NCOA2_DANRE
ID NCOA2_DANRE Reviewed; 1505 AA.
AC Q98TW1; B3DK53;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Nuclear receptor coactivator 2 {ECO:0000303|PubMed:17583703};
DE Short=NCoA-2 {ECO:0000250|UniProtKB:Q15596};
DE Short=NCoA2 {ECO:0000303|PubMed:17583703};
DE AltName: Full=Glucocorticoid receptor-interacting protein 1 {ECO:0000250|UniProtKB:Q61026};
DE AltName: Full=Steroid receptor coactivator 2 {ECO:0000303|PubMed:17997606};
DE AltName: Full=Transcriptional intermediary factor 2 {ECO:0000312|EMBL:AAI63724.1};
GN Name=ncoa2 {ECO:0000312|ZFIN:ZDB-GENE-010406-3};
GN Synonyms=grip1 {ECO:0000303|PubMed:17997606},
GN src2 {ECO:0000303|PubMed:17997606}, tif2 {ECO:0000312|EMBL:AAI63724.1,
GN ECO:0000312|ZFIN:ZDB-GENE-010406-3};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAK11608.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM E20A), PARTIAL NUCLEOTIDE
RP SEQUENCE [MRNA] (ISOFORM E20B), INTERACTION WITH THRB, TISSUE SPECIFICITY,
RP AND ALTERNATIVE SPLICING.
RC STRAIN=AB {ECO:0000269|PubMed:18248177};
RX PubMed=18248177; DOI=10.1089/zeb.2005.2.33;
RA Tan J.-H., Quek S.-I., Chan W.-K.;
RT "Cloning, genomic organization, and expression analysis of zebrafish
RT nuclear receptor coactivator, TIF2.";
RL Zebrafish 2:33-46(2005).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAI63724.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E20A).
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=17997606; DOI=10.1371/journal.pgen.0030188;
RA Bertrand S., Thisse B., Tavares R., Sachs L., Chaumot A., Bardet P.-L.,
RA Escriva H., Duffraisse M., Marchand O., Safi R., Thisse C., Laudet V.;
RT "Unexpected novel relational links uncovered by extensive developmental
RT profiling of nuclear receptor expression.";
RL PLoS Genet. 3:E188-E188(2007).
RN [4] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18295965; DOI=10.1016/j.exphem.2007.12.014;
RA Zhuravleva J., Solary E., Chluba J., Bastie J.-N., Delva L.;
RT "A role for the transcription intermediary factor 2 in zebrafish
RT myelopoiesis.";
RL Exp. Hematol. 36:559-567(2008).
RN [5] {ECO:0000305}
RP INTERACTION WITH THRAA.
RX PubMed=17583703; DOI=10.1016/j.ygcen.2007.04.012;
RA Takayama S., Hostick U., Haendel M., Eisen J., Darimont B.;
RT "An F-domain introduced by alternative splicing regulates activity of the
RT zebrafish thyroid hormone receptor alpha.";
RL Gen. Comp. Endocrinol. 155:176-189(2008).
RN [6] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo {ECO:0000269|PubMed:18307296};
RX PubMed=18307296; DOI=10.1021/pr700667w;
RA Lemeer S., Pinkse M.W.H., Mohammed S., van Breukelen B., den Hertog J.,
RA Slijper M., Heck A.J.R.;
RT "Online automated in vivo zebrafish phosphoproteomics: from large-scale
RT analysis down to a single embryo.";
RL J. Proteome Res. 7:1555-1564(2008).
CC -!- FUNCTION: Transcriptional coactivator for steroid receptors and nuclear
CC receptors. Coactivator of the steroid binding domain (AF-2) but not of
CC the modulating N-terminal domain (AF-1) (By similarity). Has a role in
CC primitive myelopoiesis in the differentiation of granulocytes and
CC macrophages. May play a role in the positive regulation of the
CC circadian clock (By similarity). {ECO:0000250|UniProtKB:Q15596,
CC ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:18295965}.
CC -!- SUBUNIT: Interacts with the thyroid hormone receptors thraa and thrb
CC (via the ligand-binding domain). {ECO:0000269|PubMed:17583703,
CC ECO:0000269|PubMed:18248177}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15596}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=E20a {ECO:0000269|PubMed:18248177};
CC IsoId=Q98TW1-1; Sequence=Displayed;
CC Name=E20b {ECO:0000269|PubMed:18248177};
CC IsoId=Q98TW1-2; Sequence=VSP_052992;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in the embryo and in many
CC adult tissues including the brain, gills, liver, swim bladder and skin.
