Reviewed, UniProtKB/Swiss-Prot Q9Y2I7 (FYV1_HUMAN)

Names and origin

Protein names

Recommended name:
    1-phosphatidylinositol-3-phosphate 5-kinase
      Short name=Phosphatidylinositol-3-phosphate 5-kinase
    EC=2.7.1.150
Alternative name(s):
    FYVE finger-containing phosphoinositide kinase
    PIKfyve
    Phosphatidylinositol-3-phosphate 5-kinase type III
    Type III PIP kinase
      Short name=PIPkin-III

Gene names

Name:	PIKFYVE
Synonyms:	KIAA0981, PIP5K3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2098 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Ref.8
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 3-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,5-bisphosphate.
Subunit structure	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. Ref.8 Ref.4
Involvement in 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. Ref.12
Sequence similarities	Contains 1 DEP domain. Contains 1 FYVE-type zinc finger. Contains 1 PIPK domain.

Ontologies

Keywords
Cellular component	Endosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cellular protein metabolic process Inferred from electronic annotation. Source: InterPro intracellular signaling cascade Inferred from electronic annotation. Source: InterPro phosphatidylinositol metabolic process Inferred from electronic annotation. Source: InterPro protein localization in nucleus Inferred from mutant phenotype. Source: UniProtKB retrograde transport, endosome to Golgi Inferred from mutant phenotype. Source: UniProtKB
Cellular component	early endosome membrane Inferred from direct assay. Source: UniProtKB membrane raft Inferred from direct assay. Source: HGNC
Molecular function	1-phosphatidylinositol-4-phosphate 5-kinase activity Traceable author statement. Source: HGNC ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2098	2098	1-phosphatidylinositol-3-phosphate 5-kinase		PRO_0000185452
Regions
	Domain	365 – 440	76	DEP
	Domain	1758 – 2084	327	PIPK
	Zinc finger	158 – 218	61	FYVE-type
	Region	1842 – 2098	257	Catalytic
Amino acid modifications
	Modified residue	7	1	Phosphothreonine Ref.10
	Modified residue	46	1	Phosphotyrosine Ref.5
	Modified residue	76	1	Phosphoserine Ref.10
	Modified residue	299	1	Phosphoserine Ref.10
	Modified residue	307	1	Phosphoserine Ref.10
	Modified residue	318	1	Phosphoserine Ref.11
	Modified residue	329	1	Phosphoserine Ref.11
	Modified residue	352	1	Phosphoserine Ref.10
	Modified residue	1155	1	Phosphotyrosine Ref.7
	Modified residue	1544	1	Phosphoserine Ref.10
	Modified residue	1549	1	Phosphoserine Ref.10
	Modified residue	1754	1	Phosphoserine Ref.10
	Modified residue	1772	1	Phosphotyrosine Ref.6
Natural variations
	Natural variant	617	1	M → V: dbSNP rs16840913.		VAR_057097
	Natural variant	1033	1	S → A: dbSNP rs999890.		VAR_057098
	Natural variant	1103	1	K → R in CFD. Ref.12		VAR_025309
	Natural variant	1858	1	R → Q: dbSNP rs2289170.		VAR_057099

