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CHD7

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CHD7
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2CKC, 2V0E, 2V0F

Identifikatori
AliasiCHD7
Vanjski ID-jeviOMIM: 608892 MGI: 2444748 HomoloGene: 19067 GeneCards: CHD7
Lokacija gena (čovjek)
Hromosom 8 (čovjek)
Hrom.Hromosom 8 (čovjek)[1]
Hromosom 8 (čovjek)
Genomska lokacija za CHD7
Genomska lokacija za CHD7
Bend8q12.2Početak60,678,740 bp[1]
Kraj60,868,028 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za CHD7
Genomska lokacija za CHD7
Bend4 A1|4 3.68 cMPočetak8,690,406 bp[2]
Kraj8,867,659 bp[2]
Ontologija gena
Molekularna funkcija nucleotide binding
vezivanje sa DNK
GO:0008026 helicase activity
chromatin binding
GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
hydrolase activity, acting on acid anhydrides
GO:0001948, GO:0016582 vezivanje za proteine
hydrolase activity
ATP binding
promoter-specific chromatin binding
Ćelijska komponenta jedro
nukleoplazma
Jedarce
Biološki proces skeletal system development
olfactory behavior
semicircular canal morphogenesis
GO:0009373 regulation of transcription, DNA-templated
kognitivna funkcija
locomotory behavior
adult heart development
cranial nerve development
heart morphogenesis
olfactory nerve development
in utero embryonic development
sluh
Krvotok
transcription, DNA-templated
epithelium development
genitalia development
limb development
ear morphogenesis
regulation of growth hormone secretion
central nervous system development
T cell differentiation
face development
blood vessel development
retina development in camera-type eye
inner ear morphogenesis
artery morphogenesis
positive regulation of multicellular organism growth
rRNA processing
camera-type eye development
olfactory bulb development
nose development
female genitalia development
regulation of neurogenesis
adult walking behavior
embryonic hindlimb morphogenesis
ventricular trabecula myocardium morphogenesis
tissue remodeling
aorta morphogenesis
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
right ventricular compact myocardium morphogenesis
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
aorta development
atrioventricular canal development
blood vessel remodeling
chromatin remodeling
cardiac septum morphogenesis
innervation
GO:0031497, GO:0006336, GO:0034724, GO:0001301, GO:0007580, GO:0034652, GO:0010847 chromatin organization
roof of mouth development
secondary palate development
response to bacterium
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_017780
NM_001316690
NM_017783

NM_001033395
NM_001081417
NM_001277149
NM_001355382

RefSeq (bjelančevina)

NP_001303619
NP_060250

NP_001264078
NP_001342311

Lokacija (UCSC)Chr 8: 60.68 – 60.87 MbChr 4: 8.69 – 8.87 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Hromodomenskohelikazni DNK-vezujući protein 7, poznat i kao ATP-ovisna helikaza CHD7 je enzim koji je kod ljudi kodiran genom CHD7.[5][6]

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je čak 2.977 aminokiselina, а molekulska težina 335.927 Da.[7]

