VDRA_DANRE
ID VDRA_DANRE Reviewed; 453 AA.
AC Q9PTN2; B3DFZ0;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Vitamin D3 receptor A;
DE Short=VDR-A;
DE AltName: Full=1,25-dihydroxyvitamin D3 receptor A;
DE AltName: Full=Nuclear receptor subfamily 1 group I member 1-A;
GN Name=vdra; Synonyms=nr1i1a, vdr;
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kouzmenko A.P.;
RT "Danio rerio vitamin D receptor.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
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]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 156-453 IN COMPLEX WITH VITAMIN
RP D3 ANALOG AND NCOA1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17346665; DOI=10.1016/j.abb.2007.01.031;
RA Rochel N., Hourai S., Perez-Garcia X., Rumbo A., Mourino A., Moras D.;
RT "Crystal structure of the vitamin D nuclear receptor ligand binding domain
RT in complex with a locked side chain analog of calcitriol.";
RL Arch. Biochem. Biophys. 460:172-176(2007).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 156-453 IN COMPLEXES WITH VITAMIN
RP D3; LIGAND ANALOG AND NCOA1, FUNCTION, INTERACTION WITH NCOA1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17218092; DOI=10.1016/j.jsbmb.2006.12.003;
RA Ciesielski F., Rochel N., Moras D.;
RT "Adaptability of the vitamin D nuclear receptor to the synthetic ligand
RT Gemini: remodelling the LBP with one side chain rotation.";
RL J. Steroid Biochem. Mol. Biol. 103:235-242(2007).
CC -!- FUNCTION: Nuclear receptor for calcitriol, the active form of vitamin
CC D3 which mediates the action of this vitamin on cells. Enters the
CC nucleus upon vitamin D3 binding where it forms heterodimers with the
CC retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific
CC response elements on DNA and activate the transcription of vitamin D3-
CC responsive target genes. Recruited to promoters via its interaction
CC with BAZ1B/WSTF which mediates the interaction with acetylated
CC histones, an essential step for VDR-promoter association. Plays a
CC central role in calcium homeostasis. {ECO:0000250|UniProtKB:P11473}.
CC -!- SUBUNIT: Homodimer in the absence of bound vitamin D3. Heterodimer with
CC RXRA after vitamin D3 binding (By similarity). Interacts with ncoa1 and
CC possibly other coactivators, leading to a strong increase of
CC transcription of target genes (PubMed:17218092, PubMed:17346665).
CC {ECO:0000250|UniProtKB:P11473, ECO:0000269|PubMed:17218092,
CC ECO:0000269|PubMed:17346665}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11473,
CC ECO:0000255|PROSITE-ProRule:PRU00407}. Cytoplasm
CC {ECO:0000250|UniProtKB:P11473}. Note=Localizes mainly to the nucleus.
CC Translocated into the nucleus via both ligand-dependent and ligand-
CC independent pathways; ligand-independent nuclear translocation is
CC mediated by IPO4. {ECO:0000250|UniProtKB:P11473}.
CC -!- TISSUE SPECIFICITY: Detected in embryo 24 to 48 hours after
CC fertilization and in gastrula. {ECO:0000269|PubMed:17997606}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC {ECO:0000250|UniProtKB:P11473}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P11473}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF164512; AAF21427.1; -; mRNA.
DR EMBL; BC162213; AAI62213.1; -; mRNA.
DR EMBL; BC162226; AAI62226.1; -; mRNA.
DR RefSeq; NP_570994.1; NM_130919.1.
DR PDB; 2HBH; X-ray; 2.65 A; A=156-453.
DR PDB; 2HC4; X-ray; 2.20 A; A=156-453.
DR PDB; 2HCD; X-ray; 2.60 A; A=156-453.
DR PDB; 3DR1; X-ray; 2.70 A; A=156-453.
DR PDB; 3O1D; X-ray; 2.40 A; A=156-453.
DR PDB; 3O1E; X-ray; 2.50 A; A=156-453.
DR PDB; 4FHH; X-ray; 2.33 A; A=156-453.
DR PDB; 4FHI; X-ray; 2.40 A; A=156-453.
DR PDB; 4G1D; X-ray; 2.90 A; A=156-453.
DR PDB; 4G1Y; X-ray; 2.85 A; A=156-453.
DR PDB; 4G1Z; X-ray; 2.50 A; A=156-453.
DR PDB; 4G20; X-ray; 2.90 A; A=156-453.
DR PDB; 4G21; X-ray; 2.90 A; A=156-453.
DR PDB; 4G2H; X-ray; 2.50 A; A=156-453.
DR PDB; 4IA1; X-ray; 2.44 A; A=156-453.
DR PDB; 4IA2; X-ray; 2.95 A; A=156-453.
DR PDB; 4IA3; X-ray; 2.70 A; A=156-453.
DR PDB; 4IA7; X-ray; 2.70 A; A=156-453.
DR PDB; 4Q0A; X-ray; 1.90 A; C=156-453.
