General Information of the Protein
Protein ID
PT04732
Protein Name
1-phosphatidylinositol 3-phosphate 5-kinase
Secondarily
Protein Name
FYVE finger-containing phosphoinositide kinase
PIKfyve
Phosphatidylinositol 3-phosphate 5-kinase type III
Serine-protein kinase PIKFYVE
Gene Name
PIKFYVE
Secondarily
Gene Name
KIAA0981
PIP5K3
Sequence
MATDDKTSPTLDSANDLPRSPTSPSHLTHFKPLTPDQDEPPFKSAYSSFVNLFRFNKERAEGGQGEQQPLSGSWTSPQLPSRTQSVRSPTPYKKQLNEELQRRSSALDTRRKAEPTFGGHDPRTAVQLRSLSTVLKRLKEIMEGKSQDSDLKQYWMPDSQCKECYDCSEKFTTFRRRHHCRLCGQIFCSRCCNQEIPGKFMGYTGDLRACTYCRKIALSYAHSTDSNSIGEDLNALSDSACSVSVLDPSEPRTPVGSRKASRNIFLEDDLAWQSLIHPDSSNTPLSTRLVSVQEDAGKSPARNRSASITNLSLDRSGSPMVPSYETSVSPQANRTYVRTETTEDERKILLDSVQLKDLWKKICHHSSGMEFQDHRYWLRTHPNCIVGKELVNWLIRNGHIATRAQAIAIGQAMVDGRWLDCVSHHDQLFRDEYALYRPLQSTEFSETPSPDSDSVNSVEGHSEPSWFKDIKFDDSDTEQIAEEGDDNLANSASPSKRTSVSSFQSTVDSDSAASISLNVELDNVNFHIKKPSKYPHVPPHPADQKEYLISDTGGQQLSISDAFIKESLFNRRVEEKSKELPFTPLGWHHNNLELLREENGEKQAMERLLSANHNHMMALLQQLLHSDSLSSSWRDIIVSLVCQVVQTVRPDVKNQDDDMDIRQFVHIKKIPGGKKFDSVVVNGFVCTKNIAHKKMSSCIKNPKILLLKCSIEYLYREETKFTCIDPIVLQEREFLKNYVQRIVDVRPTLVLVEKTVSRIAQDMLLEHGITLVINVKSQVLERISRMTQGDLVMSMDQLLTKPHLGTCHKFYMQIFQLPNEQTKTLMFFEGCPQHLGCTIKLRGGSDYELARVKEILIFMICVAYHSQLEISFLMDEFAMPPTLMQNPSFHSLIEGRGHEGAVQEQYGGGSIPWDPDIPPESLPCDDSSLLELRIVFEKGEQENKNLPQAVASVKHQEHSTTACPAGLPCAFFAPVPESLLPLPVDDQQDALGSEQPETLQQTVVLQDPKSQIRAFRDPLQDDTGLYVTEEVTSSEDKRKTYSLAFKQELKDVILCISPVITFREPFLLTEKGMRCSTRDYFAEQVYWSPLLNKEFKEMENRRKKQLLRDLSGLQGMNGSIQAKSIQVLPSHELVSTRIAEHLGDSQSLGRMLADYRARGGRIQPKNSDPFAHSKDASSTSSGQSGSKNEGDEERGLILSDAVWSTKVDCLNPINHQRLCVLFSSSSAQSSNAPSACVSPWIVTMEFYGKNDLTLGIFLERYCFRPSYQCPSMFCDTPMVHHIRRFVHGQGCVQIILKELDSPVPGYQHTILTYSWCRICKQVTPVVALSNESWSMSFAKYLELRFYGHQYTRRANAEPCGHSIHHDYHQYFSYNQMVASFSYSPIRLLEVCVPLPKIFIKRQAPLKVSLLQDLKDFFQKVSQVYVAIDERLASLKTDTFSKTREEKMEDIFAQKEMEEGEFKNWIEKMQARLMSSSVDTPQQLQSVFESLIAKKQSLCEVLQAWNNRLQDLFQQEKGRKRPSVPPSPGRLRQGEESKISAMDASPRNISPGLQNGEKEDRFLTTLSSQSSTSSTHLQLPTPPEVMSEQSVGGPPELDTASSSEDVFDGHLLGSTDSQVKEKSTMKAIFANLLPGNSYNPIPFPFDPDKHYLMYEHERVPIAVCEKEPSSIIAFALSCKEYRNALEELSKATQWNSAEEGLPTNSTSDSRPKSSSPIRLPEMSGGQTNRTTETEPQPTKKASGMLSFFRGTAGKSPDLSSQKRETLRGADSAYYQVGQTGKEGTENQGVEPQDEVDGGDTQKKQLINPHVELQFSDANAKFYCRLYYAGEFHKMREVILDSSEEDFIRSLSHSSPWQARGGKSGAAFYATEDDRFILKQMPRLEVQSFLDFAPHYFNYITNAVQQKRPTALAKILGVYRIGYKNSQNNTEKKLDLLVMENLFYGRKMAQVFDLKGSLRNRNVKTDTGKESCDVVLLDENLLKMVRDNPLYIRSHSKAVLRTSIHSDSHFLSSHLIIDYSLLVGRDDTSNELVVGIIDYIRTFTWDKKLEMVVKSTGILGGQGKMPTVVSPELYRTRFCEAMDKYFLMVPDHWTGLGLNC
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Transferase
Function
Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:33098764). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (PubMed:30612035). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (By similarity). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (By similarity). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus (PubMed:17909029).
