PIKFYVE

Protein identityUniProt · HPA

UniProt accession

Q9Y2I7

Gene

PIKFYVE

Ensembl

ENSG00000115020

Chromosome

2

Canonical length

2098 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

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. The protein plays a key role in cell entry of ebola virus and SARS-CoV-2 by endocytosis 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. [provided by RefSeq, Jul 2021]

Canonical amino-acid sequenceUniProt

2098 residues, UniProt reviewed canonical sequence.

>Q9Y2I7|PIKFYVE
     1  MATDDKTSPT LDSANDLPRS PTSPSHLTHF KPLTPDQDEP PFKSAYSSFV NLFRFNKERA
    61  EGGQGEQQPL SGSWTSPQLP SRTQSVRSPT PYKKQLNEEL QRRSSALDTR RKAEPTFGGH
   121  DPRTAVQLRS LSTVLKRLKE IMEGKSQDSD LKQYWMPDSQ CKECYDCSEK FTTFRRRHHC
   181  RLCGQIFCSR CCNQEIPGKF MGYTGDLRAC TYCRKIALSY AHSTDSNSIG EDLNALSDSA
   241  CSVSVLDPSE PRTPVGSRKA SRNIFLEDDL AWQSLIHPDS SNTPLSTRLV SVQEDAGKSP
   301  ARNRSASITN LSLDRSGSPM VPSYETSVSP QANRTYVRTE TTEDERKILL DSVQLKDLWK
   361  KICHHSSGME FQDHRYWLRT HPNCIVGKEL VNWLIRNGHI ATRAQAIAIG QAMVDGRWLD
   421  CVSHHDQLFR DEYALYRPLQ STEFSETPSP DSDSVNSVEG HSEPSWFKDI KFDDSDTEQI
   481  AEEGDDNLAN SASPSKRTSV SSFQSTVDSD SAASISLNVE LDNVNFHIKK PSKYPHVPPH
   541  PADQKEYLIS DTGGQQLSIS DAFIKESLFN RRVEEKSKEL PFTPLGWHHN NLELLREENG
   601  EKQAMERLLS ANHNHMMALL QQLLHSDSLS SSWRDIIVSL VCQVVQTVRP DVKNQDDDMD
   661  IRQFVHIKKI PGGKKFDSVV VNGFVCTKNI AHKKMSSCIK NPKILLLKCS IEYLYREETK
   721  FTCIDPIVLQ EREFLKNYVQ RIVDVRPTLV LVEKTVSRIA QDMLLEHGIT LVINVKSQVL
   781  ERISRMTQGD LVMSMDQLLT KPHLGTCHKF YMQIFQLPNE QTKTLMFFEG CPQHLGCTIK
   841  LRGGSDYELA RVKEILIFMI CVAYHSQLEI SFLMDEFAMP PTLMQNPSFH SLIEGRGHEG
   901  AVQEQYGGGS IPWDPDIPPE SLPCDDSSLL ELRIVFEKGE QENKNLPQAV ASVKHQEHST
   961  TACPAGLPCA FFAPVPESLL PLPVDDQQDA LGSEQPETLQ QTVVLQDPKS QIRAFRDPLQ
  1021  DDTGLYVTEE VTSSEDKRKT YSLAFKQELK DVILCISPVI TFREPFLLTE KGMRCSTRDY
  1081  FAEQVYWSPL LNKEFKEMEN RRKKQLLRDL SGLQGMNGSI QAKSIQVLPS HELVSTRIAE
  1141  HLGDSQSLGR MLADYRARGG RIQPKNSDPF AHSKDASSTS SGQSGSKNEG DEERGLILSD
  1201  AVWSTKVDCL NPINHQRLCV LFSSSSAQSS NAPSACVSPW IVTMEFYGKN DLTLGIFLER
  1261  YCFRPSYQCP SMFCDTPMVH HIRRFVHGQG CVQIILKELD SPVPGYQHTI LTYSWCRICK
  1321  QVTPVVALSN ESWSMSFAKY LELRFYGHQY TRRANAEPCG HSIHHDYHQY FSYNQMVASF
  1381  SYSPIRLLEV CVPLPKIFIK RQAPLKVSLL QDLKDFFQKV SQVYVAIDER LASLKTDTFS
  1441  KTREEKMEDI FAQKEMEEGE FKNWIEKMQA RLMSSSVDTP QQLQSVFESL IAKKQSLCEV
  1501  LQAWNNRLQD LFQQEKGRKR PSVPPSPGRL RQGEESKISA MDASPRNISP GLQNGEKEDR
  1561  FLTTLSSQSS TSSTHLQLPT PPEVMSEQSV GGPPELDTAS SSEDVFDGHL LGSTDSQVKE
  1621  KSTMKAIFAN LLPGNSYNPI PFPFDPDKHY LMYEHERVPI AVCEKEPSSI IAFALSCKEY
  1681  RNALEELSKA TQWNSAEEGL PTNSTSDSRP KSSSPIRLPE MSGGQTNRTT ETEPQPTKKA
  1741  SGMLSFFRGT AGKSPDLSSQ KRETLRGADS AYYQVGQTGK EGTENQGVEP QDEVDGGDTQ
  1801  KKQLINPHVE LQFSDANAKF YCRLYYAGEF HKMREVILDS SEEDFIRSLS HSSPWQARGG
  1861  KSGAAFYATE DDRFILKQMP RLEVQSFLDF APHYFNYITN AVQQKRPTAL AKILGVYRIG
  1921  YKNSQNNTEK KLDLLVMENL FYGRKMAQVF DLKGSLRNRN VKTDTGKESC DVVLLDENLL
  1981  KMVRDNPLYI RSHSKAVLRT SIHSDSHFLS SHLIIDYSLL VGRDDTSNEL VVGIIDYIRT
  2041  FTWDKKLEMV VKSTGILGGQ GKMPTVVSPE LYRTRFCEAM DKYFLMVPDH WTGLGLNC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PIKFYVE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

