NCOA3_RAT
ID NCOA3_RAT Reviewed; 1082 AA.
AC Q9EPU2;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Nuclear receptor coactivator 3;
DE Short=NCoA-3;
DE EC=2.3.1.48;
DE AltName: Full=Amplified in breast cancer-1 protein homolog;
DE Short=AIB-1;
DE Flags: Fragment;
GN Name=Ncoa3; Synonyms=Aib1;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=10906038; DOI=10.1095/biolreprod63.2.361;
RA Nephew K.P., Ray S., Hlaing M., Ahluwalia A., Wu S.D., Long X., Hyder S.M.,
RA Bigsby R.M.;
RT "Expression of estrogen receptor coactivators in the rat uterus.";
RL Biol. Reprod. 63:361-367(2000).
CC -!- FUNCTION: Nuclear receptor coactivator that directly binds nuclear
CC receptors and stimulates the transcriptional activities in a hormone-
CC dependent fashion. Plays a central role in creating a multisubunit
CC coactivator complex, probably via remodeling of chromatin. Involved in
CC the coactivation of different nuclear receptors, such as for steroids
CC (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin
CC D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase
CC activity. Also involved in the coactivation of the NF-kappa-B pathway
CC via its interaction with the NFKB1 subunit (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC -!- ACTIVITY REGULATION: Coactivator activity on nuclear receptors and NF-
CC kappa-B pathways is enhanced by various hormones, and the TNF cytokine,
CC respectively. TNF stimulation probably enhances phosphorylation, which
CC in turn activates coactivator function. In contrast, acetylation by
CC CREBBP apparently suppresses coactivation of target genes by disrupting
CC its association with nuclear receptors (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Present in a complex containing NCOA2, IKKA, IKKB, IKBKG and
CC the histone acetyltransferase protein CREBBP. Interacts with PCAF and
CC CARM1. Interacts with CASP8AP2 and NR3C1 (By similarity). Interacts
CC with ATAD2 and this interaction is enhanced by estradiol (By
CC similarity). Interacts with PSMB9. Binds to CSNK1D (By similarity).
CC Found in a complex containing NCOA3, AR and MAK. Interacts with DDX5.
CC Interacts with NPAS2 (By similarity). Interacts with NR4A3 (By
CC similarity). Interacts with ESRRB; mediates the interaction between
CC ESRRB and RNA polymerase II complexes and allows NCOA3 corecruitment to
CC ESRRB, KLF4, NANOG, and SOX2 enhancer regions to trigger ESRRB-
CC dependent gene activation involved in self-renewal and pluripotency (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:O09000}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Mainly cytoplasmic and weakly nuclear. Upon TNF activation and
CC subsequent phosphorylation, it translocates from the cytoplasm to the
CC nucleus (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed constitutively in uterus.
CC {ECO:0000269|PubMed:10906038}.
CC -!- DOMAIN: Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. Motifs 1 and
CC 2 are essential for the association with nuclear receptors, and
CC constitute the RID domain (Receptor-interacting domain) (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Acetylated by CREBBP. Acetylation occurs in the RID domain, and
CC disrupts the interaction with nuclear receptors and regulates its
CC function (By similarity). {ECO:0000250}.
CC -!- PTM: Methylated by CARM1. {ECO:0000250}.
CC -!- PTM: Phosphorylated by IKK complex. Regulated its function (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator
CC family. {ECO:0000305}.
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DR EMBL; AF322224; AAG42837.1; -; mRNA.
DR STRING; 10116.ENSRNOP00000059144; -.
DR iPTMnet; Q9EPU2; -.
DR PhosphoSitePlus; Q9EPU2; -.
DR PaxDb; Q9EPU2; -.
DR PRIDE; Q9EPU2; -.
DR UCSC; RGD:620109; rat.
DR RGD; 620109; Ncoa3.
DR eggNOG; KOG3561; Eukaryota.
DR InParanoid; Q9EPU2; -.
DR PhylomeDB; Q9EPU2; -.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0004402; F:histone acetyltransferase activity; ISO:RGD.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:RGD.
DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IMP:RGD.
DR GO; GO:0000993; F:RNA polymerase II complex binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0043697; P:cell dedifferentiation; ISS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; ISO:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central.
DR GO; GO:0048589; P:developmental growth; ISO:RGD.
DR GO; GO:0060713; P:labyrinthine layer morphogenesis; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0060744; P:mammary gland branching involved in thelarche; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; ISO:RGD.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IDA:RGD.
DR GO; GO:0033145; P:positive regulation of intracellular steroid hormone receptor signaling pathway; IMP:RGD.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:RGD.
DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:2000035; P:regulation of stem cell division; ISS:UniProtKB.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISO:RGD.
DR GO; GO:0072091; P:regulation of stem cell proliferation; ISO:RGD.
DR GO; GO:0060068; P:vagina development; ISO:RGD.
