INP5E_MOUSE
ID INP5E_MOUSE Reviewed; 647 AA.
AC Q9JII1; Q3TCC9;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Phosphatidylinositol polyphosphate 5-phosphatase type IV;
DE AltName: Full=72 kDa inositol polyphosphate 5-phosphatase {ECO:0000303|PubMed:10806194};
DE AltName: Full=Inositol polyphosphate-5-phosphatase E;
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 5-phosphatase;
DE EC=3.1.3.36 {ECO:0000250|UniProtKB:Q9NRR6};
DE AltName: Full=Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase;
DE EC=3.1.3.86 {ECO:0000269|PubMed:10806194};
DE Flags: Precursor;
GN Name=Inpp5e;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10806194; DOI=10.1074/jbc.m000874200;
RA Kong A.M., Speed C.J., O'Malley C.J., Layton M.J., Meehan T.,
RA Loveland K.L., Cheema S., Ooms L.M., Mitchell C.A.;
RT "Cloning and characterization of a 72-kDa inositol-polyphosphate 5-
RT phosphatase localized to the Golgi network.";
RL J. Biol. Chem. 275:24052-24064(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Aorta, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19668215; DOI=10.1038/ng.427;
RA Jacoby M., Cox J.J., Gayral S., Hampshire D.J., Ayub M., Blockmans M.,
RA Pernot E., Kisseleva M.V., Compere P., Schiffmann S.N., Gergely F.,
RA Riley J.H., Perez-Morga D., Woods C.G., Schurmans S.;
RT "INPP5E mutations cause primary cilium signaling defects, ciliary
RT instability and ciliopathies in human and mouse.";
RL Nat. Genet. 41:1027-1031(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103; THR-197 AND SER-259, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=26051944; DOI=10.1007/s10048-015-0450-4;
RA Yang A.W., Sachs A.J., Nystuen A.M.;
RT "Deletion of Inpp5a causes ataxia and cerebellar degeneration in mice.";
RL Neurogenetics 16:277-285(2015).
CC -!- FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically
CC hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate
CC (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2). Specific for lipid substrates, inactive towards water
CC soluble inositol phosphates. Specific for lipid substrates, inactive
CC towards water soluble inositol phosphates (By similarity)
CC (PubMed:10806194). Plays an essential role in the primary cilium by
CC controlling ciliary growth and phosphoinositide 3-kinase (PI3K)
CC signaling and stability (PubMed:19668215).
CC {ECO:0000250|UniProtKB:Q9NRR6, ECO:0000269|PubMed:10806194,
CC ECO:0000269|PubMed:19668215}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456; EC=3.1.3.36;
CC Evidence={ECO:0000250|UniProtKB:Q9NRR6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765;
CC Evidence={ECO:0000250|UniProtKB:Q9NRR6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658,
CC ChEBI:CHEBI:57836; EC=3.1.3.86;
CC Evidence={ECO:0000269|PubMed:10806194};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305|PubMed:10806194};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3-phosphate) + phosphate; Xref=Rhea:RHEA:32955,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57923,
CC ChEBI:CHEBI:58088; Evidence={ECO:0000269|PubMed:10806194};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32956;
CC Evidence={ECO:0000305|PubMed:10806194};
CC -!- SUBUNIT: Interacts (when prenylated) with PDE6D; this is important for
CC normal location in cilia. {ECO:0000250|UniProtKB:Q9NRR6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000269|PubMed:19668215}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000269|PubMed:10806194}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10806194}; Cytoplasmic side
CC {ECO:0000269|PubMed:10806194}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q9WVR1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9WVR1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9WVR1}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9WVR1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9WVR1}. Nucleus {ECO:0000269|PubMed:26051944}.
CC Note=Peripheral membrane protein associated with Golgi stacks.
CC {ECO:0000269|PubMed:10806194}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis, in pachytene and
CC diplotene spermatocytes, but not in more mature elongating spermatids.
CC Detected in neurons throughout the brain.
CC {ECO:0000269|PubMed:10806194}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice display signs of ciliopathies
CC including prenatal and perinatal lethality, polycystic kidneys, arrest
CC of eye development, abnormalities in primary cilia, cerebral
CC developmental defects, and skeletal defects.
CC {ECO:0000269|PubMed:19668215}.
CC -!- SIMILARITY: Belongs to the inositol polyphosphate 5-phosphatase family.
CC {ECO:0000305}.
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DR EMBL; AF226683; AAF86957.1; -; mRNA.
DR EMBL; AK080075; BAC37823.1; -; mRNA.
DR EMBL; AK154097; BAE32374.1; -; mRNA.
DR EMBL; AK170786; BAE42028.1; -; mRNA.
DR EMBL; BC052717; AAH52717.1; -; mRNA.
DR EMBL; BC080295; AAH80295.1; -; mRNA.
DR CCDS; CCDS15805.1; -.
DR RefSeq; NP_001277366.1; NM_001290437.1.
DR RefSeq; NP_149125.1; NM_033134.3.