27 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PIKFYVE.

Disease | AllUniProt

Conditions PIKFYVE is implicated in, by any mechanism.

• Corneal dystrophy, fleck (CFD) MIM:121850

Disease | GeneticClinVar

24 pathogenic / likely-pathogenic of 507 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Fleck corneal dystrophy
• PIKFYVE-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.39

gnomAD pLI

0

gnomAD missense Z

2.05

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• antigen processing and presentation of exogenous peptide antigen via MHC class II
• intracellular signal transduction
• melanosome organization
• neutrophil chemotaxis
• peptidyl-serine autophosphorylation
• phagosome maturation
• phagosome-lysosome fusion
• phosphatidylinositol 5-phosphate metabolic process
• phosphatidylinositol biosynthetic process
• protein localization to nucleus
• protein targeting to membrane
• receptor-mediated endocytosis of virus by host cell
• regulation of autophagosome assembly
• regulation of reactive oxygen species biosynthetic process
• retrograde transport, endosome to Golgi
• 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate metabolic process

Molecular functions

• 1-phosphatidylinositol-3-phosphate 5-kinase activity
• 1-phosphatidylinositol-4-phosphate 5-kinase activity
• 1-phosphatidylinositol-5-kinase activity
• ATP binding
• phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• zinc ion binding

Cellular components

• cytoplasmic vesicle
• cytosol
• early endosome membrane
• endosome membrane
• Golgi membrane
• late endosome membrane
• membrane raft
• phagocytic vesicle membrane
• vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• FYVE zinc finger
• DEP domain
• Chaperonin Cpn60/GroEL/TCP-1 family
• Phosphatidylinositol-4-phosphate 4/5-kinase, core
• Zinc finger, FYVE/PHD-type
• Zinc finger, RING/FYVE/PHD-type
• Zinc finger, FYVE-related
• GroEL-like apical domain superfamily
• TCP-1-like chaperonin intermediate domain superfamily
• Phosphatidylinositol-4-phosphate 4/5-kinase, C-terminal domain superfamily
• Phosphatidylinositol-4-phosphate 5-kinase, N-terminal
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• TCP-1/cpn60 chaperonin family
• Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
• FYVE zinc finger
• Phosphatidylinositol-4-phosphate 5-Kinase
• PIKfyve, DEP domain
• 1-phosphatidylinositol-3phosphate-5-kinase
• 1-phosphatidylinositol-3-phosphate 5-kinase, PIPK catalytic domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Corneal dystrophy
• Cytoplasmic vesicle
• Endosome
• Host-virus interaction
• Kinase
• Lipid metabolism
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Transferase
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of PIKFYVE in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EGFR
• SPAG9
• RABEPK
• FIG4
• VAC14