MED23_HUMAN
ID MED23_HUMAN Reviewed; 1368 AA.
AC Q9ULK4; B9TX55; O95403; Q5JWT3; Q5JWT4; Q6P9H6; Q9H0J2; Q9NTT9; Q9NTU0;
AC Q9Y5P7; Q9Y667;
DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 23;
DE AltName: Full=Activator-recruited cofactor 130 kDa component;
DE Short=ARC130;
DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 3;
DE Short=CRSP complex subunit 3;
DE AltName: Full=Mediator complex subunit 23;
DE AltName: Full=Protein sur-2 homolog;
DE Short=hSur-2;
DE AltName: Full=Transcriptional coactivator CRSP130;
DE AltName: Full=Vitamin D3 receptor-interacting protein complex 130 kDa component;
DE Short=DRIP130;
GN Name=MED23; Synonyms=ARC130, CRSP3, DRIP130, KIAA1216, SUR2;
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), PROTEIN SEQUENCE OF 254-280;
RP 1317-1326 AND 1331-1337, AND IDENTIFICATION IN ARC COMPLEX.
RC TISSUE=Cervix carcinoma;
RX PubMed=10235266; DOI=10.1038/19783;
RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M.,
RA Erdjument-Bromage H., Tempst P., Freedman L.P.;
RT "Ligand-dependent transcription activation by nuclear receptors requires
RT the DRIP complex.";
RL Nature 398:824-828(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, AND INTERACTION WITH E1A
RP AND CDK8.
RX PubMed=10353252; DOI=10.1038/20466;
RA Boyer T.G., Martin M.E.D., Lees E., Ricciardi R.P., Berk A.J.;
RT "Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein.";
RL Nature 399:276-279(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND IDENTIFICATION IN THE CRSP
RP COMPLEX.
RX PubMed=9989412; DOI=10.1038/17141;
RA Ryu S., Zhou S., Ladurner A.G., Tjian R.;
RT "The transcriptional cofactor complex CRSP is required for activity of the
RT enhancer-binding protein Sp1.";
RL Nature 397:446-450(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Placenta;
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 IDENTIFICATION IN THE ARC COMPLEX, AND PROTEIN SEQUENCE OF 465-473 AND
RP 1302-1311.
RX PubMed=10235267; DOI=10.1038/19789;
RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.;
RT "Composite co-activator ARC mediates chromatin-directed transcriptional
RT activation.";
RL Nature 398:828-832(1999).
RN [11]
RP INTERACTION WITH MED6.
RX PubMed=10993082; DOI=10.1038/35024111;
RA Akoulitchev S., Chuikov S., Reinberg D.;
RT "TFIIH is negatively regulated by cdk8-containing mediator complexes.";
RL Nature 407:102-106(2000).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR
RP COMPLEX.
RX PubMed=11867769; DOI=10.1073/pnas.261715899;
RA Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G.;
RT "The TRAP/Mediator coactivator complex interacts directly with estrogen
RT receptors alpha and beta through the TRAP220 subunit and directly enhances
RT estrogen receptor function in vitro.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002).
RN [13]
RP FUNCTION, AND INTERACTION WITH CEBPB.
RX PubMed=14759369; DOI=10.1016/s1097-2765(03)00521-5;
RA Mo X., Kowenz-Leutz E., Xu H., Leutz A.;
RT "Ras induces mediator complex exchange on C/EBP beta.";
RL Mol. Cell 13:241-250(2004).
RN [14]
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 [15]
RP INTERACTION WITH MED1 AND MED10, IDENTIFICATION BY MASS SPECTROMETRY,
RP IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR
RP 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 [16]
RP INTERACTION WITH CDK8; CTNNB1 AND GLI3.
RX PubMed=17000779; DOI=10.1128/mcb.00443-06;
RA Zhou H., Kim S., Ishii S., Boyer T.G.;
RT "Mediator modulates Gli3-dependent Sonic hedgehog signaling.";
RL Mol. Cell. Biol. 26:8667-8682(2006).
RN [17]
RP FUNCTION, AND INTERACTION WITH MED1 AND MED10.
RX PubMed=16595664; DOI=10.1074/jbc.m601983200;
RA Baek H.J., Kang Y.K., Roeder R.G.;
RT "Human Mediator enhances basal transcription by facilitating recruitment of
RT transcription factor IIB during preinitiation complex assembly.";
RL J. Biol. Chem. 281:15172-15181(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP INTERACTION WITH CEBPB.
