MED28_HUMAN
ID MED28_HUMAN Reviewed; 178 AA.
AC Q9H204; Q9BZJ5;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Mediator of RNA polymerase II transcription subunit 28;
DE AltName: Full=Endothelial-derived protein 1;
DE AltName: Full=Mediator complex subunit 28;
DE AltName: Full=Merlin and Grb2-interacting cytoskeletal protein;
DE Short=Magicin;
DE AltName: Full=Tumor angiogenesis marker EG-1;
GN Name=MED28; Synonyms=EG1; ORFNames=FKSG20;
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], AND INDUCTION.
RX PubMed=11779215; DOI=10.1006/bbrc.2001.6119;
RA Liu C., Zhang L., Shao Z.-M., Beatty P., Sartippour M., Lane T.F.,
RA Barsky S.H., Livingston E., Nguyen M.H.;
RT "Identification of a novel endothelial-derived gene EG-1.";
RL Biochem. Biophys. Res. Commun. 290:602-612(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang Y.-G., Gong L.;
RT "Cloning of FKSG20, a novel gene expressed in adrenal gland tumor
RT tissues.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mai N., Liu C.;
RT "A gene from tumor.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
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 [6]
RP FUNCTION IN SIGNALING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH ACTIN; NF2 AND GRB2.
RX PubMed=15467741; DOI=10.1038/sj.onc.1208110;
RA Wiederhold T., Lee M.-F., James M., Neujahr R., Smith N., Murthy A.,
RA Hartwig J., Gusella J.F., Ramesh V.;
RT "Magicin, a novel cytoskeletal protein associates with the NF2 tumor
RT suppressor merlin and Grb2.";
RL Oncogene 23:8815-8825(2004).
RN [7]
RP INTERACTION WITH CCNC; MED1; MED6; MED12; MED13; MED16; MED17; MED20; MED21
RP AND MED24, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA
RP 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 [8]
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).
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. May be part of a complex
CC containing NF2/merlin that participates in cellular signaling to the
CC actin cytoskeleton downstream of tyrosine kinase signaling pathways.
CC {ECO:0000269|PubMed:15467741}.
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. Forms a ternary complex
CC with NF2/merlin and GRB2. Binds to actin. {ECO:0000269|PubMed:15175163,
CC ECO:0000269|PubMed:15989967}.
CC -!- INTERACTION:
CC Q9H204; Q8NA61: CBY2; NbExp=3; IntAct=EBI-514199, EBI-741724;
CC Q9H204; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-514199, EBI-11524851;
CC Q9H204; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-514199, EBI-21603100;
CC Q9H204; P06241: FYN; NbExp=6; IntAct=EBI-514199, EBI-515315;
CC Q9H204; P62993: GRB2; NbExp=3; IntAct=EBI-514199, EBI-401755;
CC Q9H204; P42858: HTT; NbExp=9; IntAct=EBI-514199, EBI-466029;
CC Q9H204; P06239: LCK; NbExp=4; IntAct=EBI-514199, EBI-1348;
CC Q9H204; Q5TCQ9: MAGI3; NbExp=2; IntAct=EBI-514199, EBI-310506;
CC Q9H204; Q9NVC6: MED17; NbExp=2; IntAct=EBI-514199, EBI-394562;
CC Q9H204; Q15528: MED22; NbExp=2; IntAct=EBI-514199, EBI-394687;
CC Q9H204; Q9NX70: MED29; NbExp=3; IntAct=EBI-514199, EBI-394656;
CC Q9H204; Q96HR3: MED30; NbExp=6; IntAct=EBI-514199, EBI-394659;
CC Q9H204; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-514199, EBI-2801965;
CC Q9H204; Q92597: NDRG1; NbExp=3; IntAct=EBI-514199, EBI-716486;
CC Q9H204; P35240: NF2; NbExp=4; IntAct=EBI-514199, EBI-1014472;
CC Q9H204; P35240-1: NF2; NbExp=2; IntAct=EBI-514199, EBI-1014500;
CC Q9H204; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-514199, EBI-912440;
CC Q9H204; Q9UHX1: PUF60; NbExp=6; IntAct=EBI-514199, EBI-1053259;
CC Q9H204; P12931: SRC; NbExp=3; IntAct=EBI-514199, EBI-621482;
CC Q9H204; P51687: SUOX; NbExp=3; IntAct=EBI-514199, EBI-3921347;
CC Q9H204; Q8WWU5-7: TCP11; NbExp=3; IntAct=EBI-514199, EBI-17721485;
CC Q9H204; P07947: YES1; NbExp=2; IntAct=EBI-514199, EBI-515331;
CC Q9H204; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-514199, EBI-6260909;
CC Q9H204; Q9CQI9: Med30; Xeno; NbExp=2; IntAct=EBI-514199, EBI-309220;
CC Q9H204; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-514199, EBI-7990252;
CC Q9H204; P03255; Xeno; NbExp=2; IntAct=EBI-514199, EBI-2603114;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15467741}. Cytoplasm
CC {ECO:0000269|PubMed:15467741}. Membrane {ECO:0000269|PubMed:15467741};
CC Peripheral membrane protein {ECO:0000269|PubMed:15467741}.
CC Note=According to PubMed:15467741, it is cytoplasmic and mainly
CC membrane-associated.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in vascular
CC tissues such as placenta, testis and liver.