CC Shows highest expression in the ovary and testis, and lower expression
CC in the intestine, eye and skin. Only isoform E20b is expressed in the
CC muscle and heart. {ECO:0000269|PubMed:17997606,
CC ECO:0000269|PubMed:18248177, ECO:0000269|PubMed:18295965}.
CC -!- DOMAIN: Contains 3 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs
CC are essential for the association with nuclear receptors and are, at
CC least in part, functionally redundant (By similarity).
CC {ECO:0000250|UniProtKB:Q15596}.
CC -!- DOMAIN: The LLXXLXXXL motif is involved in transcriptional coactivation
CC and CREBBP/CBP binding. {ECO:0000250|UniProtKB:Q15596}.
CC -!- DOMAIN: Contains 2 C-terminal transcription activation domains (AD1 and
CC AD2) that can function independently. {ECO:0000250|UniProtKB:Q15596}.
CC -!- SIMILARITY: Belongs to the SRC/p160 nuclear receptor coactivator
CC family. {ECO:0000255}.
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DR EMBL; AF323989; AAK11608.1; -; mRNA.
DR EMBL; AY210802; AAP69780.1; -; Genomic_DNA.
DR EMBL; BC163724; AAI63724.1; -; mRNA.
DR RefSeq; NP_571852.1; NM_131777.1. [Q98TW1-1]
DR AlphaFoldDB; Q98TW1; -.
DR STRING; 7955.ENSDARP00000107210; -.
DR iPTMnet; Q98TW1; -.
DR PaxDb; Q98TW1; -.
DR PRIDE; Q98TW1; -.
DR GeneID; 81884; -.
DR KEGG; dre:81884; -.
DR CTD; 10499; -.
DR ZFIN; ZDB-GENE-010406-3; ncoa2.
DR eggNOG; KOG3561; Eukaryota.
DR InParanoid; Q98TW1; -.
DR OrthoDB; 59971at2759; -.
DR PhylomeDB; Q98TW1; -.
DR Reactome; R-DRE-159418; Recycling of bile acids and salts.
DR Reactome; R-DRE-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-DRE-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-DRE-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-DRE-211976; Endogenous sterols.
DR Reactome; R-DRE-3214847; HATs acetylate histones.
DR Reactome; R-DRE-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-DRE-9018519; Estrogen-dependent gene expression.
DR Reactome; R-DRE-9707564; Cytoprotection by HMOX1.
DR PRO; PR:Q98TW1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IBA:GO_Central.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISS:UniProtKB.
DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central.
DR GO; GO:0043009; P:chordate embryonic development; IMP:ZFIN.
DR GO; GO:0030851; P:granulocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060215; P:primitive hemopoiesis; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 4.10.280.10; -; 1.
DR Gene3D; 6.10.140.410; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR010011; NCO_DUF1518.
DR InterPro; IPR028822; NCOA2.
DR InterPro; IPR032565; NCOA2/3_DUF4927.
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; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR014935; SRC/p160_LXXLL.
DR PANTHER; PTHR10684; PTHR10684; 1.
DR PANTHER; PTHR10684:SF2; PTHR10684:SF2; 1.
DR Pfam; PF07469; DUF1518; 2.
DR Pfam; PF16279; DUF4927; 1.
DR Pfam; PF08815; Nuc_rec_co-act; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08832; SRC-1; 1.
DR PIRSF; PIRSF038181; Nuclear_receptor_coactivator; 1.
