Target Information
| Target General Information | Top | |||||
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| Target ID |
T97729
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| Target Name |
HUMAN two pore channel subtype 2 (TPC2)
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| Synonyms |
Voltage-dependent calcium channel protein TPC2; TPC2
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| Gene Name |
TPCN2
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| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Hypertension [ICD-11: BA00-BA04] | |||||
| 2 | Ventricular tachyarrhythmia [ICD-11: BC71] | |||||
| Function |
Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal membrane. May be involved in smooth muscle contraction.
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| UniProt ID | ||||||
| Sequence |
MAEPQAESEPLLGGARGGGGDWPAGLTTYRSIQVGPGAAARWDLCIDQAVVFIEDAIQYR
SINHRVDASSMWLYRRYYSNVCQRTLSFTIFLILFLAFIETPSSLTSTADVRYRAAPWEP PCGLTESVEVLCLLVFAADLSVKGYLFGWAHFQKNLWLLGYLVVLVVSLVDWTVSLSLVC HEPLRIRRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTMFGMLLFAG GKQDDGQDRERLTYFQNLPESLTSLLVLLTTANNPDVMIPAYSKNRAYAIFFIVFTVIGS LFLMNLLTAIIYSQFRGYLMKSLQTSLFRRRLGTRAAFEVLSSMVGEGGAFPQAVGVKPQ NLLQVLQKVQLDSSHKQAMMEKVRSYGSVLLSAEEFQKLFNELDRSVVKEHPPRPEYQSP FLQSAQFLFGHYYFDYLGNLIALANLVSICVFLVLDADVLPAERDDFILGILNCVFIVYY LLEMLLKVFALGLRGYLSYPSNVFDGLLTVVLLVLEISTLAVYRLPHPGWRPEMVGLLSL WDMTRMLNMLIVFRFLRIIPSMKLMAVVASTVLGLVQNMRAFGGILVVVYYVFAIIGINL FRGVIVALPGNSSLAPANGSAPCGSFEQLEYWANNFDDFAAALVTLWNLMVVNNWQVFLD AYRRYSGPWSKIYFVLWWLVSSVIWVNLFLALILENFLHKWDPRSHLQPLAGTPEATYQM TVELLFRDILEEPGEDELTERLSQHPHLWLCR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Drugs in Phase 2 Trial | [+] 2 | + | ||||
| 1 | Amiodarone | Drug Info | Approved | Ventricular tachycardia | [2] | |
| 2 | Verapamil | Drug Info | Approved | Hypertension | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Blocker | [+] 2 Blocker drugs | + | ||||
| 1 | Amiodarone | Drug Info | [1] | |||
| 2 | Verapamil | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctanoate | Ligand Info | |||||
| Structure Description | Cryo-EM structure of human TPC2 channel in the ligand-bound closed state | PDB:6NQ2 | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [4] |
| PDB Sequence |
AARWDLCIDQ
48 AVVFIEDAIQ58 YRSINHRVDA68 SSMWLYRRYY78 SNVCQRTLSF88 TIFLILFLAF 98 IETPSSLTST108 ADVRYRAAPW118 EPPCGLTESV128 EVLCLLVFAA138 DLSVKGYLFG 148 WAHFQKNLWL158 LGYLVVLVVS168 LVDWTVSLSL178 VCHEPLRIRR188 LLRPFFLLQN 198 SSMMKKTLKC208 IRWSLPEMAS218 VGLLLAIHLC228 LFTMFGMLLF238 AGLTYFQNLP 259 ESLTSLLVLL269 TTANNPDVMI279 PAYSKNRAYA289 IFFIVFTVIG299 SLFLMNLLTA 309 IIYSQFRGYL319 MKSLQTSLFR329 RRLGTRAAFE339 VLSSMVGAVG356 VKPQNLLQVL 366 QKVQLDSSHK376 QAMMEKVRSY386 GSVLLSAEEF396 QKLFNELDRS406 VVKEHPPRPE 416 YQSPFLQSAQ426 FLFGHYYFDY436 LGNLIALANL446 VSICVFLVLD456 ADVLPAERDD 466 FILGILNCVF476 IVYYLLEMLL486 KVFALGLRGY496 LSYPSNVFDG506 LLTVVLLVLE 516 ISTLAVYRLS539 LWDMTRMLNM549 LIVFRFLRII559 PSMKPMAVVA569 STVLGLVQNM 579 RAFGGILVVV589 YYVFAIIGIN599 LFRGVIVALS620 APCGSFEQLE630 YWANNFDDFA 640 AALVTLWNLM650 VVNNWQVFLD660 AYRRYSGPWS670 KIYFVLWWLV680 SSVIWVNLFL 690 ALILENFLHK700 W
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
|---|---|---|---|
| Polycystic kidney disease 2-like 1 (TRPP2) | 28.846 (45/156) | 4.73E-04 |
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Pancreatic secretion | hsa04972 | Affiliated Target |
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| Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| References | Top | |||||
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| REF 1 | Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020 Mar 27;11(1):1620. | |||||
| REF 2 | FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 204742. | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 071881. | |||||
| REF 4 | Structural mechanisms of phospholipid activation of the human TPC2 channel. Elife. 2019 Mar 12;8:e45222. | |||||
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