MED26_HUMAN
ID MED26_HUMAN Reviewed; 600 AA.
AC O95402; A1A4S3; Q0VGB6;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 26;
DE AltName: Full=Activator-recruited cofactor 70 kDa component;
DE Short=ARC70;
DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 7;
DE Short=CRSP complex subunit 7;
DE AltName: Full=Mediator complex subunit 26;
DE AltName: Full=Transcriptional coactivator CRSP70;
GN Name=MED26; Synonyms=ARC70, CRSP7;
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=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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Uterus;
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 [3]
RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 294-305 AND 478-489.
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 [4]
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 [5]
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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447; SER-470 AND SER-535, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP STRUCTURE BY NMR OF 1-92.
RX PubMed=26861138; DOI=10.1007/s12104-016-9673-z;
RA Peruzzini R., Lens Z., Verger A., Dewitte F., Ferreira E., Baert J.L.,
RA Villeret V., Landrieu I., Cantrelle F.X.;
RT "1H, 15N and 13C assignments of the N-terminal domain of the Mediator
RT complex subunit MED26.";
RL Biomol. NMR. Assign. 10:233-236(2016).
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 pre-initiation complex with RNA polymerase II
CC and the general transcription factors.
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 CEBPB (when
CC not methylated)(PubMed:20111005). {ECO:0000269|PubMed:10235267,
CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967,
CC ECO:0000269|PubMed:20111005}.
CC -!- INTERACTION:
CC O95402; Q96JC9: EAF1; NbExp=5; IntAct=EBI-394392, EBI-769261;
CC O95402; Q9NPJ6: MED4; NbExp=11; IntAct=EBI-394392, EBI-394607;
CC O95402; O43513: MED7; NbExp=8; IntAct=EBI-394392, EBI-394632;
CC O95402; Q8C1S0: Med19; Xeno; NbExp=2; IntAct=EBI-394392, EBI-398761;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95402-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95402-2; Sequence=VSP_028151, VSP_028152;
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 26 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF104253; AAD12722.1; -; mRNA.
DR EMBL; BC110430; AAI10431.1; -; mRNA.
DR EMBL; BC127215; AAI27216.1; -; mRNA.
DR CCDS; CCDS12347.1; -. [O95402-1]
DR RefSeq; NP_004822.2; NM_004831.3. [O95402-1]
DR PDB; 5ODD; NMR; -; A=1-92.
DR PDB; 6ZV3; NMR; -; A=1-87.
DR PDB; 7EMF; EM; 3.50 A; Z=1-600.
DR PDB; 7ENA; EM; 4.07 A; z=1-600.
DR PDB; 7ENC; EM; 4.13 A; z=1-600.
DR PDB; 7ENJ; EM; 4.40 A; Z=1-600.
DR PDBsum; 5ODD; -.
DR PDBsum; 6ZV3; -.
DR PDBsum; 7EMF; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7ENJ; -.
DR AlphaFoldDB; O95402; -.
DR SMR; O95402; -.
DR BioGRID; 114831; 101.
DR ComplexPortal; CPX-3227; Core mediator complex.
DR CORUM; O95402; -.
DR DIP; DIP-31464N; -.
DR IntAct; O95402; 97.
DR MINT; O95402; -.
DR STRING; 9606.ENSP00000263390; -.
DR iPTMnet; O95402; -.
DR PhosphoSitePlus; O95402; -.
DR BioMuta; MED26; -.
DR EPD; O95402; -.
DR jPOST; O95402; -.
DR MassIVE; O95402; -.
DR MaxQB; O95402; -.
DR PaxDb; O95402; -.
DR PeptideAtlas; O95402; -.
DR PRIDE; O95402; -.
DR ProteomicsDB; 50854; -. [O95402-1]
DR ProteomicsDB; 50855; -. [O95402-2]
DR TopDownProteomics; O95402-1; -. [O95402-1]
DR Antibodypedia; 14206; 291 antibodies from 33 providers.
DR DNASU; 9441; -.
DR Ensembl; ENST00000263390.8; ENSP00000263390.3; ENSG00000105085.11. [O95402-1]
DR Ensembl; ENST00000611692.4; ENSP00000484490.1; ENSG00000105085.11. [O95402-2]
DR GeneID; 9441; -.
DR KEGG; hsa:9441; -.
DR MANE-Select; ENST00000263390.8; ENSP00000263390.3; NM_004831.5; NP_004822.2.
DR UCSC; uc002nen.2; human. [O95402-1]
DR CTD; 9441; -.
DR DisGeNET; 9441; -.
DR GeneCards; MED26; -.
DR HGNC; HGNC:2376; MED26.
DR HPA; ENSG00000105085; Tissue enhanced (testis).
DR MIM; 605043; gene.
DR neXtProt; NX_O95402; -.
DR OpenTargets; ENSG00000105085; -.
DR PharmGKB; PA162395623; -.
