Protein:RARA |
Protein Summary |
 Gene summary |
| Gene name: RARA | ASpdb.0 ID: 5914 | Gene | Gene symbol | RARA | Gene ID | 5914 |
| Gene name | retinoic acid receptor alpha |
| Synonyms | NR1B1|RAR|RARalpha |
| Cytomap | 17q21.2 |
| Type of gene | protein-coding |
| Description | retinoic acid receptor alphaPML-DDX5-RARA fusionPML-DDX5-RARA fusion proteinRAR-alphanuclear receptor subfamily 1 group B member 1nucleophosmin-retinoic acid receptor alpha fusion protein NPM-RAR long formretinoic acid receptor, alpha polypeptide |
| Modification date | 20240411 |
| UniProtAcc | P10276 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | RARA | GO:0000785 | chromatin | 17363140|21131358 |
| Gene | RARA | GO:0000977 | RNA polymerase II transcription regulatory region sequence-specific DNA binding | 19917671 |
| Gene | RARA | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 20080953|21131358 |
| Gene | RARA | GO:0001972 | retinoic acid binding | 2825025 |
| Gene | RARA | GO:0003682 | chromatin binding | 20080953 |
| Gene | RARA | GO:0003700 | DNA-binding transcription factor activity | 18922886|20413580 |
| Gene | RARA | GO:0004879 | nuclear receptor activity | 2825025|21131358 |
| Gene | RARA | GO:0005102 | signaling receptor binding | 19628791 |
| Gene | RARA | GO:0005634 | nucleus | 18845237|19917671|20080953 |
| Gene | RARA | GO:0005654 | nucleoplasm | - |
| Gene | RARA | GO:0005730 | nucleolus | - |
| Gene | RARA | GO:0005737 | cytoplasm | 19850744 |
| Gene | RARA | GO:0005829 | cytosol | - |
| Gene | RARA | GO:0005886 | plasma membrane | 2825025 |
| Gene | RARA | GO:0015629 | actin cytoskeleton | - |
| Gene | RARA | GO:0030853 | negative regulation of granulocyte differentiation | 19917671 |
| Gene | RARA | GO:0031490 | chromatin DNA binding | 19917671 |
| Gene | RARA | GO:0032689 | negative regulation of type II interferon production | 18416830 |
| Gene | RARA | GO:0032720 | negative regulation of tumor necrosis factor production | 18416830 |
| Gene | RARA | GO:0032736 | positive regulation of interleukin-13 production | 18416830 |
| Gene | RARA | GO:0032753 | positive regulation of interleukin-4 production | 18416830 |
| Gene | RARA | GO:0032754 | positive regulation of interleukin-5 production | 18416830 |
| Gene | RARA | GO:0032991 | protein-containing complex | 19917671|20080953 |
| Gene | RARA | GO:0042789 | mRNA transcription by RNA polymerase II | 1310351 |
| Gene | RARA | GO:0044323 | retinoic acid-responsive element binding | 19917671 |
| Gene | RARA | GO:0045630 | positive regulation of T-helper 2 cell differentiation | 18416830 |
| Gene | RARA | GO:0045892 | negative regulation of DNA-templated transcription | 20080953 |
| Gene | RARA | GO:0045893 | positive regulation of DNA-templated transcription | 18845237|19850744|20080953 |
| Gene | RARA | GO:0045944 | positive regulation of transcription by RNA polymerase II | 9430642|19850744|19917671|21131358 |
| Gene | RARA | GO:0048384 | retinoic acid receptor signaling pathway | 2825025|19917671 |
| Gene | RARA | GO:0051018 | protein kinase A binding | 20215566 |
| Gene | RARA | GO:0071391 | cellular response to estrogen stimulus | 20080953 |
| Gene | RARA | GO:0090575 | RNA polymerase II transcription regulator complex | 1310351 |
| Gene | RARA | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P10276-1 | P10276-1_3a9e_B.pdb | 3A9E | X-ray | 2.75 | B | 177 | 415 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P10276 | RARA | P10276-1 | P10276-2 | 462 | 457 | 1 | 60 | Substitution | MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT | MYESVEVGGPTPNPFLVVDFYNQNRACLLPEKGLPAPGPYSTPLRTPLWNGSNHS | 1 | 55 |
| P10276 | RARA | P10276-1 | P10276-3 | 462 | 365 | 61 | 157 | Deletion | none | none | 60 | 60 |
| Multiple sequence alignment of our canonical and alternatively spliced RARA |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of RARA |
| UniProt-id | ENSG | ENST | ENSP |
| P10276-1 | ENSG00000131759.18 | ENST00000254066.10 | ENSP00000254066.5 |
| P10276-1 | ENSG00000131759.18 | ENST00000394089.6 | ENSP00000377649.2 |
| P10276-2 | ENSG00000131759.18 | ENST00000394081.7 | ENSP00000377643.3 |
| P10276-3 | ENSG00000131759.18 | ENST00000425707.7 | ENSP00000389993.3 |
