NHR49_CAEEL
ID NHR49_CAEEL Reviewed; 501 AA.
AC O45666; Q8I4H3; Q8I4H4; Q8WQE4; Q9BJL0; Q9GTG4; Q9GTG5; Q9GTG6; Q9GTG7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Nuclear hormone receptor family member nhr-49;
GN Name=nhr-49; ORFNames=K10C3.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-501 (ISOFORMS A; C AND D).
RX PubMed=15983867; DOI=10.1007/s00239-004-0175-8;
RA Robinson-Rechavi M., Maina C.V., Gissendanner C.R., Laudet V., Sluder A.;
RT "Explosive lineage-specific expansion of the orphan nuclear receptor HNF4
RT in nematodes.";
RL J. Mol. Evol. 60:577-586(2005).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15719061; DOI=10.1371/journal.pbio.0030053;
RA Van Gilst M.R., Hadjivassiliou H., Jolly A., Yamamoto K.R.;
RT "Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid
RT composition in C. elegans.";
RL PLoS Biol. 3:e53-e53(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25981666; DOI=10.1016/j.cell.2015.04.026;
RA Ma D.K., Li Z., Lu A.Y., Sun F., Chen S., Rothe M., Menzel R., Sun F.,
RA Horvitz H.R.;
RT "Acyl-CoA dehydrogenase drives heat adaptation by sequestering fatty
RT acids.";
RL Cell 161:1152-1163(2015).
RN [5]
RP 9AATAD MOTIF.
RX PubMed=30468856; DOI=10.1016/j.jsbmb.2018.11.008;
RA Piskacek M., Havelka M., Jendruchova K., Knight A.;
RT "Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA
RT activation pathways.";
RL J. Steroid Biochem. Mol. Biol. 187:118-123(2019).
CC -!- FUNCTION: Orphan nuclear receptor (PubMed:25981666). Regulates
CC expression of genes involved in fat metabolism and in maintaining
CC homeostasis of fatty acid saturation, such as lipid desaturase fat-7,
CC and acyl-CoA synthetase acs-2 (PubMed:25981666, PubMed:15719061). May
CC form part of a negative feedback loop with fat-7 to limit beta-
CC oxidation, in which it stimulates expression of fat-7 and acs-2, and in
CC turn fat-7 indirectly inhibits acs-2 and other genes also involved in
CC beta-oxidation (PubMed:15719061). {ECO:0000269|PubMed:15719061,
CC ECO:0000269|PubMed:25981666}.
CC -!- INTERACTION:
CC O45666; Q21955: mdt-15; NbExp=4; IntAct=EBI-318820, EBI-318240;
CC O45666; Q9N4Q7: nhr-13; NbExp=7; IntAct=EBI-318820, EBI-317894;
CC O45666; O16346: nhr-181; NbExp=5; IntAct=EBI-318820, EBI-2417265;
CC O45666; Q09528: nhr-19; NbExp=4; IntAct=EBI-318820, EBI-318797;
CC O45666; Q09565: nhr-20; NbExp=3; IntAct=EBI-318820, EBI-314918;
CC O45666; Q9NAJ3: nhr-234; NbExp=4; IntAct=EBI-318820, EBI-325014;
CC O45666; Q65CM0: nhr-76; NbExp=4; IntAct=EBI-318820, EBI-324921;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=c;
CC IsoId=O45666-1; Sequence=Displayed;
CC Name=a;
CC IsoId=O45666-2; Sequence=VSP_015670;
CC Name=b;
CC IsoId=O45666-3; Sequence=VSP_015670, VSP_015672;
CC Name=d;
CC IsoId=O45666-4; Sequence=VSP_015671;
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000305|PubMed:30468856}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown eliminates the effect of
CC C11 or C12 chain fatty acids in activating fat-7 expression and blocks
CC overexpression of fat-7 in acdh-11 mutants (PubMed:25981666). Increased
CC ratio of stearic acid to oleic acid (C18:0/C18:1n9) (PubMed:15719061).
CC Drastically reduced life span (PubMed:15719061).
CC {ECO:0000269|PubMed:15719061, ECO:0000269|PubMed:25981666}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family.
CC {ECO:0000305}.
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DR EMBL; BX284601; CAB05772.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD21653.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD57702.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD57703.1; -; Genomic_DNA.
DR EMBL; AF273792; AAG15140.1; -; mRNA.
DR EMBL; AF273793; AAG15141.1; -; mRNA.
DR EMBL; AF273794; AAG15142.1; -; mRNA.
DR EMBL; AF273795; AAG15143.1; -; mRNA.