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Uniprot ID
Primary ID:
Q9Y2I7

Secondarily ID:
Q08AR7
Q08AR8
Q53ST3
Q53T36
Q8N5H0
Q8NB67
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Ensembl ID
ENSG00000115020
HGNC ID
HGNC:23785
Subcellular Location
Endosome membrane
Early endosome membrane
Cytoplasmic vesicle
Phagosome membrane
Late endosome membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Compound ID Compound Name Compound Formula
CP0970282
4-(2-Amino-5,6,7,8-tetrahydropyrimido[4',5':3,4]cyclohepta[1,2-b]indol-11-yl)but-3-yn-2-ol
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C17H18N4O
 1
1
IC50 = 4.05 nM
   TI
   LI
   LO
   TS
CP0968902
1-(2-Amino-5,6,7,8-tetrahydropyrimido[4',5':3,4]cyclohepta[1,2-b]indol-11-yl)-3-methylpent-1-yn-3-ol
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C19H22N4O
 1
1
IC50 = 9.65 nM
   TI
   LI
   LO
   TS
CP0130395
4-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylbut-3-yn-2-ol
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C20H20N4O
 1
1
IC50 = 14.1 nM
   TI
   LI
   LO
   TS
CP0564497
4-[3-(2-aminopyrimidin-4-yl)-1H-indol-5-yl]-2-methylbut-3-yn-2-ol
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C17H16N4O
 1
1
IC50 = 21.1 nM
   TI
   LI
   LO
   TS
CP0563006
2-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)ethanol
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C17H18N4O
 1
1
IC50 = 40 nM
   TI
   LI
   LO
   TS
CP0964723
1-(2-Amino-5,6,7,8-tetrahydropyrimido[4',5':3,4]cyclohepta[1,2-b]indol-11-yl)-4-methylpent-1-yn-3-ol
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C21H22N4O
 1
1
IC50 = 45.7 nM
   TI
   LI
   LO
   TS
CP0573497
10-[3-(dimethylamino)prop-1-ynyl]-6,7-dihydro-5H-pyrimido[5,4-c]carbazol-2-amine
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C19H19N5
 1
1
IC50 = 123 nM
   TI
   LI
   LO
   TS
CP0575846
4-(2-amino-6,7-dihydro-5H-pyrimido[5,4-c]carbazol-10-yl)-2-methylbut-3-yn-2-ol
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C19H18N4O
 1
1
IC50 = 220 nM
   TI
   LI
   LO
   TS
CP0545396
1-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylpropan-2-ol
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C19H22N4O
 1
1
IC50 = 290 nM
   TI
   LI
   LO
   TS
CP0579518
10-(2-cyclopropylethynyl)-6,7-dihydro-5H-pyrimido[5,4-c]carbazol-2-amine
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C19H16N4
 1
1
IC50 = 300 nM
   TI
   LI
   LO
   TS
CP0576179
16-(2-methoxypropan-2-yl)-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-4-amine
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C19H22N4O
 1
1
IC50 = 314 nM
   TI
   LI
   LO
   TS
CP0577175
17-[3-(dimethylamino)prop-1-ynyl]-3,5,13-triazatetracyclo[10.7.0.02,7.014,19]nonadeca-1(12),2,4,6,14(19),15,17-heptaen-4-amine
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C21H23N5
 1
1
IC50 = 683 nM
   TI
   LI
   LO
   TS
CP0495094
N-[2-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)propan-2-yl]methanesulfonamide
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C19H23N5O2S
 1
1
IC50 = 1600 nM
   TI
   LI
   LO
   TS
CP0495098
2-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylpropan-1-ol
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C19H22N4O
 1
1
IC50 = 2160 nM
   TI
   LI
   LO
   TS
CP0573496
17-(4-fluorophenyl)-3,5,13-triazatetracyclo[10.7.0.02,7.014,19]nonadeca-1(12),2,4,6,14(19),15,17-heptaen-4-amine
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C22H19FN4
 1
1
IC50 = 2560 nM
   TI
   LI
   LO
   TS
CP0575250
10-(2-pyridin-4-ylethynyl)-6,7-dihydro-5H-pyrimido[5,4-c]carbazol-2-amine
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C21H15N5
 1
1
IC50 = 2980 nM
   TI
   LI
   LO
   TS
CP0545395
17-(2-pyridin-4-ylethynyl)-3,5,13-triazatetracyclo[10.7.0.02,7.014,19]nonadeca-1(12),2,4,6,14(19),15,17-heptaen-4-amine
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C23H19N5
 1
1
IC50 = 5290 nM
   TI
   LI
   LO
   TS
CP0561400
17-[2-(3-methylimidazol-4-yl)ethynyl]-3,5,13-triazatetracyclo[10.7.0.02,7.014,19]nonadeca-1(12),2,4,6,14(19),15,17-heptaen-4-amine
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C22H20N6
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0575847
N-[2-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)propan-2-yl]acetamide
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C20H23N5O
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0545449
APILIMOD
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C23H26N6O2
 1
1 IC50 = 14 nM
CP0527909
6-amino-N-[3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenyl]pyridine-3-carboxamide
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C25H21N7O3
 1
1 IC50 = 33 nM
Clinical Information about the Protein
Target 1 ( Phosphatidylinositol-3-phosphate 5-kinase (PIP5K3) )
Target Type Clinical trial Target
Target 2 ( HUMAN phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) )
Target Type Unknown Type Target
Disease 1 Target-related Disease  1
1 Coronavirus Disease 2019 (COVID-19) [ICD-11: 1D6Y]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 Apilimod Preclinical
Coronavirus Disease 2019 (COVID-19)