EP300

S Wikipedije, slobodne enciklopedije
EP300
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1L3E, 1P4Q, 2K8F, 2MH0, 2MZD, 3BIY, 3I3J, 3IO2, 3P57, 3T92, 4BHW, 4PZR, 4PZS, 4PZT, 5BT3

Identifikatori
AliasiEP300
Vanjski ID-jeviOMIM: 602700 MGI: 1276116 HomoloGene: 1094 GeneCards: EP300
Lokacija gena (čovjek)
Hromosom 22 (čovjek)
Hrom.Hromosom 22 (čovjek)[1]
Hromosom 22 (čovjek)
Genomska lokacija za EP300
Genomska lokacija za EP300
Bend22q13.2Početak41,092,592 bp[1]
Kraj41,180,077 bp[1]
Lokacija gena (miš)
Hromosom 15 (miš)
Hrom.Hromosom 15 (miš)[2]
Hromosom 15 (miš)
Genomska lokacija za EP300
Genomska lokacija za EP300
Bend15|15 E1Početak81,469,552 bp[2]
Kraj81,536,278 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija protein C-terminus binding
transcription factor binding
GO:0001104 transcription coregulator activity
vezivanje iona metala
acyltransferase activity
aktivnost sa transferazom
beta-catenin binding
pre-mRNA intronic binding
vezivanje iona cinka
chromatin binding
oštećeno vezivanje sa DNK
GO:0001948, GO:0016582 vezivanje za proteine
acetyltransferase activity
vezivanje sa DNK
GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific
GO:0001105 transcription coactivator activity
p53 binding
androgen receptor binding
chromatin DNA binding
histone acetyltransferase activity
lysine N-acetyltransferase activity, acting on acetyl phosphate as donor
peptide N-acetyltransferase activity
peptide-lysine-N-acetyltransferase activity
protein propionyltransferase activity
STAT family protein binding
peptide butyryltransferase activity
histone crotonyltransferase activity
histone butyryltransferase activity
GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Ćelijska komponenta jedro
histone acetyltransferase complex
transcription regulator complex
nukleoplazma
citoplazma
citosol
hromosom
Biološki proces somitogenesis
rhythmic process
transcription by RNA polymerase II
histone H2B acetylation
animal organ morphogenesis
ćelijski ciklus
B cell differentiation
GO:0097285 apoptoza
GO:0009373 regulation of transcription, DNA-templated
lung development
N-terminal peptidyl-lysine acetylation
platelet formation
stimulatory C-type lectin receptor signaling pathway
transcription, DNA-templated
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
heart development
regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0022415 viral process
protein acetylation
Notch signaling pathway
cellular response to UV
protein stabilization
positive regulation of DNA-binding transcription factor activity
GO:1901227 negative regulation of transcription by RNA polymerase II
nervous system development
regulation of autophagy
regulation of androgen receptor signaling pathway
positive regulation of protein binding
positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response
fat cell differentiation
positive regulation by host of viral transcription
megakaryocyte development
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
internal protein amino acid acetylation
regulation of cell cycle
regulation of tubulin deacetylation
GO:1901313 positive regulation of gene expression
histone H4 acetylation
regulation of cellular response to heat
transcription-coupled nucleotide-excision repair
skeletal muscle tissue development
positive regulation of type I interferon production
response to estrogen
response to hypoxia
regulation of signal transduction by p53 class mediator
internal peptidyl-lysine acetylation
beta-catenin-TCF complex assembly
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
macrophage derived foam cell differentiation
Jednodnevni biološki ritam
protein deubiquitination
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
protein destabilization
regulation of megakaryocyte differentiation
histone acetylation
epigenetic maintenance of chromatin in transcription-competent conformation
peptidyl-lysine propionylation
peptidyl-lysine crotonylation
peptidyl-lysine butyrylation
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001429
NM_001362843

NM_177821

RefSeq (bjelančevina)

NP_001420
NP_001349772

NP_808489

Lokacija (UCSC)Chr 22: 41.09 – 41.18 MbChr 15: 81.47 – 81.54 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Histon-acetiltransferaza p300, znana i kao p300 HAT ili E1A-vezani protein p300 (gdje je E1A = adenovirusna rana regija 1A) također poznat kao i kao EP300 ili p300, jest enzim koji je kod ljudi kodiran genom EP300 sa hromosoma 22.[5] Funkcioniše kao histon-acetiltransferaza koja reguliše transkripciju gena putem remodeliranja hromatina, dozvoljavajući histonskim proteinima da manje čvrsto omotaju DNK. Ovaj enzim ima esencijalnu ulogu u regulaciji ćelijskog rasta i diobe, podstičući ćelije da sazrijevaju i preuzmu specijalizirane funkcije (diferencijacije), te sprječavaju rast kancerogenih tumora. Čini se da je protein p300 kritičan za normalan razvoj prije i nakon rođenja.

Gen EP300 se nalazi na dugom (q) kraku ljudskog hromosoma 22 na poziciji 13.2. Ovaj gen kodira adenovirusni E1A povezan sa ćelijskim p300 transkripcijskim koaktivatorskim proteinom.

