O60244 (MED14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mediator of RNA polymerase II transcription subunit 14

Alternative name(s):
Activator-recruited cofactor 150 kDa component
Short name=ARC150
Cofactor required for Sp1 transcriptional activation subunit 2
Short name=CRSP complex subunit 2
Mediator complex subunit 14
RGR1 homolog
Short name=hRGR1
Thyroid hormone receptor-associated protein complex 170 kDa component
Short name=Trap170
Transcriptional coactivator CRSP150
Vitamin D3 receptor-interacting protein complex 150 kDa component
Short name=DRIP150

Gene names

Name:	MED14
Synonyms:	ARC150, CRSP2, CXorf4, DRIP150, EXLM1, RGR1, TRAP170

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1454 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Ref.13 Ref.14 Ref.16
Subunit structure	Interacts with GATA1 By similarity. Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with AR, ESR1, SREBF1 and STAT2. Ref.3 Ref.4 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Nucleus Probable.
Tissue specificity	Ubiquitous.
Sequence similarities	Belongs to the Mediator complex subunit 14 family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	androgen receptor signaling pathway Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12037571. Source: MGI stem cell maintenance Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	mediator complex Inferred from direct assay PubMed 10198638. Source: UniProtKB
Molecular_function	RNA polymerase II transcription cofactor activity Inferred from direct assay PubMed 10198638. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Non-traceable author statement Ref.3. Source: UniProtKB receptor activity Inferred from direct assay Ref.9. Source: UniProtKB thyroid hormone receptor binding Inferred from direct assay PubMed 10198638. Source: UniProtKB vitamin D receptor binding Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-394489,EBI-375543
FYN	P06241	1	EBI-394489,EBI-515315
GRB2	P62993	1	EBI-394489,EBI-401755
NCK1	P16333	1	EBI-394489,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1454	1454	Mediator of RNA polymerase II transcription subunit 14		PRO_0000079357
Regions
	Region	188 – 566	379	Interaction with STAT2
	Region	500 – 824	325	Interaction with SREBF1
	Motif	69 – 73	5	LXXLL motif 1
	Motif	1182 – 1186	5	LXXLL motif 2
	Compositional bias	1002 – 1165	164	Pro-rich
Amino acid modifications
	Modified residue	617	1	Phosphoserine Ref.17 Ref.19
	Modified residue	986	1	Phosphoserine Ref.19
	Modified residue	1112	1	Phosphoserine Ref.20 Ref.21
	Modified residue	1119	1	Phosphoserine Ref.21
	Modified residue	1128	1	Phosphoserine Ref.18 Ref.20 Ref.21
	Modified residue	1136	1	Phosphoserine Ref.18 Ref.20 Ref.21
	Modified residue	1144	1	Phosphoserine Ref.18
Natural variations
	Natural variant	1325	1	F → L in a breast cancer sample; somatic mutation. Ref.23		VAR_036608
Experimental info
	Sequence conflict	309 – 310	2	HS → LT in AAD24360. Ref.4
	Sequence conflict	1265	1	V → L in BAA28626. Ref.1
	Sequence conflict	1265	1	V → L in AAD12725. Ref.2
	Sequence conflict	1265	1	V → L in AAG22547. Ref.3
	Sequence conflict	1451	1	G → V in BAA28626. Ref.1
	Sequence conflict	1451	1	G → V in AAD12725. Ref.2
	Sequence conflict	1451	1	G → V in AAG22547. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O60244 [UniParc]. Last modified April 17, 2007. Version 2. Checksum: 144308E3F08D3D9B	FASTA	1,454	160,607