DR EMBL; AF332206; AAK17977.1; -; mRNA.
DR PIR; T23554; T23554.
DR RefSeq; NP_492612.1; NM_060211.4.
DR RefSeq; NP_492613.1; NM_060212.4. [O45666-3]
DR RefSeq; NP_871798.1; NM_181998.4.
DR RefSeq; NP_871799.1; NM_181999.4. [O45666-4]
DR AlphaFoldDB; O45666; -.
DR SMR; O45666; -.
DR BioGRID; 38262; 66.
DR DIP; DIP-24928N; -.
DR IntAct; O45666; 54.
DR STRING; 6239.K10C3.6c.1; -.
DR iPTMnet; O45666; -.
DR EPD; O45666; -.
DR PaxDb; O45666; -.
DR PeptideAtlas; O45666; -.
DR EnsemblMetazoa; K10C3.6a.1; K10C3.6a.1; WBGene00003639. [O45666-2]
DR EnsemblMetazoa; K10C3.6a.2; K10C3.6a.2; WBGene00003639. [O45666-2]
DR EnsemblMetazoa; K10C3.6b.1; K10C3.6b.1; WBGene00003639. [O45666-3]
DR EnsemblMetazoa; K10C3.6b.2; K10C3.6b.2; WBGene00003639. [O45666-3]
DR EnsemblMetazoa; K10C3.6c.1; K10C3.6c.1; WBGene00003639. [O45666-1]
DR EnsemblMetazoa; K10C3.6d.1; K10C3.6d.1; WBGene00003639. [O45666-4]
DR GeneID; 172839; -.
DR UCSC; K10C3.6c.1; c. elegans. [O45666-1]
DR CTD; 172839; -.
DR WormBase; K10C3.6a; CE12084; WBGene00003639; nhr-49. [O45666-2]
DR WormBase; K10C3.6b; CE28943; WBGene00003639; nhr-49. [O45666-3]
DR WormBase; K10C3.6c; CE32693; WBGene00003639; nhr-49. [O45666-1]
DR WormBase; K10C3.6d; CE32694; WBGene00003639; nhr-49. [O45666-4]
DR eggNOG; KOG4215; Eukaryota.
DR InParanoid; O45666; -.
DR OMA; NQEMTTH; -.
DR OrthoDB; 622732at2759; -.
DR PhylomeDB; O45666; -.
DR SignaLink; O45666; -.
DR PRO; PR:O45666; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003639; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; O45666; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IMP:WormBase.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:WormBase.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..501
FT /note="Nuclear hormone receptor family member nhr-49"
FT /id="PRO_0000053785"
FT DOMAIN 157..422
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 8..83
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 11..31
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 47..71
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 109..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 413..421
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:30468856"
FT COMPBIAS 133..152
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform a and isoform b)"
FT /evidence="ECO:0000303|PubMed:15983867"
FT /id="VSP_015670"
FT VAR_SEQ 1..24
FT /note="MDYFLDASKHIQLNQIDEESSDDF -> MKNLQMIVI (in isoform
FT d)"
FT /evidence="ECO:0000303|PubMed:15983867"
FT /id="VSP_015671"
FT VAR_SEQ 222
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_015672"
FT CONFLICT 412..413
FT /note="DS -> PP (in Ref. 2; AAG15142)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 501 AA; 55388 MW; BC69815507B2C811 CRC64;
MDYFLDASKH IQLNQIDEES SDDFMDLVDP LAEPCAVCGD KSTGTHYGVI SCNGCKGFFR
RTVLRDQKFT CRFNKRCVID KNFRCACRYC RFQKCVQVGM KREAIQFERD PVGSPTSGAS
LNGTPFKKDR SPGYENGNSN GVGSNGMGQE NMRTVPQSSS VIDALMEMEA RVNQEMCNRY
RRSQIFANGS GGSNGNDTDI QQGSDSGASA FAPPNRPCTT EVDLNEISRT TLLLMVEWAK
TINPFMDLSM EDKIILLKNY APQHLILMPA FRSPDTTRVC LFNNTYMTRD NNTDLNGFAA
FKTSNITPRV LDEIVWPMRQ LQMREQEFVC LKALAFLHPE AKGLSNSSQI MIRDARNRVL
KALYAFILDQ MPDDAPTRYG NILLLAPALK ALTQLLIENM TLTKFFGLAE VDSLLSEFIL
DDINDHSTAP VSLQQHLSSP TTLPTNGVSP LNPAGSVGSV SSVSGITPTG MLSATLAAPL
AIHPLQSQDS ILNSEQNNHM L
