BCL9

BCL9
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2GL7, 2VP7, 2VPB, 2VPD, 2VPE, 2VPG, 3SL9
Identifikatori
Aliasi	BCL9
Vanjski ID-jevi	OMIM: 602597 MGI: 1924828 HomoloGene: 3191 GeneCards: BCL9
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	147,626,216 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	97,205,233 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• beta-catenin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • GO:0001105 transcription coactivator activity;
Ćelijska komponenta	• citoplazma; • cis-Golgi network; • Golđijev aparat; • jedro; • nukleoplazma; • beta-catenin-TCF complex;
Biološki proces	• skeletal muscle cell differentiation; • canonical Wnt signaling pathway; • Wnt-signalni put; • somatic stem cell population maintenance; • myotube differentiation involved in skeletal muscle regeneration; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • regulation of transforming growth factor beta receptor signaling pathway; • beta-catenin-TCF complex assembly;
	Izvori:Amigo / QuickGO
Ortolozi
	607
	77578
	ENSG00000116128
	ENSMUSG00000038256
	O00512
	Q9D219
	NM_004326
	NM_029933
	NP_004317
	NP_084209
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

B-ćelijski protein CLL/limfoma 9 jest protein koji je kod ljudi kodiran genom BCL9 sa hromosoma 1.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.426 aminokiselina, a molekulska 149.290 težina Da.^[7]

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
MHSSNPKVRS	SPSGNTQSSP	KSKQEVMVRP	PTVMSPSGNP	QLDSKFSNQG
KQGGSASQSQ	PSPCDSKSGG	HTPKALPGPG	GSMGLKNGAG	NGAKGKGKRE
RSISADSFDQ	RDPGTPNDDS	DIKECNSADH	IKSQDSQHTP	HSMTPSNATA
PRSSTPSHGQ	TTATEPTPAQ	KTPAKVVYVF	STEMANKAAE	AVLKGQVETI
VSFHIQNISN	NKTERSTAPL	NTQISALRND	PKPLPQQPPA	PANQDQNSSQ
NTRLQPTPPI	PAPAPKPAAP	PRPLDRESPG	VENKLIPSVG	SPASSTPLPP
DGTGPNSTPN	NRAVTPVSQG	SNSSSADPKA	PPPPPVSSGE	PPTLGENPDG
LSQEQLEHRE	RSLQTLRDIQ	RMLFPDEKEF	TGAQSGGPQQ	NPGVLDGPQK
KPEGPIQAMM	AQSQSLGKGP	GPRTDVGAPF	GPQGHRDVPF	SPDEMVPPSM
NSQSGTIGPD	HLDHMTPEQI	AWLKLQQEFY	EEKRRKQEQV	VVQQCSLQDM
MVHQHGPRGV	VRGPPPPYQM	TPSEGWAPGG	TEPFSDGINM	PHSLPPRGMA
PHPNMPGSQM	RLPGFAGMIN	SEMEGPNVPN	PASRPGLSGV	SWPDDVPKIP
DGRNFPPGQG	IFSGPGRGER	FPNPQGLSEE	MFQQQLAEKQ	LGLPPGMAME
GIRPSMEMNR	MIPGSQRHME	PGNNPIFPRI	PVEGPLSPSR	GDFPKGIPPQ
MGPGRELEFG	MVPSGMKGDV	NLNVNMGSNS	QMIPQKMREA	GAGPEEMLKL
RPGGSDMLPA	QQKMVPLPFG	EHPQQEYGMG	PRPFLPMSQG	PGSNSGLRNL
REPIGPDQRT	NSRLSHMPPL	PLNPSSNPTS	LNTAPPVQRG	LGRKPLDISV
AGSQVHSPGI	NPLKSPTMHQ	VQSPMLGSPS	GNLKSPQTPS	QLAGMLAGPA
AAASIKSPPV	LGSAAASPVH	LKSPSLPAPS	PGWTSSPKPP	LQSPGIPPNH
KAPLTMASPA	MLGNVESGGP	PPPTASQPAS	VNIPGSLPSS	TPYTMPPEPT
LSQNPLSIMM	SRMSKFAMPS	STPLYHDAIK	TVASSDDDSP	PARSPNLPSM
NNMPGMGINT	QNPRISGPNP	VVPMPTLSPM	GMTQPLSHSN	QMPSPNAVGP
NIPPHGVPMG	PGLMSHNPIM	GHGSQEPPMV	PQGRMGFPQG	FPPVQSPPQQ
VPFPHNGPSG	GQGSFPGGMG	FPGEGPLGRP	SNLPQSSADA	ALCKPGGPGG
PDSFTVLGNS	MPSVFTDPDL	QEVIRPGATG	IPEFDLSRII	PSEKPSQTLQ
YFPRGEVPGR	KQPQGPGPGF	SHMQGMMGEQ	APRMGLALPG	MGGPGPVGTP
DIPLGTAPSM	PGHNPMRPPA	FLQQGMMGPH	HRMMSPAQST	MPGQPTLMSN
PAAAVGMIPG	KDRGPAGLYT	HPGPVGSPGM	MMSMQGMMGP	QQNIMIPPQM
RPRGMAADVG	MGGFSQGPGN	PGNMMF

