.
DR PharmGKB; PA134984839; -.
DR VEuPathDB; HostDB:ENSG00000104973; -.
DR eggNOG; ENOG502QRN5; Eukaryota.
DR GeneTree; ENSGT00940000160439; -.
DR HOGENOM; CLU_007594_0_0_1; -.
DR InParanoid; Q71SY5; -.
DR OMA; NDQQKIP; -.
DR OrthoDB; 340324at2759; -.
DR PhylomeDB; Q71SY5; -.
DR TreeFam; TF329598; -.
DR PathwayCommons; Q71SY5; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR SignaLink; Q71SY5; -.
DR SIGNOR; Q71SY5; -.
DR BioGRID-ORCS; 81857; 152 hits in 1083 CRISPR screens.
DR ChiTaRS; MED25; human.
DR EvolutionaryTrace; Q71SY5; -.
DR GeneWiki; MED25; -.
DR GenomeRNAi; 81857; -.
DR Pharos; Q71SY5; Tbio.
DR PRO; PR:Q71SY5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q71SY5; protein.
DR Bgee; ENSG00000104973; Expressed in oocyte and 183 other tissues.
DR ExpressionAtlas; Q71SY5; baseline and differential.
DR Genevisible; Q71SY5; HS.
DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IPI:UniProtKB.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IPI:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IMP:UniProtKB.
DR GO; GO:2001178; P:positive regulation of mediator complex assembly; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IC:ComplexPortal.
DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; IC:ComplexPortal.
DR Gene3D; 2.40.290.30; -; 1.
DR InterPro; IPR045105; Med25/PTOV1.
DR InterPro; IPR021394; Med25_PTOV.
DR InterPro; IPR038196; Med25_PTOV_sf.
DR InterPro; IPR021406; Mediator_Med25_NR-box.
DR InterPro; IPR021397; Mediator_Med25_SD1.
DR InterPro; IPR021419; Mediator_Med25_VWA.
DR InterPro; IPR036465; vWFA_dom_sf.
DR PANTHER; PTHR12433; PTHR12433; 1.
DR Pfam; PF11232; Med25; 1.
DR Pfam; PF11244; Med25_NR-box; 1.
DR Pfam; PF11235; Med25_SD1; 1.
DR Pfam; PF11265; Med25_VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Charcot-Marie-Tooth disease;
KW Direct protein sequencing; Disease variant; Intellectual disability;
KW Methylation; Neurodegeneration; Neuropathy; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..747
FT /note="Mediator of RNA polymerase II transcription subunit
FT 25"
FT /id="PRO_0000304952"
FT REGION 1..226
FT /note="Interaction with the Mediator complex"
FT REGION 233..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..543
FT /note="Interaction with VP16"
FT REGION 395..545
FT /note="Interaction with CREBBP"
FT /evidence="ECO:0000269|PubMed:17641689"
FT REGION 548..747
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 564..653
FT /note="Interaction with RARA"
FT /evidence="ECO:0000269|PubMed:17641689"
FT REGION 640..707
FT /note="Interaction with RARA"
FT /evidence="ECO:0000269|PubMed:17641689"
FT MOTIF 646..650
FT /note="LXXLL motif"
FT COMPBIAS 319..345
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 577..607
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..638
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..712
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 725
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCB2"
FT VAR_SEQ 61..273
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047570"
FT VAR_SEQ 303..319
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028143"
FT VAR_SEQ 716..747
FT /note="GQMLLSGGPRGPVPQPGLQPSVMEDDILMDLI -> AAKRKREGEGRVFREK
FT WERAYFFVEVKSMPMCLICKQIVSVLKEYNLKRHYESKHSKSYDQYTEQTRRIRARPIW
FT PDP (in isoform 4)"
FT /evidence="ECO:0000303|Ref.10"
FT /id="VSP_028146"
FT VARIANT 39
FT /note="Y -> C (in BVSYS; the mutation impairs interaction
FT with the Mediator complex; dbSNP:rs794729668)"
FT /evidence="ECO:0000269|PubMed:25792360"
FT /id="VAR_073949"
FT VARIANT 140
FT /note="R -> W (found in a patient with syndromic
FT intellectual disability; unknown pathological significance;
FT dbSNP:rs781140315)"
FT /evidence="ECO:0000269|PubMed:25527630"
FT /id="VAR_073950"
FT VARIANT 335
FT /note="A -> V (in CMT2B2; dbSNP:rs145770066)"
FT /evidence="ECO:0000269|PubMed:19290556"
FT /id="VAR_063521"
FT MUTAGEN 646
FT /note="L->A: Abrogates interaction with RARA."