EP300 je blisko povezan sa drugim genom, CREB vezujući protein, koji se nalazi na ljudskom hromosomu 16.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 2.414 aminokiselina, a molekulska težina 264.161 Da.

1020304050
MAENVVEPGPPSAKRPKLSSPALSASASDGTDFGSLFDLEHDLPDELINS
TELGLTNGGDINQLQTSLGMVQDAASKHKQLSELLRSGSSPNLNMGVGGP
GQVMASQAQQSSPGLGLINSMVKSPMTQAGLTSPNMGMGTSGPNQGPTQS
TGMMNSPVNQPAMGMNTGMNAGMNPGMLAAGNGQGIMPNQVMNGSIGAGR
GRQNMQYPNPGMGSAGNLLTEPLQQGSPQMGGQTGLRGPQPLKMGMMNNP
NPYGSPYTQNPGQQIGASGLGLQIQTKTVLSNNLSPFAMDKKAVPGGGMP
NMGQQPAPQVQQPGLVTPVAQGMGSGAHTADPEKRKLIQQQLVLLLHAHK
CQRREQANGEVRQCNLPHCRTMKNVLNHMTHCQSGKSCQVAHCASSRQII
SHWKNCTRHDCPVCLPLKNAGDKRNQQPILTGAPVGLGNPSSLGVGQQSA
PNLSTVSQIDPSSIERAYAALGLPYQVNQMPTQPQVQAKNQQNQQPGQSP
QGMRPMSNMSASPMGVNGGVGVQTPSLLSDSMLHSAINSQNPMMSENASV
PSLGPMPTAAQPSTTGIRKQWHEDITQDLRNHLVHKLVQAIFPTPDPAAL
KDRRMENLVAYARKVEGDMYESANNRAEYYHLLAEKIYKIQKELEEKRRT
RLQKQNMLPNAAGMVPVSMNPGPNMGQPQPGMTSNGPLPDPSMIRGSVPN
QMMPRITPQSGLNQFGQMSMAQPPIVPRQTPPLQHHGQLAQPGALNPPMG
YGPRMQQPSNQGQFLPQTQFPSQGMNVTNIPLAPSSGQAPVSQAQMSSSS
CPVNSPIMPPGSQGSHIHCPQLPQPALHQNSPSPVPSRTPTPHHTPPSIG
AQQPPATTIPAPVPTPPAMPPGPQSQALHPPPRQTPTPPTTQLPQQVQPS
LPAAPSADQPQQQPRSQQSTAASVPTPTAPLLPPQPATPLSQPAVSIEGQ
VSNPPSTSSTEVNSQAIAEKQPSQEVKMEAKMEVDQPEPADTQPEDISES
KVEDCKMESTETEERSTELKTEIKEEEDQPSTSATQSSPAPGQSKKKIFK
PEELRQALMPTLEALYRQDPESLPFRQPVDPQLLGIPDYFDIVKSPMDLS
TIKRKLDTGQYQEPWQYVDDIWLMFNNAWLYNRKTSRVYKYCSKLSEVFE
QEIDPVMQSLGYCCGRKLEFSPQTLCCYGKQLCTIPRDATYYSYQNRYHF
CEKCFNEIQGESVSLGDDPSQPQTTINKEQFSKRKNDTLDPELFVECTEC
GRKMHQICVLHHEIIWPAGFVCDGCLKKSARTRKENKFSAKRLPSTRLGT
FLENRVNDFLRRQNHPESGEVTVRVVHASDKTVEVKPGMKARFVDSGEMA
ESFPYRTKALFAFEEIDGVDLCFFGMHVQEYGSDCPPPNQRRVYISYLDS
VHFFRPKCLRTAVYHEILIGYLEYVKKLGYTTGHIWACPPSEGDDYIFHC
HPPDQKIPKPKRLQEWYKKMLDKAVSERIVHDYKDIFKQATEDRLTSAKE
LPYFEGDFWPNVLEESIKELEQEEEERKREENTSNESTDVTKGDSKNAKK
KNNKKTSKNKSSLSRGNKKKPGMPNVSNDLSQKLYATMEKHKEVFFVIRL
IAGPAANSLPPIVDPDPLIPCDLMDGRDAFLTLARDKHLEFSSLRRAQWS
TMCMLVELHTQSQDRFVYTCNECKHHVETRWHCTVCEDYDLCITCYNTKN
HDHKMEKLGLGLDDESNNQQAAATQSPGDSRRLSIQRCIQSLVHACQCRN
ANCSLPSCQKMKRVVQHTKGCKRKTNGGCPICKQLIALCCYHAKHCQENK
CPVPFCLNIKQKLRQQQLQHRLQQAQMLRRRMASMQRTGVVGQQQGLPSP
TPATPTTPTGQQPTTPQTPQPTSQPQPTPPNSMPPYLPRTQAAGPVSQGK
AAGQVTPPTPPQTAQPPLPGPPPAAVEMAMQIQRAAETQRQMAHVQIFQR
PIQHQMPPMTPMAPMGMNPPPMTRGPSGHLEPGMGPTGMQQQPPWSQGGL
PQPQQLQSGMPRPAMMSVAQHGQPLNMAPQPGLGQVGISPLKPGTVSQQA
LQNLLRTLRSPSSPLQQQQVLSILHANPQLLAAFIKQRAAKYANSNPQPI
PGQPGMPQGQPGLQPPTMPGQQGVHSNPAMQNMNPMQAGVQRAGLPQQQP
QQQLQPPMGGMSPQAQQMNMNHNTMPSQFRDILRRQQMMQQQQQQGAGPG
IGPGMANHNQFQQPQGVGYPPQQQQRMQHHMQQMQQGNMGQIGQLPQALG
AEAGASLQAYQQRLLQQQMGSPVQPNPMSPQQHMLPNQAQSPHLQGQQIP
NSLSNQVRSPQPVPSPRPQSQPPHSSPSPRMQPQPSPHHVSPQTSSPHPG
LVAAQANPMEQGHFASPDQNSMLSQLASNPGMANLHGASATDLGLSTDNS
DLNSNLSQSTLDIH

