UniProt functional annotation for P11473



	UniProt functional annotation for P11473

UniProt code: P11473.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:28698609, PubMed:16913708, PubMed:15728261, PubMed:10678179). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). {ECO:0000250|UniProtKB:P13053, ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:15728261, ECO:0000269|PubMed:16913708, ECO:0000269|PubMed:28698609}.

Subunit: Homodimer in the absence of bound vitamin D3 (PubMed:11980721). Heterodimer with RXRA after vitamin D3 binding (PubMed:15225774, PubMed:11980721, PubMed:10678179). Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (PubMed:10866662, PubMed:15728261, PubMed:28698609, PubMed:9267036). Interacts with the corepressor NCOR1 (PubMed:28698609). Interacts with SNW1 (PubMed:9632709). Interacts with IRX4, the interaction does not affect its transactivation activity (PubMed:22323358). Interacts with CRY1 (By similarity). Interacts with CRY2 in a ligand-dependent manner (By similarity). {ECO:0000250|UniProtKB:P48281, ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:11980721, ECO:0000269|PubMed:15225774, ECO:0000269|PubMed:15728261, ECO:0000269|PubMed:22323358, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:9267036, ECO:0000269|PubMed:9632709}.

Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:28698609}. Cytoplasm {ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:28698609}. Note=Localizes mainly to the nucleus (PubMed:28698609, PubMed:12145331). Localization to the nucleus is enhanced by vitamin D3. {ECO:0000269|PubMed:12145331, ECO:0000269|PubMed:28698609}.

Domain: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Domain: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000305|PubMed:30468856}.

Polymorphism: Genetic variations in VDR may determine Mycobacterium tuberculosis susceptibility [MIM:607948]. {ECO:0000269|PubMed:15032981}.

Disease: Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets. {ECO:0000269|PubMed:1652893, ECO:0000269|PubMed:17970811, ECO:0000269|PubMed:2177843, ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:7828346, ECO:0000269|PubMed:8106618, ECO:0000269|PubMed:8381803, ECO:0000269|PubMed:8392085, ECO:0000269|PubMed:8675579, ECO:0000269|PubMed:8961271, ECO:0000269|PubMed:9005998}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the nuclear hormone receptor family. NR1 subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAH60832.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAP88938.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:28698609, PubMed:16913708, PubMed:15728261, PubMed:10678179). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). {ECO:0000250\|UniProtKB:P13053, ECO:0000269\|PubMed:10678179, ECO:0000269\|PubMed:15728261, ECO:0000269\|PubMed:16913708, ECO:0000269\|PubMed:28698609}.


Subunit:		Homodimer in the absence of bound vitamin D3 (PubMed:11980721). Heterodimer with RXRA after vitamin D3 binding (PubMed:15225774, PubMed:11980721, PubMed:10678179). Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (PubMed:10866662, PubMed:15728261, PubMed:28698609, PubMed:9267036). Interacts with the corepressor NCOR1 (PubMed:28698609). Interacts with SNW1 (PubMed:9632709). Interacts with IRX4, the interaction does not affect its transactivation activity (PubMed:22323358). Interacts with CRY1 (By similarity). Interacts with CRY2 in a ligand-dependent manner (By similarity). {ECO:0000250\|UniProtKB:P48281, ECO:0000269\|PubMed:10678179, ECO:0000269\|PubMed:10866662, ECO:0000269\|PubMed:11980721, ECO:0000269\|PubMed:15225774, ECO:0000269\|PubMed:15728261, ECO:0000269\|PubMed:22323358, ECO:0000269\|PubMed:28698609, ECO:0000269\|PubMed:9267036, ECO:0000269\|PubMed:9632709}.
Subcellular location:		Nucleus {ECO:0000255\|PROSITE-ProRule:PRU00407, ECO:0000269\|PubMed:12145331, ECO:0000269\|PubMed:28698609}. Cytoplasm {ECO:0000269\|PubMed:12145331, ECO:0000269\|PubMed:28698609}. Note=Localizes mainly to the nucleus (PubMed:28698609, PubMed:12145331). Localization to the nucleus is enhanced by vitamin D3. {ECO:0000269\|PubMed:12145331, ECO:0000269\|PubMed:28698609}.
Domain:		Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Domain:		The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000305\|PubMed:30468856}.
Polymorphism:		Genetic variations in VDR may determine Mycobacterium tuberculosis susceptibility [MIM:607948]. {ECO:0000269\|PubMed:15032981}.
Disease:		Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets. {ECO:0000269\|PubMed:1652893, ECO:0000269\|PubMed:17970811, ECO:0000269\|PubMed:2177843, ECO:0000269\|PubMed:2849209, ECO:0000269\|PubMed:28698609, ECO:0000269\|PubMed:7828346, ECO:0000269\|PubMed:8106618, ECO:0000269\|PubMed:8381803, ECO:0000269\|PubMed:8392085, ECO:0000269\|PubMed:8675579, ECO:0000269\|PubMed:8961271, ECO:0000269\|PubMed:9005998}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the nuclear hormone receptor family. NR1 subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAH60832.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAP88938.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};