Funkcija

BCL9, zajedno sa svojim paralognim genom BCL9L (slično BCL9 ili BCL9.2), opsežno je proučavan zbog njihove uloge kofaktora transkripcije beta-katenina, osnovnih za transkripciju Wnt-signalizacija|Wnt-ciljnih gena]].^[8]

Nedavni rad, koristeći miša (Mus musculus) i zebricu (Danio rerio) kao modelne organizme, identifikovao je drevnu ulogu BCL9 i BCL9L kao ključnih faktora potrebnih za razvoj srca.^[9] Ovaj rad naglašava tkivno specifičnu prirodu mehanizma djelovanja Wnt/β-katenina i implicira promjene u BCL9 i BCL9L kod ljudskih urođenih srčanih mahana.

Pokazalo se da BCL9 i BCL9L učestvuju u drugim tkivno-specifičnim molekulskim mehanizmima, pokazujući da je njihova uloga u Wnt signalnoj kaskadi samo jedan aspekt njihovog načina djelovanja.^[10]

Klinički značaj

B-ćelijskom akutnom limfoblastnom leukemijom. Može biti meta translokacije kod maligniteta B-ćelija s abnormalnostima 1q21. Prekomjerna ekspresija BCL9 može biti od patogenog značaja kod maligniteta B-ćelija.^[6]

BCL9 i BCL9L su potencijalne kliničke mete za ljudske karcinome; naprimjer, promjene ekspresije gena koje oni promoviraju povezane su sa lošim ishodom kod kolorektumskog karcinoma.^[11]

Poput BCL2, BCL3, BCL5, BCL6, BCL7A i BCL10, ima klinički značaj kod limfoma.

Uobičajene varijacije gena BCL9, koji se nalazi u distalnom području, daju rizik od shizofrenije i mogu biti povezane s bipolarnim poremećajem i velikim depresivnim poremećajem.^[12]

BCL9, zajedno sa paralognim proteinom BCL9l i PYGO2, također ima citoplazmatske funkcije tokom razvoja zuba i posebno je važan za formiranje gleđi. Miševi kojima nedostaju i Pygo1 i Pygo2 ili oba Bcl9 i Bcl9l razvijaju zube, proces koji zahtijeva regulaciju transkripcije Wnt/β-katenina, ali caklina je strukturno neorganizirana i sadrži manje gvožđa od zuba kontrolnih miševa. Bcl9, Bcl9l i Pygo2 su prisutni u citoplazmi ameloblasta, ćelija koje luče proteine cakline, a nalaze se u tim ćelijama sa amelogeninom, glavnom komponentom cakline, kodirane genom AMELX, koji je već impliciran kao uzročni faktor amelogenesis imperfecta kod ljudi. Bcl9 stupa u interakciju s amelogeninom i proteinima uključenim u egzocitozu i vezikulski promet, što sugerira da ovi proteini funkcioniraju u prometu ili izlučivanju proteina cakline. Stoga, Bcl9, Bcl9l i Pygo2 imaju citoplazmatske funkcije različite od njihove uloge kofaktora transkripcije nizvodno od Wnt signalizacije.^[13] Ovo novo otkriće moglo bi poboljšati razumijevanje liječenja karijesa kod ljudi.^[14]

