IRF2BPL

IRF2BPL
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2CS3
Identifikatori
Aliasi	IRF2BPL
Vanjski ID-jevi	OMIM: 611720 MGI: 2442463 HomoloGene: 11555 GeneCards: IRF2BPL
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	77,028,708 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	86,931,572 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje iona metala; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • molekularna funkcija; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:1904264, GO:1904822, GO:0090622, GO:0090302 ubiquitin protein ligase activity; • aktivnost sa transferazom;
Ćelijska komponenta	• jedro; • nukleoplazma; • Vanćelijsko; • kompleks ubikvitin-ligaze;
Biološki proces	• GO:1901227 negative regulation of transcription by RNA polymerase II; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • development of secondary female sexual characteristics; • nervous system development; • protein ubiquitination;
	Izvori:Amigo / QuickGO
Ortolozi
	64207
	238330
	ENSG00000119669
	ENSMUSG00000034168
	Q9H1B7
	Q8K3X4
	NM_024496
	NM_145836
	NP_078772
	NP_665835
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Proteinoliki interferonski regulatorno vezujući faktor 2 ie protein koji je kod ljudi kodiran genom IRF2BPL.^[5]^[6]^[7]

Mutacije su mu povezane sa neurološkim problemima.^[8] Preciznije, mutacije ovog gena uzrokuju sindrom NEDAMSS, čija skraćenica znači NEurorazvojni poremećaj s regresijom, abnormalnim pokretima, gubitkom govora i napadima, prvi put opisanom u 2018.

Analizom genomske sekvence i radijacijso-hibridnim mapranjem , Rampazzo et al. (2000) locirali si gen C14ORF4 na hromosomskoj poziciji 14q24.3. Također su odredili da je ovaj gen bez introna. Bočno područje s 5' mjesta ne sadrži TATA ili CAATT okvire, ali ima puno GC sadržaja i uključuje dva mjesta koja vežu SP1. 3-bazni kraj sadrži dva signala poliadenilacije.^[9]

Molekuska genetika

U sedam nepovezanih pacijenata s neurorazvojnim poremećajem s regresijom, abnormalnim pokretima, gubitkom govora i napadima (NEDAMSS), Marcogliese et al. (2018) identificirali su heterozigotne mutacije u genu IRF2BPL . Mutacije su pronađene sekvenciranjem egzona i potvrđene sangerovskim sekvenciranjem. Mutacije su se dogodile de novo kod svih pacijenata kod kojih je roditeljska DNK bila dostupna za analizu. Pet pacijenata nosilo je nonsens mutacije, dok su dva s nešto manje ozbiljnim fenotipom nosil misens mutacije. Prekomjerne ekspresija nonmsens mutacija kod drozofile nije izazvala smrtnost, kao što je uočeno kod prekomjerne ekspresije gena divljeg tipa, što sugerira da su nonsens mutacije rezultirale gubitkom funkcije. Ekspresija mutacije K418N rezultirala je smrtnošću pri višim temperaturama, što upućuje na to da uzrokuje djelomični gubitak funkcije, dok je ekspresija varijante P372R rezultirala smrtnošću, slično divljem tipu. Djelimično nokidiranje gena jama u Drosophila, korištenjem RNKi izazvalo je progresivni poremećaj nervne motorike i disfunkciju učenja, a specifično nokautiranje gena u fotoreceptorima oka uzrokovalo je progresivne abnormalnosti. Kompletni poremećaj gena drozofilskih jama bio je toksičan za mušicu, što je rezultiralo letalnošću, kao i prekomjerna ekspresija obje jame i IRF2BPL. Nalazi sugeriraju da je gen IRF2BPL uključen i u neurološki razvoj i u održavanje neurona.