Funkcija[uredi | uredi izvor]

p300 HAT funkcionira kao histon-acetiltransferaza[6] koji regulira transkripciju putem remodeliranja hromatina i važan je u procesima proliferacije i diferencijacije ćelija. Posreduje u regulaciji cAMP-gena, tako što se specifično vezuje za fosforilizirani CREB protein.

p300 HAT sadrži bromodomain koji je uključen u IL6 signalizaciju.[7]:3.1

Ovaj gen je također identificiran kao koaktivator HIF1A (faktor 1 alfa induciran hipoksijom), te stoga ima ulogu u stimulaciji gena izazvanih hipoksijom, kao što je VEGF.[8]

Mehanizam[uredi | uredi izvor]

Protein p300 obavlja svoju funkciju aktivacije transkripcije vezivanjem za transkripcijski faktor i transkripcijski mehanizam. Na osnovu ove funkcije, p300 se naziva transkripcijski koaktivator. Interakcijom p300 sa faktorima transkripcije upravlja jedan ili više p300 domena: jedarni receptorski domen interakcije (RID), KIX domen (CREB i MYB domen interakcije), cistein/histidin regije (TAZ1/CH1 i TAZ2/CH3) i interferonski domen za vezivanje odgovora (IBiD). Posljednja četiri domena, KIX, TAZ1, TAZ2 i IBiD od p300, svaki se čvrsto vezuje za sekvencu koja obuhvata oba trasaltivacijska domena 9aaTAD faktora transkripcije p53.[9]

Klinički značaj[uredi | uredi izvor]

Mutacije u genu EP300 odgovorne su za mali procent slučajeva Rubinstein-Taybijevog sindroma. Ove mutacije rezultiraju gubitkom jedne kopije gena u svakoj ćeliji, što smanjuje količinu p300 proteina za polovinu. Neke mutacije dovode do proizvodnje vrlo kratke, nefunkcionalne verzije proteina p300, dok druge sprječavaju da jedna kopija gena uopće napravi bilo koji protein. Iako se ne zna kako smanjenje količine p300 proteina dovodi do specifičnih karakteristika Rubinstein-Taybijevog sindroma, jasno je da gubitak jedne kopije gena EP300 remeti normalan razvoj.

Preuređenje hromosoma koji uključuje hromosom 22 rijetko je povezano s određenim tipovima raka. Ova preuređivanja, zvana translokacije, remete regiju hromosoma 22 koji sadrži gen EP300. Naprimjer, nađena je translokaciju između hromosoma 8 i 22 kod nekoliko ljudi s rakom krvnih ćelija pod nazivom akutna mijeloidna leukemija (AML). Još jedna translokacija, koja uključuje hromosome 11 i 22, pronađena je kod malog broja ljudi koji su bili podvrgnuti liječenju raka. Ova hromosomska promjena povezana je s razvojem AML-a nakon hemoterapija za druge oblike raka.

Mutacije u genu EP300 identificirane su u nekoliko drugih tipova raka. Ove mutacije su somatske, što znači da se stiču tokom života osobe i prisutne su samo u određenim ćelijama. Somatske mutacije u genu EP300 pronađene su u malom broju solidnih tumora, uključujući karcinom debelog crijeva i rektuma, želuca, dojke i [ [rak gušterače|gušterače]]. Studije sugeriraju da mutacije EP300 također mogu imati ulogu u razvoju nekih karcinoma prostate i mogu pomoći u predviđanju da li će se ovi tumori povećati dimenzije ili proširiti na druge dijelove tijela. U ćelijama raka, mutacije EP300 sprečavaju gen da proizvodi bilo koji funkcionalni protein. Bez p300, ćelije ne mogu efikasno obuzdati rast i podjelu, što može omogućiti nastanak kanceroznih tumora.

Interakcije[uredi | uredi izvor]

Pokazalo se da EP300 reaguje sa:

Reference[uredi | uredi izvor]

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