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Q13772 (NCOA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor coactivator 4

Short name=NCoA-4
Alternative name(s):
Androgen receptor coactivator 70 kDa protein
Short name=70 kDa AR-activator
Short name=70 kDa androgen receptor coactivator
Androgen receptor-associated protein of 70 kDa
Ret-activating protein ELE1
Gene names
Name:NCOA4
Synonyms:ARA70, ELE1, RFG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length614 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Enhances the androgen receptor transcriptional activity in prostate cancer cells. Ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma. Ref.10

Subunit structure

Interacts with the androgen receptor and the retinoid X receptor (RXR) in a ligand-dependent manner.

Tissue specificity

Widely expressed. Also detected in adipose tissues and in different cell lines. Isoform Beta is only expressed in testis.

Involvement in disease

Thyroid papillary carcinoma (TPC) [MIM:188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells.
Note: The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving NCOA4 is found in thyroid papillary carcinomas. Inversion inv10(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene that has been found in sporadic and radiation-associated post-Chernobyl thyroid papillary carcinomas.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Alpha (identifier: Q13772-1)

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 Beta (identifier: Q13772-2)

The sequence of this isoform differs from the canonical sequence as follows:
     239-565: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q13772-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGAQLTTFALAGAVRRM
Note: No experimental confirmation available.
Isoform 4 (identifier: Q13772-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGAQLTTFALAGAVRRM
     614-614: M → AYFKMNFQDVTVGNFQIPCGF
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 614614Nuclear receptor coactivator 4
PRO_0000094410

Sites

Site238 – 2392Breakpoint for rearrangement to form RET/PTC3 oncogene

Natural variations

Alternative sequence11M → MGAQLTTFALAGAVRRM in isoform 3 and isoform 4.
VSP_046348
Alternative sequence239 – 565327Missing in isoform Beta.
VSP_003409
Alternative sequence6141M → AYFKMNFQDVTVGNFQIPCG F in isoform 4.
VSP_046349
Natural variant941S → L. Ref.9
VAR_009190
Natural variant1541F → L. Ref.9
VAR_009191
Natural variant3501C → R. Ref.9
VAR_009192
Natural variant4741P → R.
Corresponds to variant rs1132111 [ dbSNP | Ensembl ].
VAR_014928
Natural variant5611L → P. Ref.9
VAR_009193

Experimental info

Mutagenesis95 – 962LL → AA: Decreased interaction with PPAR and RXR.
Sequence conflict711Y → H in BAG65022. Ref.3
Sequence conflict1621I → T in CAA50536. Ref.8
Sequence conflict1831G → S in CAA50536. Ref.8
Sequence conflict2711K → R in AK310849. Ref.3
Isoform 3:
Sequence conflict81F → V in BAG65022. Ref.3
Isoform 4:
Sequence conflict81F → V in AK310849. Ref.3

Secondary structure

... 614
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 36B6D97C7D072BFF

FASTA61469,726
        10         20         30         40         50         60 
MNTFQDQSGS SSNREPLLRC SDARRDLELA IGGVLRAEQQ IKDNLREVKA QIHSCISRHL 

        70         80         90        100        110        120 
ECLRSREVWL YEQVDLIYQL KEETLQQQAQ QLYSLLGQFN CLTHQLECTQ NKDLANQVSV 

       130        140        150        160        170        180 
CLERLGSLTL KPEDSTVLLF EADTITLRQT ITTFGSLKTI QIPEHLMAHA SSANIGPFLE 

       190        200        210        220        230        240 
KRGCISMPEQ KSASGIVAVP FSEWLLGSKP ASGYQAPYIP STDPQDWLTQ KQTLENSQTS 

       250        260        270        280        290        300 
SRACNFFNNV GGNLKGLENW LLKSEKSSYQ KCNSHSTTSS FSIEMEKVGD QELPDQDEMD 

       310        320        330        340        350        360 
LSDWLVTPQE SHKLRKPENG SRETSEKFKL LFQSYNVNDW LVKTDSCTNC QGNQPKGVEI 

       370        380        390        400        410        420 
ENLGNLKCLN DHLEAKKPLS TPSMVTEDWL VQNHQDPCKV EEVCRANEPC TSFAECVCDE 

       430        440        450        460        470        480 
NCEKEALYKW LLKKEGKDKN GMPVEPKPEP EKHKDSLNMW LCPRKEVIEQ TKAPKAMTPS 

       490        500        510        520        530        540 
RIADSFQVIK NSPLSEWLIR PPYKEGSPKE VPGTEDRAGK QKFKSPMNTS WCSFNTADWV 

       550        560        570        580        590        600 
LPGKKMGNLS QLSSGEDKWL LRKKAQEVLL NSPLQEEHNF PPDHYGLPAV CDLFACMQLK 

       610 
VDKEKWLYRT PLQM 

« Hide

Isoform Beta [UniParc].

Checksum: 411914FCC6AD6387
Show »

FASTA28732,562
Isoform 3 [UniParc].

Checksum: CC77B233C7B8849A
Show »

FASTA63071,371
Isoform 4 [UniParc].

