RAR-alfa

RAR-alfa
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1DKF, 1DSZ, 3A9E, 3KMR, 3KMZ, 4DQM, 5K13
Identifikatori
Aliasi	RARA
Vanjski ID-jevi	OMIM: 180240 MGI: 97856 HomoloGene: 20262 GeneCards: RARA
Lokacija gena (čovjek) Hrom. Hromosom 17 (čovjek) Bend 17q21.2 Početak 40,309,180 bp Kraj 40,357,643 bp
Lokacija gena (miš) Hrom. Hromosom 11 (miš) Bend 11 D|11 62.76 cM Početak 98,818,644 bp Kraj 98,865,768 bp
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • retinoic acid binding • GO:0001106 transcription corepressor activity • protein domain specific binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity • mRNA 5'-UTR binding • signaling receptor binding • RNA polymerase II transcription regulatory region sequence-specific DNA binding • retinoic acid-responsive element binding • transcription factor binding • vezivanje iona metala • steroid hormone receptor activity • vezivanje enzima • vezivanje iona cinka • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje sa DNK • sequence-specific DNA binding • GO:0001105 transcription coactivator activity • protein kinase A binding • protein kinase B binding • translation repressor activity, mRNA regulatory element binding • alpha-actinin binding • protein heterodimerization activity • chromatin DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • histone deacetylase binding • GO:0000975 transcription cis-regulatory region binding • nuclear receptor coactivator activity • signaling receptor activity Ćelijska komponenta • citoplazma • actin cytoskeleton • perinuklearno područje citoplazme • neuron projection • jedro • cell surface • nukleoplazma • soma • dendrit • citosol • RNA polymerase II transcription regulator complex Biološki proces • growth plate cartilage development • germ cell development • cellular response to retinoic acid • ureteric bud development • positive regulation of interleukin-5 production • prostate gland development • limb development • apoptotic cell clearance • chondroblast differentiation • regulation of granulocyte differentiation • protein phosphorylation • response to vitamin A • face development • Spermatogeneza • response to ethanol • negative regulation of cell population proliferation • steroid hormone mediated signaling pathway • regulation of apoptotic process • response to cytokine • negative regulation of translation • GO:0009373 regulation of transcription, DNA-templated • negative regulation of cell differentiation • negative regulation of gene expression • transcription, DNA-templated • cellular response to estrogen stimulus • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • positive regulation of cell cycle • regulation of myelination • positive regulation of neuron differentiation • negative regulation of tumor necrosis factor production • transcription initiation from RNA polymerase II promoter • trachea cartilage development • glandular epithelial cell development • male gonad development • negative regulation of cartilage development • response to retinoic acid • negative regulation of granulocyte differentiation • multicellular organism growth • female pregnancy • negative regulation of apoptotic process • GO:1901227 negative regulation of transcription by RNA polymerase II • positive regulation of interleukin-4 production • regulation of synaptic plasticity • outflow tract septum morphogenesis • GO:0045996 negative regulation of transcription, DNA-templated • negative regulation of interferon-gamma production • response to estradiol • negative regulation of translational initiation • embryonic camera-type eye development • positive regulation of interleukin-13 production • neural tube closure • positive regulation of binding • retinoic acid receptor signaling pathway • GO:1901313 positive regulation of gene expression • Sertoli cell fate commitment • positive regulation of cell population proliferation • positive regulation of T-helper 2 cell differentiation • ventricular cardiac muscle cell differentiation • liver development • cellular response to lipopolysaccharide • bone development • hippocampus development • GO:0072468 Transdukcija signala • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • multicellular organism development • hormone-mediated signaling pathway • Ćelijska diferencijacija • response to lipid • gland development • bone morphogenesis • epithelium development Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	5914	19401
Ensembl	ENSG00000131759	ENSMUSG00000037992
UniProt	P10276 Q6I9R7	P11416
RefSeq (mRNK)	NM_000964 NM_001024809 NM_001033603 NM_001145301 NM_001145302	NM_001176528 NM_001177302 NM_001177303 NM_009024 NM_001361954
RefSeq (bjelančevina)	NP_000955 NP_001019980 NP_001138773 NP_001138774 NP_000955.1 NP_001138773.1	NP_001169999 NP_001170773 NP_001170774 NP_033050 NP_001348883
Lokacija (UCSC)	Chr 17: 40.31 – 40.36 Mb	Chr 11: 98.82 – 98.87 Mb
PubMed pretraga
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Receptor alfa retinojske kiseline (RAR-α), znan i kao NR1B1 (član 1 grupe B potporodice 1 jedarnih receptora) jest jedarni receptorski protein koji je kod ljudi kodiran genom RARA sa hromosoma 17.