DR AlphaFoldDB; Q9JII1; -.
DR SMR; Q9JII1; -.
DR BioGRID; 211076; 2.
DR STRING; 10090.ENSMUSP00000119485; -.
DR iPTMnet; Q9JII1; -.
DR PhosphoSitePlus; Q9JII1; -.
DR MaxQB; Q9JII1; -.
DR PaxDb; Q9JII1; -.
DR PRIDE; Q9JII1; -.
DR ProteomicsDB; 269316; -.
DR Antibodypedia; 32176; 99 antibodies from 24 providers.
DR DNASU; 64436; -.
DR Ensembl; ENSMUST00000145701; ENSMUSP00000119485; ENSMUSG00000026925.
DR GeneID; 64436; -.
DR KEGG; mmu:64436; -.
DR UCSC; uc008ivf.2; mouse.
DR CTD; 56623; -.
DR MGI; MGI:1927753; Inpp5e.
DR VEuPathDB; HostDB:ENSMUSG00000026925; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000158199; -.
DR HOGENOM; CLU_011711_5_5_1; -.
DR InParanoid; Q9JII1; -.
DR OMA; HADYKLR; -.
DR OrthoDB; 885595at2759; -.
DR PhylomeDB; Q9JII1; -.
DR TreeFam; TF323475; -.
DR BRENDA; 3.1.3.36; 3474.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-MMU-5624958; ARL13B-mediated ciliary trafficking of INPP5E.
DR BioGRID-ORCS; 64436; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Inpp5e; mouse.
DR PRO; PR:Q9JII1; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JII1; protein.
DR Bgee; ENSMUSG00000026925; Expressed in floor plate of midbrain and 245 other tissues.
DR ExpressionAtlas; Q9JII1; baseline and differential.
DR Genevisible; Q9JII1; MM.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001726; C:ruffle; ISO:MGI.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; ISO:MGI.
DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; ISO:MGI.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IEA:RHEA.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IDA:MGI.
DR GO; GO:0106019; F:phosphatidylinositol-4,5-bisphosphate phosphatase activity; ISO:MGI.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:1903565; P:negative regulation of protein localization to cilium; IMP:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:MGI.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:MGI.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR042478; INPP5E.
DR InterPro; IPR000300; IPPc.
DR PANTHER; PTHR46625; PTHR46625; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SMART; SM00128; IPPc; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cilium; Cytoplasm; Cytoskeleton;
KW Golgi apparatus; Hydrolase; Lipid metabolism; Lipoprotein; Membrane;
KW Methylation; Nucleus; Phosphoprotein; Prenylation; Reference proteome;
KW Repeat.
FT CHAIN 1..644
FT /note="Phosphatidylinositol polyphosphate 5-phosphatase
FT type IV"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR6"
FT /id="PRO_0000209748"
FT PROPEP 645..647
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR6"
FT /id="PRO_0000431689"
FT REPEAT 52..55
FT /note="1"
FT REPEAT 76..79
FT /note="2"
FT REPEAT 240..243
FT /note="3"
FT REGION 1..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 52..243
FT /note="3 X 4 AA repeats of P-X-X-P"
FT REGION 101..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..196
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..75
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 105..131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 197
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVR1"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 644
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR6"
FT LIPID 644
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR6"
SQ SEQUENCE 647 AA; 71915 MW; 4BBE3A39DB7ECB0E CRC64;
MPSKSACLRH TEAPGQLEGR MLQGQPPNTE KKLIPTPGFL PASDSQGSET NPMPPFSIPA
KTSNQNPQTK ANLITPQPPI RPKLERTLSL DDKGWRRRRF RGSQEDLTVQ NGASPCRGSL
QDSVAQSPAY SRPLPCLSTS LQEIPKSRRA TGSEGGSPSL WSDCLSGMIS TSLDLLHRDA
ASGGPPSRLA SLHASHTPPA MDLSIASSSL RTANKVDPEH TDYKLRMQTR LVRAHSNLGP
SRPRSPLAGD DHSIHSARSF SLLAPIRTKD IRSRSYLEGS LLASGALLGA EELARYFPDR
NMALFVATWN MQGQKELPAS LDEFLLPTEA DYTQDLYVIG IQEGCSDRRE WETRLQETLG
PQYVLLSSAA HGVLYMSLFI RRDLIWFCSE VEYSTVTTRI VSQIKTKGAL GVSFTFFGTS
FLFITSHFTS GDGKVAERLL DYSRTIQALA LPRNVPDTNP YRSSAGDVTT RFDEVFWFGD
FNFRLSGGRV AVEAFLKQKP EVDVLALLQH DQLTREMKKG SIFRGFEEAE IHFLPSYKFD
IGKDTYDSTS KQRTPSYTDR VLYKSRHKGD ICPMKYSSCP GIKTSDHRPV YGLFQVKVRP
GRDNIPLAAG KFDRELYLIG IKRRISKEIQ RQEALKSQSS SAVCTVS