Checksum: 504B983AA6E76D83
Show »

FASTA65073,649

References

« Hide 'large scale' references
[1]"Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells."
Yeh S., Chang C.
Proc. Natl. Acad. Sci. U.S.A. 93:5517-5521(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Prostatic carcinoma.
[2]"Molecular characterization of RET/PTC3; a novel rearranged version of the RETproto-oncogene in a human thyroid papillary carcinoma."
Santoro M., Dathan N.A., Berlingieri M.T., Bongarzone I., Paulin C., Grieco M., Pierotti M.A., Vecchio G., Fusco A.
Oncogene 9:509-516(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thyroid.
[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. expand/collapse author list , 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 ALPHA; 3 AND 4).
Tissue: Testis and Trachea.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Melanoma.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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 ALPHA).
Tissue: Placenta.
[8]"Frequent activation of ret protooncogene by fusion with a new activating gene in papillary thyroid carcinomas."
Bongarzone I., Butti M.G., Coronelli S., Borrello M.G., Santoro M., Mondellini P., Pilotti S., Fusco A., Della Porta G., Pierotti M.A.
Cancer Res. 54:2979-2985(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-238.
Tissue: Thyroid tumor.
[9]"Interaction of the putative androgen receptor-specific coactivator ARA70/ELE1alpha with multiple steroid receptors and identification of an internally deleted ELE1beta isoform."
Alen P., Claessens F., Schoenmakers E., Swinnen J.V., Verhoeven G., Rombauts W., Peeters B.
Mol. Endocrinol. 13:117-128(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), VARIANTS LEU-94; LEU-154; ARG-350 AND PRO-561.
Tissue: Cervix carcinoma, Mammary cancer and Prostatic carcinoma.
[10]"Identification of ARA70 as a ligand-enhanced coactivator for the peroxisome proliferator-activated receptor gamma."
Heinlein C.A., Ting H.-J., Yeh S., Chang C.
J. Biol. Chem. 274:16147-16152(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L49399 mRNA. Translation: AAC37591.1.
X77548 mRNA. Translation: CAA54673.1.
AK292480 mRNA. Translation: BAF85169.1.
AK304123 mRNA. Translation: BAG65022.1.
AK310849 mRNA. No translation available.
AL162047 mRNA. Translation: CAB82390.1.
AL450342 Genomic DNA. Translation: CAI14478.1.
CH471260 Genomic DNA. Translation: EAW53686.1.
BC001562 mRNA. Translation: AAH01562.1.
X71413 mRNA. Translation: CAA50536.1.
PIRS61532.
RefSeqNP_001138732.1. NM_001145260.1.
NP_001138733.1. NM_001145261.1.
NP_001138734.1. NM_001145262.1.
NP_001138735.1. NM_001145263.1.
NP_005428.1. NM_005437.3.
UniGeneHs.643658.
Hs.709644.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1T5ZX-ray2.30B322-336[»]
ProteinModelPortalQ13772.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113726. 12 interactions.
DIPDIP-5957N.
IntActQ13772. 5 interactions.
MINTMINT-2864695.
STRING9606.ENSP00000395465.

PTM databases

PhosphoSiteQ13772.

Polymorphism databases

DMDM8928226.

Proteomic databases

PaxDbQ13772.
PRIDEQ13772.

Protocols and materials databases

DNASU8031.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344348; ENSP00000344552; ENSG00000138293. [Q13772-1]
ENST00000374087; ENSP00000363200; ENSG00000138293. [Q13772-1]
ENST00000438493; ENSP00000405146; ENSG00000138293. [Q13772-3]
ENST00000443446; ENSP00000390713; ENSG00000138293. [Q13772-1]
ENST00000452682; ENSP00000395465; ENSG00000138293. [Q13772-4]
ENST00000578454; ENSP00000463027; ENSG00000266412. [Q13772-4]
ENST00000579039; ENSP00000463455; ENSG00000266412. [Q13772-3]
ENST00000581486; ENSP00000462943; ENSG00000266412. [Q13772-1]
ENST00000583565; ENSP00000463476; ENSG00000266412. [Q13772-1]
ENST00000585132; ENSP00000464054; ENSG00000266412. [Q13772-1]
GeneID8031.
KEGGhsa:8031.
UCSCuc001jis.4. human. [Q13772-1]

Organism-specific databases

CTD8031.
GeneCardsGC10P051565.
HGNCHGNC:7671. NCOA4.
HPAHPA051260.
MIM188550. phenotype.
601984. gene.
neXtProtNX_Q13772.
Orphanet146. Papillary or follicular thyroid carcinoma.
PharmGKBPA31473.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40301.
HOGENOMHOG000013175.
HOVERGENHBG052584.
InParanoidQ13772.
KOK09289.
OMAECVCDEN.
PhylomeDBQ13772.
TreeFamTF333204.

Gene expression databases

ArrayExpressQ13772.
BgeeQ13772.
CleanExHS_NCOA4.
GenevestigatorQ13772.

Family and domain databases

InterProIPR022174. ARA70.
[Graphical view]
PfamPF12489. ARA70. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13772.
GeneWikiNCOA4.
GenomeRNAi8031.
NextBio30615.
PROQ13772.
SOURCESearch...

Entry information

Entry nameNCOA4_HUMAN
AccessionPrimary (citable) accession number: Q13772
Secondary accession number(s): A8K8W5 expand/collapse secondary AC list , B4E260, E9PAV7, J3KQN8, Q14239
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: March 19, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM