Linked Life Data

P10276

Source:http://identifiers.org/uniprot/P10276

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand- dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis. SUBUNIT: Heterodimer; with RXRA. Binds DNA preferentially as a heterodimer. Interacts with CDK7 (By similarity). Interacts with coactivators NCOA3 and NCOA6. Interacts with NCOA7; the interaction requires ligand-binding. Interacts with MLL5. Interacts (via the ligand-binding domain) with PRAME; the interaction is ligand (retinoic acid)-dependent. Interacts with AKT1; the interaction phosphorylates RARA and repressses transactivation. Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity. Interacts with NCOR1 and NCOR2. Interacts with PRMT2. Interacts with LRIF1. Interacts with ASXL1 and NCOA1. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=Alpha-1; IsoId=P10276-1; Sequence=Displayed; Name=Alpha-2; IsoId=P10276-2; Sequence=VSP_003629; Name=Alpha-1-deltaBC; IsoId=P10276-3; Sequence=VSP_043143; Note=Does not bind nor transactivate RARE on its own but may do so as a heterodimer with Alpha-1; DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. PTM: Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity (By similarity). Phosphorylation by AKT1 is required for the repressor activity but has no effect on DNA binding, protein stability nor subcellular localization. Phosphorylated by PKA in vitro. This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling. PTM: Sumoylated by SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated transcriptional activity. PTM: Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation. PTM: Ubiquitinated. DISEASE: Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled- coil domain functions in blocking RA-mediated transactivation and cell differentiation. SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 subfamily. SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. SEQUENCE CAUTION: Sequence=AAB00112.1; Type=Erroneous initiation; Sequence=AAB00113.1; Type=Erroneous initiation; Sequence=BAB62809.1; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RARAID46.html"; WEB RESOURCE: Name=Wikipedia; Note=Retinoic acid receptor entry; URL="http://en.wikipedia.org/wiki/Retinoic_acid_receptor"; GENE SYNONYMS:RARA NR1B1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 462 AA; 50771 MW; E8D1CF9A1E57CB99 CRC64;
biopax3:xref
biopax3:displayName
RARA_HUMAN
biopax3:name
Nuclear receptor subfamily 1 group B member 1, RAR-alpha, RARA
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biopax3:organism
biopax3:sequence
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
biopax3:standardName
Retinoic acid receptor alpha