Q9NVC6 (MED17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mediator of RNA polymerase II transcription subunit 17

Alternative name(s):
Activator-recruited cofactor 77 kDa component
Short name=ARC77
Cofactor required for Sp1 transcriptional activation subunit 6
Short name=CRSP complex subunit 6
Mediator complex subunit 17
Thyroid hormone receptor-associated protein complex 80 kDa component
Short name=Trap80
Transcriptional coactivator CRSP77
Vitamin D3 receptor-interacting protein complex 80 kDa component
Short name=DRIP80

Gene names

Name:	MED17
Synonyms:	ARC77, CRSP6, DRIP77, DRIP80, TRAP80

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	651 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.12
Subunit structure	Interacts with GATA1 and PPARG 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 STAT2. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Nucleus Probable.
Tissue specificity	Ubiquitous. Ref.1
Involvement in disease	Microcephaly, postnatal progressive, with seizures and brain atrophy (MCPHSBA) [MIM:613668]: A disorder characterized by postnatal progressive microcephaly and severe developmental retardation associated with cerebral and cerebellar atrophy. Infants manifest swallowing difficulties leading to failure to thrive, jitteriness, poor visual fixation, truncal arching, seizures. There is no acquisition of developmental milestones and patients suffer from marked spasticity and profound retardation. Progressive microcephaly becomes evident few months after birth. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17
Sequence similarities	Belongs to the Mediator complex subunit 17 family.
Sequence caution	The sequence AAD30856.1 differs from that shown. Reason: Frameshift at positions 333, 335, 341 and 346.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Activator
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	androgen receptor signaling pathway Inferred from direct assay PubMed 12218053. 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 PubMed 12218053. Source: UniProtKB
Cellular_component	mediator complex Inferred from direct assay Ref.1. Source: UniProtKB transcription factor complex Inferred from direct assay Ref.6. Source: MGI
Molecular_function	RNA polymerase II transcription cofactor activity Inferred from direct assay Ref.1. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Non-traceable author statement Ref.2. Source: UniProtKB receptor activity Inferred from direct assay PubMed 12218053. Source: UniProtKB thyroid hormone receptor binding Inferred from direct assay Ref.1. Source: UniProtKB vitamin D receptor binding Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NVC6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NVC6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     140-145: NPQTLQ → VFVDFN
     146-651: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 651	651	Mediator of RNA polymerase II transcription subunit 17		PRO_0000079359
Natural variations
	Alternative sequence	140 – 145	6	NPQTLQ → VFVDFN in isoform 2.		VSP_028115
	Alternative sequence	146 – 651	506	Missing in isoform 2.		VSP_028116
	Natural variant	69	1	E → D. Ref.1 Ref.2 Ref.3 Ref.5 Ref.15 Ref.16 Corresponds to variant rs2848477 [ dbSNP | Ensembl ].		VAR_063126
	Natural variant	357	1	F → L. Corresponds to variant rs35313315 [ dbSNP | Ensembl ].		VAR_057781
	Natural variant	371	1	L → P in MCPHSBA. Ref.17		VAR_065066
Experimental info
	Sequence conflict	21	1	E → G in BAB13973. Ref.3
	Sequence conflict	58	1	E → G in BAB13973. Ref.3
	Sequence conflict	356	1	K → N in AAD30856. Ref.2
	Sequence conflict	409	1	G → Q AA sequence Ref.1
	Sequence conflict	531	1	Q → H in AAD12723. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 47011210952D287B	FASTA	651	72,890
	10 20 30 40 50 60 MSGVRAVRIS IESACEKQVH EVGLDGTETY LPPLSMSQNL ARLAQRIDFS QGSGSEEEEA 70 80 90 100 110 120 AGTEGDAQEW PGAGSSADQD DEEGVVKFQP SLWPWDSVRN NLRSALTEMC VLYDVLSIVR 130 140 150 160 170 180 DKKFMTLDPV SQDALPPKQN PQTLQLISKK KSLAGAAQIL LKGAERLTKS VTENQENKLQ 190 200 210 220 230 240 RDFNSELLRL RQHWKLRKVG DKILGDLSYR SAGSLFPHHG TFEVIKNTDL DLDKKIPEDY 250 260 270 280 290 300 CPLDVQIPSD LEGSAYIKVS IQKQAPDIGD LGTVNLFKRP LPKSKPGSPH WQTKLEAAQN 310 320 330 340 350 360 VLLCKEIFAQ LSREAVQIKS QVPHIVVKNQ IISQPFPSLQ LSISLCHSSN DKKSQKFATE 370 380 390 400 410 420 KQCPEDHLYV LEHNLHLLIR EFHKQTLSSI MMPHPASAPF GHKRMRLSGP QAFDKNEINS 430 440 450 460 470 480 LQSSEGLLEK IIKQAKHIFL RSRAAATIDS LASRIEDPQI QAHWSNINDV YESSVKVLIT 490 500 510 520 530 540 SQGYEQICKS IQLQLNIGVE QIRVVHRDGR VITLSYQEQE LQDFLLSQMS QHQVHAVQQL 550 560 570 580 590 600 AKVMGWQVLS FSNHVGLGPI ESIGNASAIT VASPSGDYAI SVRNGPESGS KIMVQFPRNQ 610 620 630 640 650 CKDLPKSDVL QDNKWSHLRG PFKEVQWNKM EGRNFVYKME LLMSALSPCL L