RX PubMed=20111005; DOI=10.1038/emboj.2010.3;
RA Kowenz-Leutz E., Pless O., Dittmar G., Knoblich M., Leutz A.;
RT "Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and
RT SWI/SNF/Mediator implies an indexing transcription factor code.";
RL EMBO J. 29:1105-1115(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP INVOLVEMENT IN MRT18, VARIANT MRT18 GLN-611, AND CHARACTERIZATION OF
RP VARIANT MRT18 GLN-611.
RX PubMed=21868677; DOI=10.1126/science.1206638;
RA Hashimoto S., Boissel S., Zarhrate M., Rio M., Munnich A., Egly J.M.,
RA Colleaux L.;
RT "MED23 mutation links intellectual disability to dysregulation of immediate
RT early gene expression.";
RL Science 333:1161-1163(2011).
CC -!- FUNCTION: Required for transcriptional activation subsequent to the
CC assembly of the pre-initiation complex (By similarity). Component of
CC the Mediator complex, a coactivator involved in the regulated
CC transcription of nearly all RNA polymerase II-dependent genes. Mediator
CC functions as a bridge to convey information from gene-specific
CC regulatory proteins to the basal RNA polymerase II transcription
CC machinery. Mediator is recruited to promoters by direct interactions
CC with regulatory proteins and serves as a scaffold for the assembly of a
CC functional pre-initiation complex with RNA polymerase II and the
CC general transcription factors. Required for transcriptional activation
CC by adenovirus E1A protein. Required for ELK1-dependent transcriptional
CC activation in response to activated Ras signaling. {ECO:0000250,
CC ECO:0000269|PubMed:10353252, ECO:0000269|PubMed:14759369,
CC ECO:0000269|PubMed:16595664}.
CC -!- SUBUNIT: Interacts with ELK1 (By similarity). Component of the Mediator
CC complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9,
CC MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18,
CC MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29,
CC MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and
CC CDK8 subunits form a distinct module termed the CDK8 module. Mediator
CC containing the CDK8 module is less active than Mediator lacking this
CC module in supporting transcriptional activation. Individual
CC preparations of the Mediator complex lacking one or more distinct
CC subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and
CC TRAP. Interacts with CEBPB (when not methylated), CTNNB1, and GLI3.
CC Interacts with the adenovirus E1A protein.
CC {ECO:0000250|UniProtKB:Q80YQ2, ECO:0000269|PubMed:10235266,
CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:10353252,
CC ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:11867769,
CC ECO:0000269|PubMed:14759369, ECO:0000269|PubMed:15175163,
CC ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16595664,
CC ECO:0000269|PubMed:17000779, ECO:0000269|PubMed:20111005,
CC ECO:0000269|PubMed:9989412}.
CC -!- INTERACTION:
CC Q9ULK4; O60244: MED14; NbExp=4; IntAct=EBI-311161, EBI-394489;
CC Q9ULK4; Q9Y2X0: MED16; NbExp=4; IntAct=EBI-311161, EBI-394541;
CC Q9ULK4; Q71SY5: MED25; NbExp=4; IntAct=EBI-311161, EBI-394558;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9ULK4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ULK4-2; Sequence=VSP_004034, VSP_004036, VSP_004037;
CC Name=3;
CC IsoId=Q9ULK4-3; Sequence=VSP_004034, VSP_004035;
CC Name=4;
CC IsoId=Q9ULK4-4; Sequence=VSP_004035;
CC Name=5;
CC IsoId=Q9ULK4-5; Sequence=VSP_028380;
CC Name=6;
CC IsoId=Q9ULK4-6; Sequence=VSP_047860, VSP_047861;
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 18,
CC with or without epilepsy (MRT18) [MIM:614249]: A disorder characterized
CC by significantly below average general intellectual functioning
CC associated with impairments in adaptive behavior and manifested during
CC the developmental period. {ECO:0000269|PubMed:21868677}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 23 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD12724.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD31729.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA86530.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF105332; AAD31729.1; ALT_FRAME; mRNA.
DR EMBL; AF135022; AAD30202.1; -; mRNA.
DR EMBL; AF104255; AAD12724.1; ALT_INIT; mRNA.
DR EMBL; EU392526; ACB88854.1; -; mRNA.
