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)
Kraj	40,357,643 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
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
	5914
	19401
	ENSG00000131759
	ENSMUSG00000037992
	P10276; Q6I9R7
	P11416
	NM_000964; NM_001024809; NM_001033603; NM_001145301; NM_001145302
	NM_001176528; NM_001177302; NM_001177303; NM_009024; NM_001361954
NP_000955; NP_001019980; NP_001138773; NP_001138774; NP_000955.1;
	NP_001138773.1
	NP_001169999; NP_001170773; NP_001170774; NP_033050; NP_001348883
	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.^[5]^[6]

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.^[7]^[8]

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.^[9]

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.^[8]^[10]

Kada se retinoična kiselina veže za RAR, oni pokreću transkripciju i omogućavaju ekspresiju njihovog gena.^[10]

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.^[10]

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.^[11]

Interakcije

Pokazalo se da receptor alfa retinojske kiseline reaguje sa:

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.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000131759 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037992 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Giguere V, Ong ES, Segui P, Evans RM (1987). "Identification of a receptor for the morphogen retinoic acid". Nature. 330 (6149): 624–9. Bibcode:1987Natur.330..624G. doi:10.1038/330624a0. PMID 2825036. S2CID 4308015.
^ Anderson LA, Friedman L, Osborne-Lawrence S, Lynch E, Weissenbach J, Bowcock A, King MC (septembar 1993). "High-density genetic map of the BRCA1 region of chromosome 17q12-q21". Genomics. 17 (3): 618–23. doi:10.1006/geno.1993.1381. PMID 8244378.
^ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Pristupljeno 27. 4. 2021.
^ ^a ^b "OMIM Entry - * 180240 - RETINOIC ACID RECEPTOR, ALPHA; RARA". www.omim.org. Pristupljeno 27. 4. 2021.
^ "Entrez Gene: retinoic acid receptor".
^ ^a ^b ^c Kam RK, Deng Y, Chen Y, Zhao H (mart 2012). "Retinoic acid synthesis and functions in early embryonic development". Cell & Bioscience. 2 (1): 11. doi:10.1186/2045-3701-2-11. PMC 3325842. PMID 22439772.
^ Vitoux D, Nasr R, de The H (2007). "Acute promyelocytic leukemia: new issues on pathogenesis and treatment response". The International Journal of Biochemistry & Cell Biology. 39 (6): 1063–70. doi:10.1016/j.biocel.2007.01.028. PMID 17468032.
^ Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X, et al. (juli 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". The Journal of Biological Chemistry. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID 9642262.
^ ^a ^b McNamara P, Seo SB, Rudic RD, Sehgal A, Chakravarti D, FitzGerald GA (juni 2001). "Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock". Cell. 105 (7): 877–89. doi:10.1016/S0092-8674(01)00401-9. PMID 11439184. S2CID 6251321.
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^ Ko L, Cardona GR, Chin WW (maj 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961.
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^ Hong SH, David G, Wong CW, Dejean A, Privalsky ML (august 1997). "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 94 (17): 9028–33. Bibcode:1997PNAS...94.9028H. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429.
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^ Seol W, Choi HS, Moore DD (maj 1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science. 272 (5266): 1336–9. Bibcode:1996Sci...272.1336S. doi:10.1126/science.272.5266.1336. PMID 8650544. S2CID 32853062.
^ Seol W, Hanstein B, Brown M, Moore DD (oktobar 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Molecular Endocrinology. 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978.
^ Perlmann T, Jansson L (april 1995). "A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1". Genes & Development. 9 (7): 769–82. doi:10.1101/gad.9.7.769. PMID 7705655.
^ Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H, et al. (novembar 1999). "A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins". Nature Genetics. 23 (3): 287–95. doi:10.1038/15463. PMID 10610177. S2CID 23613492.
^ Benkoussa M, Brand C, Delmotte MH, Formstecher P, Lefebvre P (juli 2002). "Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter". Molecular and Cellular Biology. 22 (13): 4522–34. doi:10.1128/MCB.22.13.4522-4534.2002. PMC 133906. PMID 12052862.
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Dopunska literatura

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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.
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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.
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Vanjski linkovi

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000131759 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000037992 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2825036-5] Giguere V, Ong ES, Segui P, Evans RM (1987). "Identification of a receptor for the morphogen retinoic acid". Nature. 330 (6149): 624–9. Bibcode:1987Natur.330..624G. doi:10.1038/330624a0. PMID 2825036. S2CID 4308015.

[pmid8244378-6] Anderson LA, Friedman L, Osborne-Lawrence S, Lynch E, Weissenbach J, Bowcock A, King MC (septembar 1993). "High-density genetic map of the BRCA1 region of chromosome 17q12-q21". Genomics. 17 (3): 618–23. doi:10.1006/geno.1993.1381. PMID 8244378.

[7] "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Pristupljeno 27. 4. 2021.

[:0-8] "OMIM Entry - * 180240 - RETINOIC ACID RECEPTOR, ALPHA; RARA". www.omim.org. Pristupljeno 27. 4. 2021.

[entrez-9] "Entrez Gene: retinoic acid receptor".

[:1-10] Kam RK, Deng Y, Chen Y, Zhao H (mart 2012). "Retinoic acid synthesis and functions in early embryonic development". Cell & Bioscience. 2 (1): 11. doi:10.1186/2045-3701-2-11. PMC 3325842. PMID 22439772.

[pmid17468032-11] Vitoux D, Nasr R, de The H (2007). "Acute promyelocytic leukemia: new issues on pathogenesis and treatment response". The International Journal of Biochemistry & Cell Biology. 39 (6): 1063–70. doi:10.1016/j.biocel.2007.01.028. PMID 17468032.

[pmid9642262-12] Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X, et al. (juli 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". The Journal of Biological Chemistry. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID 9642262.

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