Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA4LDE)

DTT Name	Calcineurin (PPP3CA)
Synonyms	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform; Calmodulin-dependent calcineurin A subunit alpha isoform; CNA; CAM-PRP catalytic subunit; CALNA
Gene Name	PPP3CA
DTT Type	Successful target	[1]
BioChemical Class	Phosphoric monoester hydrolase
UniProt ID	PP2BA_HUMAN
TTD ID	T25464
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 3.1.3.16
Sequence	MSEPKAIDPKLSTTDRVVKAVPFPPSHRLTAKEVFDNDGKPRVDILKAHLMKEGRLEESV ALRIITEGASILRQEKNLLDIDAPVTVCGDIHGQFFDLMKLFEVGGSPANTRYLFLGDYV DRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKYSERVYDACMD AFDCLPLAALMNQQFLCVHGGLSPEINTLDDIRKLDRFKEPPAYGPMCDILWSDPLEDFG NEKTQEHFTHNTVRGCSYFYSYPAVCEFLQHNNLLSILRAHEAQDAGYRMYRKSQTTGFP SLITIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCSPHPYWLPNFMDVFTWSLPFVGEK VTEMLVNVLNICSDDELGSEEDGFDGATAAARKEVIRNKIRAIGKMARVFSVLREESESV LTLKGLTPTGMLPSGVLSGGKQTLQSATVEAIEADEAIKGFSPQHKITSFEEAKGLDRIN ERMPPRRDAMPSDANLNSINKALTSETNGTDSNGSNSSNIQ
Function	Many of the substrates contain a PxIxIT motif and/or a LxVP motif. In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation. In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion. Dephosphorylates heat shock protein HSPB1. Dephosphorylates and activates transcription factor NFATC1. In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32. May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins. Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals.
KEGG Pathway	MAPK signaling pathway (hsa04010 ) Calcium signaling pathway (hsa04020 ) cGMP-PKG signaling pathway (hsa04022 ) Oocyte meiosis (hsa04114 ) Apoptosis (hsa04210 ) Wnt signaling pathway (hsa04310 ) Axon guidance (hsa04360 ) VEGF signaling pathway (hsa04370 ) Osteoclast differentiation (hsa04380 ) Natural killer cell mediated cytotoxicity (hsa04650 ) T cell receptor signaling pathway (hsa04660 ) B cell receptor signaling pathway (hsa04662 ) Long-term potentiation (hsa04720 ) Glutamatergic synapse (hsa04724 ) Dopaminergic synapse (hsa04728 ) Oxytocin signaling pathway (hsa04921 ) Glucagon signaling pathway (hsa04922 ) Alzheimer's disease (hsa05010 ) Amyotrophic lateral sclerosis (ALS) (hsa05014 ) Amphetamine addiction (hsa05031 ) Tuberculosis (hsa05152 ) HTLV-I infection (hsa05166 )
Reactome Pathway	FCERI mediated Ca+2 mobilization (R-HSA-2871809 ) Ca2+ pathway (R-HSA-4086398 ) DARPP-32 events (R-HSA-180024 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[1]
Pimecrolimus	DMZLGRB	Atopic dermatitis	EA80	Approved	[2]
Tacrolimus	DMZ7XNQ	Graft-versus-host disease	4B24	Approved	[3]
Voclosporin	DMWIJTN	Lupus nephritis	4A40.0Y	Approved	[4]
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1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-685,818	DMJUQT1	Discovery agent	N.A.	Investigative	[5]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	5.29E-01	1.74E-03	9.99E-03
Atopic dermatitis	EA90	Skin	1.31E-09	-0.27	-2.69
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References

1	Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2007 May;19(3):238-45.
2	Treatment of chronic blepharokeratoconjunctivitis with local calcineurin inhibitors. Ophthalmologe. 2009 Jul;106(7):635-8.
3	Emerging drugs for ocular allergy. Expert Opin Emerg Drugs. 2005 Aug;10(3):505-20.
4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
5	Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother. 2000 Mar;44(3):739-46.