Koristeći sekvenciranje egzoma, Tran Mau-Them et al. (2019) identificirali su različite de novo heterozigotne nonsens mutacije pomjeranja okvira u genu IRF2BPL kod 11 nepovezanih pacijenata s NEDAMSS-om. Sve mutacije izostale su iz baze podataka gnomAD i očekivalo se da kodiraju protein kojem nedostaje C-terminalni RING-prstni domen.^[10]

Životinjski model

Marcogliese et al. (2018) otkrili su da je široko konzerviran najbliži ortolog genu IRF2BPL u Drosophila, zvani pits, uključujući i u nervni sistem. Ekspresija je otkrivena u različitim dijelovima mozga, uključujući ćelijsko tijelo, jedro i neuronske aksone. Prekid gena jama bio je toksičan za mušicu, što je rezultiralo smrtonosnošću, kao i prekomjerna ekspresija oba pits-a i IRF2BPL. Kod Drosophila, gen pits nalazi se na X hromosomu.^[11]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 796 aminokiselina, a molekulska težina 82-659 Da.^[12].

10	20	30	40	50
MSAAQVSSSR	RQSCYLCDLP	RMPWAMIWDF	SEPVCRGCVN	YEGADRIEFV
IETARQLKRA	HGCFQDGRSP	GPPPPVGVKT	VALSAKEAAA	AAAAAAAAAA
AAQQQQQQQQ	QQQQQQQQQQ	QQQQQQQLNH	VDGSSKPAVL	AAPSGLERYG
LSAAAAAAAA	AAAAVEQRSR	FEYPPPPVSL	GSSSHTARLP	NGLGGPNGFP
KPTPEEGPPE	LNRQSPNSSS	AAASVASRRG	THGGLVTGLP	NPGGGGGPQL
TVPPNLLPQT	LLNGPASAAV	LPPPPPHALG	SRGPPTPAPP	GAPGGPACLG
GTPGVSATSS	SASSSTSSSV	AEVGVGAGGK	RPGSVSSTDQ	ERELKEKQRN
AEALAELSES	LRNRAEEWAS	KPKMVRDTLL	TLAGCTPYEV	RFKKDHSLLG
RVFAFDAVSK	PGMDYELKLF	IEYPTGSGNV	YSSASGVAKQ	MYQDCMKDFG
RGLSSGFKYL	EYEKKHGSGD	WRLLGDLLPE	AVRFFKEGVP	GADMLPQPYL
DASCPMLPTA	LVSLSRAPSA	PPGTGALPPA	APSGRGAAAS	LRKRKASPEP
PDSAEGALKL	GEEQQRQQWM	ANQSEALKLT	MSAGGFAAPG	HAAGGPPPPP
PPLGPHSNRT	TPPESAPQNG	PSPMAALMSV	ADTLGTAHSP	KDGSSVHSTT
ASARRNSSSP	VSPASVPGQR	RLASRNGDLN	LQVAPPPPSA	HPGMDQVHPQ
NIPDSPMANS	GPLCCTICHE	RLEDTHFVQC	PSVPSHKFCF	PCSRESIKAQ
GATGEVYCPS	GEKCPLVGSN	VPWAFMQGEI	ATILAGDVKV	KKERDP

Simboli

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

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000119669 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000034168 - 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.
^ Rampazzo A, Pivotto F, Occhi G, Tiso N, Bortoluzzi S, Rowen L, Hood L, Nava A, Danieli GA (Nov 2000). "Characterization of C14orf4, a novel intronless human gene containing a polyglutamine repeat, mapped to the ARVD1 critical region". Biochemical and Biophysical Research Communications. 278 (3): 766–74. doi:10.1006/bbrc.2000.3883. PMID 11095982.
^ Heger S, Mastronardi C, Dissen GA, Lomniczi A, Cabrera R, Roth CL, Jung H, Galimi F, Sippell W, Ojeda SR (Aug 2007). "Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis". The Journal of Clinical Investigation. 117 (8): 2145–54. doi:10.1172/JCI31752. PMC 1906733. PMID 17627301.
^ "IRF2BPL interferon regulatory factor 2 binding protein like [Homo sapiens (human) ]".
^ Paul C. Marcogliese; et al. (2018). "IRF2BPL Is Associated with Neurological Phenotypes". American Journal of Human Genetics. 103 (2): 245–260. doi:10.1016/j.ajhg.2018.07.006. PMC 6081494. PMID 30057031.
^ Rampazzo, A., Pivotto, F., Occhi, G., Tiso, N., Bortoluzzi, S., Rowen, L., Hood, L., Nava, A., Danieli, G. A. Characterization of C14orf4, a novel intronless human gene containing a polyglutamine repeat, mapped to the ARVD1 critical region. Biochem. Biophys. Res. Commun. 278: 766-774, 2000. PubMed: 11095982
^ Tran Mau-Them, F., Guibaud, L., Duplomb, L., Keren, B., Lindstrom, K., Marey, I., Mochel, F., van den Boogaard, M. J., Oegema, R., Nava, C., Masurel, A., Jouan, T., and 26 others. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet. Med. 21: 1008-1014, 2019. PubMed: 30166628
^ Marcogliese, P. C., Shashi, V., Spillmann, R. C., Stong, N., Rosenfeld, J. A., Koenig, M. K., Martinez-Agosto, J. A., Herzog, M., Chen, A. H., Dickson, P. I., Lin, H. J., Vera, M. U., and 22 others. IRF2BPL is associated with neurological phenotypes. Am. J. Hum. Genet. 103: 245-260, 2018. Note: Erratum: Am. J. Hum. Genet. 103: 456 only, 2018. PubMed: 30057031
^ "UniProt, Q9H1B7". Pristupljeno 26. 7. 2021.