NR1B1 je gen sa proteinskim proizvodom i ima hromosomsku lokaciju 17q21.2. RARA kodira receptora jedarnog hormona, receptor retinojske kiseline, podtip alfa i sam je transkripcijski faktor. Postoje još dva podtipa RAR-a, beta i gama.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 462 aminokiseline, a molekulska težina 50.771 Da.

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MASNSSSCPT		PGGGHLNGYP		VPPYAFFFPP		MLGGLSPPGA		LTTLQHQLPV
SGYSTPSPAT		IETQSSSSEE		IVPSPPSPPP		LPRIYKPCFV		CQDKSSGYHY
GVSACEGCKG		FFRRSIQKNM		VYTCHRDKNC		IINKVTRNRC		QYCRLQKCFE
VGMSKESVRN		DRNKKKKEVP		KPECSESYTL		TPEVGELIEK		VRKAHQETFP
ALCQLGKYTT		NNSSEQRVSL		DIDLWDKFSE		LSTKCIIKTV		EFAKQLPGFT
TLTIADQITL		LKAACLDILI		LRICTRYTPE		QDTMTFSDGL		TLNRTQMHNA
GFGPLTDLVF		AFANQLLPLE		MDDAETGLLS		AICLICGDRQ		DLEQPDRVDM
LQEPLLEALK		VYVRKRRPSR		PHMFPKMLMK		ITDLRSISAK		GAERVITLKM
EIPGSMPPLI		QEMLENSEGL		DTLSGQPGGG		GRDGGGLAPP		PGSCSPSLSP
SSNRSSPATH		SP

Funkcija

Retinoidnu signalizaciju transduciraju članovi dvije porodice jedarnih receptora, receptor retinojske kiseline (RAR) i retinoidnui X-receptor (RXR), koji formiraju RXR/RAR heterodimere. U nedostatku liganda, DNK vezani RXR/RARA potiskuje transkripciju, regrutacijom korepresora NCOR1, SMRT (NCOR2), i histon-deacetilaze. Kada se ligand veže za kompleks, inducira konformacijsku promjenu koja omogućava regrutovanje koaktivatora, histon-acetiltransferaza i osnovnog transkripcijskog mehanizma.

Receptor retinoične kiseline alfa, protein, stupa u interakciju sa retinojskom kiselinom, derivatom vitamina A, koji ima važnu ulogu u rastu ćelija, diferencijaciji i formiranju organa u razvoju embriona.

Kada se retinoična kiselina veže za RAR, oni pokreću transkripciju i omogućavaju ekspresiju njihovog gena.

Klinički značaj

RA signalizacija je u korelacijama sa nekoliko signalnih puteva u ranom embrionskom razvoju. Prvo, učestvuje u formiranju embrionske osovine, koja uspostavlja simetriju u potomstvu. RA također utiče na nervnu diferencijaciju. regulacijom ekspresije proneurvnog indukcionog faktora meurogenina 2 (neurog2). RA utiče na kardiogenezu, jer ima posebnu ulogu u formiranju srčane pretkomore. RA također ima ulogu u razvoju pankreasa, bubrega, pluća i ekstremiteta.

Translokacije koje uvijek uključuju preuređivanje gena RARA su kardinalna karakteristika akutne promijelocitne leukemije (APL; MIM 612376). Najčešća translokacija je t(15,17)(q21;q22), koja spaja gen RARA sa genom PML.

Interakcije

Pokazalo se da receptor alfa retinojske kiseline reaguje sa:

• BAG1,
• CLOCK,
• CCND3,
• NCOA6,
• NCOR1,
• NCOR2,
• NPAS2,
• NRIP1,
• NR0B2,
• NR4A2,
• PML
• RXRA.
• Src,
• TADA3L, i
• ZBTB16.

Genetic Studies

Knock-out mice studies showed that a deletion in one of the copies of the RARA gene did not create any observable defect, while deletion of both copies shoes symptoms similar to that of Vitamin A deficiency. This proved that all 3 subtypes of RARs work redundantly.

