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Protein

Nuclear receptor coactivator 6

Gene

NCOA6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Coactivates expression in an agonist- and AF2-dependent manner. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as a general coactivator, rather than just a nuclear receptor coactivator. May also be involved in the coactivation of the NF-kappa-B pathway. May coactivate expression via a remodeling of chromatin and its interaction with histone acetyltransferase proteins.

Miscellaneous

Frequently amplified or overexpressed in colon, breast and lung cancers.

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • retinoid X receptor binding Source: UniProtKB
  • thyroid hormone receptor binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • brain development Source: UniProtKB
  • cellular response to DNA damage stimulus Source: MGI
  • DNA recombination Source: UniProtKB
  • DNA repair Source: UniProtKB
  • DNA replication Source: UniProtKB
  • DNA-templated transcription, initiation Source: UniProtKB
  • glucocorticoid receptor signaling pathway Source: UniProtKB
  • heart development Source: UniProtKB
  • intracellular estrogen receptor signaling pathway Source: UniProtKB
  • myeloid cell differentiation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • regulation of lipid metabolic process Source: Reactome
  • response to hormone Source: UniProtKB

Keywordsi

Molecular functionActivator
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1368082 RORA activates gene expression
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-1989781 PPARA activates gene expression
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor coactivator 6
Alternative name(s):
Activating signal cointegrator 2
Short name:
ASC-2
Amplified in breast cancer protein 3
Cancer-amplified transcriptional coactivator ASC-2
Nuclear receptor coactivator RAP250
Short name:
NRC RAP250
Nuclear receptor-activating protein, 250 kDa
Peroxisome proliferator-activated receptor-interacting protein
Short name:
PPAR-interacting protein
Short name:
PRIP
Thyroid hormone receptor-binding protein
Gene namesi
Name:NCOA6
Synonyms:AIB3, KIAA0181, RAP250, TRBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000198646.13
HGNCiHGNC:15936 NCOA6
MIMi605299 gene
neXtProtiNX_Q14686

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi883 – 894TSPLL…LLQSD → ENPLLVNLLQFI: Reduced binding to THRB, RXRA, ESR2 and ESR1. 1 PublicationAdd BLAST12
Mutagenesisi883 – 894TSPLL…LLQSD → NLPLLVNLLQHT: Reduced binding to THRB, RXRA, ESR2 and ESR1. 1 PublicationAdd BLAST12
Mutagenesisi883 – 894TSPLL…LLQSD → VNPLLVNLLQFI: Reduced binding to THRB, RXRA, ESR2 and ESR1. 1 PublicationAdd BLAST12
Mutagenesisi883 – 884TS → SY: Strong increase in binding to THRB, RXRA and ESR2, but dramatic decrease in binding to ESR1. 2
Mutagenesisi884 – 894SPLLVNLLQSD → NPLLVNLLQLL: Reduced binding to THRB, RXRA, ESR2 and ESR1. Add BLAST11

Organism-specific databases

DisGeNETi23054
OpenTargetsiENSG00000198646
PharmGKBiPA31475

Polymorphism and mutation databases

BioMutaiNCOA6
DMDMi116242672

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944131 – 2063Nuclear receptor coactivator 6Add BLAST2063

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei95Asymmetric dimethylarginineCombined sources1
Modified residuei884Phosphoserine; by MAPK; in vitro1 Publication1
Modified residuei1047Asymmetric dimethylarginineBy similarity1
Modified residuei1058Asymmetric dimethylarginineBy similarity1
Modified residuei1096Asymmetric dimethylarginineBy similarity1
Modified residuei1819N6-acetyllysineBy similarity1
Modified residuei1822N6-acetyllysineBy similarity1
Modified residuei2018PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by PRKDC.
Phosphorylation on Ser-884 leads to a strong decrease in binding to ESR1 and ESR2.2 Publications

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiQ14686
MaxQBiQ14686
PaxDbiQ14686
PeptideAtlasiQ14686
PRIDEiQ14686
ProteomicsDBi60120

PTM databases

iPTMnetiQ14686
PhosphoSitePlusiQ14686

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in brain, prostate, testis and ovary; weakly expressed in lung, thymus and small intestine.

Gene expression databases

BgeeiENSG00000198646
CleanExiHS_NCOA6
ExpressionAtlasiQ14686 baseline and differential
GenevisibleiQ14686 HS

Organism-specific databases

HPAiHPA004198
HPA050211

Interactioni

Subunit structurei

Monomer and homodimer. Interacts with RBM39 (By similarity). Interacts in vitro with the basal transcription factors GTF2A and TBP, suggesting an autonomous transactivation function. Interacts with NCOA1, CRSP3, RBM14, the histone acetyltransferases EP300 and CREBBP, and with the methyltransferases NCOA6IP and PRMT2/HRMT1L1. Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with ZNF335; may enhance ligand-dependent transcriptional activation by nuclear hormone receptors.By similarity11 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • retinoid X receptor binding Source: UniProtKB
  • thyroid hormone receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116691, 82 interactors
CORUMiQ14686
DIPiDIP-30934N
IntActiQ14686, 40 interactors
MINTiQ14686
STRINGi9606.ENSP00000351894