Srodni genetički poremećaji

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000116128 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038256 - 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.
^ Willis TG, Zalcberg IR, Coignet LJ, Wlodarska I, Stul M, Jadayel DM, Bastard C, Treleaven JG, Catovsky D, Silva ML, Dyer MJ (Mar 1998). "Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21". Blood. 91 (6): 1873–81. doi:10.1182/blood.V91.6.1873. PMID 9490669.
^ ^a ^b "Entrez Gene: BCL9 B-cell CLL/lymphoma 9".
^ "UniProt, O00512" (jezik: en.). Pristupljeno 8. 12. 2021.CS1 održavanje: nepoznati jezik (link)
^ Mosimann C, Hausmann G, Basler K (Apr 2009). "Beta-catenin hits chromatin: regulation of Wnt target gene activation". Nature Reviews. Molecular Cell Biology. 10 (4): 276–86. doi:10.1038/nrm2654. PMID 19305417. S2CID 7602580.
^ Cantù, Claudio; Felker, Anastasia; Zimmerli, Dario; Prummel, Karin; Cabello, Elena; Chiavacci, Elena; Mendez-Acevedo, Kevin; Kirchgeorg, Lucia; Sibylle, Burger; Ripoll, Jorge; Valenta, Tomas; Hausmann, George; Vilain, Nathalie; Aguet, Michel; Burger, Alexa; Panáková, Daniela; Basler, Konrad; Mosimann, Christian (1. 11. 2018). "Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling". Genes & Development. 32 (21–22): 1443–1458. doi:10.1101/gad.315531.118. PMC 6217730. PMID 30366904.
^ Cantù C, Zimmerli D, Hausmann G, Valenta T, Moor A, Aguet M, Basler K (Sep 2014). "Pax6-dependent, but β-catenin-independent, function of Bcl9 proteins in mouse lens development". Genes & Development. 28 (17): 1879–84. doi:10.1101/gad.246140.114. PMC 4197948. PMID 25184676.
^ Moor AE, Anderle P, Cantù C, Rodriguez P, Wiedemann N, Baruthio F, Deka J, André S, Valenta T (1. 12. 2015). "BCL9/9L-β-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer". EBioMedicine. 2 (12): 1932–1943. doi:10.1016/j.ebiom.2015.10.030. PMC 4703711. PMID 26844272.
^ Li J, Zhou G, Ji W, Feng G, Zhao Q, Liu J, Li T, Li Y, Chen P, Zeng Z, Wang T, Hu Z, Zheng L, Wang Y, Shen Y, He L, Shi Y (2011). "Common variants in the BCL9 gene conferring risk of schizophrenia". Archives of General Psychiatry. 68 (3): 232–40. doi:10.1001/archgenpsychiatry.2011.1. PMID 21383261.
^ Cantù C, Pagella P, Shajiei TD, Zimmerli D, Valenta T, Hausmann G, Basler K, Mitsiadis TA (7. 2. 2017). "A cytoplasmic role of Wnt/β-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation". Sci. Signal. 10 (465): eaah4598. doi:10.1126/scisignal.aah4598. ISSN 1945-0877. PMID 28174279. S2CID 6845295.
^ "Mutated genes lead to tooth enamel defects that increase risk of caries". News-Medical.net. 7. 2. 2017. Pristupljeno 8. 2. 2017.

Dopunska literatura

Busson-Le Coniat M, Salomon-Nguyen F, Dastugue N, Maarek O, Lafage-Pochitaloff M, Mozziconacci MJ, Baranger L, Brizard F, Radford I, Jeanpierre M, Bernard OA, Berger R (Dec 1999). "Fluorescence in situ hybridization analysis of chromosome 1 abnormalities in hematopoietic disorders: rearrangements of DNA satellite II and new recurrent translocations". Leukemia. 13 (12): 1975–81. doi:10.1038/sj/leu/2401587. PMID 10602418.
Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S, Murone M, Züllig S, Basler K (Apr 2002). "Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex" (PDF). Cell. 109 (1): 47–60. doi:10.1016/S0092-8674(02)00679-7. PMID 11955446. S2CID 16720801. Arhivirano s originala (PDF), 26. 9. 2021. Pristupljeno 8. 12. 2021.
Knoll A, Dvorák J, Rohrer GA, Cepica S (Apr 2002). "Linkage and cytogenetic mapping of the BCL9 gene to porcine chromosome 4". Animal Genetics. 33 (2): 162–3. doi:10.1046/j.1365-2052.2002.0831e.x. PMID 12047235.
Townsley FM, Thompson B, Bienz M (Feb 2004). "Pygopus residues required for its binding to Legless are critical for transcription and development". The Journal of Biological Chemistry. 279 (7): 5177–83. doi:10.1074/jbc.M309722200. PMID 14612447.
Hoffmans R, Basler K (Sep 2004). "Identification and in vivo role of the Armadillo-Legless interaction". Development. 131 (17): 4393–400. doi:10.1242/dev.01296. PMID 15294866.
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. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W (Oct 2006). "Crystal structure of a beta-catenin/BCL9/Tcf4 complex". Molecular Cell. 24 (2): 293–300. doi:10.1016/j.molcel.2006.09.001. PMID 17052462.
Hoffmans R, Basler K (Jan 2007). "BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling". Mechanisms of Development. 124 (1): 59–67. doi:10.1016/j.mod.2006.09.006. PMID 17113272. S2CID 17642255.