1020304050
MADPGMMSLFGEDGNIFSEGLEGLGECGYPENPVNPMGQQMPIDQGFASL
QPSLHHPSTNQNQTKLTHFDHYNQYEQQKMHLMDQPNRMMSNTPGNGLAS
PHSQYHTPPVPQVPHGGSGGGQMGVYPGMQNERHGQSFVDSSSMWGPRAV
QVPDQIRAPYQQQQPQPQPPQPAPSGPPAQGHPQHMQQMGSYMARGDFSM
QQHGQPQQRMSQFSQGQEGLNQGNPFIATSGPGHLSHVPQQSPSMAPSLR
HSVQQFHHHPSTALHGESVAHSPRFSPNPPQQGAVRPQTLNFSSRSQTVP
SPTINNSGQYSRYPYSNLNQGLVNNTGMNQNLGLTNNTPMNQSVPRYPNA
VGFPSNSGQGLMHQQPIHPSGSLNQMNTQTMHPSQPQGTYASPPPMSPMK
AMSNPAGTPPPQVRPGSAGIPMEVGSYPNMPHPQPSHQPPGAMGIGQRNM
GPRNMQQSRPFIGMSSAPRELTGHMRPNGCPGVGLGDPQAIQERLIPGQQ
HPGQQPSFQQLPTCPPLQPHPGLHHQSSPPHPHHQPWAQLHPSPQNTPQK
VPVHQHSPSEPFLEKPVPDMTQVSGPNAQLVKSDDYLPSIEQQPQQKKKK
KKNNHIVAEDPSKGFGKDDFPGGVDNQELNRNSLDGSQEEKKKKKRSKAK
KDPKEPKEPKEKKEPKEPKTPKAPKIPKEPKEKKAKTATPKPKSSKKSSN
KKPDSEASALKKKVNKGKTEGSENSDLDKTPPPSPPPEEDEDPGVQKRRS
SRQVKRKRYTEDLEFKISDEEADDADAAGRDSPSNTSQSEQQESVDAEGP
VVEKIMSSRSVKKQKESGEEVEIEEFYVKYKNFSYLHCQWASIEDLEKDK
RIQQKIKRFKAKQGQNKFLSEIEDELFNPDYVEVDRIMDFARSTDDRGEP
VTHYLVKWCSLPYEDSTWERRQDIDQAKIEEFEKLMSREPETERVERPPA
DDWKKSESSREYKNNNKLREYQLEGVNWLLFNWYNMRNCILADEMGLGKT
IQSITFLYEIYLKGIHGPFLVIAPLSTIPNWEREFRTWTELNVVVYHGSQ
ASRRTIQLYEMYFKDPQGRVIKGSYKFHAIITTFEMILTDCPELRNIPWR
CVVIDEAHRLKNRNCKLLEGLKMMDLEHKVLLTGTPLQNTVEELFSLLHF
LEPSRFPSETTFMQEFGDLKTEEQVQKLQAILKPMMLRRLKEDVEKNLAP
KEETIIEVELTNIQKKYYRAILEKNFTFLSKGGGQANVPNLLNTMMELRK
CCNHPYLINGAEEKILEEFKETHNAESPDFQLQAMIQAAGKLVLIDKLLP
KLKAGGHRVLIFSQMVRCLDILEDYLIQRRYPYERIDGRVRGNLRQAAID
RFSKPDSDRFVFLLCTRAGGLGINLTAADTCIIFDSDWNPQNDLQAQARC
HRIGQSKSVKIYRLITRNSYEREMFDKASLKLGLDKAVLQSMSGRENATN
GVQQLSKKEIEDLLRKGAYGALMDEEDEGSKFCEEDIDQILLRRTHTITI
ESEGKGSTFAKASFVASGNRTDISLDDPNFWQKWAKKAELDIDALNGRNN
LVIDTPRVRKQTRLYSAVKEDELMEFSDLESDSEEKPCAKPRRPQDKSQG
YARSECFRVEKNLLVYGWGRWTDILSHGRYKRQLTEQDVETICRTILVYC
LNHYKGDENIKSFIWDLITPTADGQTRALVNHSGLSAPVPRGRKGKKVKA
QSTQPVVQDADWLASCNPDALFQEDSYKKHLKHHCNKVLLRVRMLYYLRQ
EVIGDQADKILEGADSSEADVWIPEPFHAEVPADWWDKEADKSLLIGVFK
HGYEKYNSMRADPALCFLERVGMPDAKAIAAEQRGTDMLADGGDGGEFDR
EDEDPEYKPTRTPFKDEIDEFANSPSEDKEESMEIHATGKHSESNAELGQ
LYWPNTSTLTTRLRRLITAYQRSYKRQQMRQEALMKTDRRRRRPREEVRA
LEAEREAIISEKRQKWTRREEADFYRVVSTFGVIFDPVKQQFDWNQFRAF
ARLDKKSDESLEKYFSCFVAMCRRVCRMPVKPDDEPPDLSSIIEPITEER
ASRTLYRIELLRKIREQVLHHPQLGERLKLCQPSLDLPEWWECGRHDRDL
LVGAAKHGVSRTDYHILNDPELSFLDAHKNFAQNRGAGNTSSLNPLAVGF
VQTPPVISSAHIQDERVLEQAEGKVEEPENPAAKEKCEGKEEEEETDGSG
KESKQECEAEASSVKNELKGVEVGADTGSKSISEKGSEEDEEEKLEDDDK
SEESSQPEAGAVSRGKNFDEESNASMSTARDETRDGFYMEDGDPSVAQLL
HERTFAFSFWPKDRVMINRLDNICEAVLKGKWPVNRRQMFDFQGLIPGYT
PTTVDSPLQKRSFAELSMVGQASISGSEDITTSPQLSKEDALNLSVPRQR
RRRRRKIEIEAERAAKRRNLMEMVAQLRESQVVSENGQEKVVDLSKASRE
ATSSTSNFSSLSSKFILPNVSTPVSDAFKTQMELLQAGLSRTPTRHLLNG
SLVDGEPPMKRRRGRRKNVEGLDLLFMSHKRTSLSAEDAEVTKAFEEDIE
TPPTRNIPSPGQLDPDTRIPVINLEDGTRLVGEDAPKNKDLVEWLKLHPT
YTVDMPSYVPKNADVLFSSFQKPKQKRHRCRNPNKLDINTLTGEERVPVV
NKRNGKKMGGAMAPPMKDLPRWLEENPEFAVAPDWTDIVKQSGFVPESMF
DRLLTGPVVRGEGASRRGRRPKSEIARAAAAAAAVASTSGINPLLVNSLF
AGMDLTSLQNLQNLQSLQLAGLMGFPPGLATAATAGGDAKNPAAVLPLML
PGMAGLPNVFGLGGLLNNPLSAATGNTTTASSQGEPEDSTSKGEEKGNEN
EDENKDSEKSTDAVSAADSANGSVGAATAPAGLPSNPLAFNPFLLSTMAP
GLFYPSMFLPPGLGGLTLPGFPALAGLQNAVGSSEEKAADKAEGGPFKDG
ETLEGSDAEESLDKTAESSLLEDEIAQGEELDSLDGGDEIENNENDE