DR EMBL; AB033042; BAA86530.1; ALT_INIT; mRNA.
DR EMBL; AL136776; CAB66710.1; -; mRNA.
DR EMBL; AL121575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48052.1; -; Genomic_DNA.
DR EMBL; BC060759; AAH60759.1; -; mRNA.
DR CCDS; CCDS5146.1; -. [Q9ULK4-3]
DR CCDS; CCDS5147.1; -. [Q9ULK4-1]
DR CCDS; CCDS59039.1; -. [Q9ULK4-5]
DR RefSeq; NP_001257450.1; NM_001270521.1. [Q9ULK4-4]
DR RefSeq; NP_001257451.1; NM_001270522.1. [Q9ULK4-5]
DR RefSeq; NP_004821.2; NM_004830.3. [Q9ULK4-1]
DR RefSeq; NP_057063.2; NM_015979.3. [Q9ULK4-3]
DR PDB; 6H02; X-ray; 2.80 A; A=1-1368.
DR PDB; 7EMF; EM; 3.50 A; W=1-1368.
DR PDB; 7ENA; EM; 4.07 A; w=1-1368.
DR PDB; 7ENC; EM; 4.13 A; w=1-1368.
DR PDB; 7ENJ; EM; 4.40 A; W=1-1368.
DR PDB; 7LBM; EM; 4.80 A; 1=1-1368.
DR PDBsum; 6H02; -.
DR PDBsum; 7EMF; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7ENJ; -.
DR PDBsum; 7LBM; -.
DR AlphaFoldDB; Q9ULK4; -.
DR SMR; Q9ULK4; -.
DR BioGRID; 114829; 233.
DR ComplexPortal; CPX-3227; Core mediator complex.
DR CORUM; Q9ULK4; -.
DR DIP; DIP-31461N; -.
DR IntAct; Q9ULK4; 152.
DR MINT; Q9ULK4; -.
DR STRING; 9606.ENSP00000357047; -.
DR BindingDB; Q9ULK4; -.
DR ChEMBL; CHEMBL4146; -.
DR iPTMnet; Q9ULK4; -.
DR PhosphoSitePlus; Q9ULK4; -.
DR SwissPalm; Q9ULK4; -.
DR BioMuta; MED23; -.
DR DMDM; 28558074; -.
DR EPD; Q9ULK4; -.
DR jPOST; Q9ULK4; -.
DR MassIVE; Q9ULK4; -.
DR MaxQB; Q9ULK4; -.
DR PaxDb; Q9ULK4; -.
DR PeptideAtlas; Q9ULK4; -.
DR PRIDE; Q9ULK4; -.
DR ProteomicsDB; 7541; -.
DR ProteomicsDB; 85057; -. [Q9ULK4-1]
DR ProteomicsDB; 85058; -. [Q9ULK4-2]
DR ProteomicsDB; 85059; -. [Q9ULK4-3]
DR ProteomicsDB; 85060; -. [Q9ULK4-4]
DR ProteomicsDB; 85061; -. [Q9ULK4-5]
DR ABCD; Q9ULK4; 1 sequenced antibody.
DR Antibodypedia; 19677; 253 antibodies from 33 providers.
DR DNASU; 9439; -.
DR Ensembl; ENST00000354577.8; ENSP00000346588.4; ENSG00000112282.18. [Q9ULK4-3]
DR Ensembl; ENST00000368053.8; ENSP00000357032.4; ENSG00000112282.18. [Q9ULK4-2]
DR Ensembl; ENST00000368060.7; ENSP00000357039.3; ENSG00000112282.18. [Q9ULK4-5]
DR Ensembl; ENST00000368068.8; ENSP00000357047.3; ENSG00000112282.18. [Q9ULK4-1]
DR Ensembl; ENST00000539158.1; ENSP00000445072.1; ENSG00000112282.18. [Q9ULK4-6]
DR GeneID; 9439; -.
DR KEGG; hsa:9439; -.
DR MANE-Select; ENST00000368068.8; ENSP00000357047.3; NM_004830.4; NP_004821.2.
DR UCSC; uc003qcq.5; human. [Q9ULK4-1]
DR CTD; 9439; -.
DR DisGeNET; 9439; -.
DR GeneCards; MED23; -.
DR HGNC; HGNC:2372; MED23.
DR HPA; ENSG00000112282; Low tissue specificity.