Dopunska literatura

Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (Apr 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT (Aug 2002). "Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1". The Journal of Biological Chemistry. 277 (31): 28238–46. doi:10.1074/jbc.M202783200. PMID 12029088.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP (Nov 2004). "Phosphoproteomic analysis of the developing mouse brain". Molecular & Cellular Proteomics. 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.

Vanjski linkovi

Lokacija ljudskog genoma IRF2BPL i stranica sa detaljima o genu IRF2BPL u UCSC Genome Browseru.
Parent Group Europe http://irf2bpl.de

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000119669 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000034168 - 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.

[pmid11095982-5] Rampazzo A, Pivotto F, Occhi G, Tiso N, Bortoluzzi S, Rowen L, Hood L, Nava A, Danieli GA (Nov 2000). "Characterization of C14orf4, a novel intronless human gene containing a polyglutamine repeat, mapped to the ARVD1 critical region". Biochemical and Biophysical Research Communications. 278 (3): 766–74. doi:10.1006/bbrc.2000.3883. PMID 11095982.

[pmid17627301-6] Heger S, Mastronardi C, Dissen GA, Lomniczi A, Cabrera R, Roth CL, Jung H, Galimi F, Sippell W, Ojeda SR (Aug 2007). "Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis". The Journal of Clinical Investigation. 117 (8): 2145–54. doi:10.1172/JCI31752. PMC 1906733. PMID 17627301.

[entrez-7] "IRF2BPL interferon regulatory factor 2 binding protein like [Homo sapiens (human) ]".

[8] Paul C. Marcogliese; et al. (2018). "IRF2BPL Is Associated with Neurological Phenotypes". American Journal of Human Genetics. 103 (2): 245–260. doi:10.1016/j.ajhg.2018.07.006. PMC 6081494. PMID 30057031.

[9] Rampazzo, A., Pivotto, F., Occhi, G., Tiso, N., Bortoluzzi, S., Rowen, L., Hood, L., Nava, A., Danieli, G. A. Characterization of C14orf4, a novel intronless human gene containing a polyglutamine repeat, mapped to the ARVD1 critical region. Biochem. Biophys. Res. Commun. 278: 766-774, 2000. PubMed: 11095982

[10] Tran Mau-Them, F., Guibaud, L., Duplomb, L., Keren, B., Lindstrom, K., Marey, I., Mochel, F., van den Boogaard, M. J., Oegema, R., Nava, C., Masurel, A., Jouan, T., and 26 others. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet. Med. 21: 1008-1014, 2019. PubMed: 30166628

[11] Marcogliese, P. C., Shashi, V., Spillmann, R. C., Stong, N., Rosenfeld, J. A., Koenig, M. K., Martinez-Agosto, J. A., Herzog, M., Chen, A. H., Dickson, P. I., Lin, H. J., Vera, M. U., and 22 others. IRF2BPL is associated with neurological phenotypes. Am. J. Hum. Genet. 103: 245-260, 2018. Note: Erratum: Am. J. Hum. Genet. 103: 456 only, 2018. PubMed: 30057031

[UniProt-12] "UniProt, Q9H1B7". Pristupljeno 26. 7. 2021.

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