CACNA1S Membrane Protein Introduction

Introduction of CACNA1S

CACNA1S, calcium channel, voltage-dependent, L type, alpha 1S subunit, also known as CACNA1S or Ca_v1.1, is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and dihydropyridine receptor - DHPR, this naming is due to its blocking action to DHP. It is one of the five subunits of L type voltage-dependent calcium channel. Mutations in this gene are associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis, and malignant hyperthermia susceptibility.

Basic Information of CACNA1S
Protein Name	Voltage-dependent L-type calcium channel subunit alpha-1S
Gene Name	CACNA1S
Aliases	Calcium channel, L type, alpha-1 polypeptide, isoform 3, Voltage-gated calcium channel subunit alpha Ca_v1.1, CACH1, CACN1, CACNL1A3
Organism	Homo sapiens (Human)
UniProt ID	Q13698
Transmembrane Times	28
Length (aa)	1873
Sequence	MEPSSPQDEGLRKKQPKKPVPEILPRPPRALFCLTLENPLRKACISIVEWKPFETIILLTIFANCVALAVYLPMPEDDNNSLNLGLEKLEYFFLIVFSIEAAMKIIAYGFLFHQDAYLRSGWNVLDFTIVFLGVFTVILEQVNVIQSHTAPMSSKGAGLDVKALRAFRVLRPLRLVSGVPSLQVVLNSIFKAMLPLFHIALLVLFMVIIYAIIGLELFKGKMHKTCYFIGTDIVATVENEEPSPCARTGSGRRCTINGSECRGGWPGPNHGITHFDNFGFSMLTVYQCITMEGWTDVLYWVNDAIGNEWPWIYFVTLILLGSFFILNLVLGVLSGEFTKEREKAKSRGTFQKLREKQQLDEDLRGYMSWITQGEVMDVEDFREGKLSLDEGGSDTESLYEIAGLNKIIQFIRHWRQWNRIFRWKCHDIVKSKVFYWLVILIVALNTLSIASEHHNQPLWLTRLQDIANRVLLSLFTTEMLMKMYGLGLRQYFMSIFNRFDCFVVCSGILEILLVESGAMTPLGISVLRCIRLLRIFKITKYWTSLSNLVASLLNSIRSIASLLLLLFLFIVIFALLGMQLFGGRYDFEDTEVRRSNFDNFPQALISVFQVLTGEDWTSMMYNGIMAYGGPSYPGMLVCIYFIILFVCGNYILLNVFLAIAVDNLAEAESLTSAQKAKAEEKKRRKMSKGLPDKSEEEKSTMAKKLEQKPKGEGIPTTAKLKIDEFESNVNEVKDPYPSADFPGDDEEDEPEIPLSPRPRPLAELQLKEKAVPIPEASSFFIFSPTNKIRVLCHRIVNATWFTNFILLFILLSSAALAAEDPIRADSMRNQILKHFDIGFTSVFTVEIVLKMTTYGAFLHKGSFCRNYFNMLDLLVVAVSLISMGLESSAISVVKILRVLRVLRPLRAINRAKGLKHVVQCMFVAISTIGNIVLVTTLLQFMFACIGVQLFKGKFFRCTDLSKMTEEECRGYYYVYKDGDPMQIELRHREWVHSDFHFDNVLSAMMSLFTVSTFEGWPQLLYKAIDSNAEDVGPIYNNRVEMAIFFIIYIILIAFFMMNIFVGFVIVTFQEQGETEYKNCELDKNQRQCVQYALKARPLRCYIPKNPYQYQVWYIVTSSYFEYLMFALIMLNTICLGMQHYNQSEQMNHISDILNVAFTIIFTLEMILKLMAFKARGYFGDPWNVFDFLIVIGSIIDVILSEIDTFLASSGGLYCLGGGCGNVDPDESARISSAFFRLFRVMRLIKLLSRAEGVRTLLWTFIKSFQALPYVALLIVMLFFIYAVIGMQMFGKIALVDGTQINRNNNFQTFPQAVLLLFRCATGEAWQEILLACSYGKLCDPESDYAPGEEYTCGTNFAYYYFISFYMLCAFLVINLFVAVIMDNFDYLTRDWSILGPHHLDEFKAIWAEYDPEAKGRIKHLDVVTLLRRIQPPLGFGKFCPHRVACKRLVGMNMPLNSDGTVTFNATLFALVRTALKIKTEGNFEQANEELRAIIKKIWKRTSMKLLDQVIPPIGDDEVTVGKFYATFLIQEHFRKFMKRQEEYYGYRPKKDIVQIQAGLRTIEEEAAPEICRTVSGDLAAEEELERAMVEAAMEEGIFRRTGGLFGQVDNFLERTNSLPPVMANQRPLQFAEIEMEEMESPVFLEDFPQDPRTNPLARANTNNANANVAYGNSNHSNSHVFSSVHYEREFPEETETPATRGRALGQPCRVLGPHSKPCVEMLKGLLTQRAMPRGQAPPAPCQCPRVESSMPEDRKSSTPGSLHEETPHSRSTRENTSRCSAPATALLIQKALVRGGLGTLAADANFIMATGQALADACQMEPEEVEIMATELLKGREAPEGMASSLGCLNLGSSLGSLDQHQGSQETLIPPRL

