Gene Symbol: Cacnb2
Description: calcium voltage-gated channel auxiliary subunit beta 2
Alias: Cacnlb2, voltage-dependent L-type calcium channel subunit beta-2, CAB2, calcium channel voltage-dependent subunit beta 2, calcium channel, voltage-dependent, beta 2 subunit
Species: rat
Products:     Cacnb2

Top Publications

  1. Van Petegem F, Clark K, Chatelain F, Minor D. Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. Nature. 2004;429:671-5 pubmed
    ..Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore. ..
  2. Opatowsky Y, Chomsky Hecht O, Kang M, Campbell K, Hirsch J. The voltage-dependent calcium channel beta subunit contains two stable interacting domains. J Biol Chem. 2003;278:52323-32 pubmed
    ..Domain II is responsible for this binding, but domain I enhances it. ..
  3. Colecraft H, Alseikhan B, Takahashi S, Chaudhuri D, Mittman S, Yegnasubramanian V, et al. Novel functional properties of Ca(2+) channel beta subunits revealed by their expression in adult rat heart cells. J Physiol. 2002;541:435-52 pubmed
    ..Overall, the work establishes a powerful experimental paradigm to explore novel functions of ion channel subunits in their native environments. ..
  4. Dionisio N, Smani T, Woodard G, Castellano A, Salido G, Rosado J. Homer proteins mediate the interaction between STIM1 and Cav1.2 channels. Biochim Biophys Acta. 2015;1853:1145-53 pubmed publisher
    ..2-expressing cells. Altogether, these findings provide evidence for a new role of Homer1 supporting the regulation of Cav1.2 channels by STIM1. ..
  5. Catterall W. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3:a003947 pubmed publisher
    ..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties. ..
  6. Grueter C, Abiria S, Wu Y, Anderson M, Colbran R. Differential regulated interactions of calcium/calmodulin-dependent protein kinase II with isoforms of voltage-gated calcium channel beta subunits. Biochemistry. 2008;47:1760-7 pubmed publisher
    ..In combination, these data show that phosphorylation dynamically regulates the interactions of specific isoforms of the Ca2+ channel beta subunits with CaMKII. ..
  7. Gonzalez Gutierrez G, Miranda Laferte E, Neely A, Hidalgo P. The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction. J Biol Chem. 2007;282:2156-62 pubmed
    ..Our findings define a novel function for the beta-subunit through its Src homology 3 domain and establish a link between voltage-gated calcium channel activity and the cell endocytic machinery. ..
  8. Burgess D, Biddlecome G, McDonough S, Diaz M, Zilinski C, Bean B, et al. beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. Mol Cell Neurosci. 1999;13:293-311 pubmed
    ..The existence of beta subunit reshuffling demonstrates that molecular plasticity of Ca2+ channel assembly, a normal feature of early brain development, is retained in the mature brain. ..
  9. Stölting G, de Oliveira R, Guzman R, Miranda Laferte E, Conrad R, Jordan N, et al. Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes. J Biol Chem. 2015;290:4561-72 pubmed publisher
    ..We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. ..

More Information


  1. Rokita A, Anderson M. New therapeutic targets in cardiology: arrhythmias and Ca2+/calmodulin-dependent kinase II (CaMKII). Circulation. 2012;126:2125-39 pubmed publisher
  2. Hong G, Chen X, Liu Y, Liu Y, Fu X, Lin S, et al. Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population. Genet Mol Res. 2013;12:6220-7 pubmed publisher
    ..However, SNP rs4373814, a variant in CACNB2, showed a relevant association with a decreased risk of hypertension...
  3. Carrillo E, Escobar Y, Gonzalez G, Hernández A, Galindo J, Garcia M, et al. Posttranscriptional regulation of the ?2-subunit of cardiac L-type Ca2+ channels by MicroRNAs during long-term exposure to isoproterenol in rats. J Cardiovasc Pharmacol. 2011;58:470-8 pubmed publisher
    ..The effects of long-term ?-adrenergic administration on the expression levels of the cardiac L-type Ca channel ?2 subunit, which regulates channel trafficking and function, were characterized in adult rats...
