Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE6THL)

• DTT Name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (ATP2A2)
• Synonyms: SR Ca(2+)Sarcoplasmic/endoplasmic reticulum calcium ATPase 2-ATPase 2; SR Ca(2+)-ATPase 2; SR Ca(2+)-ATPase; SR Ca(2+) pump; SERCA2; Endoplasmic reticulum class 1/2 Ca(2+) ATPase; Cardiacsarcoplasmic reticulum calcium ATPase; CardiacCa2+ ATPase (SERCA2a); Calciumpump 2; Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform; Calcium pump 2; ATP2B
• Gene Name: ATP2A2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cation transporting ATPase
• UniProt ID: AT2A2_HUMAN
• TTD ID: T15377
• EC Number: EC 7.2.2.10
• Sequence:
  MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDL
  LVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILVANAIVGVWQERNAENAIEALK
  EYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL
  TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMV
  ATEQERTPLQQKLDEFGEQLSKVISLICIAVWIINIGHFNDPVHGGSWIRGAIYYFKIAV
  ALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ
  MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALC
  NDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTELKGLSKIERANACNSVIKQLMK
  KEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV
  KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLD
  PPRIEVASSVKLCRQAGIRVIMITGDNKGTAVAICRRIGIFGQDEDVTSKAFTGREFDEL
  NPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG
  SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAAL
  GFPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMNKPPRNPKEPLISGWLFFRYLAIG
  CYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL
  SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITP
  LNVTQWLMVLKISLPVILMDETLKFVARNYLEPGKECVQPATKSCSFSACTDGISWPFVL
  LIMPLVIWVYSTDTNFSDMFWS
• Function: Isoform 2 is involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cGMP-PKG signaling pathway (hsa04022)
  cAMP signaling pathway (hsa04024)
  Cardiac muscle contraction (hsa04260)
  Adrenergic signaling in cardiomyocytes (hsa04261)
  Thyroid hormone signaling pathway (hsa04919)
  Pancreatic secretion (hsa04972)
  Alzheimer's disease (hsa05010)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Ion transport by P-type ATPases (R-HSA-936837)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[1]
Mydicar	DM25VY8	Heart failure	BD10-BD13	Phase 2	[2]

References

• [1] Interaction of D-600 with the transmembrane domain of the sarcoplasmic reticulum Ca(2+)-ATPase. Am J Physiol Cell Physiol. 2000 Jul;279(1):C166-72.
• [2] Clinical pipeline report, company report or official report of Celladon.