DR MalaCards; MED23; -.
DR MIM; 605042; gene.
DR MIM; 614249; phenotype.
DR neXtProt; NX_Q9ULK4; -.
DR OpenTargets; ENSG00000112282; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA162395499; -.
DR VEuPathDB; HostDB:ENSG00000112282; -.
DR eggNOG; KOG1883; Eukaryota.
DR GeneTree; ENSGT00390000010380; -.
DR HOGENOM; CLU_002773_0_0_1; -.
DR InParanoid; Q9ULK4; -.
DR OMA; HALYVTC; -.
DR OrthoDB; 94121at2759; -.
DR PhylomeDB; Q9ULK4; -.
DR TreeFam; TF324163; -.
DR PathwayCommons; Q9ULK4; -.
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; Q9ULK4; -.
DR SIGNOR; Q9ULK4; -.
DR BioGRID-ORCS; 9439; 164 hits in 1105 CRISPR screens.
DR ChiTaRS; MED23; human.
DR GeneWiki; CRSP3; -.
DR GenomeRNAi; 9439; -.
DR Pharos; Q9ULK4; Tbio.
DR PRO; PR:Q9ULK4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9ULK4; protein.
DR Bgee; ENSG00000112282; Expressed in right hemisphere of cerebellum and 200 other tissues.
DR ExpressionAtlas; Q9ULK4; baseline and differential.
DR Genevisible; Q9ULK4; 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; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; IC:ComplexPortal.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:ProtInc.
DR InterPro; IPR021629; Mediator_Med23.
DR PANTHER; PTHR12691; PTHR12691; 1.
DR Pfam; PF11573; Med23; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing;
KW Disease variant; Intellectual disability; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..1368
FT /note="Mediator of RNA polymerase II transcription subunit
FT 23"
FT /id="PRO_0000079358"
FT REGION 1343..1368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1349..1368
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 292
FT /note="Q -> QTLNIAQ (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:9989412"
FT /id="VSP_004034"
FT VAR_SEQ 457..475
FT /note="FLQQSLRNKSLQMNDYKIA -> SAFANCFQITCMGDLTHTP (in
FT isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047860"
FT VAR_SEQ 476..1368
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047861"
FT VAR_SEQ 870..880
FT /note="AMRSHEGNEAQ -> VRINTFLSLFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9989412"
FT /id="VSP_004036"
FT VAR_SEQ 881..1368
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9989412"
FT /id="VSP_004037"
FT VAR_SEQ 1360..1368
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_004035"
FT VAR_SEQ 1361..1368
FT /note="PVSLPVTQ -> DTLT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10353252"
FT /id="VSP_028380"
FT VARIANT 611
FT /note="R -> Q (in MRT18; specifically impairs the response
FT of JUN and FOS immediate early genes to serum mitogens by
FT altering the interaction between enhancer-bound
FT transcription factors TCF7L2 and ELK1 and the Mediator
FT complex; dbSNP:rs370667926)"
FT /evidence="ECO:0000269|PubMed:21868677"
FT /id="VAR_082644"
FT CONFLICT 59
FT /note="C -> W (in Ref. 9; AAH60759)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="Y -> N (in Ref. 1; AAD31729)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="F -> V (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="V -> E (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="N -> H (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="F -> V (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="I -> L (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="G -> A (in Ref. 2; AAD30202)"
FT /evidence="ECO:0000305"
FT HELIX 2..21
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 35..40
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 56..68
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 73..88
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 94..103
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 131..146
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 180..190
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 203..210
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 213..218
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 267..274
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 280..287
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 298..315
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 319..324
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 328..343
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 349..360
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 369..383
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 392..394
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 395..402
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 419..422
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 424..437
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 452..462
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 469..472
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 473..480
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 481..483
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 485..488
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 489..500
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 506..508
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 510..513
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 525..528
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 533..552
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 556..558
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 561..570
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 577..580
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 581..586