Structurei

3D structure databases

ProteinModelPortaliQ14686
SMRiQ14686
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 1310NCOA1-binding regionAdd BLAST1310
Regioni1 – 1057CREBBP-binding regionAdd BLAST1057
Regioni1 – 928TBP/GTF2A-binding regionAdd BLAST928
Regioni773 – 927NCOA6IP-binding regionAdd BLAST155
Regioni1641 – 2063EP300/CRSP3-binding regionAdd BLAST423

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi887 – 891LXXLL motif 15
Motifi1491 – 1495LXXLL motif 25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi227 – 1041Gln-richAdd BLAST815
Compositional biasi372 – 377Poly-Pro6
Compositional biasi913 – 918Poly-Lys6

Domaini

Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Only motif 1 is essential for the association with nuclear receptors, while adjacent Ser-884 displays selectivity for nuclear receptors.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IK20 Eukaryota
ENOG410XW4F LUCA
GeneTreeiENSGT00730000111114
HOVERGENiHBG052586
InParanoidiQ14686
KOiK14971
OMAiMTANQGW
OrthoDBiEOG091G00CR
PhylomeDBiQ14686
TreeFamiTF332639

Family and domain databases

InterProiView protein in InterPro
IPR026638 NCOA6
IPR032715 NCOA6_nucleic_acid-bd
PANTHERiPTHR15690 PTHR15690, 2 hits
PfamiView protein in Pfam
PF13820 Nucleic_acid_bd, 1 hit

Sequencei

Sequence statusi: Complete.

Q14686-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLDDLPNLE DIYTSLCSST MEDSEMDFDS GLEDDDTKSD SILEDSTIFV
60 70 80 90 100
AFKGNIDDKD FKWKLDAILK NVPNLLHMES SKLKVQKVEP WNSVRVTFNI
110 120 130 140 150
PREAAERLRI LAQSNNQQLR DLGILSVQIE GEGAINLALA QNRSQDVRMN
160 170 180 190 200
GPMGAGNSVR MEAGFPMASG PGIIRMNNPA TVMIPPGGNV SSSMMAPGPN
210 220 230 240 250
PELQPRTPRP ASQSDAMDPL LSGLHIQQQS HPSGSLAPPH HPMQPVSVNR
260 270 280 290 300
QMNPANFPQL QQQQQQQQQQ QQQQQQQQQQ QQQQQLQARP PQQHQQQQPQ
310 320 330 340 350
GIRPQFTAPT QVPVPPGWNQ LPSGALQPPP AQGSLGTMTA NQGWKKAPLP
360 370 380 390 400
GPMQQQLQAR PSLATVQTPS HPPPPYPFGS QQASQAHTNF PQMSNPGQFT
410 420 430 440 450
APQMKSLQGG PSRVPTPLQQ PHLTNKSPAS SPSSFQQGSP ASSPTVNQTQ
460 470 480 490 500
QQMGPRPPQN NPLPQGFQQP VSSPGRNPMV QQGNVPPNFM VMQQQPPNQG
510 520 530 540 550
PQSLHPGLGG MPKRLPPGFS AGQANPNFMQ GQVPSTTATT PGNSGAPQLQ
560 570 580 590 600
ANQNVQHAGG QGAGPPQNQM QVSHGPPNMM QPSLMGIHGN MNNQQAGTSG
610 620 630 640 650
VPQVNLSNMQ GQPQQGPPSQ LMGMHQQIVP SQGQMVQQQG TLNPQNPMIL
660 670 680 690 700
SRAQLMPQGQ MMVNPPSQNL GPSPQRMTPP KQMLSQQGPQ MMAPHNQMMG
710 720 730 740 750
PQGQVLLQQN PMIEQIMTNQ MQGNKQQFNT QNQSNVMPGP AQIMRGPTPN
760 770 780 790 800
MQGNMVQFTG QMSGQMLPQQ GPVNNSPSQV MGIQGQVLRP PGPSPHMAQQ
810 820 830 840 850
HGDPATTANN DVSLSQMMPD VSIQQTNMVP PHVQAMQGNS ASGNHFSGHG
860 870 880 890 900
MSFNAPFSGA PNGNQMSCGQ NPGFPVNKDV TLTSPLLVNL LQSDISAGHF
910 920 930 940 950
GVNNKQNNTN ANKPKKKKPP RKKKNSQQDL NTPDTRPAGL EEADQPPLPG
960 970 980 990 1000
EQGINLDNSG PKLPEFSNRP PGYPSQPVEQ RPLQQMPPQL MQHVAPPPQP
1010 1020 1030 1040 1050
PQQQPQPQLP QQQQPPPPSQ PQSQQQQQQQ QQMMMMLMMQ QDPKSVRLPV
1060 1070 1080 1090 1100
SQNVHPPRGP LNPDSQRMPM QQSGSVPVMV SLQGPASVPP SPDKQRMPMP
1110 1120 1130 1140 1150
VNTPLGSNSR KMVYQESPQN PSSSPLAEMA SLPEASGSEA PSVPGGPNNM
1160 1170 1180 1190 1200
PSHVVLPQNQ LMMTGPKPGP SPLSATQGAT PQQPPVNSLP SSHGHHFPNV
1210 1220 1230 1240 1250
AAPTQTSRPK TPNRASPRPY YPQTPNNRPP STEPSEISLS PERLNASIAG
1260 1270 1280 1290 1300
LFPPQINIPL PPRPNLNRGF DQQGLNPTTL KAIGQAPSNL TMNPSNFATP
1310 1320 1330 1340 1350
QTHKLDSVVV NSGKQSNSGA TKRASPSNSR RSSPGSSRKT TPSPGRQNSK
1360 1370 1380 1390 1400
APKLTLASQT NAALLQNVEL PRNVLVSPTP LANPPVPGSF PNNSGLNPQN
1410 1420 1430 1440 1450
STVSVAAVGG VVEDNKESLN VPQDSDCQNS QSRKEQVNIE LKAVPAQEVK
1460 1470 1480 1490 1500
MVVPEDQSKK DGQPSDPNKL PSVEENKNLV SPAMREAPTS LSQLLDNSGA
1510 1520 1530 1540 1550
PNVTIKPPGL TDLEVTPPVV SGEDLKKASV IPTLQDLSSS KEPSNSLNLP
1560 1570 1580 1590 1600
HSNELCSSLV HPELSEVSSN VAPSIPPVMS RPVSSSSIST PLPPNQITVF
1610 1620 1630 1640 1650
VTSNPITTSA NTSAALPTHL QSALMSTVVT MPNAGSKVMV SEGQSAAQSN
1660 1670 1680 1690 1700
ARPQFITPVF INSSSIIQVM KGSQPSTIPA APLTTNSGLM PPSVAVVGPL
1710 1720 1730 1740 1750
HIPQNIKFSS APVPPNALSS SPAPNIQTGR PLVLSSRATP VQLPSPPCTS
1760 1770 1780 1790 1800
SPVVPSHPPV QQVKELNPDE ASPQVNTSAD QNTLPSSQST TMVSPLLTNS
1810 1820 1830 1840 1850
PGSSGNRRSP VSSSKGKGKV DKIGQILLTK ACKKVTGSLE KGEEQYGADG
1860 1870 1880 1890 1900
ETEGQGLDTT APGLMGTEQL STELDSKTPT PPAPTLLKMT SSPVGPGTAS
1910 1920 1930 1940 1950
AGPSLPGGAL PTSVRSIVTT LVPSELISAV PTTKSNHGGI ASESLAGGLV
1960 1970 1980 1990 2000
EEKVGSHPEL LPSIAPSQNL VSKETSTTAL QASVARPELE VNAAIVSGQS
2010 2020 2030 2040 2050
SEPKEIVEKS KIPGRRNSRT EEPTVASESV ENGHRKRSSR PASASSSTKD
2060
ITSAVQSKRR KSK
Length:2,063
Mass (Da):219,145
Last modified:October 17, 2006 - v3
Checksum:i73219502F5138427
GO