CC {ECO:0000269|PubMed:15467741}.
CC -!- INDUCTION: Up-regulated by endothelial cells when exposed to tumor
CC conditional media. {ECO:0000269|PubMed:11779215}.
CC -!- SIMILARITY: Belongs to the Mediator complex subunit 28 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK11563.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MED28ID50131ch4p15.html";
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DR EMBL; AF321617; AAG38612.1; -; mRNA.
DR EMBL; AF358829; AAK32724.1; -; mRNA.
DR EMBL; AF318059; AAL26906.1; -; mRNA.
DR EMBL; AF317680; AAK11563.1; ALT_FRAME; mRNA.
DR EMBL; BC011936; AAH11936.1; -; mRNA.
DR CCDS; CCDS33963.1; -.
DR RefSeq; NP_079481.2; NM_025205.4.
DR PDB; 7EMF; EM; 3.50 A; 1=1-178.
DR PDB; 7ENA; EM; 4.07 A; e=1-178.
DR PDB; 7ENC; EM; 4.13 A; e=1-178.
DR PDB; 7ENJ; EM; 4.40 A; 1=1-178.
DR PDB; 7LBM; EM; 4.80 A; o=1-178.
DR PDB; 7NVR; EM; 4.50 A; q=1-178.
DR PDBsum; 7EMF; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7ENJ; -.
DR PDBsum; 7LBM; -.
DR PDBsum; 7NVR; -.
DR AlphaFoldDB; Q9H204; -.
DR SMR; Q9H204; -.
DR BioGRID; 123219; 111.
DR ComplexPortal; CPX-3227; Core mediator complex.
DR CORUM; Q9H204; -.
DR IntAct; Q9H204; 77.
DR MINT; Q9H204; -.
DR STRING; 9606.ENSP00000237380; -.
DR iPTMnet; Q9H204; -.
DR PhosphoSitePlus; Q9H204; -.
DR BioMuta; MED28; -.
DR DMDM; 59799838; -.
DR EPD; Q9H204; -.
DR jPOST; Q9H204; -.
DR MassIVE; Q9H204; -.
DR MaxQB; Q9H204; -.
DR PaxDb; Q9H204; -.
DR PeptideAtlas; Q9H204; -.
DR PRIDE; Q9H204; -.
DR ProteomicsDB; 80465; -.
DR Antibodypedia; 23086; 175 antibodies from 28 providers.
DR DNASU; 80306; -.
DR Ensembl; ENST00000237380.12; ENSP00000237380.6; ENSG00000118579.13.
DR GeneID; 80306; -.
DR KEGG; hsa:80306; -.
DR MANE-Select; ENST00000237380.12; ENSP00000237380.6; NM_025205.5; NP_079481.2.
DR UCSC; uc003gpk.2; human.
DR CTD; 80306; -.
DR DisGeNET; 80306; -.
DR GeneCards; MED28; -.
DR HGNC; HGNC:24628; MED28.
DR HPA; ENSG00000118579; Low tissue specificity.
DR MIM; 610311; gene.
DR neXtProt; NX_Q9H204; -.
DR OpenTargets; ENSG00000118579; -.
DR PharmGKB; PA134935853; -.
DR VEuPathDB; HostDB:ENSG00000118579; -.
DR eggNOG; ENOG502QSN9; Eukaryota.
DR GeneTree; ENSGT00390000006192; -.
DR InParanoid; Q9H204; -.
DR OMA; MQPSPQH; -.
DR OrthoDB; 1504193at2759; -.
DR PhylomeDB; Q9H204; -.
DR TreeFam; TF326988; -.
DR PathwayCommons; Q9H204; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR SignaLink; Q9H204; -.
DR SIGNOR; Q9H204; -.
DR BioGRID-ORCS; 80306; 707 hits in 1099 CRISPR screens.
DR ChiTaRS; MED28; human.
DR GeneWiki; MED28; -.
DR GenomeRNAi; 80306; -.
DR Pharos; Q9H204; Tbio.
DR PRO; PR:Q9H204; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9H204; protein.
DR Bgee; ENSG00000118579; Expressed in amniotic fluid and 201 other tissues.
DR ExpressionAtlas; Q9H204; baseline and differential.
DR Genevisible; Q9H204; HS.
DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; IEA:Ensembl.
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 GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR InterPro; IPR021640; Mediator_Med28.
DR PANTHER; PTHR13512; PTHR13512; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Activator; Coiled coil; Cytoplasm; Membrane;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..178
FT /note="Mediator of RNA polymerase II transcription subunit
FT 28"
FT /id="PRO_0000113981"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 109..145
FT /evidence="ECO:0000255"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:7EMF"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 70..105
FT /evidence="ECO:0007829|PDB:7EMF"
FT HELIX 108..143
FT /evidence="ECO:0007829|PDB:7EMF"
SQ SEQUENCE 178 AA; 19520 MW; 63DE023972908066 CRC64;
MAAPLGGMFS GQPPGPPQAP PGLPGQASLL QAAPGAPRPS SSTLVDELES SFEACFASLV
SQDYVNGTDQ EEIRTGVDQC IQKFLDIARQ TECFFLQKRL QLSVQKPEQV IKEDVSELRN
ELQRKDALVQ KHLTKLRHWQ QVLEDINVQH KKPADIPQGS LAYLEQASAN IPAPLKPT