Reviewed,
UniProtKB/Swiss-Prot P10276 (RARA_HUMAN)
Last modified
November 3, 2009.
Version 133.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Retinoic acid receptor alpha Short name=RAR-alpha Alternative name(s): Nuclear receptor subfamily 1 group B member 1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 462 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | This is a receptor for retinoic acid. Retinoic acid has profound effects on vertebrate development, is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression. Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis. Ref.15 |
| Subunit structure | Interacts with CDK7 By similarity. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with NCOA7 in a ligand-inducible manner. Interacts with MLL5. Interacts (via the ligand-binding domain) with PRAME; interaction is direct and ligand (retinoic acid)-dependent. |
| Subcellular location | |
| Domain | Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal steroid-binding domain. |
| Post-translational modification | Phosphorylated. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity By similarity. |
| Involvement in disease | Chromosomal aberrations involving RARA may be a cause of acute promyelocytic leukemia (APL) [MIM:612376]. 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. |
| Sequence similarities | Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| EZH2 | Q15910 | 2 | EBI-413374,EBI-530054 | |
| MBD1 | Q9UIS9 | 1 | EBI-413374,EBI-867196 | |
| Ncoa6 | Q9JLI4 | 1 | EBI-413374,EBI-286271 | From a different organism. |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform Alpha-1 (identifier: P10276-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform Alpha-2 (identifier: P10276-2) The sequence of this isoform differs from the canonical sequence as follows: 1-60: MASNSSSCPT...SGYSTPSPAT → MYESVEVGGP...TPLWNGSNHS |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 462 | 462 | Retinoic acid receptor alpha | PRO_0000053461 | |||||||||||||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA binding | 88 – 153 | 66 | Nuclear receptor | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Zinc finger | 88 – 108 | 21 | NR C4-type | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Zinc finger | 124 – 148 | 25 | NR C4-type | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Region | 1 – 87 | 87 | Modulating | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Region | 154 – 199 | 46 | Hinge | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Region | 200 – 419 | 220 | Ligand-binding | ||||||||||||||||||||||||||||||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Site | 60 – 61 | 2 | Breakpoint for translocation to form PLZF-RAR-alpha, RAR-alpha1-PLZF and PML-RAR-alpha oncogenes | ||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 77 | 1 | Phosphoserine; by CDK7 By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 449 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 456 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 461 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 60 | 60 | MASNS…PSPAT → MYESVEVGGPTPNPFLVVDF YNQNRACLLPEKGLPAPGPY STPLRTPLWNGSNHS in isoform Alpha-2. | VSP_003629 | |||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 241 | 1 | E → D in AAD05222. Ref.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 89 – 91 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 97 – 99 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 106 – 117 | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 134 – 136 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 137 – 139 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 141 – 150 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 155 – 157 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 183 – 198 | 16 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 202 – 204 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 222 – 245 | 24 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 247 – 251 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 254 – 274 | 21 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 279 – 282 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 283 – 285 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 289 – 293 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 294 – 300 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 303 – 305 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 306 – 315 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 317 – 319 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 323 – 334 | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 345 – 366 | 22 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 373 – 378 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 380 – 401 | 22 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 410 – 415 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Identification of a receptor for the morphogen retinoic acid." Giguere V., Ong E.S., Segui P., Evans R.M. Nature 330:624-629(1987) [PubMed: 2825036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1). |
| [2] | "PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors." Chen Z., Guidez F., Rousselot P., Agadir A., Chen S.-J., Wang Z.-Y., Degos L., Zelent A., Waxman S., Chomienne C. Proc. Natl. Acad. Sci. U.S.A. 91:1178-1182(1994) [PubMed: 8302850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1), CHROMOSOMAL TRANSLOCATION WITH PML. |
| [3] | "Genomic structure of the human retinoic acid receptor-alpha1 gene." Hjalt T.A.H., Murray J.C. Mamm. Genome 10:528-529(1999) [PubMed: 10337631] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA-1). |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2). Tissue: Blood and Brain. |
| [5] | "Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha)." Brand N.J., Petkovich M., Chambon P. Nucleic Acids Res. 18:6799-6806(1990) [PubMed: 2175878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-80 (ISOFORM ALPHA-1). |
| [6] | "A human retinoic acid receptor which belongs to the family of nuclear receptors." Petkovich M., Brand N.J., Krust A., Chambon P. Nature 330:444-450(1987) [PubMed: 2825025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-462. |