Sequence cautioni

The sequence AAF16403 differs from that shown. Reason: Frameshift at position 88.Curated
The sequence BAA11498 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027874512P → L. Corresponds to variant dbSNP:rs6060031Ensembl.1
Natural variantiVAR_027875955N → S5 PublicationsCorresponds to variant dbSNP:rs17092079Ensembl.1
Natural variantiVAR_0365511060P → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0365521191S → R in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0278761995I → V. Corresponds to variant dbSNP:rs6060022Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF177388 mRNA Translation: AAF13595.1
AF208227 mRNA Translation: AAF16403.1 Frameshift.
AF245115 mRNA Translation: AAF78480.1
AF128458 mRNA Translation: AAF37003.1
AF171667 mRNA Translation: AAF71829.1
D80003 mRNA Translation: BAA11498.2 Different initiation.
AL109824 Genomic DNA No translation available.
CH471077 Genomic DNA Translation: EAW76254.1
CH471077 Genomic DNA Translation: EAW76255.1
BC136272 mRNA Translation: AAI36273.1
CCDSiCCDS13241.1
RefSeqiNP_001229468.1, NM_001242539.2
NP_001305169.1, NM_001318240.1
NP_054790.2, NM_014071.4
UniGeneiHs.368971
Hs.736403

Genome annotation databases

EnsembliENST00000359003; ENSP00000351894; ENSG00000198646
ENST00000374796; ENSP00000363929; ENSG00000198646
GeneIDi23054
KEGGihsa:23054
UCSCiuc002xav.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNCOA6_HUMAN
AccessioniPrimary (citable) accession number: Q14686
Secondary accession number(s): A6NLF1
, B2RMN5, E1P5P7, Q9NTZ9, Q9UH74, Q9UK86
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 12, 2003
Last sequence update: October 17, 2006
Last modified: July 18, 2018
This is version 168 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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