DR PDB; 4RUJ; X-ray; 2.35 A; A=156-453.
DR PDB; 4RUO; X-ray; 2.81 A; X=156-453.
DR PDB; 4RUP; X-ray; 2.75 A; A=156-453.
DR PDB; 5E7V; X-ray; 2.40 A; A=156-453.
DR PDB; 5LGA; X-ray; 2.50 A; A=156-453.
DR PDB; 5MX7; X-ray; 1.98 A; A1=156-453.
DR PDB; 5NKY; X-ray; 2.10 A; A=156-453.
DR PDB; 5NMA; X-ray; 2.80 A; A=156-453.
DR PDB; 5NMB; X-ray; 2.50 A; A2=156-453.
DR PDB; 5OW7; X-ray; 2.10 A; A=156-453.
DR PDB; 5OW9; X-ray; 2.40 A; A=156-453.
DR PDB; 5OWD; X-ray; 2.15 A; A=156-453.
DR PDB; 6FO7; X-ray; 2.59 A; A=156-453.
DR PDB; 6FO8; X-ray; 2.30 A; 1=156-453.
DR PDB; 6FO9; X-ray; 2.70 A; A=156-453.
DR PDB; 6FOB; X-ray; 2.75 A; A=156-453.
DR PDB; 6FOD; X-ray; 2.50 A; A=156-453.
DR PDB; 6T2M; X-ray; 3.00 A; A=156-453.
DR PDB; 6XZH; X-ray; 2.37 A; A=156-453.
DR PDB; 6XZI; X-ray; 2.10 A; A=156-453.
DR PDB; 6XZJ; X-ray; 2.10 A; A=156-453.
DR PDB; 6XZK; X-ray; 2.00 A; A=156-453.
DR PDB; 6XZV; X-ray; 2.30 A; A=156-453.
DR PDB; 7B39; X-ray; 2.13 A; A=156-453.
DR PDB; 7BNS; X-ray; 2.70 A; A2=156-453.
DR PDB; 7BNU; X-ray; 2.40 A; A2=156-453.
DR PDB; 7BO6; X-ray; 2.86 A; A=156-453.
DR PDB; 7OXZ; X-ray; 2.20 A; A=156-453.
DR PDB; 7OY4; X-ray; 2.00 A; A=156-453.
DR PDBsum; 2HBH; -.
DR PDBsum; 2HC4; -.
DR PDBsum; 2HCD; -.
DR PDBsum; 3DR1; -.
DR PDBsum; 3O1D; -.
DR PDBsum; 3O1E; -.
DR PDBsum; 4FHH; -.
DR PDBsum; 4FHI; -.
DR PDBsum; 4G1D; -.
DR PDBsum; 4G1Y; -.
DR PDBsum; 4G1Z; -.
DR PDBsum; 4G20; -.
DR PDBsum; 4G21; -.
DR PDBsum; 4G2H; -.
DR PDBsum; 4IA1; -.
DR PDBsum; 4IA2; -.
DR PDBsum; 4IA3; -.
DR PDBsum; 4IA7; -.
DR PDBsum; 4Q0A; -.
DR PDBsum; 4RUJ; -.
DR PDBsum; 4RUO; -.
DR PDBsum; 4RUP; -.
DR PDBsum; 5E7V; -.
DR PDBsum; 5LGA; -.
DR PDBsum; 5MX7; -.
DR PDBsum; 5NKY; -.
DR PDBsum; 5NMA; -.
DR PDBsum; 5NMB; -.
DR PDBsum; 5OW7; -.
DR PDBsum; 5OW9; -.
DR PDBsum; 5OWD; -.
DR PDBsum; 6FO7; -.
DR PDBsum; 6FO8; -.
DR PDBsum; 6FO9; -.
DR PDBsum; 6FOB; -.
DR PDBsum; 6FOD; -.
DR PDBsum; 6T2M; -.
DR PDBsum; 6XZH; -.
DR PDBsum; 6XZI; -.
DR PDBsum; 6XZJ; -.
DR PDBsum; 6XZK; -.
DR PDBsum; 6XZV; -.
DR PDBsum; 7B39; -.
DR PDBsum; 7BNS; -.
DR PDBsum; 7BNU; -.
DR PDBsum; 7BO6; -.
DR PDBsum; 7OXZ; -.
DR PDBsum; 7OY4; -.
DR AlphaFoldDB; Q9PTN2; -.
DR SMR; Q9PTN2; -.
DR BioGRID; 78317; 2.
DR STRING; 7955.ENSDARP00000063213; -.
DR BindingDB; Q9PTN2; -.
DR ChEMBL; CHEMBL3217399; -.
DR DrugCentral; Q9PTN2; -.
DR GeneID; 30076; -.
DR KEGG; dre:30076; -.
DR CTD; 30076; -.
DR ZFIN; ZDB-GENE-000210-31; vdra.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q9PTN2; -.