Sequences

	Sequence		Length	Mass (Da)
	Q9Y2I7-1 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: 174B4102057292B7	FASTA	2,098	237,108
	10 20 30 40 50 60 MATDDKTSPT LDSANDLPRS PTSPSHLTHF KPLTPDQDEP PFKSAYSSFV NLFRFNKERA 70 80 90 100 110 120 EGGQGEQQPL SGSWTSPQLP SRTQSVRSPT PYKKQLNEEL QRRSSALDTR RKAEPTFGGH 130 140 150 160 170 180 DPRTAVQLRS LSTVLKRLKE IMEGKSQDSD LKQYWMPDSQ CKECYDCSEK FTTFRRRHHC 190 200 210 220 230 240 RLCGQIFCSR CCNQEIPGKF MGYTGDLRAC TYCRKIALSY AHSTDSNSIG EDLNALSDSA 250 260 270 280 290 300 CSVSVLDPSE PRTPVGSRKA SRNIFLEDDL AWQSLIHPDS SNTPLSTRLV SVQEDAGKSP 310 320 330 340 350 360 ARNRSASITN LSLDRSGSPM VPSYETSVSP QANRTYVRTE TTEDERKILL DSVQLKDLWK 370 380 390 400 410 420 KICHHSSGME FQDHRYWLRT HPNCIVGKEL VNWLIRNGHI ATRAQAIAIG QAMVDGRWLD 430 440 450 460 470 480 CVSHHDQLFR DEYALYRPLQ STEFSETPSP DSDSVNSVEG HSEPSWFKDI KFDDSDTEQI 490 500 510 520 530 540 AEEGDDNLAN SASPSKRTSV SSFQSTVDSD SAASISLNVE LDNVNFHIKK PSKYPHVPPH 550 560 570 580 590 600 PADQKEYLIS DTGGQQLSIS DAFIKESLFN RRVEEKSKEL PFTPLGWHHN NLELLREENG 610 620 630 640 650 660 EKQAMERLLS ANHNHMMALL QQLLHSDSLS SSWRDIIVSL VCQVVQTVRP DVKNQDDDMD 670 680 690 700 710 720 IRQFVHIKKI PGGKKFDSVV VNGFVCTKNI AHKKMNSCIK NPKILLLKCS IEYLYREETK 730 740 750 760 770 780 FTCIDPIVLQ EREFLKNYVQ RIVDVRPTLV LVEKTVSRIA QDMLLEHGIT LVINVKSQVL 790 800 810 820 830 840 ERISRMTQGD LVMSMDQLLT KPHLGTCHKF YMQIFQLPNE QTKTLMFFEG CPQHLGCTIK 850 860 870 880 890 900 LRGGSDYELA RVKEILIFMI CVAYHSQLEI SFLMDEFAMP PTLMQNPSFH SLIEGRGHEG 910 920 930 940 950 960 AVQEQYGGGS IPWDPDIPPE SLPCDDSSLL ESRIVFEKGE QENKNLPQAV ASVKHQEHST 970 980 990 1000 1010 1020 TACPAGLPCA FFAPVPESLL PLPVDDQQDA LGSELPESLQ QTVVLQDPKS QIRAFRDPLQ 1030 1040 1050 1060 1070 1080 DDTGLYVTEE VTSSEDKRKT YSLAFKQELK DVILCISPVI TFREPFLLTE KGMRCSTRDY 1090 1100 1110 1120 1130 1140 FAEQVYWSPL LNKEFKEMEN RRKKQLLRDL SGLQGMNGSI QAKSIQVLPS HELVSTRIAE 1150 1160 1170 1180 1190 1200 HLGDSQSLGR MLADYRARGG RIQPKNSDPF AHSKDASSTS SGKSGSKNEG DEERGLILSD 1210 1220 1230 1240 1250 1260 AVWSTKVDCL NPINHQRLCV LFSSSSAQSS NAPSACVSPW IVTMEFYGKN DLTLGIFLER 1270 1280 1290 1300 1310 1320 YCFRPSYQCP SMFCDTPMVH HIRRFVHGQG CVQIILKELD SPVPGYQHTI LTYSWCRICK 1330 1340 1350 1360 1370 1380 QVTPVVALSN ESWSMSFAKY LELRFYGHQY TRRANAEPCG HSIHHDYHQY FSYNQMVASF 1390 1400 1410 1420 1430 1440 SYSPIRLLEV CVPLPKIFIK RQAPLKVSLL QDLKDFFQKV SQVYVAIDER LASLKTDTFS 1450 1460 1470 1480 1490 1500 KTREEKMEDI FAQKEMEEGE FKNWIEKMQA RLMSSSVDTP QQLQSVFESL IAKKQSLCEV 1510 1520 1530 1540 1550 1560 LQAWNNRLQD LFQQEKGRKR PSVPPSPGRL RQGEESKISA MDASPRNISP GLQNGEKEDR 1570 1580 1590 1600 1610 1620 FLTTLSSQSS TSSTHLQLPT PPEVMSEQSV GGPPELDTAS SSEDVFDGHL LGSTDSQVKE 1630 1640 1650 1660 1670 1680 KSTMKAIFAN LLPGNSYNPI PFPFDPDKHY LMYEHERVPI AVCEKEPSSI IAFALSCKEY 1690 1700 1710 1720 1730 1740 RNALEELSKA TQWNSAEEGL PTNSTSDSRP KSSSPIRLPE MSGGQTNRTT ETEPQPTKKA 1750 1760 1770 1780 1790 1800 SGMLSFFRGT AGKSPDLSSQ KRETLRGADS AYYQVGQTGK EGTENQGVEP QDEVDGGDTQ 1810 1820 1830 1840 1850 1860 KKQLINPHVE LQFSDANAKF YCRLYYAGEF HKMREVILDS SEEDFIRSLS HSSPWQARGG 1870 1880 1890 1900 1910 1920 KSGAAFYATE DDRFILKQMP RLEVQSFLDF APHYFNYITN AVQQKRPTAL AKILGVYRIG 1930 1940 1950 1960 1970 1980 YKNSQNNTEK KLDLLVMENL FYGRKMAQVF DLKGSLRNRN VKTDTGKESC DVVLLDENLL 1990 2000 2010 2020 2030 2040 KMVRDNPLYI RSHSKAVLRT SIHSDSHFLS SHLIIDYSLL VGRDDTSNEL VVGIIDYIRT 2050 2060 2070 2080 2090 FTWDKKLEMV VKSTGILGGQ GKMPTVVSPE LYRTRFCEAM DKYFLMVPDH WTGLGLNC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human PIKfyve, a PI3P 5-kinase that regulates endocytic trafficking." Cabezas A., Pattni K., Stenmark H. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1073-2098. Tissue: Brain.
[3]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed: 10231032] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1521-2098. Tissue: Brain.
