Q13772 (NCOA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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.
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. Ref.7
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	Defects in NCOA4 are a cause of thyroid papillary carcinoma (TPC) [MIM:188550]. TPC is 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=A chromosomal aberration involving NCOA4 is found in thyroid papillary carcinomas. 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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	androgen receptor signaling pathway Non-traceable author statement. Source: UniProtKB male gonad development Traceable author statement. Source: ProtInc positive regulation of transcription, DNA-dependent Non-traceable author statement. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Traceable author statement. Source: ProtInc
Molecular function	androgen receptor binding Non-traceable author statement. Source: UniProtKB transcription coactivator activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 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.

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 Ref.8

Natural variations

Alternative sequence

239 – 565

327

Missing in isoform Beta.

VSP_003409

Natural variant

94

1

S → L. Ref.6

VAR_009190

Natural variant

154

1

F → L. Ref.6

VAR_009191

Natural variant

350

1

C → R. Ref.6

VAR_009192

Natural variant

474

1

P → R.
Corresponds to variant rs1132111 [ dbSNP | Ensembl ].

VAR_014928

Natural variant

561

1

L → P. Ref.6

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	FASTA	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 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: 17974005] [Abstract] 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 LEU-94; LEU-154; ARG-350 AND PRO-561. 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: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00015145.
IPI00221177.

PIR

S61532.

RefSeq

NP_001138732.1. NM_001145260.1.
NP_001138734.1. NM_001145262.1.
NP_001138735.1. NM_001145263.1.
NP_005428.1. NM_005437.3.

UniGene

Hs.643658.
Hs.709644.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

Q13772.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5957N.

IntAct

Q13772. 5 interactions.

MINT

MINT-2864695.

STRING

Q13772.

PTM databases

PhosphoSite

Q13772.

Polymorphism databases

DMDM

8928226.

Proteomic databases

PRIDE

Q13772.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344348; ENSP00000344552; ENSG00000138293.
ENST00000374087; ENSP00000363200; ENSG00000138293.
ENST00000430396; ENSP00000393053; ENSG00000138293.
ENST00000438493; ENSP00000405146; ENSG00000138293.
ENST00000443446; ENSP00000390713; ENSG00000138293.

GeneID

8031.

KEGG

hsa:8031.

UCSC

uc001jis.2. human.

Organism-specific databases

CTD

8031.

GeneCards

GC10P051565.

H-InvDB

HIX0008823.

HGNC

HGNC:7671. NCOA4.

MIM

188550. phenotype.
601984. gene.

neXtProt

NX_Q13772.

Orphanet

146. Papillary or follicular thyroid carcinoma.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06777.

GeneTree

ENSGT00390000008403.

HOVERGEN

HBG052584.

InParanoid

Q13772.

OrthoDB

EOG4G4GQ3.

PhylomeDB

Q13772.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q13772.

Bgee

Q13772.

CleanEx

HS_NCOA4.

Genevestigator

Q13772.

GermOnline

ENSG00000138293. Homo sapiens.

Family and domain databases

InterPro

IPR022174. ARA70.
[Graphical view]

KO

K09289.

Pfam

PF12489. ARA70. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 120 of the entry and version 1 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.