Reviewed, UniProtKB/Swiss-Prot Q13772 (NCOA4_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	614 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB male gonad development Ref.1 Traceable author statement. Source: ProtInc positive regulation of transcription, DNA-dependent Non-traceable author statement. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Non-traceable author statement. Source: UniProtKB
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	androgen receptor binding Non-traceable author statement. Source: UniProtKB transcription coactivator activity Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	1	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 614

614

Nuclear receptor coactivator 4

PRO_0000094410

Sites

Site

238 – 239

2

Breakpoint for rearrangement to form RET/PTC3 oncogene

Amino acid modifications

Modified residue

456

1

Phosphoserine

Natural variations

Alternative sequence

239 – 565

327

Missing in isoform Beta.

VSP_003409

Natural variant

94

1

S → L

VAR_009190

Natural variant

154

1

F → L

VAR_009191

Natural variant

350

1

C → R

VAR_009192

Natural variant

474

1

P → R: dbSNP rs1132111.

VAR_014928

Natural variant

561

1

L → P

VAR_009193

Experimental info

Mutagenesis

95 – 96

2

LL → AA: Decreased interaction with PPAR and RXR

Sequence conflict

162

1

I → T in CAA50536. Ref.5

Sequence conflict

183

1

G → S in CAA50536. Ref.5

Secondary structure

1

.

.

.

614

Helix Strand Turn

Details...

Helix

327 – 333

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 36B6D97C7D072BFF	FASTA	614	69,726
	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
	Isoform Beta [UniParc]. Checksum: 411914FCC6AD6387		287	32,562
	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 KQTLENSQQE 250 260 270 280 VLLNSPLQEE HNFPPDHYGL PAVCDLFACM QLKVDKEKWL YRTPLQM

References

	« Hide 'large scale' referencesShow '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

EMBLGenBankDDBJ

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.

PIR

S61532.

RefSeq

NP_005428.1.

UniGene

Hs.643658
Hs.705534

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T5Z	X-ray	2.30	B	322-336	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13772.

PTM databases

PhosphoSite

Q13772.

Genome annotation databases

Ensembl

ENSG00000138293. Homo sapiens. [Contig view]

GeneID

8031.

KEGG

hsa:8031.

Organism-specific databases

H-InvDB

HIX0008823.

HGNC

HGNC:7671. NCOA4.

MIM

188550. phenotype.
601984. gene.

Orphanet

146. Thyroid carcinoma, papillary or follicular.

PharmGKB

PA31473.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q13772.

HOVERGEN

Q13772.

Gene expression databases

CleanEx

HS_NCOA4.

GermOnline

ENSG00000138293. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other Resources

LinkHub

Q13772.

NextBio

30615.

SOURCE

Search...

Entry information

Entry name

NCOA4_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)