| [7] | Chambon P. Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [8] | "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion." Redner R.L., Rush E.A., Faas S., Rudert W.A., Corey S.J. Blood 87:882-886(1996) [PubMed: 8562957] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-462, CHROMOSOMAL TRANSLOCATION WITH NPM. Tissue: Bone marrow. |
| [9] | "Homo sapiens retinoic acid receptor alpha (RAR-alpha) gene, promoter and 5' region of RAR-alpha 2 isoform." Chen A., Petrie K., Waxman S., Zelent A. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54 (ISOFORM ALPHA-2). |
| [10] | "Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation." Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M. Leuk. Lymphoma 44:111-115(2003) [PubMed: 12691149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 61-68, CHROMOSOMAL TRANSLOCATION WITH PML. |
| [11] | "Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300." Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M. Cell 90:569-580(1997) [PubMed: 9267036] [Abstract] Cited for: INTERACTION WITH NCOA3. |
| [12] | "A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo." Lee S.-K., Anzick S.L., Choi J.-E., Bubendorf L., Guan X.-Y., Jung Y.-K., Kallioniemi O.-P., Kononen J., Trent J.M., Azorsa D., Jhun B.-H., Cheong J.H., Lee Y.C., Meltzer P.S., Lee J.W. J. Biol. Chem. 274:34283-34293(1999) [PubMed: 10567404] [Abstract] Cited for: INTERACTION WITH NCOA6. |
| [13] | "ERAP140, a conserved tissue-specific nuclear receptor coactivator." Shao W., Halachmi S., Brown M. Mol. Cell. Biol. 22:3358-3372(2002) [PubMed: 11971969] [Abstract] Cited for: INTERACTION WITH NCOA7. |
| [14] | "The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling." Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R. Cell 122:835-847(2005) [PubMed: 16179254] [Abstract] Cited for: INTERACTION WITH PRAME. |
| [15] | "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis." Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G., Kitagawa H., Kato S. Nature 459:455-459(2009) [PubMed: 19377461] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLL5. |
| + | Additional computationally mapped references. |
Web resources
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| Wikipedia Retinoic acid receptor entry |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| X06614 mRNA. Translation: CAA29829.1. X06538 mRNA. Translation: CAA29787.1. AF088895 AF088894 Genomic DNA. Translation: AAD05222.1. BC008727 mRNA. Translation: AAH08727.1. BC071733 mRNA. Translation: AAH71733.1. X56058, X58685 mRNA. Translation: CAA39533.1. X58685 mRNA. Translation: CAA41532.1. U41742 mRNA. Translation: AAB00112.1. Different initiation. U41743 mRNA. Translation: AAB00113.1. Different initiation. AF283809 Genomic DNA. Translation: AAF87249.1. AB067754 mRNA. Translation: BAB62809.1. Different initiation. | |||||||||||||||||||
| IPI | IPI00020071. IPI00218375. | ||||||||||||||||||
| PIR | A29491. | ||||||||||||||||||
| RefSeq | NP_000955.1. NP_001019980.1. NP_001138773.1. | ||||||||||||||||||
| UniGene | Hs.654583 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| |||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP:34N. | ||||||||||||||||||
| IntAct | P10276. 9 interactions. | ||||||||||||||||||
| STRING | P10276. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | P10276. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | P10276. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000254066; ENSP00000254066; ENSG00000131759; Homo sapiens. [Genome view] ENST00000319149; ENSP00000316769; ENSG00000131759; Homo sapiens. [Genome view] ENST00000394081; ENSP00000377643; ENSG00000131759; Homo sapiens. [Genome view] ENST00000394086; ENSP00000377648; ENSG00000131759; Homo sapiens. [Genome view] ENST00000394089; ENSP00000377649; ENSG00000131759; Homo sapiens. [Genome view] ENST00000420042; ENSP00000388570; ENSG00000131759; Homo sapiens. [Genome view] ENST00000425707; ENSP00000389993; ENSG00000131759; Homo sapiens. [Genome view] ENST00000441856; ENSP00000399453; ENSG00000131759; Homo sapiens. [Genome view] | ||||||||||||||||||
| GeneID | 5914. | ||||||||||||||||||
| KEGG | hsa:5914. | ||||||||||||||||||
| UCSC | uc002huk.1. human. uc002hun.1. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 5914. | ||||||||||||||||||
| GeneCards | GC17P035718. | ||||||||||||||||||
| H-InvDB | HIX0017867. | ||||||||||||||||||
| HGNC | HGNC:9864. RARA. | ||||||||||||||||||
| MIM | 180240. gene. 612376. phenotype. | ||||||||||||||||||
| Orphanet | 520. Leukemia, promyelocytic, acute. | ||||||||||||||||||
| PharmGKB | PA34225. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| HOVERGEN | P10276. | ||||||||||||||||||
| OMA | NSSSCPT. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | retinoic_acid_pathway. Retinoic acid receptors-mediated signaling. rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | P10276. | ||||||||||||||||||
| Bgee | P10276. | ||||||||||||||||||
| CleanEx | HS_RARA. | ||||||||||||||||||
| Genevestigator | P10276. | ||||||||||||||||||
| GermOnline | ENSG00000131759. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. IPR003078. Retinoic_acid_rcpt. IPR001723. Str_hrmn_rcpt. IPR001628. Znf_hrmn_rcpt. [Graphical view] | ||||||||||||||||||
| Gene3D | G3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit. | ||||||||||||||||||
| PANTHER | PTHR11865:SF169. Rtnoid_rcpt. 1 hit. | ||||||||||||||||||
| Pfam | PF00104. Hormone_recep. 1 hit. PF00105. zf-C4. 1 hit. [Graphical view] | ||||||||||||||||||
| PRINTS | PR01292. RETNOICACIDR. PR00398. STRDHORMONER. PR00047. STROIDFINGER. | ||||||||||||||||||
| ProDom | PD000035. Znf_C4steroid. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||
| SMART | SM00430. HOLI. 1 hit. SM00399. ZnF_C4. 1 hit. [Graphical view] | ||||||||||||||||||
| PROSITE | PS00031. NUCLEAR_REC_DBD_1. 1 hit. PS51030. NUCLEAR_REC_DBD_2. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| DrugBank | DB00459. Acitretin. DB00210. Adapalene. DB00523. Alitretinoin. DB00926. Etretinate. DB00982. Isotretinoin. DB04942. Tamibarotene. DB00799. Tazarotene. | ||||||||||||||||||
| NextBio | 23018. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | RARA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P10276 Secondary accession number(s): P78456 Q9NQS0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


