NCOA4_HUMAN
ID NCOA4_HUMAN Reviewed; 614 AA.
AC Q13772; A8K8W5; B4E260; E9PAV7; J3KQN8; Q14239;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Nuclear receptor coactivator 4;
DE Short=NCoA-4;
DE AltName: Full=Androgen receptor coactivator 70 kDa protein;
DE Short=70 kDa AR-activator;
DE Short=70 kDa androgen receptor coactivator;
DE AltName: Full=Androgen receptor-associated protein of 70 kDa;
DE AltName: Full=Ret-activating protein ELE1;
GN Name=NCOA4; Synonyms=ARA70, ELE1, RFG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Prostatic carcinoma;
RX PubMed=8643607; DOI=10.1073/pnas.93.11.5517;
RA Yeh S., Chang C.;
RT "Cloning and characterization of a specific coactivator, ARA70, for the
RT androgen receptor in human prostate cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5517-5521(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL REARRANGEMENT WITH RET.
RC TISSUE=Thyroid;
RX PubMed=8290261;
RA Santoro M., Dathan N.A., Berlingieri M.T., Bongarzone I., Paulin C.,
RA Grieco M., Pierotti M.A., Vecchio G., Fusco A.;
RT "Molecular characterization of RET/PTC3; a novel rearranged version of the
RT RETproto-oncogene in a human thyroid papillary carcinoma.";
RL Oncogene 9:509-516(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA; 3 AND 4).
RC TISSUE=Testis, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-238, AND CHROMOSOMAL REARRANGEMENT WITH
RP RET.
RC TISSUE=Thyroid tumor;
RX PubMed=8187085;
RA Bongarzone I., Butti M.G., Coronelli S., Borrello M.G., Santoro M.,
RA Mondellini P., Pilotti S., Fusco A., Della Porta G., Pierotti M.A.;
RT "Frequent activation of ret protooncogene by fusion with a new activating
RT gene in papillary thyroid carcinomas.";
RL Cancer Res. 54:2979-2985(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA), AND VARIANTS LEU-94;
RP LEU-154; ARG-350 AND PRO-561.
RC TISSUE=Cervix carcinoma, Mammary cancer, and Prostatic carcinoma;
RX PubMed=9892017; DOI=10.1210/mend.13.1.0214;
RA Alen P., Claessens F., Schoenmakers E., Swinnen J.V., Verhoeven G.,
RA Rombauts W., Peeters B.;
RT "Interaction of the putative androgen receptor-specific coactivator
RT ARA70/ELE1alpha with multiple steroid receptors and identification of an
RT internally deleted ELE1beta isoform.";
RL Mol. Endocrinol. 13:117-128(1999).
RN [10]
RP FUNCTION.
RX PubMed=10347167; DOI=10.1074/jbc.274.23.16147;
RA Heinlein C.A., Ting H.-J., Yeh S., Chang C.;
RT "Identification of ARA70 as a ligand-enhanced coactivator for the
RT peroxisome proliferator-activated receptor gamma.";
RL J. Biol. Chem. 274:16147-16152(1999).
CC -!- FUNCTION: Enhances the androgen receptor transcriptional activity in
CC prostate cancer cells. Ligand-independent coactivator of the peroxisome
CC proliferator-activated receptor (PPAR) gamma.
CC {ECO:0000269|PubMed:10347167}.
CC -!- SUBUNIT: Interacts with the androgen receptor and the retinoid X
CC receptor (RXR) in a ligand-dependent manner.
CC -!- INTERACTION:
CC Q13772-3; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-12054609, EBI-702390;
CC Q13772-3; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-12054609, EBI-1055254;
CC Q13772-3; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-12054609, EBI-10172526;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=Alpha;
CC IsoId=Q13772-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q13772-2; Sequence=VSP_003409;
CC Name=3;
CC IsoId=Q13772-3; Sequence=VSP_046348;
CC Name=4;
CC IsoId=Q13772-4; Sequence=VSP_046348, VSP_046349;
CC -!- TISSUE SPECIFICITY: Widely expressed. Also detected in adipose tissues
CC and in different cell lines. Isoform Beta is only expressed in testis.
CC -!- DISEASE: Note=A chromosomal aberration involving NCOA4 is found in
CC papillary thyroid carcinomas (PTCs). Inversion inv(10)(q11.2;q11.2)
CC generates the RET/NCOA4 (PTC3) oncogene. {ECO:0000269|PubMed:8187085,
CC ECO:0000269|PubMed:8290261}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NCOA4ID218ch10q11.html";
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DR EMBL; L49399; AAC37591.1; -; mRNA.
