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Reviewed, UniProtKB/Swiss-Prot Q13772 (NCOA4_HUMAN)

Last modified November 4, 2008. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

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

Protein attributes

Sequence length614 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

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.

Polymorphism

Polymorphisms are specific to isoform alpha. Not found in isoform beta. Could be encoded by two different genes.

Involvement in disease

A chromosomal aberration involving NCOA4 is a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene that has been found in sporadic and radiation-associated post-Chernobyl thyroid papillary carcinomas.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ARP102751EBI-954501,EBI-608057

Alternative products

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

Notes: 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.
Notes: 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

Amino acid modifications

Modified residue4561Phosphoserine

Natural variations

Alternative sequence239 – 565327Missing in isoform Beta.
VSP_003409
Natural variant941S → L
VAR_009190
Natural variant1541F → L
VAR_009191
Natural variant3501C → R
VAR_009192
Natural variant4741P → R: dbSNP rs1132111.
VAR_014928
Natural variant5611L → P
VAR_009193

Experimental info

Mutagenesis95 – 962LL → AA: Decreased interaction with PPAR and RXR
Sequence conflict1621I → T in CAA50536. Ref.5
Sequence conflict1831G → S in CAA50536. Ref.5

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 »

28732,562

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: 8643607] [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: 8290261] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thyroid.
[3]The German cDNA consortium
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Melanoma.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
Tissue: Placenta.
[5]"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: 8187085] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-238.
Tissue: Thyroid tumor.
[6]"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: 9892017] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), VARIANTS.
Tissue: Cervix carcinoma, Mammary cancer and Prostatic carcinoma.
[7]"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: 10347167] [Abstract]
Cited for: FUNCTION.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456, MASS SPECTROMETRY.
Tissue: Epithelium.

Cross-references

Sequence databases

L49399 mRNA. Translation: AAC37591.1.
X77548 mRNA. Translation: CAA54673.1.
AL162047 mRNA. Translation: CAB82390.1.
BC001562 mRNA. Translation: AAH01562.1.
X71413 mRNA. Translation: CAA50536.1.
PIRS61532.
RefSeqNP_005428.1.
UniGeneHs.643658
Hs.705534

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1T5ZX-ray2.30B322-336[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ13772.

PTM databases

PhosphoSiteQ13772.

Genome annotation databases

EnsemblENSG00000138293. Homo sapiens. [Contig view]
GeneID8031.
KEGGhsa:8031.

Organism-specific databases

H-InvDBHIX0008823.
HGNCHGNC:7671. NCOA4.
MIM188550. phenotype.
601984. gene.
Orphanet146. Thyroid carcinoma, papillary or follicular.
PharmGKBPA31473.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ13772.
HOVERGENQ13772.

Gene expression databases

CleanExHS_NCOA4.
GermOnlineENSG00000138293. Homo sapiens.

Family and domain databases

ProtoNetSearch...

Other Resources

LinkHubQ13772.
NextBio30615.
SOURCESearch...

Entry information

Entry nameNCOA4_HUMAN
AccessionPrimary (citable) accession number: Q13772
Secondary accession number(s): Q14239
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: November 4, 2008
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 10

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents