Human Gene PIKFYVE (ENST00000407449.5) from GENCODE V44
Description: Homo sapiens phosphoinositide kinase, FYVE-type zinc finger containing (PIKFYVE), transcript variant 4, mRNA. (from RefSeq NM_001178000) RefSeq Summary (NM_001178000): Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]. Gencode Transcript: ENST00000407449.5 Gencode Gene: ENSG00000115020.17 Transcript (Including UTRs) Position: hg38 chr2:208,266,278-208,305,128 Size: 38,851 Total Exon Count: 12 Strand: + Coding Region Position: hg38 chr2:208,271,520-208,305,024 Size: 33,505 Coding Exon Count: 11
ID:FYV1_HUMAN DESCRIPTION: RecName: Full=1-phosphatidylinositol 3-phosphate 5-kinase; Short=Phosphatidylinositol 3-phosphate 5-kinase; EC=2.7.1.150; AltName: Full=FYVE finger-containing phosphoinositide kinase; AltName: Full=PIKfyve; AltName: Full=Phosphatidylinositol 3-phosphate 5-kinase type III; Short=PIPkin-III; Short=Type III PIP kinase; FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo- inositol ring, to form phosphatidylinositol 3,5-bisphosphate. Required for endocytic-vacuolar pathway and nuclear migration. Plays a role in the biogenesis of endosome carrier vesicles (ECV)/ multivesicular bodies (MVB) transport intermediates from early endosomes. CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 3- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate. SUBUNIT: Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold. SUBCELLULAR LOCATION: Endosome membrane. Note=Mainly associated with membranes of the late endocytic pathway. DISEASE: Defects in PIKFYVE are the cause of corneal fleck dystrophy (CFD) [MIM:121850]. CFD is an autosomal dominant disorder of the cornea characterized by numerous small white flecks scattered in all levels of the stroma. Although CFD may occasionally cause mild photophobia, patients are typically asymptomatic and have normal vision. SIMILARITY: Contains 1 DEP domain. SIMILARITY: Contains 1 FYVE-type zinc finger. SIMILARITY: Contains 1 PIPK domain. SEQUENCE CAUTION: Sequence=BAC03674.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00118 - TCP-1/cpn60 chaperonin family PF00610 - Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) PF01363 - FYVE zinc finger PF01504 - Phosphatidylinositol-4-phosphate 5-Kinase
ModBase Predicted Comparative 3D Structure on Q9Y2I7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HQ447333 - Synthetic construct Homo sapiens clone IMAGE:100070650; CCSB009671_02 phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III (PIP5K3) gene, encodes complete protein. KJ895796 - Synthetic construct Homo sapiens clone ccsbBroadEn_05190 PIKFYVE gene, encodes complete protein. KJ905642 - Synthetic construct Homo sapiens clone ccsbBroadEn_15283 PIKFYVE gene, encodes complete protein. BC032389 - Homo sapiens phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III, mRNA (cDNA clone IMAGE:5173829), complete cds. BC017736 - Homo sapiens phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III, mRNA (cDNA clone IMAGE:4400828). AY457063 - Homo sapiens FYVE domain-containing phosphoinositide kinase mRNA, complete cds. EU794609 - Homo sapiens epididymis luminal protein 37 (HEL37) mRNA, complete cds. LP895399 - Sequence 263 from Patent EP3253886. BC125052 - Homo sapiens phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III, mRNA (cDNA clone IMAGE:40116610), complete cds. BC125053 - Homo sapiens phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III, mRNA (cDNA clone IMAGE:40116619), complete cds. AK127769 - Homo sapiens cDNA FLJ45870 fis, clone OCBBF3005330, highly similar to FYVE finger-containing phosphoinositide kinase (EC 2.7.1.68). CU689366 - Synthetic construct Homo sapiens gateway clone IMAGE:100019462 5' read PIP5K3 mRNA. BC156451 - Synthetic construct Homo sapiens clone IMAGE:100062990, MGC:190655 phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III (PIP5K3) mRNA, encodes complete protein. BC172527 - Synthetic construct Homo sapiens clone IMAGE:100069221, MGC:199232 phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, type III (PIP5K3) mRNA, encodes complete protein. DQ575465 - Homo sapiens piRNA piR-43577, complete sequence. JD379129 - Sequence 360153 from Patent EP1572962. JD524975 - Sequence 505999 from Patent EP1572962. JD249591 - Sequence 230615 from Patent EP1572962. JD402793 - Sequence 383817 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00562 - Inositol phosphate metabolism hsa04070 - Phosphatidylinositol signaling system hsa04810 - Regulation of actin cytoskeleton
Reactome (by CSHL, EBI, and GO)
Protein Q9Y2I7 (Reactome details) participates in the following event(s):
R-HSA-1675866 PI is phosphorylated to PI5P by PIKFYVE at the late endosome membrane R-HSA-1676020 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the late endosome membrane R-HSA-1675910 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the late endosome membrane R-HSA-1676005 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the Golgi membrane R-HSA-1675921 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the Golgi membrane R-HSA-1676174 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the early endosome membrane R-HSA-1676168 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the early endosome membrane R-HSA-1660517 Synthesis of PIPs at the late endosome membrane R-HSA-1660514 Synthesis of PIPs at the Golgi membrane R-HSA-1660516 Synthesis of PIPs at the early endosome membrane R-HSA-1483255 PI Metabolism R-HSA-1483257 Phospholipid metabolism R-HSA-556833 Metabolism of lipids R-HSA-1430728 Metabolism
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