| UniProt-id | NM ID | NP ID |
| P10276-1 | NM_000964.3 | NP_000955.1 |
| P10276-1 | NM_001145301.2 | NP_001138773.1 |
| P10276-1 | XM_005257553.1 | XP_005257610.1 |
| P10276-1 | XM_005257554.1 | XP_005257611.1 |
| P10276-1 | XM_011525095.1 | XP_011523397.1 |
| P10276-2 | NM_001024809.3 | NP_001019980.1 |
| P10276-3 | NM_001145302.2 | NP_001138774.1 |
| Amino acid sequences of our canonical and alternatively spliced RARA |
| accession_id | Protein sequence |
| P10276-1 | MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFV CQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILI LRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSP |
| P10276-2 | MYESVEVGGPTPNPFLVVDFYNQNRACLLPEKGLPAPGPYSTPLRTPLWNGSNHSIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKS SGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVG ELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICT RYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRK RRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRS |
| P10276-3 | MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATVRNDRNKKKKEVPKPECSESYTLTPEVGEL IEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRY TPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRR PSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSP |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| RARA (go to UniProt):P10276 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P10276 | DNA binding | 88 | 153 | Note=Nuclear receptor;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00407 | Type=Deletion;Start=61;End=157 |
| P10276 | Zinc finger | 88 | 108 | Note=NR C4-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00407 | Type=Deletion;Start=61;End=157 |
| P10276 | Zinc finger | 124 | 148 | Note=NR C4-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00407 | Type=Deletion;Start=61;End=157 |
| P10276 | Region | 1 | 87 | Note=Modulating | Type=Substitution;Start=1;End=60 |
| P10276 | Region | 1 | 87 | Note=Modulating | Type=Deletion;Start=61;End=157 |
| P10276 | Region | 52 | 77 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=1;End=60 |
| P10276 | Region | 52 | 77 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=61;End=157 |
| P10276 | Region | 154 | 182 | Note=Hinge | Type=Deletion;Start=61;End=157 |
| P10276 | Compositional bias | 52 | 71 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=1;End=60 |
| P10276 | Compositional bias | 52 | 71 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=61;End=157 |
Gene Isoform Structures and Expression Levels for RARA |
| Gene structures of our canonical and alternative spliced genes of RARA * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P10276-1 |
| 3D view using mol* of P10276-2 |
| 3D view using mol* of P10276-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P10276-1 |
 |
| pLDDT distribution across the protein length of P10276-2 |
 |
| pLDDT distribution across the protein length of P10276-3 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P10276-1 |
 |
| Ramachandran plot of P10276-2 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P10276-1 | 1.298 | 128 | 1.381 | 167.041 | 0.238 | 0.968 | 1.31 | 4.434 | 0.429 | 10.324 | 0.732 | 198,199,225,228,229,231,232,235,236,238,266,269,27 0,272,273,276,286,287,301,302,305,391,394,395,398, 410,414 |
| P10276-2 | 1.231 | 136 | 1.313 | 215.061 | 0.393 | 0.881 | 1.172 | 3.463 | 0.478 | 7.24 | 1.168 | 193,194,195,220,223,224,226,227,229,230,231,233,26 1,264,265,267,268,271,281,282,296,297,300,386,389, 390,393,405,409 |
| P10276-3 | 1.279 | 132 | 1.351 | 164.64 | 0.312 | 0.965 | 1.277 | 3.843 | 0.517 | 7.439 | 0.947 | 101,102,103,128,131,134,135,137,138,139,141,169,17 2,173,175,176,179,189,190,204,205,208,294,297,298, 301,309,313,317 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P10276-1_P10276-1_3a9e_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P10276-1_3a9e_B_P10276-2.pdb |
| 3D view using mol* of P10276-1_3a9e_B_P10276-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P10276-1_P10276-2.pdb |
| 3D view using mol* of P10276-1_P10276-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P10276-1_vs_P10276-2.png |
 < |