Funkcija

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CHD7 je ovisan o ATP-u remodelator hromatina homologan proteinu Drosophila grupa tritoraksni kismet.[8] Mutacije u CHD7 povezane su sa sindromom CHARGE.[9] Ovaj protein pripada većoj grupi kompleksa za remodeliranje hromatina ovisnih o ATP-u, potporodica CHD.

Modelni organizmi

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Fenotip nokaut-miša Chd7
Svojstvo Fenotip
Vijabilnost homozigota Nenormalan
Studija letalne recesivnosti Nenormalan
Plodnost Normalan
Tjelesna težina Normalan
Anksioznost otvorenog polja Normalan
Neurološka procjena Nenormalan[10]
Snaga stiska Normalan
Test vruće ploče Normalan
Dismorfologija Normalan
Indirektna kalorimetrija Normalan
Test tolerancije glukoze Normalan
Slušni odgovor moždanog stabla Normalan
DEXA Normalan
Radiografija Normalan[11]
Tjelesna temperatura Normalan
Morfologija oka Nenormalan[12]
Klinička hemija Normalan
Hematologija Normalan
Limfociti periferne krvi Normalan
Mikronukleus test Normalan
Težina srca Normalan
Histopatologija mozga Nenormalan
Salmonella infekcija Normalan[13]
Citrobacter infekcija Normalan[14]
Svi testovi i analize su prema[15][16]

U studiji finkcije CHD7 upotrebljeni su i modelni organizmi. Uslovna linija nokaut-miševa, zvana Chd7tm2a (EUCOMM) Wtsi[17][18] generirana je kao dio progtama Međunarodnog konzorcija za nokaut-miševe — visokopropusnog projekta mutageneze za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.[19][20][21]

Histološki presjek Bergmeisterove papile

Mužjaci i ženke podvrgnuti su standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti delecija.[15][22] Na mutantnim miševima izvedena su 24 ispitivanja i uočeno je pet značajnih abnormalnosti.[15] Nijedan homozigotni mutantni embrion nije identificiran tokom gestacije, pa stoga nijedan nije preživio do odbijanja. Preostali testovi provedeni su na heterozigotnim mutantnim odraslim miševima. Muški heterozigoti pokazali su abnormalnu elevaciju karlica u modificiranom SHIRPA testu i imaju visoku učestalost Bergmeisterove papile na oba oka. Prilikom proučavanja mozga heterozigotnih životinjprimijećeno je odsustvo corpus callosum.[15]

Klinički značaj

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Mutacije u ovom genu povezane su sa sindromom CHARGE.

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171316 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041235 - 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.
  5. ^ Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (Feb 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
  6. ^ "Entrez Gene: chromodomain helicase DNA binding protein 7".
  7. ^ "UniProt, Q9P2D1". Pristupljeno 15. 9. 2021.
  8. ^ Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, Chang CP, Zhao Y, Swigut T, Wysocka J (Feb 2010). "CHD7 cooperates with PBAF to control multipotent neural crest formation". Nature. 463 (7283): 958–62. Bibcode:2010Natur.463..958B. doi:10.1038/nature08733. PMC 2890258. PMID 20130577.
  9. ^ Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG (Sep 2004). "Mutations in a new member of the chromodomain gene family cause CHARGE syndrome". Nature Genetics. 36 (9): 955–7. doi:10.1038/ng1407. PMID 15300250.
  10. ^ "Neurological assessment data for Chd7". Wellcome Trust Sanger Institute.
  11. ^ "Radiography data for Chd7". Wellcome Trust Sanger Institute.
  12. ^ "Eye morphology data for Chd7". Wellcome Trust Sanger Institute.
  13. ^ "Salmonella infection data for Chd7". Wellcome Trust Sanger Institute.
  14. ^ "Citrobacter infection data for Chd7". Wellcome Trust Sanger Institute.
  15. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  16. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  17. ^ "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 10. 2. 2012.
  18. ^ "Mouse Genome Informatics".
  19. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  20. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  21. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  22. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Dopunska literatura

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Vanjski linkovi

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