DR SMART; SM01151; DUF1518; 2.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00091; PAS; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR SUPFAM; SSF69125; SSF69125; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Biological rhythms; Developmental protein;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT CHAIN 1..1505
FT /note="Nuclear receptor coactivator 2"
FT /id="PRO_0000356221"
FT DOMAIN 27..84
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 113..183
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 578..676
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 835..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 939..962
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1246..1265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1277..1334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1372..1436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1475..1505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 630..634
FT /note="LXXLL motif 1"
FT /evidence="ECO:0000255"
FT MOTIF 686..690
FT /note="LXXLL motif 2"
FT /evidence="ECO:0000255"
FT MOTIF 742..746
FT /note="LXXLL motif 3"
FT /evidence="ECO:0000255"
FT MOTIF 1069..1077
FT /note="LLXXLXXXL motif"
FT /evidence="ECO:0000255"
FT COMPBIAS 12..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..427
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..643
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 835..860
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1292..1306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1308..1327
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1372..1389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1399..1436
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1475..1495
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18307296"
FT VAR_SEQ 1309..1378
FT /note="Missing (in isoform E20b)"
FT /evidence="ECO:0000303|PubMed:18248177"
FT /id="VSP_052992"
FT CONFLICT 44
FT /note="S -> N (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="S -> G (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
FT CONFLICT 576
FT /note="P -> T (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="T -> N (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
FT CONFLICT 978
FT /note="G -> R (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
FT CONFLICT 1298
FT /note="L -> P (in Ref. 2; AAI63724)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1505 AA; 161793 MW; 88BD0A8435B14497 CRC64;
MSAVGENSSD PARSEAQKRK EGPSDLLGPS PKRSTEKRNR EHESKYIEEL AELIFANFND
IDNFNVKPDK CAILKETVKQ IRQIKEQEKA AAANEDEVQK ADVSSTGQSV IDKDALGPMM
LEALDGFFFV VNMEGNIVFV SENVTQYLRY NQEELMNTSV YSILHVGDHA EFIKNLLPKS
HVNGVPWSSE NPRRNSHTFN CRMLVNPHSE AEETQDHEAQ QKYETMQCFA VSEPKSIKEE
GEDFQSCLIC VARRVPMKER PMLPTQESFT TRQDLQGKIT SLDTSLLRAS MKPGWEDLVR
RCIQRFHLQN DGDISFAKRH QQEVIRHGQA FSPIYRFSLS DGTIVSAHTK SKLVRSSSTN
EPQLYMSLHI LQREQPVCGM ASDLGNAQTM GKPMNPMSSP NTAGSSCTPQ GQDATISSNT
STFPSPGAQK EPGAMHRFGC PGTMSHSATM QAATPQGSGY PLKLSSPSQG SPGMLSPRHR
ASPGVAGSPR LPPPQFSPAG SLHSPASMCT SSTGGNGGAG ANHGYTSSSL NALQALSECH
GVSHGQSLGS PDRKLGSPAA HSVAVSHHLI NKMSVPESFG EQNQSEQGTP GQDEGIDLPR
DEKGNLGQFG NLDGSDPQSR LRDNKSHTKL LQLLTTKTEP IESTSPPPMA GGEPGCKDGG
AGNGGMGSQG GNGSHATSLK EKHKILHRLL QNSSSPVDLA KLTAEATGKE LCQDSAGGTA
GVPELAIKQE PVSPKKKDNA LLRYLLDKDD NVLKGKGIKM EPGEIKEEGG KMTGIKTEKT
DGGYDRVEPS SELDDILDDL QNSQPGLFTD SRPVSLPSAV DKQSIINDIL QMTGESGANM
SPQQQRALQT AVSQQNFPAP RPGQPGRAPP VRSVSLDMNM PPKGAQGQYP MMRNNNPYSI
MQQQGMMGNH AVMPNQPNMV NAGVMGNNGP RVGMQQDGWG AQGTVGSAAS PATAAPAGQH
SLPQGALHSR MVPNPATGMP MRPNSQPGPR PMLQPQMMAN AQSNMDMGMA GHQFPQQQAP
PNQTAPWPDS VMPIEPVPFG NQSSSMYGGS QEDVLCPPAS EGPADEGALL SQLYSALKDF
DGLEEIDRAL GIPALVGQAQ PVEQDQFPGQ DPSMMMDQKP PMYGQQQYAS SPANMQQAGY
TPMQDATFHG LQGQMGQRPG YPMLRMQARP GLRPGGVVPN QPNTLRLQLQ HRLQAQQNRQ
PMMNQMGGVS NMNLPLRPNV PNQGTINAQM LAQRQRELLS NHLRQRQLDQ QRQQQQQQQQ
QRSLAMRAQG LTMPPNMAAA AAGMPGAMSN PRIPQANLQQ FPYPPNYGTG LASPPPSTSP
FSPGSPNLPA PQLLSHSAMH GSQMSLANQG MLGSLSGQFG AVMSPQMQHS AFQFPSSGMS
QQSDGGFGGA ATPQSPLMSP RMGHAQSPMM QQAQGNSSFQ SSPDMNGWPQ GNINTNSMFT
QQSPPQFSQQ ANNNMYNGNG MNLNVSMAAN SSNMGQMGNQ MSMSSMNSGP GSGMANMGPE
QQKYC