DR EMBL; X77548; CAA54673.1; -; mRNA.
DR EMBL; AK292480; BAF85169.1; -; mRNA.
DR EMBL; AK304123; BAG65022.1; -; mRNA.
DR EMBL; AK310849; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL162047; CAB82390.1; -; mRNA.
DR EMBL; AL450342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471260; EAW53686.1; -; Genomic_DNA.
DR EMBL; BC001562; AAH01562.1; -; mRNA.
DR EMBL; X71413; CAA50536.1; -; mRNA.
DR CCDS; CCDS73092.1; -. [Q13772-1]
DR CCDS; CCDS73093.1; -. [Q13772-3]
DR CCDS; CCDS73094.1; -. [Q13772-4]
DR PIR; S61532; S61532.
DR RefSeq; NP_001138732.1; NM_001145260.1. [Q13772-4]
DR RefSeq; NP_001138733.1; NM_001145261.1. [Q13772-3]
DR RefSeq; NP_001138734.1; NM_001145262.1. [Q13772-1]
DR RefSeq; NP_001138735.1; NM_001145263.1. [Q13772-1]
DR RefSeq; NP_005428.1; NM_005437.3. [Q13772-1]
DR PDB; 1T5Z; X-ray; 2.30 A; B=322-336.
DR PDBsum; 1T5Z; -.
DR AlphaFoldDB; Q13772; -.
DR SMR; Q13772; -.
DR BioGRID; 113726; 50.
DR DIP; DIP-5957N; -.
DR IntAct; Q13772; 23.
DR STRING; 9606.ENSP00000463027; -.
DR GlyGen; Q13772; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13772; -.
DR PhosphoSitePlus; Q13772; -.
DR BioMuta; NCOA4; -.
DR DMDM; 8928226; -.
DR EPD; Q13772; -.
DR jPOST; Q13772; -.
DR MassIVE; Q13772; -.
DR MaxQB; Q13772; -.
DR PaxDb; Q13772; -.
DR PeptideAtlas; Q13772; -.
DR PRIDE; Q13772; -.
DR ProteomicsDB; 19088; -.
DR ProteomicsDB; 59681; -. [Q13772-1]
DR ProteomicsDB; 59682; -. [Q13772-2]
DR Antibodypedia; 72715; 423 antibodies from 34 providers.
DR DNASU; 8031; -.
DR Ensembl; ENST00000578454.5; ENSP00000463027.1; ENSG00000266412.6. [Q13772-4]
DR Ensembl; ENST00000579039.2; ENSP00000463455.1; ENSG00000266412.6. [Q13772-3]
DR Ensembl; ENST00000581486.6; ENSP00000462943.1; ENSG00000266412.6. [Q13772-1]
DR Ensembl; ENST00000583565.5; ENSP00000463476.1; ENSG00000266412.6. [Q13772-1]
DR Ensembl; ENST00000585132.5; ENSP00000464054.1; ENSG00000266412.6. [Q13772-1]
DR GeneID; 8031; -.
DR KEGG; hsa:8031; -.
DR MANE-Select; ENST00000581486.6; ENSP00000462943.1; NM_001145263.2; NP_001138735.1.
DR UCSC; uc001jis.5; human. [Q13772-1]
DR CTD; 8031; -.
DR DisGeNET; 8031; -.
DR GeneCards; NCOA4; -.
DR HGNC; HGNC:7671; NCOA4.
DR HPA; ENSG00000266412; Low tissue specificity.
DR MalaCards; NCOA4; -.
DR MIM; 601984; gene.
DR neXtProt; NX_Q13772; -.
DR OpenTargets; ENSG00000266412; -.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR PharmGKB; PA31473; -.
DR VEuPathDB; HostDB:ENSG00000266412; -.
DR eggNOG; ENOG502QQ6V; Eukaryota.
DR GeneTree; ENSGT00390000008403; -.
DR HOGENOM; CLU_034170_0_0_1; -.
DR InParanoid; Q13772; -.
DR OMA; FPPDCYG; -.
DR PhylomeDB; Q13772; -.
DR TreeFam; TF333204; -.
DR PathwayCommons; Q13772; -.
DR SignaLink; Q13772; -.
DR SIGNOR; Q13772; -.
DR BioGRID-ORCS; 8031; 154 hits in 1082 CRISPR screens.
DR ChiTaRS; NCOA4; human.
DR EvolutionaryTrace; Q13772; -.
DR GeneWiki; NCOA4; -.
DR GenomeRNAi; 8031; -.