See also

• Retinoic acid receptor
• Retinoic X Receptor
• Acute promyelocytic leukemia

Dopunska literatura

• Petkovich M, Brand NJ, Krust A, Chambon P (1988). "A human retinoic acid receptor which belongs to the family of nuclear receptors". Nature. 330 (6147): 444–50. doi:10.1038/330444a0. PMID 2825025. S2CID 4271628.
• Sirulnik A, Melnick A, Zelent A, Licht JD (septembar 2003). "Molecular pathogenesis of acute promyelocytic leukaemia and APL variants". Best Practice & Research. Clinical Haematology. 16 (3): 387–408. doi:10.1016/S1521-6926(03)00062-8. PMID 12935958.
• Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (januar 1992). "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling". Nature. 355 (6359): 446–9. Bibcode:1992Natur.355..446K. doi:10.1038/355446a0. PMC 6159885. PMID 1310351.
• Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, et al. (februar 1992). "Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins". The EMBO Journal. 11 (2): 629–42. doi:10.1002/j.1460-2075.1992.tb05095.x. PMC 556495. PMID 1311253.
• Baniahmad A, Köhne AC, Renkawitz R (mart 1992). "A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor". The EMBO Journal. 11 (3): 1015–23. doi:10.1002/j.1460-2075.1992.tb05140.x. PMC 556542. PMID 1347744.
• de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (august 1991). "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR". Cell. 66 (4): 675–84. doi:10.1016/0092-8674(91)90113-D. PMID 1652369. S2CID 40272758.
• de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A (oktobar 1990). "The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus". Nature. 347 (6293): 558–61. Bibcode:1990Natur.347..558D. doi:10.1038/347558a0. PMID 2170850. S2CID 4314933.
• Brand NJ, Petkovich M, Chambon P (decembar 1990). "Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha)". Nucleic Acids Research. 18 (23): 6799–806. doi:10.1093/nar/18.23.6799. PMC 332734. PMID 2175878.
• Borrow J, Goddard AD, Sheer D, Solomon E (septembar 1990). "Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17". Science. 249 (4976): 1577–80. Bibcode:1990Sci...249.1577B. doi:10.1126/science.2218500. PMID 2218500.
• Arveiler B, Petkovich M, Mandel JL, Chambon P (juli 1988). "A PstI RFLP for the human retinoic acid receptor in 17q21". Nucleic Acids Research. 16 (13): 6252. doi:10.1093/nar/16.13.6252. PMC 336887. PMID 2899875.
• Chen JD, Evans RM (oktobar 1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature. 377 (6548): 454–7. Bibcode:1995Natur.377..454C. doi:10.1038/377454a0. PMID 7566127. S2CID 4361329.
• Fisher GJ, Talwar HS, Xiao JH, Datta SC, Reddy AP, Gaub MP, et al. (august 1994). "Immunological identification and functional quantitation of retinoic acid and retinoid X receptor proteins in human skin". The Journal of Biological Chemistry. 269 (32): 20629–35. doi:10.1016/S0021-9258(17)32039-2. PMID 8051161.
• Chen Z, Guidez F, Rousselot P, Agadir A, Chen SJ, Wang ZY, et al. (februar 1994). "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". Proceedings of the National Academy of Sciences of the United States of America. 91 (3): 1178–82. Bibcode:1994PNAS...91.1178C. doi:10.1073/pnas.91.3.1178. PMC 521477. PMID 8302850.
• Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ (februar 1996). "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion". Blood. 87 (3): 882–6. doi:10.1182/blood.V87.3.882.bloodjournal873882. PMID 8562957.
• Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, et al. (maj 1996). "A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors". Cell. 85 (3): 403–14. doi:10.1016/S0092-8674(00)81118-6. PMID 8616895. S2CID 16273727.
• Liu W, Hellman P, Li Q, Yu WR, Juhlin C, Nordlinder H, et al. (decembar 1996). "Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid cells". Biochemical and Biophysical Research Communications. 229 (3): 922–9. doi:10.1006/bbrc.1996.1903. PMID 9005841.
• Thénot S, Henriquet C, Rochefort H, Cavaillès V (maj 1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". The Journal of Biological Chemistry. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.

Vanjski linkovi

Šablon:Modulatori retinoidnog receptora Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.