FT /evidence="ECO:0000269|PubMed:17641689"
FT MUTAGEN 649..650
FT /note="LL->AA: Abrogates interaction with RARA."
FT /evidence="ECO:0000269|PubMed:17641689"
FT CONFLICT 20
FT /note="F -> S (in Ref. 1; AAM20739)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="P -> L (in Ref. 2; CAE84581 and 4; CAB66680)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="V -> I (in Ref. 1; AAM20739)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="L -> M (in Ref. 3; AAS45401)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="G -> D (in Ref. 3; AAS45401)"
FT /evidence="ECO:0000305"
FT CONFLICT 703
FT /note="S -> F (in Ref. 1; AAM20739)"
FT /evidence="ECO:0000305"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 27..31
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 32..38
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 114..131
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 166..174
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 189..197
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 396..409
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 414..417
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 424..434
FT /evidence="ECO:0007829|PDB:2KY6"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 446..454
FT /evidence="ECO:0007829|PDB:2KY6"
FT HELIX 455..461
FT /evidence="ECO:0007829|PDB:2KY6"
FT HELIX 462..465
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 466..475
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:2L6U"
FT HELIX 480..493
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 494..499
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:2L23"
FT STRAND 510..515
FT /evidence="ECO:0007829|PDB:2KY6"
FT TURN 517..519
FT /evidence="ECO:0007829|PDB:2KY6"
FT STRAND 521..529
FT /evidence="ECO:0007829|PDB:2KY6"
FT HELIX 530..545
FT /evidence="ECO:0007829|PDB:2KY6"
SQ SEQUENCE 747 AA; 78171 MW; 6FE13FB45786402D CRC64;
MVPGSEGPAR AGSVVADVVF VIEGTANLGP YFEGLRKHYL LPAIEYFNGG PPAETDFGGD
YGGTQYSLVV FNTVDCAPES YVQCHAPTSS AYEFVTWLDG IKFMGGGGES CSLIAEGLST
ALQLFDDFKK MREQIGQTHR VCLLICNSPP YLLPAVESTT YSGCTTENLV QQIGERGIHF
SIVSPRKLPA LRLLFEKAAP PALLEPLQPP TDVSQDPRHM VLVRGLVLPV GGGSAPGPLQ
SKQPVPLPPA APSGATLSAA PQQPLPPVPP QYQVPGNLSA AQVAAQNAVE AAKNQKAGLG
PRFSPITPLQ QAAPGVGPPF SQAPAPQLPP GPPGAPKPPP ASQPSLVSTV APGSGLAPTA
QPGAPSMAGT VAPGGVSGPS PAQLGAPALG GQQSVSNKLL AWSGVLEWQE KPKPASVDAN
TKLTRSLPCQ VYVNHGENLK TEQWPQKLIM QLIPQQLLTT LGPLFRNSRM VQFHFTNKDL
ESLKGLYRIM GNGFAGCVHF PHTAPCEVRV LMLLYSSKKK IFMGLIPYDQ SGFVNGIRQV
ITNHKQVQQQ KLEQQQRGMG GQQAPPGLGP ILEDQARPSQ NLLQLRPPQP QPQGTVGASG
ATGQPQPQGT AQPPPGAPQG PPGAASGPPP PGPILRPQNP GANPQLRSLL LNPPPPQTGV
PPPQASLHHL QPPGAPALLP PPHQGLGQPQ LGPPLLHPPP AQSWPAQLPP RAPLPGQMLL
SGGPRGPVPQ PGLQPSVMED DILMDLI