Vanjski linkovi

Lokacija ljudskog genoma BCL9 i stranica sa detaljima o genu BCL9 u UCSC Genome Browseru.
O00512

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000116128 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000038256 - 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.

[pmid9490669-5] Willis TG, Zalcberg IR, Coignet LJ, Wlodarska I, Stul M, Jadayel DM, Bastard C, Treleaven JG, Catovsky D, Silva ML, Dyer MJ (Mar 1998). "Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21". Blood. 91 (6): 1873–81. doi:10.1182/blood.V91.6.1873. PMID 9490669.

[entrez-6] "Entrez Gene: BCL9 B-cell CLL/lymphoma 9".

[UniProt-7] "UniProt, O00512" (jezik: en.). Pristupljeno 8. 12. 2021.CS1 održavanje: nepoznati jezik (link)

[8] Mosimann C, Hausmann G, Basler K (Apr 2009). "Beta-catenin hits chromatin: regulation of Wnt target gene activation". Nature Reviews. Molecular Cell Biology. 10 (4): 276–86. doi:10.1038/nrm2654. PMID 19305417. S2CID 7602580.

[9] Cantù, Claudio; Felker, Anastasia; Zimmerli, Dario; Prummel, Karin; Cabello, Elena; Chiavacci, Elena; Mendez-Acevedo, Kevin; Kirchgeorg, Lucia; Sibylle, Burger; Ripoll, Jorge; Valenta, Tomas; Hausmann, George; Vilain, Nathalie; Aguet, Michel; Burger, Alexa; Panáková, Daniela; Basler, Konrad; Mosimann, Christian (1. 11. 2018). "Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling". Genes & Development. 32 (21–22): 1443–1458. doi:10.1101/gad.315531.118. PMC 6217730. PMID 30366904.

[10] Cantù C, Zimmerli D, Hausmann G, Valenta T, Moor A, Aguet M, Basler K (Sep 2014). "Pax6-dependent, but β-catenin-independent, function of Bcl9 proteins in mouse lens development". Genes & Development. 28 (17): 1879–84. doi:10.1101/gad.246140.114. PMC 4197948. PMID 25184676.

[11] Moor AE, Anderle P, Cantù C, Rodriguez P, Wiedemann N, Baruthio F, Deka J, André S, Valenta T (1. 12. 2015). "BCL9/9L-β-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer". EBioMedicine. 2 (12): 1932–1943. doi:10.1016/j.ebiom.2015.10.030. PMC 4703711. PMID 26844272.

[pmid21383261-12] Li J, Zhou G, Ji W, Feng G, Zhao Q, Liu J, Li T, Li Y, Chen P, Zeng Z, Wang T, Hu Z, Zheng L, Wang Y, Shen Y, He L, Shi Y (2011). "Common variants in the BCL9 gene conferring risk of schizophrenia". Archives of General Psychiatry. 68 (3): 232–40. doi:10.1001/archgenpsychiatry.2011.1. PMID 21383261.

[13] Cantù C, Pagella P, Shajiei TD, Zimmerli D, Valenta T, Hausmann G, Basler K, Mitsiadis TA (7. 2. 2017). "A cytoplasmic role of Wnt/β-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation". Sci. Signal. 10 (465): eaah4598. doi:10.1126/scisignal.aah4598. ISSN 1945-0877. PMID 28174279. S2CID 6845295.

[14] "Mutated genes lead to tooth enamel defects that increase risk of caries". News-Medical.net. 7. 2. 2017. Pristupljeno 8. 2. 2017.

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