  4. Yamada Y, Nagashima M, Tsutsuura M, Kobayashi T, Seki S, Makita N, et al. Cloning of a functional splice variant of L-type calcium channel beta 2 subunit from rat heart. J Biol Chem. 2001;276:47163-70 pubmed
    ..Taken together, these observations suggest that the beta(2c) subunit is a functional beta(2) subunit expressed in heart and that the short N-terminal region plays a major role in modifying inactivation kinetics. ..
  5. Williams M, Feldman D, McCue A, Brenner R, Velicelebi G, Ellis S, et al. Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992;8:71-84 pubmed
    ..At least two forms of neuronal alpha 1D were identified. Different forms of alpha 2 and beta transcripts were also identified in CNS, skeletal muscle, and aorta tissues. ..
  6. Thomas J, Hagen J, Soh D, Lee A. Molecular moieties masking Ca2+-dependent facilitation of voltage-gated Cav2.2 Ca2+ channels. J Gen Physiol. 2018;150:83-94 pubmed publisher
    ..Our results reveal a functional divergence in the CDF regulatory domains of Cav2 channels, which may help to diversify the modes by which Cav2.1 and Cav2.2 can modify synaptic transmission. ..
  7. Cens T, Rousset M, Kajava A, Charnet P. Molecular determinant for specific Ca/Ba selectivity profiles of low and high threshold Ca2+ channels. J Gen Physiol. 2007;130:415-25 pubmed
    ..These data therefore attribute to the DCS a unique role in the specific shaping of the Ca(2+) influx between the different HVA channels...
  8. Taviaux S, Williams M, Harpold M, Nargeot J, Lory P. Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent Ca2+ channels to chromosomes 10p12 and 2q22-q23. Hum Genet. 1997;100:151-4 pubmed
    ..b>CACNB2 (beta 2) and CACNB4 (beta 4), to human chromosomes 10p12 and 2q22-q23, respectively, by fluorescence in situ ..
  9. Perez Reyes E, Castellano A, Kim H, Bertrand P, Baggstrom E, Lacerda A, et al. Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. J Biol Chem. 1992;267:1792-7 pubmed
    ..These results indicate that the cardiac L-type Ca2+ channel has a similar subunit structure as in skeletal muscle, and provides evidence for the modulatory role of the beta subunit. ..
  10. Li L, Cao X, Chen S, Han H, Lopez Berestein G, Sood A, et al. Up-regulation of Cav?3 subunit in primary sensory neurons increases voltage-activated Ca2+ channel activity and nociceptive input in neuropathic pain. J Biol Chem. 2012;287:6002-13 pubmed publisher
    ..Targeting the Cav?(3) subunit at the spinal level represents an effective strategy for treating neuropathic pain. ..
  11. Lautermilch N, Few A, Scheuer T, Catterall W. Modulation of CaV2.1 channels by the neuronal calcium-binding protein visinin-like protein-2. J Neurosci. 2005;25:7062-70 pubmed
    ..Differential regulation of CaV2.1 channels by CaM, VILIP-2, CaBP1, and other neurospecific Ca2+-binding proteins is a potentially important determinant of Ca2+ entry in neurotransmission. ..
  12. Miriyala J, Nguyen T, Yue D, Colecraft H. Role of CaVbeta subunits, and lack of functional reserve, in protein kinase A modulation of cardiac CaV1.2 channels. Circ Res. 2008;102:e54-64 pubmed publisher
    ..These results redefine the role of beta subunits in PKA modulation of Ca(V)1.2 channels and uncover a new design principle of this phenomenon in the heart, vis à vis a limited functional reserve. ..
  13. Yang L, Liu G, Zakharov S, Bellinger A, Mongillo M, Marx S. Protein kinase G phosphorylates Cav1.2 alpha1c and beta2 subunits. Circ Res. 2007;101:465-74 pubmed
    ..2 current was significantly reduced by coexpression of an alanine-substituted Ca(v)1.2 beta(2a) subunit (Ser(496)). Our results identify a molecular mechanism by which cGMP-PKG regulates Ca(v)1.2 phosphorylation and function. ..
  14. Antzelevitch C, Pollevick G, Cordeiro J, Casis O, Sanguinetti M, Aizawa Y, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 2007;115:442-9 pubmed
    ..and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel...
  15. Ball S, Powers P, Shin H, Morgans C, Peachey N, Gregg R. Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest Ophthalmol Vis Sci. 2002;43:1595-603 pubmed
    ..The expression of both of these subunits is required for normal maintenance and/or formation of the OPL and synaptic transmission. ..
