Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 Jan 22;2854:2527-36. doi: 10.1074/jbc.M109.022236.
Show Gene links
Show Anatomy links
The beta subunit of voltage-gated Ca2+ channels interacts with and regulates the activity of a novel isoform of Pax6.
Zhang Y, Yamada Y, Fan M, Bangaru SD, Lin B, Yang J.
???displayArticle.abstract???
Ca(2+) channel beta subunits (Ca(v)betas) are essential for regulating the surface expression and gating of high voltage-activated Ca(2+) channels through their interaction with Ca(2+) channel alpha(1) subunits. In efforts to uncover new interacting partners and new functions for Ca(v)beta, we identified a new splicing isoform of Pax6, a transcription factor crucial for the development of the eye, nose, brain, and pancreas. Pax6 contains two DNA binding domains (paired domain and homeodomain), a glycine-rich linker connecting these two domains and a C-terminal proline-, serine-, and threonine-rich transactivation domain. The protein sequence and function of Pax6 are highly conserved from invertebrate to human. The newly isolated isoform, named Pax6(S), retains the paired domain, linker, and homeodomain of Pax6, but its C terminus is composed of a truncated classic proline, serine, and threonine domain and a unique S tail. Pax6(S) shows a similar level of transcriptional activity in vitro as does Pax6, but only in primates is the protein sequence highly conserved. Its spatial-temporal expression profiles are also different from those of Pax6. These divergences suggest a noncanonical role of Pax6(S) during development. The interaction between Pax6(S) and Ca(v)beta is mainly endowed by the S tail. Co-expression of Pax6(S) with a Ca(2+) channel complex containing the beta(3) subunit in Xenopus oocytes does not affect channel properties. Conversely, however, beta(3) is able to suppress the transcriptional activity of Pax6(S). Furthermore, in the presence of Pax6(S), beta(3) is translocated from the cytoplasm to the nucleus. These results suggest that full-length Ca(v)beta may act directly as a transcription regulator independent of its role in regulating Ca(2+) channel activity.
Altmann,
Lens induction by Pax-6 in Xenopus laevis.
1997, Pubmed,
Xenbase
Altmann,
Lens induction by Pax-6 in Xenopus laevis.
1997,
Pubmed
,
Xenbase Arikkath,
Auxiliary subunits: essential components of the voltage-gated calcium channel complex.
2003,
Pubmed Béguin,
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem.
2001,
Pubmed
,
Xenbase Béguin,
Nuclear sequestration of beta-subunits by Rad and Rem is controlled by 14-3-3 and calmodulin and reveals a novel mechanism for Ca2+ channel regulation.
2006,
Pubmed Birnbaumer,
Structures and functions of calcium channel beta subunits.
1998,
Pubmed
,
Xenbase Bolognani,
RNA-protein interactions and control of mRNA stability in neurons.
2008,
Pubmed Brink,
Promoter elements in endocrine pancreas development and hormone regulation.
2003,
Pubmed Callaerts,
PAX-6 in development and evolution.
1997,
Pubmed Cannell,
How do microRNAs regulate gene expression?
2008,
Pubmed Carrière,
Nuclear localization signals, DNA binding, and transactivation properties of quail Pax-6 (Pax-QNR) isoforms.
1995,
Pubmed Chen,
Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels.
2004,
Pubmed Cheng,
Interaction between the dihydropyridine receptor Ca2+ channel beta-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling.
2005,
Pubmed Chow,
Pax6 induces ectopic eyes in a vertebrate.
1999,
Pubmed
,
Xenbase Colecraft,
Novel functional properties of Ca(2+) channel beta subunits revealed by their expression in adult rat heart cells.
2002,
Pubmed Czerny,
DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5).
1995,
Pubmed Dahl,
Pax genes and organogenesis.
1997,
Pubmed Dohrmann,
Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas.
2000,
Pubmed Dolphin,
Beta subunits of voltage-gated calcium channels.
2003,
Pubmed Engel,
Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation.
1998,
Pubmed Evans,
Translational control of maternal RNAs.
2005,
Pubmed Finlin,
Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases.
2003,
Pubmed Glaser,
PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects.
1994,
Pubmed Gonzalez-Gutierrez,
The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction.
2007,
Pubmed
,
Xenbase Guinez,
O-GlcNAc glycosylation: a signal for the nuclear transport of cytosolic proteins?
2005,
Pubmed Haase,
Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation.