Function ofCACNA1S Membrane Protein

CACNA1S is also called Ca_v1.1. This kind of voltage-sensitive L type calcium channel mediates the calcium influx in skeletal muscle. It encodes alpha-1S subunit (one of the five subunits) of the slowly inactivating L type voltage-dependent calcium channel. CACNA1S plays an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which can trigger calcium release from the sarcoplasmic reticulum, then finally results in muscle contraction. The mutations of this gene are associated with the following diseases: hypokalemic periodic paralysis, thyrotoxic periodic paralysis, and malignant hyperthermia susceptibility.

Fig.1 Working model of CACNA1S, (Jorquera, 2013)

Application of CACNA1S Membrane Protein in Literature

Schartner V., et al. Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy. Acta Neuropathol. 2017, 133(4): 517-533. PubMed ID: 28012042

This article indicates that DHPR is important for perinatal muscle function in human, and the studies demonstrate that CACNA1S and ECC can be considered as therapeutic targets for the development of treatments.
Schiemann A.H and Stowell K.M. Comparison of pathogenicity prediction tools on missense variants in RYR1 and CACNA1S associated with malignant hyperthermia. Br J Anaesth. 2016, 117(1): 124-8. PubMed ID: 27147545

This article predicts the impact of a missense variant on RYR1 and CACNA1S function, and suggests that the prediction should be a combination with other available data including functional assays and segregation analysis.
Zhang T., et al. Calpain inhibition rescues troponin T3 fragmentation, increases Ca_v1.1, and enhances skeletal muscle force in aging sedentary mice. Aging Cell. 2016, 15(3): 488-98. PubMed ID: 26892246

This study demonstrates that fast skeletal muscle troponin T3 can regulate transcription of Cacna1s, also known as Ca_v1.1. Calpain inhibitor can prevent TnT3 fragmentation, and cause CACNA1S downregulation and finally improve the muscle fore in aging sedentary mice.
Fiszer D., et al. Next-generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness. Anesthesiology. 2015, 122(5): 1033-46. PubMed ID: 25658027

This article provides the next-generation sequencing which is efficient at identifying diagnostically useful and potentially important variants in RYR1and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness.
Polster A., et al. Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca²⁺ channels. Proc Natl Acad Sci U S A. 2015, 112(2): 602-6. PubMed ID: 25548159

This article reveals that Stac3 is a necessary chaperone of CACNA1S in skeletal muscle via regulating trafficking and function of calcium channel.

CACNA1S Preparation Options

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Reference

Jorquera G, et al. (2013). Ca_v1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity. J Cell Sci. 126(Pt 5):1189-98.

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