CACNA1H

Calcium channel, voltage-dependent, T type, alpha 1H subunit

Identifiers

CACNA1H ; CACNA1HB; Cav3.2; ECA6; EIG6

External IDs

OMIM: 607904 MGI: 1928842 HomoloGene: 56913 IUPHAR: 536 ChEMBL: 1859 GeneCards: CACNA1H Gene

Gene ontology
Molecular function	• low voltage-gated calcium channel activity • metal ion binding • scaffold protein binding
Cellular component	• plasma membrane • voltage-gated calcium channel complex • caveola • integral component of membrane • sarcolemma
Biological process	• transport • muscle contraction • axon guidance • muscle organ development • myoblast fusion • regulation of heart contraction • aldosterone biosynthetic process • cellular response to hormone stimulus • ion transmembrane transport • cortisol biosynthetic process • regulation of ion transmembrane transport • cellular response to potassium ion • regulation of membrane potential • calcium ion import • calcium ion transmembrane transport • membrane depolarization during action potential • positive regulation of acrosome reaction
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
1.15 – 1.22 Mb

Chr 17:
25.37 – 25.43 Mb

PubMed search

Calcium channel, voltage-dependent, T type, alpha 1H subunit, also known as CACNA1H, is a protein which in humans is encoded by the CACNA1H gene.^[1]^[2]^[3]

Function

This gene encodes Ca_v3.2, a T-type member of the α₁ subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of α₁, α₂δ, β, and γ subunits in a 1:1:1:1 ratio. The α₁ subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here.^[1]

Clinical significance

Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE).^[4] Variants of Ca_v3.2 with increased channel activity contribute to susceptibility to idiopathic generalized epilepsy (IGE), but are not sufficient to induce epilepsy on their own. ^[5] The SFARIgene database lists CACNA1H with an autism score of 2.1, indicating a candidate causal relationship with autism.

References

1 2 "Entrez Gene: CACNA1H calcium channel, voltage-dependent, T type, alpha 1H subunit".
↑ Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E (July 1998). "Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family". Circ. Res. 83 (1): 103–9. doi:10.1161/01.res.83.1.103. PMID 9670923.
↑ Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (December 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol. Rev. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099.
↑ Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z, Ding K, Lo WH, Qiang B, Chan P, Shen Y, Wu X (August 2003). "Association between genetic variation of CACNA1H and childhood absence epilepsy". Ann. Neurol. 54 (2): 239–43. doi:10.1002/ana.10607. PMID 12891677.
↑ Heron SE, Khosravani H, Varela D, Bladen C, Williams TC, Newman MR, Scheffer IE, Berkovic SF, Mulley JC, Zamponi GW (December 2007). "Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants". Ann. Neurol. 62 (6): 560–8. doi:10.1002/ana.21169. PMID 17696120.

Crunelli V, Tóth TI, Cope DW; et al. (2005). "The 'window' T-type calcium current in brain dynamics of different behavioural states.". J. Physiol. (Lond.) 562 (Pt 1): 121–9. doi:10.1113/jphysiol.2004.076273. PMC 1665496. PMID 15498803.
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2006). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels.". Pharmacol. Rev. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099.
Andersson B, Wentland MA, Ricafrente JY; et al. (1996). "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
Yu W, Andersson B, Worley KC; et al. (1997). "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Cribbs LL, Lee JH, Yang J; et al. (1998). "Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family.". Circ. Res. 83 (1): 103–9. doi:10.1161/01.res.83.1.103. PMID 9670923.
Williams ME, Washburn MS, Hans M; et al. (1999). "Structure and functional characterization of a novel human low-voltage activated calcium channel.". J. Neurochem. 72 (2): 791–9. doi:10.1046/j.1471-4159.1999.0720791.x. PMID 9930755.
Perez-Reyes E, Lee JH, Cribbs LL (1999). "Molecular characterization of two members of the T-type calcium channel family.". Ann. N. Y. Acad. Sci. 868: 131–43. doi:10.1111/j.1749-6632.1999.tb11283.x. PMID 10414291.
Bijlenga P, Liu JH, Espinos E; et al. (2000). "T-type alpha 1H Ca2+ channels are involved in Ca2+ signaling during terminal differentiation (fusion) of human myoblasts.". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7627–32. doi:10.1073/pnas.97.13.7627. PMC 16596. PMID 10861024.
Daniels RJ, Peden JF, Lloyd C; et al. (2001). "Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.". Hum. Mol. Genet. 10 (4): 339–52. doi:10.1093/hmg/10.4.339. PMID 11157797.
Jagannathan S, Punt EL, Gu Y; et al. (2002). "Identification and localization of T-type voltage-operated calcium channel subunits in human male germ cells. Expression of multiple isoforms.". J. Biol. Chem. 277 (10): 8449–56. doi:10.1074/jbc.M105345200. PMID 11751928.
Mariot P, Vanoverberghe K, Lalevee N; et al. (2002). "Overexpression of an alpha 1H (Cav3.2) T-type calcium channel during neuroendocrine differentiation of human prostate cancer cells.". J. Biol. Chem. 277 (13): 10824–33. doi:10.1074/jbc.M108754200. PMID 11799114.
Chemin J, Monteil A, Perez-Reyes E; et al. (2002). "Specific contribution of human T-type calcium channel isotypes (alpha(1G), alpha(1H) and alpha(1I)) to neuronal excitability.". J. Physiol. (Lond.) 540 (Pt 1): 3–14. doi:10.1113/jphysiol.2001.013269. PMC 2290209. PMID 11927664.
Shin JB, Martinez-Salgado C, Heppenstall PA, Lewin GR (2003). "A T-type calcium channel required for normal function of a mammalian mechanoreceptor.". Nat. Neurosci. 6 (7): 724–30. doi:10.1038/nn1076. PMID 12808460.
Wolfe JT, Wang H, Howard J; et al. (2003). "T-type calcium channel regulation by specific G-protein betagamma subunits.". Nature 424 (6945): 209–13. doi:10.1038/nature01772. PMID 12853961.
Kaku T, Lee TS, Arita M; et al. (2004). "The gating and conductance properties of Cav3.2 low-voltage-activated T-type calcium channels.". Jpn. J. Physiol. 53 (3): 165–72. doi:10.2170/jjphysiol.53.165. PMID 14529577.
Welsby PJ, Wang H, Wolfe JT; et al. (2003). "A mechanism for the direct regulation of T-type calcium channels by Ca2+/calmodulin-dependent kinase II.". J. Neurosci. 23 (31): 10116–21. PMID 14602827.
Chen CC, Lamping KG, Nuno DW; et al. (2003). "Abnormal coronary function in mice deficient in alpha1H T-type Ca2+ channels.". Science 302 (5649): 1416–8. doi:10.1126/science.1089268. PMID 14631046.
Khosravani H, Altier C, Simms B; et al. (2004). "Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy.". J. Biol. Chem. 279 (11): 9681–4. doi:10.1074/jbc.C400006200. PMID 14729682.
Martin J, Han C, Gordon LA; et al. (2005). "The sequence and analysis of duplication-rich human chromosome 16.". Nature 432 (7020): 988–94. doi:10.1038/nature03187. PMID 15616553.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

This article is issued from Wikipedia - version of the Wednesday, April 29, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

CACNA1H

Function

Clinical significance

See also

References

Further reading