	10 20 30 40 50 60 MAPVQLENHQ LVPPGGGGGG SGGPPSAPAP PPPGAAVAAA AAAAASPGYR LSTLIEFLLH 70 80 90 100 110 120 RAYSELMVLT DLLPRKSDVE RKIEIVQFAS RTRQLFVRLL ALVKWANNAG KVEKCAMISS 130 140 150 160 170 180 FLDQQAILFV DTADRLASLA RDALVHARLP SFAIPYAIDV LTTGSYPRLP TCIRDKIIPP 190 200 210 220 230 240 DPITKIEKQA TLHQLNQILR HRLVTTDLPP QLANLTVANG RVKFRVEGEF EATLTVMGDD 250 260 270 280 290 300 PDVPWRLLKL EILVEDKETG DGRALVHSMQ ISFIHQLVQS RLFADEKPLQ DMYNCLHSFC 310 320 330 340 350 360 LSLQLEVLHS QTLMLIRERW GDLVQVERYH AGKCLSLSVW NQQVLGRKTG TASVHKVTIK 370 380 390 400 410 420 IDENDVSKPL QIFHDPPLPA SDSKLVERAM KIDHLSIEKL LIDSVHARAH QKLQELKAIL 430 440 450 460 470 480 RGFNANENSS IETALPALVV PILEPCGNSE CLHIFVDLHS GMFQLMLYGL DQATLDDMEK 490 500 510 520 530 540 SVNDDMKRII PWIQQLKFWL GQQRCKQSIK HLPTISSETL QLSNYSTHPI GNLSKNKLFI 550 560 570 580 590 600 KLTRLPQYYI VVEMLEVPNK PTQLSYKYYF MSVNAADRED SPAMALLLQQ FKENIQDLVF 610 620 630 640 650 660 RTKTGKQTRT NAKRKLSDDP CPVESKKTKR AGEMCAFNKV LAHFVAMCDT NMPFVGLRLE 670 680 690 700 710 720 LSNLEIPHQG VQVEGDGFSH AIRLLKIPPC KGITEETQKA LDRSLLDCTF RLQGRNNRTW 730 740 750 760 770 780 VAELVFANCP LNGTSTREQG PSRHVYLTYE NLLSEPVGGR KVVEMFLNDW NSIARLYECV 790 800 810 820 830 840 LEFARSLPDI PAHLNIFSEV RVYNYRKLIL CYGTTKGSSI SIQWNSIHQK FHISLGTVGP 850 860 870 880 890 900 NSGCSNCHNT ILHQLQEMFN KTPNVVQLLQ VLFDTQAPLN AINKLPTVPM LGLTQRTNTA 910 920 930 940 950 960 YQCFSILPQS STHIRLAFRN MYCIDIYCRS RGVVAIRDGA YSLFDNSKLV EGFYPAPGLK 970 980 990 1000 1010 1020 TFLNMFVDSN QDARRRSVNE DDNPPSPIGG DMMDSLISQL QPPPQQQPFP KQPGTSGAYP 1030 1040 1050 1060 1070 1080 LTSPPTSYHS TVNQSPSMMH TQSPGNLHAA SSPSGALRAP SPASFVPTPP PSSHGISIGP 1090 1100 1110 1120 1130 1140 GASFASPHGT LDPSSPYTMV SPSGRAGNWP GSPQVSGPSP AARMPGMSPA NPSLHSPVPD 1150 1160 1170 1180 1190 1200 ASHSPRAGTS SQTMPTNMPP PRKLPQRSWA ASIPTILTHS ALNILLLPSP TPGLVPGLAG 1210 1220 1230 1240 1250 1260 SYLCSPLERF LGSVIMRRHL QRIIQQETLQ LINSNEPGVI MFKTDALKCR VALSPKTNQT 1270 1280 1290 1300 1310 1320 LQLKVTPENA GQWKPDELQV LEKFFETRVA GPPFKANTLI AFTKLLGAPT HILRDCVHIM 1330 1340 1350 1360 1370 1380 KLELFPDQAT QLKWNVQFCL TIPPSAPPIA PPGTPAVVLK SKMLFFLQLT QKTSVPPQEP 1390 1400 1410 1420 1430 1440 VSIIVPIIYD MASGTTQQAD IPRQQNSSVA APMMVSNILK RFAEMNPPRQ GECTIFAAVR 1450 DLMANLTLPP GGRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Detection and isolation of a novel human gene located on Xp11.2-p11.4 that escapes X-inactivation using a two-dimensional DNA mapping method." Yoshikawa H., Fujiyama A., Nakai K., Inazawa J., Matsubara K. Genomics 49:237-246(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1." Ryu S., Zhou S., Ladurner A.G., Tjian R. Nature 397:446-450(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex." Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., Erdjument-Bromage H., Tempst P., Freedman L.P. Nature 398:824-828(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 250-263 AND 1106-1146, IDENTIFICATION IN ARC COMPLEX. Tissue: Cervix carcinoma.
[4]	"A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation." Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., Qin J., Roeder R.G. Mol. Cell 3:97-108(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SMCC COMPLEX.
[5]	Erratum Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., Qin J., Roeder R.G. Mol. Cell 3:541-541(1999)
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[7]	"NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription." Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D. Mol. Cell 2:213-222(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A FORM OF THE MEDIATOR COMPLEX.
[8]	"Composite co-activator ARC mediates chromatin-directed transcriptional activation." Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R. Nature 398:828-832(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 4-13 AND 1256-1264, IDENTIFICATION IN ARC COMPLEX.
[9]	"A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression." Wang Q., Sharma D., Ren Y., Fondell J.D. J. Biol. Chem. 277:42852-42858(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AR.
[10]	"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." Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G. Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, INTERACTION OF THE MEDIATOR COMPLEX WITH ESR1 AND ESR2.