[4]	"Phosphatidylinositol 3-phosphate-interacting domains in PIKfyve. Binding specificity and role in PIKfyve endomembrane localization." Sbrissa D., Ikonomov O.C., Shisheva A. J. Biol. Chem. 277:6073-6079(2002) [PubMed: 11706043] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-46, MASS SPECTROMETRY. Tissue: T-cell.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1772, MASS SPECTROMETRY.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1155, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex." Sbrissa D., Ikonomov O.C., Fu Z., Ijuin T., Gruenberg J., Takenawa T., Shisheva A. J. Biol. Chem. 282:23878-23891(2007) [PubMed: 17556371] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX.
[9]	"ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality." Sbrissa D., Ikonomov O.C., Fenner H., Shisheva A. J. Mol. Biol. 384:766-779(2008) [PubMed: 18950639] [Abstract] Cited for: IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-7; SER-76; SER-299; SER-307; SER-352; SER-1544; SER-1549 AND SER-1754, MASS SPECTROMETRY.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318 AND SER-329, MASS SPECTROMETRY.
[12]	"Mutations in PIP5K3 are associated with Francois-Neetens mouchetee fleck corneal dystrophy." Li S., Tiab L., Jiao X., Munier F.L., Zografos L., Frueh B.E., Sergeev Y., Smith J., Rubin B., Meallet M.A., Forster R.K., Hejtmancik J.F., Schorderet D.F. Am. J. Hum. Genet. 77:54-63(2005) [PubMed: 15902656] [Abstract] Cited for: VARIANT CFD ARG-1103.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY457063 mRNA. Translation: AAR19397.1. AK091482 mRNA. Translation: BAC03674.1. AB023198 mRNA. Translation: BAA76825.1.
IPI	IPI00396145.
RefSeq	NP_055855.2.
UniGene	Hs.173939
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y2I7.
PTM databases
PhosphoSite	Q9Y2I7.
Proteomic databases
PRIDE	Q9Y2I7.
Genome annotation databases
Ensembl	ENST00000264380; ENSP00000264380; ENSG00000115020; Homo sapiens. [Genome view] ENST00000308862; ENSP00000308715; ENSG00000115020; Homo sapiens. [Genome view] ENST00000392200; ENSP00000376036; ENSG00000115020; Homo sapiens. [Genome view] ENST00000392202; ENSP00000376038; ENSG00000115020; Homo sapiens. [Genome view] ENST00000407449; ENSP00000384356; ENSG00000115020; Homo sapiens. [Genome view] ENST00000422495; ENSP00000414477; ENSG00000115020; Homo sapiens. [Genome view] ENST00000443896; ENSP00000407692; ENSG00000115020; Homo sapiens. [Genome view] ENST00000451223; ENSP00000410691; ENSG00000115020; Homo sapiens. [Genome view] ENST00000452564; ENSP00000405736; ENSG00000115020; Homo sapiens. [Genome view] ENST00000453820; ENSP00000404713; ENSG00000115020; Homo sapiens. [Genome view]
GeneID	200576.
KEGG	hsa:200576.
UCSC	uc002vcz.1. human.
Organism-specific databases
CTD	200576.
GeneCards	GC02P208839.
H-InvDB	HIX0002785.
HGNC	HGNC:23785. PIKFYVE.
MIM	121850. phenotype. 609414. gene.
Orphanet	34533. Corneal dystrophy. 98970. Corneal flecked dystrophy, Francois-Neetens type.
PharmGKB	PA128394599.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9Y2I7.
HOVERGEN	Q9Y2I7.
Enzyme and pathway databases
BRENDA	2.7.1.150. 247. 2.7.1.68. 247.
Gene expression databases
ArrayExpress	Q9Y2I7.
Bgee	Q9Y2I7.
CleanEx	HS_PIP5K3.
Genevestigator	Q9Y2I7.
GermOnline	ENSG00000115020. Homo sapiens.
Family and domain databases
InterPro	IPR002423. Cpn60/TCP-1. IPR002498. PInositol-4-P-5-kinase_core. IPR016034. PInositol-4P-5-kinase_core_sub. IPR000591. Pleckstrin/G-protein_interact. IPR011991. Wing_hlx_DNA_bd. IPR000306. Znf_FYVE. IPR017455. Znf_FYVE-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
PANTHER	PTHR11353. Cpn60/TCP-1. 1 hit.
Pfam	PF00118. Cpn60_TCP1. 1 hit. PF00610. DEP. 1 hit. PF01363. FYVE. 1 hit. PF01504. PIP5K. 1 hit. [Graphical view]
SMART	SM00049. DEP. 1 hit. SM00064. FYVE. 1 hit. SM00330. PIPKc. 1 hit. [Graphical view]
PROSITE	PS50186. DEP. 1 hit. PS51455. PIPK. 1 hit. PS50178. ZF_FYVE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	89946.
SOURCE	Search...

Entry information

Entry name

FYV1_HUMAN

Accession

Primary (citable) accession number: Q9Y2I7
Secondary accession number(s): Q8NB67

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 10, 2004
Last modified:	November 3, 2009
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.