	Isoform 2 [UniParc]. Checksum: 20AE08169FD09570	FASTA	145	15,951
	10 20 30 40 50 60 MSGVRAVRIS IESACEKQVH EVGLDGTETY LPPLSMSQNL ARLAQRIDFS QGSGSEEEEA 70 80 90 100 110 120 AGTEGDAQEW PGAGSSADQD DEEGVVKFQP SLWPWDSVRN NLRSALTEMC VLYDVLSIVR 130 140 DKKFMTLDPV SQDALPPKQV FVDFN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators." Ito M., Yuan C.-X., Malik S., Gu W., Fondell J.D., Yamamura S., Fu Z.-Y., Zhang X., Qin J., Roeder R.G. Mol. Cell 3:361-370(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 306-319; 405-415 AND 592-602, TISSUE SPECIFICITY, IDENTIFICATION IN TRAP COMPLEX, VARIANT ASP-69. Tissue: Cervix carcinoma.
[2]	"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] (ISOFORM 1), PROTEIN SEQUENCE OF 88-99 AND 607-619, IDENTIFICATION IN ARC COMPLEX, VARIANT ASP-69. Tissue: Cervix carcinoma.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ASP-69. Tissue: Embryo.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1), VARIANT ASP-69. Tissue: Skin.
[6]	"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] OF 269-651 (ISOFORM 1).
[7]	"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: IDENTIFICATION IN ARC COMPLEX, PROTEIN SEQUENCE OF 168-179 AND 355-361.
[8]	"Identification of mammalian Mediator subunits with similarities to yeast Mediator subunits Srb5, Srb6, Med11, and Rox3." Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., Conaway J.W. J. Biol. Chem. 278:15123-15127(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MED10.
[9]	"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.
[10]	"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.
[11]	"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; MED10; MED18; MED21; MED28 AND MED30, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
[12]	"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.
[13]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[14]	"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].
[15]	"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: VARIANT [LARGE SCALE ANALYSIS] ASP-69, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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: VARIANT [LARGE SCALE ANALYSIS] ASP-69, MASS SPECTROMETRY.
[17]	"Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex." Kaufmann R., Straussberg R., Mandel H., Fattal-Valevski A., Ben-Zeev B., Naamati A., Shaag A., Zenvirt S., Konen O., Mimouni-Bloch A., Dobyns W.B., Edvardson S., Pines O., Elpeleg O. Am. J. Hum. Genet. 87:667-670(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MCPHSBA PRO-371.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF117657 mRNA. Translation: AAD22031.2. AF105421 mRNA. Translation: AAD30856.1. Frameshift. AK001674 mRNA. Translation: BAA91827.1. AK022156 mRNA. Translation: BAB13973.1. AK023209 mRNA. Translation: BAG51169.1. AC022150 Genomic DNA. No translation available. BC021101 mRNA. Translation: AAH21101.1. AF104254 mRNA. Translation: AAD12723.1.
IPI	IPI00301139. IPI00855753.
RefSeq	NP_004259.3. NM_004268.4.
UniGene	Hs.444931.
3D structure databases
ProteinModelPortal	Q9NVC6.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31451N.
IntAct	Q9NVC6. 15 interactions.
MINT	MINT-275744.
STRING	9606.ENSP00000251871.
PTM databases
PhosphoSite	Q9NVC6.
Polymorphism databases
DMDM	296437366.
Proteomic databases
PaxDb	Q9NVC6.
PRIDE	Q9NVC6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000251871; ENSP00000251871; ENSG00000042429. ENST00000530819; ENSP00000434459; ENSG00000042429.
GeneID	9440.
KEGG	hsa:9440.
UCSC	uc001pel.2. human. uc001pem.4. human.
Organism-specific databases
CTD	9440.
GeneCards	GC11P093517.
H-InvDB	HIX0010027.
HGNC	HGNC:2375. MED17.
MIM	603810. gene. 613668. phenotype.
neXtProt	NX_Q9NVC6.
PharmGKB	PA162395443.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310166.
HOGENOM	HOG000008073.
HOVERGEN	HBG103247.
InParanoid	Q9NVC6.
KO	K15133.
OMA	MVQFPRN.
OrthoDB	EOG4FXR72.
PhylomeDB	Q9NVC6.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9NVC6.
Bgee	Q9NVC6.
CleanEx	HS_MED17.
Genevestigator	Q9NVC6.
Family and domain databases
InterPro	IPR019313. Mediator_Med17. [Graphical view]
Pfam	PF10156. Med17. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MED17. human.
GenomeRNAi	9440.
NextBio	35350.
SOURCE	Search...

Entry information

Entry name

MED17_HUMAN

Accession

Primary (citable) accession number: Q9NVC6
Secondary accession number(s): B3KN07 , Q9HA81, Q9UNP7, Q9Y2W0, Q9Y660

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 106 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.