[11]	"Role of metazoan mediator proteins in interferon-responsive transcription." Lau J.F., Nusinzon I., Burakov D., Freedman L.P., Horvath C.M. Mol. Cell. Biol. 23:620-628(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAT2.
[12]	"A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology." Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., Conaway R.C. Mol. Cell 14:685-691(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX.
[13]	"Selective coactivator interactions in gene activation by SREBP-1a and -1c." Toth J.I., Datta S., Athanikar J.N., Freedman L.P., Osborne T.F. Mol. Cell. Biol. 24:8288-8300(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SREBF1.
[14]	"DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer cells is independent of LXXLL motifs." Lee J.E., Kim K., Sacchettini J.C., Smith C.V., Safe S. J. Biol. Chem. 280:8819-8830(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ESR1.
[15]	"MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription." Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., Roeder R.G. Mol. Cell 19:89-100(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MED1 AND MED10, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
[16]	"Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly." Baek H.J., Kang Y.K., Roeder R.G. J. Biol. Chem. 281:15172-15181(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MED1 AND MED10.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1128; SER-1136 AND SER-1144, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617 AND SER-986, MASS SPECTROMETRY.
[20]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1112; SER-1128 AND SER-1136, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1112; SER-1119; SER-1128 AND SER-1136, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1325.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB006651 mRNA. Translation: BAA28626.1. AB006652 Genomic DNA. Translation: BAA28627.1. AF104256 mRNA. Translation: AAD12725.1. AF304448 mRNA. Translation: AAG22547.1. AF135802 mRNA. Translation: AAD24360.1. BC098377 mRNA. Translation: AAH98377.1. BC132672 mRNA. Translation: AAI32673.1. BC132674 mRNA. Translation: AAI32675.1.
IPI	IPI00297191.
RefSeq	NP_004220.2. NM_004229.3.
UniGene	Hs.407604.
3D structure databases
ProteinModelPortal	O60244.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31460N.
IntAct	O60244. 16 interactions.
MINT	MINT-2796527.
STRING	9606.ENSP00000323720.
PTM databases
PhosphoSite	O60244.
Proteomic databases
PaxDb	O60244.
PRIDE	O60244.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324817; ENSP00000323720; ENSG00000180182.
GeneID	9282.
KEGG	hsa:9282.
UCSC	uc004dex.4. human.
Organism-specific databases
CTD	9282.
GeneCards	GC0XM040507.
HGNC	HGNC:2370. MED14.
MIM	300182. gene.
neXtProt	NX_O60244.
PharmGKB	PA26890.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG281210.
HOGENOM	HOG000045361.
HOVERGEN	HBG104308.
InParanoid	O60244.
KO	K15156.
OMA	KPLQISH.
OrthoDB	EOG4F7NJ5.
PhylomeDB	O60244.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	O60244.
Bgee	O60244.
CleanEx	HS_MED14.
Genevestigator	O60244.
GermOnline	ENSG00000180182. Homo sapiens.
Family and domain databases
InterPro	IPR013947. Mediator_Med14. [Graphical view]
Pfam	PF08638. Med14. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MED14. human.
GenomeRNAi	9282.
NextBio	34783.
SOURCE	Search...

Entry information

Entry name

MED14_HUMAN

Accession

Primary (citable) accession number: O60244
Secondary accession number(s): Q4KMR7, Q9UNB3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2003
Last sequence update:	April 17, 2007
Last modified:	April 3, 2013
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.