  16. Koval O, Guan X, Wu Y, Joiner M, Gao Z, Chen B, et al. CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proc Natl Acad Sci U S A. 2010;107:4996-5000 pubmed publisher
    ..These data show that CaMKII binding and phosphorylation sites on beta(2a) are concise but pivotal components of a molecular and biophysical and mechanism for EADs and impaired survival in adult cardiomyocytes. ..
  17. Wu J, Yan Z, Li Z, Yan C, Lu S, Dong M, et al. Structure of the voltage-gated calcium channel Cav1.1 complex. Science. 2015;350:aad2395 pubmed publisher
    ..The structure reveals the architecture of a prototypical eukaryotic Ca(v) channel and provides a framework for understanding the function and disease mechanisms of Ca(v) and Na(v) channels. ..
  18. Maltez J, Nunziato D, Kim J, Pitt G. Essential Ca(V)beta modulatory properties are AID-independent. Nat Struct Mol Biol. 2005;12:372-7 pubmed
  19. Wang D, Bansal V, Fisher T. The Ca2+ channel ?2 subunit is selectively targeted to the axon terminals of supraoptic neurons. Channels (Austin). 2014;8:216-21 pubmed
    ..These data suggest that the Ca(V)?(2) subunit is selectively targeted to axon terminals and may play a role in targeting and/or regulating the properties of Ca(2+) channels. ..
  20. Beguin P, Nagashima K, Mahalakshmi R, Vigot R, Matsunaga A, Miki T, et al. BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis. J Cell Biol. 2014;205:233-49 pubmed publisher
    ..Thus, BARP can modulate the localization of Cav? and its association with the Cav?1 subunit to negatively regulate VGCC activity. ..
  21. Miranda Laferte E, Ewers D, Guzman R, Jordan N, Schmidt S, Hidalgo P. The N-terminal domain tethers the voltage-gated calcium channel ?2e-subunit to the plasma membrane via electrostatic and hydrophobic interactions. J Biol Chem. 2014;289:10387-98 pubmed publisher
    ..Penetration of the tryptophan side chain into the lipidic core stabilizes the membrane-bound conformation. This constitutes a new mechanism for membrane anchoring among the ?-subunit family that also sustains slowed inactivation. ..
  22. Gonzalez Gutierrez G, Miranda Laferte E, Nothmann D, Schmidt S, Neely A, Hidalgo P. The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating. Proc Natl Acad Sci U S A. 2008;105:14198-203 pubmed publisher
  23. Xu K, Zhu W, Xiao R. Serine496 of ?2 subunit of L-type Ca2+ channel participates in molecular crosstalk between activation of (Na++K+)-ATPase and the channel. Biochem Biophys Res Commun. 2010;402:319-23 pubmed publisher
    ..This study provides the first evidence to demonstrate that LTCC ?2 subunit is coupled with the movement of signals in the mechanism of activation of NKA-mediated crosstalk with LTCC. ..
  24. Cui X, Yang G, Pan M, Zhang X, Yang S. Akt signals upstream of L-type calcium channels to optimize insulin secretion. Pancreas. 2012;41:15-21 pubmed publisher
    ..Akt signals upstream of L-type calcium channels to optimize glucose-stimulated insulin secretion. ..
  25. Abiria S, Colbran R. CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation. J Neurochem. 2010;112:150-61 pubmed publisher
    ..2alpha(1) and beta subunits. These findings demonstrate a biochemical mechanism underlying LTCC facilitation by CaMKII. ..
  26. Cens T, Rousset M, Charnet P. Two sets of amino acids of the domain I of Cav2.3 Ca(2+) channels contribute to their high sensitivity to extracellular protons. Pflugers Arch. 2011;462:303-14 pubmed publisher
  27. Zhang X, Xie J, Zhu S, Chen Y, Wang L, Xu B. Next-generation sequencing identifies pathogenic and modifier mutations in a consanguineous Chinese family with hypertrophic cardiomyopathy. Medicine (Baltimore). 2017;96:e7010 pubmed publisher
    ..1598C>T (p.Ser533Leu) mutation in voltage-dependent l-type calcium channel subunit beta-2 (CACNB2) was present in all severely affected HCM patients, but not in those moderately affected or genotype-positive ..