ESR1

S Wikipedije, slobodne enciklopedije
(Preusmjereno sa Estrogeni receptor alfa)
ESR1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1A52, 1ERE, 1ERR, 1G50, 1GWQ, 1GWR, 1HCP, 1HCQ, 1L2I, 1PCG, 1QKT, 1QKU, 1R5K, 1SJ0, 1UOM, 1X7E, 1X7R, 1XP1, 1XP6, 1XP9, 1XPC, 1XQC, 1YIM, 1YIN, 1ZKY, 2AYR, 2B1V, 2B1Z, 2B23, 2BJ4, 2FAI, 2G44, 2G5O, 2I0J, 2IOG, 2IOK, 2JF9, 2JFA, 2LLO, 2LLQ, 2OCF, 2OUZ, 2P15, 2POG, 2Q6J, 2Q70, 2QA6, 2QA8, 2QAB, 2QE4, 2QGT, 2QGW, 2QH6, 2QR9, 2QSE, 2QXM, 2QXS, 2QZO, 2R6W, 2R6Y, 2YAT, 2YJA, 3CBM, 3CBO, 3CBP, 3DT3, 3ERD, 3ERT, 3HLV, 3HM1, 3L03, 3OS8, 3OS9, 3OSA, 3Q95, 3Q97, 3UU7, 3UUA, 3UUC, 3UUD, 4AA6, 4DMA, 4IU7, 4IUI, 4IV2, 4IV4, 4IVW, 4IVY, 4IW6, 4IW8, 4IWC, 4IWF, 4JC3, 4JDD, 4MG5, 4MG6, 4MG7, 4MG8, 4MG9, 4MGA, 4MGB, 4MGC, 4MGD, 4O6F, 4PP6, 4PPP, 4PPS, 4PXM, 4Q13, 4Q50, 4TUZ, 4TV1, 5AK2, 5AAV, 5ACC, 5AAU, 4XI3, 4ZN9, 5FQS, 5FQR, 5FQP, 5FQT, 5FQV, 4ZN7, 5E0W, 5DUG, 4ZUC, 5DXK, 5E19, 5DXQ, 5EI1, 5DXR, 5DVS, 5DZ1, 5E0X, 5DKB, 5DWI, 5E14, 5DXB, 5BPR, 5EIT, 5E15, 4ZNS, 5EGV, 5DL4, 5DWE, 4ZNT, 5EHJ, 5DYD, 5DWG, 4ZNV, 5DWJ, 5DID, 4ZUB, 5BNU, 5DMC, 5DK9, 5DIG, 5DUH, 5DKS, 5DMF, 5DU5, 5DY8, 4ZWH, 5DVV, 5DLR, 4ZWK, 5DRM, 5DP0, 5DKE, 5DZI, 5DZ3, 4ZNU, 5DIE, 5DZ0, 5E1C, 5HYR, 5BQ4, 4ZNW, 5DUE, 5DTV, 5DRJ, 5DKG, 4ZNH, 5BP6, 5DXG, 5DI7, 5DX3, 5DYB, 5DXP, 5DZH, 5DXM

Identifikatori
AliasiESR1
Vanjski ID-jeviOMIM: 133430 MGI: 1352467 HomoloGene: 47906 GeneCards: ESR1
Lokacija gena (čovjek)
Hromosom 6 (čovjek)
Hrom.Hromosom 6 (čovjek)[1]
Hromosom 6 (čovjek)
Genomska lokacija za ESR1
Genomska lokacija za ESR1
Bend6q25.1-q25.2Početak151,656,691 bp[1]
Kraj152,129,619 bp[1]
Lokacija gena (miš)
Hromosom 10 (miš)
Hrom.Hromosom 10 (miš)[2]
Hromosom 10 (miš)
Genomska lokacija za ESR1
Genomska lokacija za ESR1
Bend10 A1|10 2.03 cMPočetak4,561,593 bp[2]
Kraj4,955,614 bp[2]
Ontologija gena
Molekularna funkcija GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity
GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific
nitric-oxide synthase regulator activity
GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity
estrogen response element binding
transcription factor binding
vezivanje iona metala
GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
steroid hormone receptor activity
steroid binding
beta-catenin binding
vezivanje iona cinka
chromatin binding
GO:0001948, GO:0016582 vezivanje za proteine
vezivanje sa DNK
sequence-specific DNA binding
ATPase binding
vezivanje identičnih proteina
lipid binding
core promoter sequence-specific DNA binding
vezivanje enzima
protein kinase binding
TFIIB-class transcription factor binding
TBP-class protein binding
estrogen receptor activity
estrogen receptor binding
transcription coactivator binding
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific
Ćelijska komponenta citoplazma
membrana
jedro
integral component of membrane
Golđijev aparat
ćelijska membrana
nukleoplazma
transcription preinitiation complex
citosol
GO:0009327 makromolekulani kompleks
Biološki proces epithelial cell development
positive regulation of phospholipase C activity
mammary gland alveolus development
transcription by RNA polymerase II
phospholipase C-activating G protein-coupled receptor signaling pathway
epithelial cell proliferation involved in mammary gland duct elongation
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
protein localization to chromatin
steroid hormone mediated signaling pathway
regulation of apoptotic process
chromatin remodeling
GO:0009373 regulation of transcription, DNA-templated
androgen metabolic process
positive regulation of fibroblast proliferation
mammary gland branching involved in pregnancy
negative regulation of gene expression
transcription, DNA-templated
negative regulation of DNA-binding transcription factor activity
cellular response to estrogen stimulus
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
positive regulation of nitric-oxide synthase activity
transcription initiation from RNA polymerase II promoter
regulation of branching involved in prostate gland morphogenesis
male gonad development
positive regulation of DNA-binding transcription factor activity
GO:1901227 negative regulation of transcription by RNA polymerase II
negative regulation of I-kappaB kinase/NF-kappaB signaling
negative regulation of production of miRNAs involved in gene silencing by miRNA
response to estrogen
uterus development
prostate epithelial cord elongation
antral ovarian follicle growth
vagina development
positive regulation of cytosolic calcium ion concentration
positive regulation of nitric oxide biosynthetic process
GO:0072468 Transdukcija signala
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
intracellular steroid hormone receptor signaling pathway
regulation of inflammatory response
response to estradiol
regulation of toll-like receptor signaling pathway
GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II
protein deubiquitination
cellular response to estradiol stimulus
intracellular estrogen receptor signaling pathway
positive regulation of RNA polymerase II transcription preinitiation complex assembly
stem cell differentiation
regulation of Wnt signaling pathway
regulation of intracellular estrogen receptor signaling pathway
phosphatidylinositol phosphate biosynthetic process
positive regulation of protein kinase B signaling
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)
NM_000125
NM_001122740
NM_001122741
NM_001122742
NM_001291230