DR VEuPathDB; HostDB:ENSG00000105085; -.
DR eggNOG; KOG1105; Eukaryota.
DR GeneTree; ENSGT00390000000259; -.
DR HOGENOM; CLU_478915_0_0_1; -.
DR InParanoid; O95402; -.
DR OMA; SHSNQIC; -.
DR OrthoDB; 459216at2759; -.
DR PhylomeDB; O95402; -.
DR TreeFam; TF328436; -.
DR PathwayCommons; O95402; -.
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; O95402; -.
DR SIGNOR; O95402; -.
DR BioGRID-ORCS; 9441; 600 hits in 1074 CRISPR screens.
DR ChiTaRS; MED26; human.
DR GeneWiki; MED26; -.
DR GenomeRNAi; 9441; -.
DR Pharos; O95402; Tbio.
DR PRO; PR:O95402; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95402; protein.
DR Bgee; ENSG00000105085; Expressed in sperm and 190 other tissues.
DR ExpressionAtlas; O95402; baseline and differential.
DR Genevisible; O95402; HS.
DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal.
DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
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; IDA:UniProtKB.
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 Gene3D; 1.20.930.10; -; 1.
DR InterPro; IPR042376; MED26.
DR InterPro; IPR031416; Med26_C.
DR InterPro; IPR031417; Med26_Mid.
DR InterPro; IPR003617; TFIIS/CRSP70_N_sub.
DR InterPro; IPR035441; TFIIS/LEDGF_dom_sf.
DR InterPro; IPR017923; TFIIS_N.
DR PANTHER; PTHR15201; PTHR15201; 1.
DR Pfam; PF08711; Med26; 1.
DR Pfam; PF15693; Med26_C; 1.
DR Pfam; PF15694; Med26_M; 1.
DR SMART; SM00509; TFS2N; 1.
DR SUPFAM; SSF47676; SSF47676; 1.
DR PROSITE; PS51319; TFIIS_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..600
FT /note="Mediator of RNA polymerase II transcription subunit
FT 26"
FT /id="PRO_0000079360"
FT DOMAIN 10..87
FT /note="TFIIS N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00649"
FT REGION 99..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 348..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 125..157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 171..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..222
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..295
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..402
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..461
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 76..92
FT /note="LLRSWQKLIEPAHQHEA -> LPGWQWACRPRGQPPGA (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028151"
FT VAR_SEQ 93..600
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028152"
FT CONFLICT 156
FT /note="L -> F (in Ref. 1; AAD12722)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="P -> A (in Ref. 2; AAI27216)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="R -> L (in Ref. 2; AAI10431)"
FT /evidence="ECO:0000305"
FT HELIX 8..18
FT /evidence="ECO:0007829|PDB:5ODD"
FT HELIX 28..40
FT /evidence="ECO:0007829|PDB:5ODD"
FT HELIX 45..50
FT /evidence="ECO:0007829|PDB:5ODD"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:5ODD"
FT HELIX 54..63
FT /evidence="ECO:0007829|PDB:5ODD"
FT HELIX 67..81
FT /evidence="ECO:0007829|PDB:5ODD"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:5ODD"
FT HELIX 485..499
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 539..542
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 550..556
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 561..564
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 580..582
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 585..588
FT /evidence="ECO:0007829|PDB:7EMF"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:7EMF"
SQ SEQUENCE 600 AA; 65446 MW; 4BEA264A3EB5A407 CRC64;
MTAAPASPQQ IRDRLLQAID PQSNIRNMVA VLEVISSLEK YPITKEALEE TRLGKLINDV
RKKTKNEELA KRAKKLLRSW QKLIEPAHQH EAALRGLAGA TGSANGGAHN CRPEVGAAGP
PRSIHDLKSR NDLQRLPGQR LDRLGSRKRR GDQRDLGHPG PPPKVSKASH DPLVPNSSPL
PTNGISGSPE SFASSLDGSG HAGPEGSRLE RDENDKHSGK IPVNAVRPHT SSPGLGKPPG
PCLQPKASVL QQLDRVDETP GPPHPKGPPR CSFSPRNSRH EGSFARQQSL YAPKGSVPSP
SPRPQALDAT QVPSPLPLAQ PSTPPVRRLE LLPSAESPVC WLEQPESHQR LAGPGCKAGL
SPAEPLLSRA GFSPDSSKAD SDAASSGGSD SKKKKRYRPR DYTVNLDGQV AEAGVKPVRL
KERKLTFDPM TRQIKPLTQK EPVRADSPVH MEQQSRTELD KQEAKASLQS PFEQTNWKEL
SRNEIIQSYL SRQSSLLSSS GAQTPGAHHF MSEYLKQEES TRQGARQLHV LVPQSPPTDL
PGLTREVTQD DLDRIQASQW PGVNGCQDTQ GNWYDWTQCI SLDPHGDDGR LNILPYVCLD