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 588..594
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 599..611
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 617..632
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 639..654
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 658..660
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 661..665
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 666..668
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 681..697
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 712..720
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 729..732
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 737..744
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 753..767
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 773..780
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 789..799
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 805..814
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 816..835
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 841..855
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 862..870
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 876..891
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 892..894
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 895..906
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 911..913
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 917..927
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 935..939
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 940..943
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 959..976
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 978..980
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 981..991
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 992..997
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1001..1011
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1013..1016
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1020..1032
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 1033..1037
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 1042..1044
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1048..1051
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1065..1080
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1092..1094
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 1095..1099
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1100..1114
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 1115..1117
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1119..1131
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 1135..1137
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1142..1155
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1158..1161
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1163..1172
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1175..1178
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1188..1190
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1193..1197
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 1200..1217
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1221..1224
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1227..1233
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 1234..1238
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1242..1252
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1253..1255
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1256..1262
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1264..1284
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1291..1304
FT /evidence="ECO:0007829|PDB:6H02"
FT TURN 1305..1308
FT /evidence="ECO:0007829|PDB:6H02"
FT STRAND 1309..1311
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1312..1318
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1323..1328
FT /evidence="ECO:0007829|PDB:6H02"
FT HELIX 1329..1331
FT /evidence="ECO:0007829|PDB:6H02"
SQ SEQUENCE 1368 AA; 156474 MW; 2BEE9FF5E328477D CRC64;
METQLQSIFE EVVKTEVIEE AFPGMFMDTP EDEKTKLISC LGAFRQFWGG LSQESHEQCI
QWIVKFIHGQ HSPKRISFLY DCLAMAVETG LLPPRLVCES LINSDTLEWE RTQLWALTFK
LVRKIIGGVD YKGVRDLLKV ILEKILTIPN TVSSAVVQQL LAAREVIAYI LERNACLLPA
YFAVTEIRKL YPEGKLPHWL LGNLVSDFVD TFRPTARINS ICGRCSLLPV VNNSGAICNS
WKLDPATLRF PLKGLLPYDK DLFEPQTALL RYVLEQPYSR DMVCNMLGLN KQHKQRCPVL
EDQLVDLVVY AMERSETEEK FDDGGTSQLL WQHLSSQLIF FVLFQFASFP HMVLSLHQKL
AGRGLIKGRD HLMWVLLQFI SGSIQKNALA DFLPVMKLFD LLYPEKEYIP VPDINKPQST
HAFAMTCIWI HLNRKAQNDN SKLQIPIPHS LRLHHEFLQQ SLRNKSLQMN DYKIALLCNA
YSTNSECFTL PMGALVETIY GNGIMRIPLP GTNCMASGSI TPLPMNLLDS LTVHAKMSLI
HSIATRVIKL AHAKSSVALA PALVETYSRL LVYMEIESLG IKGFISQLLP TVFKSHAWGI
LHTLLEMFSY RMHHIQPHYR VQLLSHLHTL AAVAQTNQNQ LHLCVESTAL RLITALGSSE
VQPQFTRFLS DPKTVLSAES EELNRALILT LARATHVTDF FTGSDSIQGT WCKDILQTIM
SFTPHNWASH TLSCFPGPLQ AFFKQNNVPQ ESRFNLKKNV EEEYRKWKSM SNENDIITHF
SMQGSPPLFL CLLWKMLLET DHINQIGYRV LERIGARALV AHVRTFADFL VYEFSTSAGG
QQLNKCIEIL NDMVWKYNIV TLDRLILCLA MRSHEGNEAQ VCYFIIQLLL LKPNDFRNRV
SDFVKENSPE HWLQNDWHTK HMNYHKKYPE KLYFEGLAEQ VDPPVQIQSP YLPIYFGNVC
LRFLPVFDIV IHRFLELLPV SKSLETLLDH LGGLYKFHDR PVTYLYNTLH YYEMHLRDRA
FLKRKLVHAI IGSLKDNRPQ GWCLSDTYLK CAMNAREENP WVPDDTYYCR LIGRLVDTMA
GKSPGPFPNC DWRFNEFPNP AAHALHVTCV ELMALAVSGK EVGNALLNVV LKSQPLVPRE
NITAWMNAIG LIITALPEPY WIVLHDRIVS VISSPSLTSE TEWVGYPFRL FDFTACHQSY
SEMSCSYTLA LAHAVWHHSS IGQLSLIPKF LTEVLLPIVK TEFQLLYVYH LVGPFLQRFQ
QERTRCMIEI GVAFYDMLLN VDQCSTHLNY MDPICDFLYH MKYMFTGDSV KEQVEKIICN
LKPALKLRLR FITHISKMEP AAVPPQAMNS GSPAPQSNQV PVSLPVTQ