| ./stats/secondary_structure/figure/P10276-1_vs_P10276-3.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P10276-1_vs_P10276-2.png |
 < |
| ./stats/relative_asa/P10276-1_vs_P10276-3.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to RARA |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P10276 | RARA | DB04942 | Tamibarotene | investigational | agonist |
| P10276 | RARA | DB00799 | Tazarotene | approved, investigational | agonist |
| P10276 | RARA | DB00523 | Alitretinoin | approved, investigational | agonist |
| P10276 | RARA | DB00755 | Tretinoin | approved, investigational, nutraceutical | agonist |
| P10276 | RARA | DB00459 | Acitretin | approved | agonist |
| P10276 | RARA | DB00926 | Etretinate | withdrawn | agonist |
| P10276 | RARA | DB05785 | LGD-1550 | investigational | |
| P10276 | RARA | DB00982 | Isotretinoin | approved | other/unknown |
| P10276 | RARA | DB00210 | Adapalene | approved | |
| P10276 | RARA | DB12808 | Trifarotene | approved, investigational | agonist |
Related Diseases to RARA |
| Previous studies relating to the alternative splicing of RARA and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| RARA | 19863682 | Expression patterns of specific promyelocytic/retinoic acid receptor-alpha transcripts in patients with acute promyelocytic leukemia. | Several additional promyelocytic/retinoic acid receptor-alpha (PML/RARalpha) transcripts besides bcr1, bcr2, and bcr3 have been identified in patients with acute promyelocytic leukemia (APL). However, the expression levels of these specific isoforms and their clinical relevance have not been studied to date. The real-time quantitative polymerase chain reaction was established to detect each specific isoform of PML/RARalpha transcripts (bcr1/2, P46R3, P4R3, bcr3, and P2R3) in 46 APL patients. Whereas P46R3 and P4R3 isoforms were concurrently expressed in both bcr1- and bcr2-positive patients, P2R3 isoform was expressed only in bcr3-positive patients. A total of 13 patients had lower expression of bcr1/2 (median 11.60%, 0.86-108.51%) than that of P46R3 (median 14.26%, 6.03-222.91%; P = 0.001). The expression level of P4R3 (median 19.10%, 0.71-266.19%) was lower than the sum of bcr1/2 and P46R3 (median 37.94%, 9.62-403.51%) in all cases (P < 0.001). All 16 cases with bcr3 had concurrent low expression of P2R3 (P < 0.001). Structural analysis revealed that both P4R3 and P2R3 splicing resulting in the generation of a premature termination codon, which was recognized by nonsense-mediated decay (NMD). We suggest that alternative splicing of PML/RARalpha transcripts might be involved in NMD and each isoform should be quantified to further understand the pathogenesis of APL, stratify the risk of relapse, and monitor minimal residual disease. | D015473 | Leukemia, Promyelocytic, Acute |
| RARA | 20155840 | Atypical mRNA fusions in PML-RARA positive, RARA-PML negative acute promyelocytic leukemia. | Reciprocal RARA-PML transcripts are not detected in approximately 25% of patients with PML-RARA positive acute promyelocytic leukemia (APL), but the reasons for this are poorly understood. We studied 21 PML-RARA positive/RARA-PML negative cases by bubble PCR and multiplex long template PCR to identify the genomic breakpoints. Additional RT-PCR analysis was performed based on the DNA findings. Three cases were found to have complex rearrangements involving a third locus: the first had a PML-CDC6-RARA forward DNA fusion and expressed a chimeric PML-CDC6-RARA mRNA in addition to a PML-RARA. The other two had HERC1-PML and NT_009714.17-PML genomic fusion sequences at their respective reciprocal breakpoints. Six patients were falsely classified as RARA-PML negative due to deletions on chromosome 15 and/or 17, or alternative splicing leading to atypical RARA-PML fusion transcripts, which were not identified by conventional RT-PCR assays. This study demonstrates that the frequency of RARA-PML expression has been underestimated and highlights remarkable complexity at chromosomal breakpoint regions in APL even in cases with an apparently simple balanced t(15;17)(q24;q12). | D015473 | Leukemia, Promyelocytic, Acute |
Clinically important variants in RARA |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |