Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT94HRF)

• DTT Name: Voltage-gated calcium channel alpha Cav1.1 (CACNA1S)
• Synonyms: Voltage-gated calcium channel subunit alpha Cav1.1; Voltage-dependent L-type calcium channel subunit alpha-1S; Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle; CACNL1A3; CACN1; CACH1
• Gene Name: CACNA1S
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: CAC1S_HUMAN
• TTD ID: T24965
• Sequence:
  MEPSSPQDEGLRKKQPKKPVPEILPRPPRALFCLTLENPLRKACISIVEWKPFETIILLT
  IFANCVALAVYLPMPEDDNNSLNLGLEKLEYFFLIVFSIEAAMKIIAYGFLFHQDAYLRS
  GWNVLDFTIVFLGVFTVILEQVNVIQSHTAPMSSKGAGLDVKALRAFRVLRPLRLVSGVP
  SLQVVLNSIFKAMLPLFHIALLVLFMVIIYAIIGLELFKGKMHKTCYFIGTDIVATVENE
  EPSPCARTGSGRRCTINGSECRGGWPGPNHGITHFDNFGFSMLTVYQCITMEGWTDVLYW
  VNDAIGNEWPWIYFVTLILLGSFFILNLVLGVLSGEFTKEREKAKSRGTFQKLREKQQLD
  EDLRGYMSWITQGEVMDVEDFREGKLSLDEGGSDTESLYEIAGLNKIIQFIRHWRQWNRI
  FRWKCHDIVKSKVFYWLVILIVALNTLSIASEHHNQPLWLTRLQDIANRVLLSLFTTEML
  MKMYGLGLRQYFMSIFNRFDCFVVCSGILEILLVESGAMTPLGISVLRCIRLLRIFKITK
  YWTSLSNLVASLLNSIRSIASLLLLLFLFIVIFALLGMQLFGGRYDFEDTEVRRSNFDNF
  PQALISVFQVLTGEDWTSMMYNGIMAYGGPSYPGMLVCIYFIILFVCGNYILLNVFLAIA
  VDNLAEAESLTSAQKAKAEEKKRRKMSKGLPDKSEEEKSTMAKKLEQKPKGEGIPTTAKL
  KIDEFESNVNEVKDPYPSADFPGDDEEDEPEIPLSPRPRPLAELQLKEKAVPIPEASSFF
  IFSPTNKIRVLCHRIVNATWFTNFILLFILLSSAALAAEDPIRADSMRNQILKHFDIGFT
  SVFTVEIVLKMTTYGAFLHKGSFCRNYFNMLDLLVVAVSLISMGLESSAISVVKILRVLR
  VLRPLRAINRAKGLKHVVQCMFVAISTIGNIVLVTTLLQFMFACIGVQLFKGKFFRCTDL
  SKMTEEECRGYYYVYKDGDPMQIELRHREWVHSDFHFDNVLSAMMSLFTVSTFEGWPQLL
  YKAIDSNAEDVGPIYNNRVEMAIFFIIYIILIAFFMMNIFVGFVIVTFQEQGETEYKNCE
  LDKNQRQCVQYALKARPLRCYIPKNPYQYQVWYIVTSSYFEYLMFALIMLNTICLGMQHY
  NQSEQMNHISDILNVAFTIIFTLEMILKLMAFKARGYFGDPWNVFDFLIVIGSIIDVILS
  EIDTFLASSGGLYCLGGGCGNVDPDESARISSAFFRLFRVMRLIKLLSRAEGVRTLLWTF
  IKSFQALPYVALLIVMLFFIYAVIGMQMFGKIALVDGTQINRNNNFQTFPQAVLLLFRCA
  TGEAWQEILLACSYGKLCDPESDYAPGEEYTCGTNFAYYYFISFYMLCAFLVINLFVAVI
  MDNFDYLTRDWSILGPHHLDEFKAIWAEYDPEAKGRIKHLDVVTLLRRIQPPLGFGKFCP
  HRVACKRLVGMNMPLNSDGTVTFNATLFALVRTALKIKTEGNFEQANEELRAIIKKIWKR
  TSMKLLDQVIPPIGDDEVTVGKFYATFLIQEHFRKFMKRQEEYYGYRPKKDIVQIQAGLR
  TIEEEAAPEICRTVSGDLAAEEELERAMVEAAMEEGIFRRTGGLFGQVDNFLERTNSLPP
  VMANQRPLQFAEIEMEEMESPVFLEDFPQDPRTNPLARANTNNANANVAYGNSNHSNSHV
  FSSVHYEREFPEETETPATRGRALGQPCRVLGPHSKPCVEMLKGLLTQRAMPRGQAPPAP
  CQCPRVESSMPEDRKSSTPGSLHEETPHSRSTRENTSRCSAPATALLIQKALVRGGLGTL
  AADANFIMATGQALADACQMEPEEVEIMATELLKGREAPEGMASSLGCLNLGSSLGSLDQ
  HQGSQETLIPPRL
• Function: Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Calcium signaling pathway (hsa04020)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Cardiac muscle contraction (hsa04260)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Vascular smooth muscle contraction (hsa04270)
  Retrograde endocannabinoid signaling (hsa04723)
  Cholinergic synapse (hsa04725)
  Serotonergic synapse (hsa04726)
  GABAergic synapse (hsa04727)
  Insulin secretion (hsa04911)
  GnRH signaling pathway (hsa04912)
  Oxytocin signaling pathway (hsa04921)
  Renin secretion (hsa04924)
  Aldosterone synthesis and secretion (hsa04925)
  Cortisol synthesis and secretion (hsa04927)
  GnRH secretion (hsa04929)
  Cushing syndrome (hsa04934)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alzheimer disease (hsa05010)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway: NCAM1 interactions (R-HSA-419037)

Molecular Interaction Atlas (MIA) of This DTT

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-(S)-BayK8644	DMEA9KH	Discovery agent	N.A.	Investigative	[1]
FPL64176	DMB8U4F	Discovery agent	N.A.	Investigative	[1]
SZ(+)-(S)-202-791	DM8L6ZF	Discovery agent	N.A.	Investigative	[1]
[3H](+)-cis-diltiazem	DMP6XL9	Discovery agent	N.A.	Investigative	[2]
[3H](+)-isradipine	DM7QE1J	Discovery agent	N.A.	Investigative	[3]
[3H](-)devapamil	DM0KGHP	Discovery agent	N.A.	Investigative	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 528).
• [2] High-affinity binding of DTZ323, a novel derivative of diltiazem, to rabbit skeletal muscle L-type Ca++ channels. J Pharmacol Exp Ther. 1997 Apr;281(1):173-9.
• [3] Biochemical characterization of plasma membrane isolated from human skeletal muscle. FEBS Lett. 1985 Sep 2;188(2):222-6.
• [4] (-)-[3H]Desmethoxyverapamil, a novel Ca2+ channel probe. Binding characteristics and target size analysis of its receptor in skeletal muscle. FEBS Lett. 1984 Oct 29;176(2):371-7.