DR Pharos; Q13772; Tbio.
DR PRO; PR:Q13772; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q13772; protein.
DR Bgee; ENSG00000266412; Expressed in jejunal mucosa and 213 other tissues.
DR ExpressionAtlas; Q13772; baseline and differential.
DR Genevisible; Q13772; HS.
DR GO; GO:0044754; C:autolysosome; IDA:MGI.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; NAS:ARUK-UCL.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; NAS:ARUK-UCL.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; NAS:ARUK-UCL.
DR GO; GO:0008584; P:male gonad development; TAS:ProtInc.
DR GO; GO:0006622; P:protein targeting to lysosome; IDA:MGI.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR IDEAL; IID00074; -.
DR InterPro; IPR022174; ARA70.
DR InterPro; IPR039947; NCoA-4.
DR PANTHER; PTHR17085; PTHR17085; 1.
DR Pfam; PF12489; ARA70; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Chromosomal rearrangement;
KW Proto-oncogene; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..614
FT /note="Nuclear receptor coactivator 4"
FT /id="PRO_0000094410"
FT REGION 501..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 238..239
FT /note="Breakpoint for rearrangement to form RET/PTC3
FT oncogene"
FT VAR_SEQ 1
FT /note="M -> MGAQLTTFALAGAVRRM (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046348"
FT VAR_SEQ 239..565
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:9892017"
FT /id="VSP_003409"
FT VAR_SEQ 614
FT /note="M -> AYFKMNFQDVTVGNFQIPCGF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046349"
FT VARIANT 94
FT /note="S -> L (in dbSNP:rs782517064)"
FT /evidence="ECO:0000269|PubMed:9892017"
FT /id="VAR_009190"
FT VARIANT 154
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:9892017"
FT /id="VAR_009191"
FT VARIANT 350
FT /note="C -> R"
FT /evidence="ECO:0000269|PubMed:9892017"
FT /id="VAR_009192"
FT VARIANT 474
FT /note="P -> R (in dbSNP:rs1132111)"
FT /id="VAR_014928"
FT VARIANT 561
FT /note="L -> P"
FT /evidence="ECO:0000269|PubMed:9892017"
FT /id="VAR_009193"
FT MUTAGEN 95..96
FT /note="LL->AA: Decreased interaction with PPAR and RXR."
FT CONFLICT 71
FT /note="Y -> H (in Ref. 3; BAG65022)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="I -> T (in Ref. 8; CAA50536)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="G -> S (in Ref. 8; CAA50536)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="K -> R (in Ref. 3; AK310849)"
FT /evidence="ECO:0000305"
FT HELIX 327..333
FT /evidence="ECO:0007829|PDB:1T5Z"
FT CONFLICT Q13772-3:8
FT /note="F -> V (in Ref. 3; BAG65022)"
FT /evidence="ECO:0000305"
FT CONFLICT Q13772-4:8
FT /note="F -> V (in Ref. 3; AK310849)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 614 AA; 69726 MW; 36B6D97C7D072BFF CRC64;
MNTFQDQSGS SSNREPLLRC SDARRDLELA IGGVLRAEQQ IKDNLREVKA QIHSCISRHL
ECLRSREVWL YEQVDLIYQL KEETLQQQAQ QLYSLLGQFN CLTHQLECTQ NKDLANQVSV
CLERLGSLTL KPEDSTVLLF EADTITLRQT ITTFGSLKTI QIPEHLMAHA SSANIGPFLE
KRGCISMPEQ KSASGIVAVP FSEWLLGSKP ASGYQAPYIP STDPQDWLTQ KQTLENSQTS
SRACNFFNNV GGNLKGLENW LLKSEKSSYQ KCNSHSTTSS FSIEMEKVGD QELPDQDEMD
LSDWLVTPQE SHKLRKPENG SRETSEKFKL LFQSYNVNDW LVKTDSCTNC QGNQPKGVEI
ENLGNLKCLN DHLEAKKPLS TPSMVTEDWL VQNHQDPCKV EEVCRANEPC TSFAECVCDE
NCEKEALYKW LLKKEGKDKN GMPVEPKPEP EKHKDSLNMW LCPRKEVIEQ TKAPKAMTPS
RIADSFQVIK NSPLSEWLIR PPYKEGSPKE VPGTEDRAGK QKFKSPMNTS WCSFNTADWV
LPGKKMGNLS QLSSGEDKWL LRKKAQEVLL NSPLQEEHNF PPDHYGLPAV CDLFACMQLK
VDKEKWLYRT PLQM
