NCOA6_RAT
ID NCOA6_RAT Reviewed; 418 AA.
AC Q9JLI4; Q9JIH6;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Nuclear receptor coactivator 6;
DE AltName: Full=Activating signal cointegrator 2;
DE Short=ASC-2;
DE AltName: Full=Amplified in breast cancer protein 3;
DE AltName: Full=Cancer-amplified transcriptional coactivator ASC-2;
DE AltName: Full=Nuclear receptor coactivator RAP250;
DE Short=NRC;
DE AltName: Full=Nuclear receptor-activating protein, 250 kDa;
DE AltName: Full=Peroxisome proliferator-activated receptor-interacting protein;
DE Short=PPAR-interacting protein;
DE Short=PRIP;
DE AltName: Full=Thyroid hormone receptor-binding protein;
DE Flags: Fragment;
GN Name=Ncoa6; Synonyms=Aib3, Rap250, Trbp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-285, AND INTERACTION WITH THRB.
RC TISSUE=Pituitary;
RX PubMed=10823961; DOI=10.1073/pnas.97.11.6212;
RA Ko L., Cardona G.R., Chin W.W.;
RT "Thyroid hormone receptor-binding protein, an LXXLL motif-containing
RT protein, functions as a general coactivator.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6212-6217(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 135-418, INTERACTION WITH THRA; THRB; RAR;
RP RXR; ESR; VDR; NR3C1, AND MUTAGENESIS OF 174-LEU--LEU-178.
RC STRAIN=Sprague-Dawley; TISSUE=Pituitary;
RX PubMed=10866662; DOI=10.1128/mcb.20.14.5048-5063.2000;
RA Mahajan M.A., Samuels H.H.;
RT "A new family of nuclear receptor coregulators that integrates nuclear
RT receptor signaling through CBP.";
RL Mol. Cell. Biol. 20:5048-5063(2000).
CC -!- FUNCTION: Nuclear receptor coactivator that directly binds nuclear
CC receptors and stimulates the transcriptional activities in a hormone-
CC dependent fashion. Coactivate expression in an agonist- and AF2-
CC dependent manner. May coactivate expression via a remodeling of
CC chromatin and its interaction with histone acetyltransferase proteins.
CC Involved in the coactivation of different nuclear receptors, such as
CC for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone
CC (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as
CC a general coactivator, rather than just a nuclear receptor coactivator.
CC May also be involved in the coactivation of the NF-kappa-B pathway (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer and homodimer. Interacts in vitro with the basal
CC transcription factors GTF2A and TBP, suggesting an autonomous
CC transactivation function. Interacts with NCOA1, CRSP3, RBM14, the
CC histone acetyltransferase proteins EP300 and CREBBP, and with
CC methyltransferase proteins NCOA6IP and PRMT2 (By similarity). Component
CC of the MLL2/3 complex (also named ASCOM complex), at least composed of
CC KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A,
CC PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (By similarity).
CC Interacts with ZNF335; may enhance ligand-dependent transcriptional
CC activation by nuclear hormone receptors (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9JLI4; P03372: ESR1; Xeno; NbExp=2; IntAct=EBI-286271, EBI-78473;
CC Q9JLI4; P10912: GHR; Xeno; NbExp=2; IntAct=EBI-286271, EBI-286316;
CC Q9JLI4; P19793: RXRA; Xeno; NbExp=2; IntAct=EBI-286271, EBI-78598;
CC Q9JLI4; P10827: THRA; Xeno; NbExp=2; IntAct=EBI-286271, EBI-286285;
CC Q9JLI4; P11473: VDR; Xeno; NbExp=2; IntAct=EBI-286271, EBI-286357;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which is
CC essential for the association with nuclear receptors.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF228043; AAF76422.1; -; mRNA.
DR EMBL; AF176351; AAF71830.1; -; mRNA.
DR AlphaFoldDB; Q9JLI4; -.
DR SMR; Q9JLI4; -.
DR IntAct; Q9JLI4; 9.
DR STRING; 10116.ENSRNOP00000024714; -.
DR PhosphoSitePlus; Q9JLI4; -.
DR PaxDb; Q9JLI4; -.
DR UCSC; RGD:620111; rat.
DR RGD; 620111; Ncoa6.
DR eggNOG; ENOG502QQMS; Eukaryota.
DR InParanoid; Q9JLI4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0035097; C:histone methyltransferase complex; ISO:RGD.
DR GO; GO:0044666; C:MLL3/4 complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:RGD.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:RGD.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IPI:RGD.
DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IPI:RGD.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IPI:RGD.
DR GO; GO:0042809; F:nuclear vitamin D receptor binding; IPI:RGD.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IMP:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0006352; P:DNA-templated transcription, initiation; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; ISO:RGD.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0030099; P:myeloid cell differentiation; ISS:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0002793; P:positive regulation of peptide secretion; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR InterPro; IPR026638; NCOA6.
DR PANTHER; PTHR15690; PTHR15690; 1.
PE 1: Evidence at protein level;
KW Activator; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN <1..418
FT /note="Nuclear receptor coactivator 6"
FT /id="PRO_0000094415"
FT REGION <1..418
FT /note="NCOA1-binding region"
FT /evidence="ECO:0000250"
FT REGION <1..352
FT /note="CREBBP-binding region"
FT /evidence="ECO:0000250"
FT REGION <1..215
FT /note="TBP/GTF2A-binding region"
FT /evidence="ECO:0000250"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 60..214
FT /note="NCOA6IP-binding region"
FT /evidence="ECO:0000250"
FT REGION 77..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 186..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 174..178
FT /note="LXXLL motif"
FT COMPBIAS 278..312
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 396..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14686"
FT MOD_RES 342
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JL19"
FT MOD_RES 353
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JL19"
FT MOD_RES 391
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JL19"
FT MUTAGEN 174..178
FT /note="LVNLL->AVNAA: Abolishes interaction with nuclear
FT receptors."
FT /evidence="ECO:0000269|PubMed:10866662"
FT NON_TER 1
SQ SEQUENCE 418 AA; 45574 MW; A90D7C4111C67CAE CRC64;
EQIMTNQMQG NKAQFNSQNQ SNVMPGPAQI MRGPTPNMQG NMVQFTGQMS GQMLPQQGPV
SNSPSQVMGI QGQVLRPPGP SPHMAQQHTD PATTANNDVN LSQMMPDVSM QQTSMVPPHV
QSMQGNSASG SHFSGHGVSF NAPFGGAPNG TQMSCGQNPG FPVNKDVTLT SPLLVNLLQS
DISAGHFGVN NKQNNTNANK QKKKKPPRKK KNCHQDLNTP DSRPAGLEEV DQQSLPGEQG
INLDNTGPKL PDFSNRPPGY PTQPVEQRPL QQMPPQLMQH VAPPPQPPQQ QPQPQLPQQQ
PQPQPPPPSQ PQSQQQQQQQ QQQQQQQMMM MLMMQQDPKS IRLPVSQNVH PPRGPLNPDS
QRVPMQQSGN VPVMVSLQGP ASVPPSPDKQ RMPMPVNTPL GSNSRKMVYQ ESPQNSSS