NM_001291241
NM_001328100
NM_001385568
NM_001385569
NM_001385570
NM_001385571
NM_001385572

NM_007956
NM_001302531
NM_001302532
NM_001302533

RefSeq (bjelančevina)
NP_000116
NP_001116212
NP_001116213
NP_001116214
NP_001278159

NP_001278170
NP_001315029

NP_001289460
NP_001289461
NP_001289462
NP_031982

Lokacija (UCSC)Chr 6: 151.66 – 152.13 MbChr 10: 4.56 – 4.96 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Estrogeni receptor alfa (ERα), znan i kao NR3A1 (član 1grupe A potporodice jedarnih receptora), jedan je od dva tipa estrogenih receptora, jedarni receptor koji se aktivira spolnim hormonom estrogenom. Kod ljudi kodiran genom ESR1 (Estrogeni receptor 1).[5][6][7]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 595 aminokiselina, а molekulska težina 66.216 Da.[8]

1020304050
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPA
VYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPL
NSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFY
RPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVW
SCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGM
MKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLA
DRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPG
KLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKS
IILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQ
HQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLH
APTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV

Struktura[uredi | uredi izvor]

Receptor estrogena (ER) je ligand-aktivirani transkripcijski faktor sastavljen od nekoliko domena važnih za vezivanje hormona, vezanjem i aktivacijom transkripcije.[9] Alternativna prerada rezultira u nekoliko transkripata ESR1 iRNK, koji se prvenstveno razlikuju po pet primarnih neprevedenih regija (UTR5'). Translatirani receptori pokazuju manju varijabilnost.[10][11]

Ligandi[uredi | uredi izvor]

Agonisti[uredi | uredi izvor]

Neselektivni[uredi | uredi izvor]

Selektivni[uredi | uredi izvor]

Selektivni agonisti ERα u odnosu na ERβ uključuju:

Mješoviti[uredi | uredi izvor]

Antagonisti[uredi | uredi izvor]

Neselektivni[uredi | uredi izvor]

Selektivni[uredi | uredi izvor]

Selektivni antagonisti ERα u odnosu na ERβ uključuju:

Afiniteti[uredi | uredi izvor]

Šablon:Afiniteti liganda estrogenog receptora ERα i ERβ

Tkivna distribucija i funkcija[uredi | uredi izvor]

ERα ima ulogu u fiziološkom razvoju i funkciji različitih organskih sistema u različitom stepenu, uključujući reproduktivni, centralni nervni, skeletni i kardiovaskularni sistem.[12] U skladu s tim, ERα je široko eksprimiran u cijelom tijelu, uključujući tkiva organa kao što su maternica i jajnici, muški reproduktivni organi, mliječne žlijezde, kosti, srce, hipotalamus, hipofiza, jetra, pluća, bubrezi, slezena i masno tkivo .[12][13][14] Razvoj i funkcija ovih tkiva poremećen je u životinjskim modelima bez aktivnih ERα gena, poput ERα nokaut-miša (ERKO), pružajući prethodno razumijevanje funkcije ERα u specifičnim ciljanim organima.[12][15]

Klinički značaj[uredi | uredi izvor]

Sindrom neosjetljivosti na estrogene je vrlo rijetko stanje koje karakterizira neispravan Erα, neosjetljiv na estrogene.[16][17][18][19] Uočeno je da klinička slika žena uključuje odsustvo razvoja dojke i drugih ženskih sekundarsnih spolnih obilježja u pubertetu, hipoplaziji maternice, primarnoj amenoreji, pri uvećanim policistastim jajnicima i pridruženom bolu u donjem dijelu trbuha, blagi hiperandrogenizam (ispoljava se kao cistaste akne) i odgođeno sazrijevanje kosti kao i povećana stopa koštanog promedta. Klinička slika kod mužjaka je uključivala nedostatak zatvaranja epifize, visok rast, osteoporozu i lošu održivost spermatozoida. Obje posmstrane osobe bile su potpuno neosetljive na egzogeni tretman estrogenom, čak i pri visokim dozama.

Genetički polimorfizmi u genu koji kodira ERα povezani su sa rakom dojke i dismenorejom kod žena, a ginekomastijom kod muškaraca.[20][21][22]

Koaktivatori[uredi | uredi izvor]

Koaktivatori ER-α uključuju:

Interakcije[uredi | uredi izvor]

Pokazano je da receptor estrogena alfa stupa u interakcije sa:

Reference[uredi | uredi izvor]

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