Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTYKGPB)

• DTP Name: Voltage-gated calcium channel alpha Cav2.1 (CACNA1A)
• Gene Name: CACNA1A
• UniProt ID: O00555 (CAC1A_HUMAN)
• VARIDT ID: DTD0518
• Synonyms: APCA; BI; Brain calcium channel I; CACH4; CACN3; CACNA1A; CACNL1A4; CAV2.1; Calcium channel, L type, alpha-1 polypeptide isoform 4; EA2; EIEE42; FHM; HPCA; MHP; MHP1; SCA6; Voltage-dependent P/Q-type calcium channel subunit alpha-1A; Voltage-gated calcium channel subunit alpha Cav2.1
• DTP Family: Voltage-Gated Ion Channel (VIC) Superfamily
• Tissue Specificity: Brain specific; mainly found in cerebellum,cerebral cortex, thalamus and hypothalamus. Expressed in the smallcell lung carcinoma cell line SCC-9. No expression in heart,kidney, liver or muscle. Purkinje cells contain predominantly P-type VSCC, the Q-type being a prominent calcium current incerebellar granule cells.
• Sequence:
  MARFGDEMPARYGGGGSGAAAGVVVGSGGGRGAGGSRQGGQPGAQRMYKQSMAQRARTMA
  LYNPIPVRQNCLTVNRSLFLFSEDNVVRKYAKKITEWPPFEYMILATIIANCIVLALEQH
  LPDDDKTPMSERLDDTEPYFIGIFCFEAGIKIIALGFAFHKGSYLRNGWNVMDFVVVLTG
  ILATVGTEFDLRTLRAVRVLRPLKLVSGIPSLQVVLKSIMKAMIPLLQIGLLLFFAILIF
  AIIGLEFYMGKFHTTCFEEGTDDIQGESPAPCGTEEPARTCPNGTKCQPYWEGPNNGITQ
  FDNILFAVLTVFQCITMEGWTDLLYNSNDASGNTWNWLYFIPLIIIGSFFMLNLVLGVLS
  GEFAKERERVENRRAFLKLRRQQQIERELNGYMEWISKAEEVILAEDETDGEQRHPFDAL
  RRTTIKKSKTDLLNPEEAEDQLADIASVGSPFARASIKSAKLENSTFFHKKERRMRFYIR
  RMVKTQAFYWTVLSLVALNTLCVAIVHYNQPEWLSDFLYYAEFIFLGLFMSEMFIKMYGL
  GTRPYFHSSFNCFDCGVIIGSIFEVIWAVIKPGTSFGISVLRALRLLRIFKVTKYWASLR
  NLVVSLLNSMKSIISLLFLLFLFIVVFALLGMQLFGGQFNFDEGTPPTNFDTFPAAIMTV
  FQILTGEDWNEVMYDGIKSQGGVQGGMVFSIYFIVLTLFGNYTLLNVFLAIAVDNLANAQ
  ELTKDEQEEEEAANQKLALQKAKEVAEVSPLSAANMSIAVKEQQKNQKPAKSVWEQRTSE
  MRKQNLLASREALYNEMDPDERWKAAYTRHLRPDMKTHLDRPLVVDPQENRNNNTNKSRA
  AEPTVDQRLGQQRAEDFLRKQARYHDRARDPSGSAGLDARRPWAGSQEAELSREGPYGRE
  SDHHAREGSLEQPGFWEGEAERGKAGDPHRRHVHRQGGSRESRSGSPRTGADGEHRRHRA
  HRRPGEEGPEDKAERRARHREGSRPARGGEGEGEGPDGGERRRRHRHGAPATYEGDARRE
  DKERRHRRRKENQGSGVPVSGPNLSTTRPIQQDLGRQDPPLAEDIDNMKNNKLATAESAA
  PHGSLGHAGLPQSPAKMGNSTDPGPMLAIPAMATNPQNAASRRTPNNPGNPSNPGPPKTP
  ENSLIVTNPSGTQTNSAKTARKPDHTTVDIPPACPPPLNHTVVQVNKNANPDPLPKKEEE
  KKEEEEDDRGEDGPKPMPPYSSMFILSTTNPLRRLCHYILNLRYFEMCILMVIAMSSIAL
  AAEDPVQPNAPRNNVLRYFDYVFTGVFTFEMVIKMIDLGLVLHQGAYFRDLWNILDFIVV
  SGALVAFAFTGNSKGKDINTIKSLRVLRVLRPLKTIKRLPKLKAVFDCVVNSLKNVFNIL
  IVYMLFMFIFAVVAVQLFKGKFFHCTDESKEFEKDCRGKYLLYEKNEVKARDREWKKYEF
  HYDNVLWALLTLFTVSTGEGWPQVLKHSVDATFENQGPSPGYRMEMSIFYVVYFVVFPFF
  FVNIFVALIIITFQEQGDKMMEEYSLEKNERACIDFAISAKPLTRHMPQNKQSFQYRMWQ
  FVVSPPFEYTIMAMIALNTIVLMMKFYGASVAYENALRVFNIVFTSLFSLECVLKVMAFG
  ILNYFRDAWNIFDFVTVLGSITDILVTEFGNNFINLSFLRLFRAARLIKLLRQGYTIRIL
  LWTFVQSFKALPYVCLLIAMLFFIYAIIGMQVFGNIGIDVEDEDSDEDEFQITEHNNFRT