2005,
Pubmed Haase,
Signaling from beta-adrenoceptor to L-type calcium channel: identification of a novel cardiac protein kinase A target possessing similarities to AHNAK.
1999,
Pubmed Habener,
A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus.
1998,
Pubmed Halder,
Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila.
1995,
Pubmed He,
Functional modularity of the beta-subunit of voltage-gated Ca2+ channels.
2007,
Pubmed Hibino,
Direct interaction with a nuclear protein and regulation of gene silencing by a variant of the Ca2+-channel beta 4 subunit.
2003,
Pubmed
,
Xenbase Hidalgo,
Multiplicity of protein interactions and functions of the voltage-gated calcium channel beta-subunit.
2007,
Pubmed Hsueh,
Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2.
2000,
Pubmed Hsueh,
The role of the MAGUK protein CASK in neural development and synaptic function.
2006,
Pubmed Jackson,
Hdm2 nuclear export, regulated by insulin-like growth factor-I/MAPK/p90Rsk signaling, mediates the transformation of human cells.
2006,
Pubmed Jans,
p34cdc2-mediated phosphorylation at T124 inhibits nuclear import of SV-40 T antigen proteins.
1991,
Pubmed Kim,
Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein kinase 2.
2006,
Pubmed Kiyonaka,
RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels.
2007,
Pubmed Kozmik,
The role of Pax genes in eye evolution.
2008,
Pubmed Kozmik,
Pax genes in eye development and evolution.
2005,
Pubmed Lefebvre,
O-glycosylation of the nuclear forms of Pax-6 products in quail neuroretina cells.
2002,
Pubmed López de Silanes,
Aberrant regulation of messenger RNA 3'-untranslated region in human cancer.
2007,
Pubmed Manuel,
Role of Pax6 in forebrain regionalization.
2005,
Pubmed Mikkola,
Phosphorylation of the transactivation domain of Pax6 by extracellular signal-regulated kinase and p38 mitogen-activated protein kinase.
1999,
Pubmed Monsigny,
Glyco-dependent nuclear import of glycoproteins, glycoplexes and glycosylated plasmids.
2004,
Pubmed Nomura,
Role of a transcription factor Pax6 in the developing vertebrate olfactory system.
2007,
Pubmed Onuma,
Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies.
2002,
Pubmed
,
Xenbase Opatowsky,
Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain.
2004,
Pubmed Osumi,
Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator.
2008,
Pubmed Pichaud,
Pax genes and eye organogenesis.
2002,
Pubmed Pickering,
The implications of structured 5' untranslated regions on translation and disease.
2005,
Pubmed Sakurai,
The neurogenesis-controlling factor, Pax6, inhibits proliferation and promotes maturation in murine astrocytes.
2008,
Pubmed Schwab,
Protein phosphorylation sites regulate the function of the bipartite NLS of nucleolin.
1997,
Pubmed
,
Xenbase Shyu,
Messenger RNA regulation: to translate or to degrade.
2008,
Pubmed Singh,
Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function.
2001,
Pubmed Stanescu,
Continuous expression of the homeobox gene Pax6 in the ageing human retina.
2007,
Pubmed Steinman,
mRNA stability control: a clandestine force in normal and malignant hematopoiesis.
2007,
Pubmed Strachan,
PAX genes.
1994,
Pubmed Takahashi,
Association of insulin-like growth-factor-I-induced DNA synthesis with phosphorylation and nuclear exclusion of p53 in human breast cancer MCF-7 cells.
1993,
Pubmed Tang,
Dissection of the transactivation function of the transcription factor encoded by the eye developmental gene PAX6.
1998,
Pubmed Tjian,
Transcriptional activation: a complex puzzle with few easy pieces.
1994,
Pubmed Ton,
Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.
1991,
Pubmed van der Velden,
The role of the 5' untranslated region of an mRNA in translation regulation during development.
1999,
Pubmed
,
Xenbase Van Petegem,
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.
2004,
Pubmed Walther,
Pax: a murine multigene family of paired box-containing genes.
1991,
Pubmed Walther,
Pax-6, a murine paired box gene, is expressed in the developing CNS.
1991,
Pubmed Yan,
Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development.
2007,
Pubmed Yang,
Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.
1998,
Pubmed
,
Xenbase Yu,
The best disease-linked Cl- channel hBest1 regulates Ca V 1 (L-type) Ca2+ channels via src-homology-binding domains.
2008,
Pubmed Ziman,
Pax genes in development and maturation of the vertebrate visual system: implications for optic nerve regeneration.
2001,
Pubmed
,
Xenbase