DR OrthoDB; 297114at2759; -.
DR PhylomeDB; Q9PTN2; -.
DR EvolutionaryTrace; Q9PTN2; -.
DR PRO; PR:Q9PTN2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:1902098; F:calcitriol binding; IDA:ZFIN.
DR GO; GO:1902121; F:lithocholic acid binding; IDA:ZFIN.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:ZFIN.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0005499; F:vitamin D binding; IDA:ZFIN.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:ZFIN.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0003146; P:heart jogging; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:ZFIN.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:ZFIN.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001503; P:ossification; IMP:ZFIN.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:ZFIN.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:ZFIN.
DR CDD; cd06955; NR_DBD_VDR; 1.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID50155; -.
DR InterPro; IPR042153; DBD_VDR.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR000324; VitD_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 PRINTS; PR00350; VITAMINDR.
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 3D-structure; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..453
FT /note="Vitamin D3 receptor A"
FT /id="PRO_0000337878"
FT DOMAIN 159..449
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 53..128
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 56..76
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 92..111
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 129..158
FT /note="Hinge"
FT /evidence="ECO:0000250|UniProtKB:P11473"
FT REGION 274..292
FT /note="Interaction with coactivator LXXLL motif"
FT /evidence="ECO:0000250|UniProtKB:P13053"
FT MOTIF 442..450
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P11473"
FT BINDING 175
FT /ligand="calciol"
FT /ligand_id="ChEBI:CHEBI:28940"
FT /evidence="ECO:0000269|PubMed:17218092,
FT ECO:0000269|PubMed:17346665"
FT BINDING 255..265
FT /ligand="calciol"
FT /ligand_id="ChEBI:CHEBI:28940"
FT /evidence="ECO:0000269|PubMed:17218092,
FT ECO:0000269|PubMed:17346665"
FT BINDING 299..306
FT /ligand="calciol"
FT /ligand_id="ChEBI:CHEBI:28940"
FT /evidence="ECO:0000269|PubMed:17218092,
FT ECO:0000269|PubMed:17346665"
FT BINDING 333
FT /ligand="calciol"
FT /ligand_id="ChEBI:CHEBI:28940"
FT /evidence="ECO:0000269|PubMed:17218092,
FT ECO:0000269|PubMed:17346665"
FT BINDING 423
FT /ligand="calciol"
FT /ligand_id="ChEBI:CHEBI:28940"
FT /evidence="ECO:0000269|PubMed:17218092,
FT ECO:0000269|PubMed:17346665"
FT CONFLICT 24
FT /note="R -> T (in Ref. 1; AAF21427)"
FT /evidence="ECO:0000305"
FT CONFLICT 32
FT /note="V -> L (in Ref. 1; AAF21427)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="E -> Q (in Ref. 1; AAF21427)"
FT /evidence="ECO:0000305"
FT CONFLICT 54
FT /note="R -> P (in Ref. 1; AAF21427)"
FT /evidence="ECO:0000305"
FT HELIX 158..174
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 180..184
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 255..274
FT /evidence="ECO:0007829|PDB:4Q0A"
FT TURN 277..281
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 284..302
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:4Q0A"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:4Q0A"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4Q0A"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:2HCD"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:4Q0A"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 335..349
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 355..366
FT /evidence="ECO:0007829|PDB:4Q0A"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:7OY4"
FT HELIX 377..398
FT /evidence="ECO:0007829|PDB:4Q0A"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:6XZJ"
FT HELIX 402..404
FT /evidence="ECO:0007829|PDB:2HBH"
FT HELIX 405..431
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 434..437
FT /evidence="ECO:0007829|PDB:4Q0A"
FT HELIX 442..448
FT /evidence="ECO:0007829|PDB:4Q0A"
SQ SEQUENCE 453 AA; 50867 MW; 87DE0415B3FF56CD CRC64;
MLTENSAVNS GGKSKCEAGA CESRVNGDAT SVMDLMAVST SATGQDEFDR NAPRICGVCG
DKATGFHFNA MTCEGCKGFF RRSMKRKASF TCPFNGNCTI TKDNRRHCQA CRLKRCIDIG
MMKEFILTDE EVQRKKDLIM KRKEEEAARE ARKPRLSDEQ MQIINSLVEA HHKTYDDSYS
DFVRFRPPVR EGPVTRSASR AASLHSLSDA SSDSFNHSPE SVDTKLNFSN LLMMYQDSGS
PDSSEEDQQS RLSMLPHLAD LVSYSIQKVI GFAKMIPGFR DLTAEDQIAL LKSSAIEIIM
LRSNQSFSLE DMSWSCGGPD FKYCINDVTK AGHTLELLEP LVKFQVGLKK LKLHEEEHVL
LMAICLLSPD RPGVQDHVRI EALQDRLCDV LQAYIRIQHP GGRLLYAKMI QKLADLRSLN
EEHSKQYRSL SFQPEHSMQL TPLVLEVFGS EVS