  FFQALMLLFRSATGEAWHNIMLSCLSGKPCDKNSGILTRECGNEFAYFYFVSFIFLCSFL
  MLNLFVAVIMDNFEYLTRDSSILGPHHLDEYVRVWAEYDPAAWGRMPYLDMYQMLRHMSP
  PLGLGKKCPARVAYKRLLRMDLPVADDNTVHFNSTLMALIRTALDIKIAKGGADKQQMDA
  ELRKEMMAIWPNLSQKTLDLLVTPHKSTDLTVGKIYAAMMIMEYYRQSKAKKLQAMREEQ
  DRTPLMFQRMEPPSPTQEGGPGQNALPSTQLDPGGALMAHESGLKESPSWVTQRAQEMFQ
  KTGTWSPEQGPPTDMPNSQPNSQSVEMREMGRDGYSDSEHYLPMEGQGRAASMPRLPAEN
  QRRRGRPRGNNLSTISDTSPMKRSASVLGPKARRLDDYSLERVPPEENQRHHQRRRDRSH
  RASERSLGRYTDVDTGLGTDLSMTTQSGDLPSKERDQERGRPKDRKHRQHHHHHHHHHHP
  PPPDKDRYAQERPDHGRARARDQRWSRSPSEGREHMAHRQGSSSVSGSPAPSTSGTSTPR
  RGRRQLPQTPSTPRPHVSYSPVIRKAGGSGPPQQQQQQQQQQQQQAVARPGRAATSGPRR
  YPGPTAEPLAGDRPPTGGHSSGRSPRMERRVPGPARSESPRACRHGGARWPASGPHVSEG
  PPGPRHHGYYRGSDYDEADGPGSGGGEEAMAGAYDAPPPVRHASSGATGRSPRTPRASGP
  ACASPSRHGRRLPNGYYPAHGLARPRGPGSRKGLHEPYSESDDDWC
• Function: This voltage-sensitive transporter mediates the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282). They are however insensitive to dihydropyridines (DHP).
• Endogenous Substrate(s): Ca2+
• TCDB ID: 1.A.1.11.27
• Gene ID: 773
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Calcium signaling pathway (hsa04020)
  Synaptic vesicle cycle (hsa04721)
  Retrograde endocannabinoid signaling (hsa04723)
  Glutamatergic synapse (hsa04724)
  Cholinergic synapse (hsa04725)
  Serotonergic synapse (hsa04726)
  GABAergic synapse (hsa04727)
  Dopaminergic synapse (hsa04728)
  Long-term depression (hsa04730)
  Taste transduction (hsa04742)
  Type II diabetes mellitus (hsa04930)
  Spinocerebellar ataxia (hsa05017)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Regulation of insulin secretion (R-HSA-422356)
  Presynaptic depolarization and calcium channel opening (R-HSA-112308)

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Voltage-gated calcium channel alpha Cav2.1 (CACNA1A) DTT Info
• DTP DTT Type: Successful

1 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flunarizine	DMZU5JP	Migraine	8A80	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XEN007	DMNKV3O	Migraine	8A80	Phase 1	[1]

1 Discontinued Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TH-9229	DMG1MPD	Reperfusion injury	ND56.Z	Terminated	[2]

3 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha-eudesmol	DMYSCQU	Discovery agent	N.A.	Investigative	[3]
CPU-228	DMM8FUT	Cardiac failure	BD10-BD13	Investigative	[4]
omega-conotoxin GVIA	DM4BQFW	Discovery agent	N.A.	Investigative	[5]

References

• [1] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008159)
• [3] Alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion. Brain Res. 2000 Aug 4;873(1):94-101.
• [4] 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: 532).
• [5] Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000 Nov 10;275(45):35335-44.