DR Gene3D; 6.10.140.410; -; 1.
DR InterPro; IPR010011; NCO_DUF1518.
DR InterPro; IPR032565; NCOA2/3_DUF4927.
DR InterPro; IPR028818; NCOA3.
DR InterPro; IPR009110; Nuc_rcpt_coact.
DR InterPro; IPR014920; Nuc_rcpt_coact_Ncoa-typ.
DR InterPro; IPR037077; Nuc_rcpt_coact_Ncoa_int_sf.
DR InterPro; IPR017426; Nuclear_rcpt_coactivator.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014935; SRC/p160_LXXLL.
DR PANTHER; PTHR10684; PTHR10684; 1.
DR PANTHER; PTHR10684:SF3; PTHR10684:SF3; 1.
DR Pfam; PF07469; DUF1518; 1.
DR Pfam; PF16279; DUF4927; 1.
DR Pfam; PF08815; Nuc_rec_co-act; 1.
DR Pfam; PF08832; SRC-1; 1.
DR SMART; SM01151; DUF1518; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR SUPFAM; SSF69125; SSF69125; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Acyltransferase; Cytoplasm; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN <1..1082
FT /note="Nuclear receptor coactivator 3"
FT /id="PRO_0000094408"
FT REGION 79..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 138..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 399..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 447..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..782
FT /note="Interaction with CREBBP"
FT /evidence="ECO:0000250"
FT REGION 786..962
FT /note="Acetyltransferase"
FT REGION 933..1004
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1016..1039
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1059..1082
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 385..389
FT /note="LXXLL motif 1"
FT MOTIF 437..441
FT /note="LXXLL motif 2"
FT MOTIF 723..727
FT /note="LXXLL motif 3"
FT COMPBIAS 138..193
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..377
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 460..479
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..520
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 528..544
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 593..617
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 989..1004
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O09000"
FT MOD_RES 316
FT /note="N6-acetyllysine; by CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 319
FT /note="N6-acetyllysine; by CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 320
FT /note="N6-acetyllysine; by CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 387
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O09000"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 860
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 866
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 877
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT MOD_RES 988
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Q9"
FT NON_TER 1
SQ SEQUENCE 1082 AA; 115134 MW; BA35D946CBC8C080 CRC64;
IIRRCIQRFF SLNDGQSWSQ KRHYQEAYIH GHAETPVYRF SLADGTIVSA QTKSKLFRNP
VTNDRHGFVS THFLQREQNG CRPNPILQDK GIRPPAAGCG MSLSPSQSVQ MLGSRTYGVA
DPSNTGQMAG ARYGASSSVA SLTPGQSLQS PSSYQSNSYG LNMSSPPHGS PGLGPNQQNI
MISPRNRGSP KMASHQFSPA AGVHSPMGSS GNTGSHSFSS SSLSALQAIS EGVGTSLLST
LSSPGPKLDN SPNMNINQPS KASSQDSKSP LGLYCEQNPV ESSVCPSNSR DPPVTKENKE
NSGEASETPR GPLESKGHKK LLQLLTCSSD DRGHSSLTNS PLDSNCKDSS ISVTSPSGVS
SSTSGAVSST SNMHGSLLQE KHRILHKLLQ NGNSPAEVAK ITAEATGKDT SSTASGGEGS
VXQEQLSPXK KENNALLRYL LDRDDPSDVL AKELQPQADG GDSKLSQCSC XTNPSSGQEK
DPKIKTEEVS GDLDNLDAIL GDLTSSDFYN SPTNGSHPGA KQQMFAGPSS LGLRSPQPVQ
SVRPPYNRAL SLDSPVSVGS VPPVKNVSAF PVLPKQPILA GNPRMMDSQE NYGANMGGPN
RNVPVNPTSS SGDWGLANSR ASRMEPLASS PLGRAGGDYS AALPRPALGS SGPTLPLRSN
RLPGARPTLM LQMRAGEVPM GMGVSPYSPA VPSNQPGSWP EGMLSMEQGP HGAQNRPLLR
NSLDELLGPP SNPEGQSDER ALLDQLHTLL SNTDATGLEE IDRALGIPEL VSQGQALESK
QDVFQGQEAA VMMDQKAALY GQTYPAQGPP LQGGFHLQGQ SPSLNSMMSQ ISQQGSFPLQ
GLHPRASMVR PRTNTPKQLR MQLQQRLQGQ QFLNQSRQAL EMKMESPTGA AVMRPMLQSQ
QAFFNAQMAA QQKRELMNHH LQQQRMAMMM SQPQPQAFSP PPNVTASPSM DGVLAGSAMP
QAPPQQFPYA TNYGMGQPPE PAFGRGSSPP SAMMSSRMGP SQNAMVQHPQ TAPMYQSSEM
KGWPSGNLAR NGSFPQQQFA PQANPAAYNM VHMNSSGSHL GQMTMTPMPM SGMPMGPDQK
YC
