INP5E_HUMAN
ID INP5E_HUMAN Reviewed; 644 AA.
AC Q9NRR6; Q15734; Q6PIV5;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Phosphatidylinositol polyphosphate 5-phosphatase type IV {ECO:0000305};
DE AltName: Full=72 kDa inositol polyphosphate 5-phosphatase;
DE AltName: Full=Inositol polyphosphate-5-phosphatase E {ECO:0000303|PubMed:19668216};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 5-phosphatase {ECO:0000305};
DE EC=3.1.3.36 {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:19668216};
DE AltName: Full=Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase {ECO:0000305};
DE EC=3.1.3.86 {ECO:0000269|PubMed:10764818};
DE Flags: Precursor;
GN Name=INPP5E;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC TISSUE=Fetal brain;
RX PubMed=10764818; DOI=10.1074/jbc.m910119199;
RA Kisseleva M.V., Wilson M.P., Majerus P.W.;
RT "The isolation and characterization of a cDNA encoding phospholipid-
RT specific inositol polyphosphate 5-phosphatase.";
RL J. Biol. Chem. 275:20110-20116(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 469-644 (ISOFORM 1).
RA Nussbaum R.L.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [7]
RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN MORMS.
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 [8]
RP SUBCELLULAR LOCATION, VARIANTS JBTS1 CYS-378; GLN-435; TRP-512; TRP-515;
RP HIS-563 AND GLU-580, CHARACTERIZATION OF VARIANTS JBTS1 CYS-378; GLN-435;
RP TRP-512; TRP-515; HIS-563 AND GLU-580, AND CATALYTIC ACTIVITY.
RX PubMed=19668216; DOI=10.1038/ng.423;
RA Bielas S.L., Silhavy J.L., Brancati F., Kisseleva M.V., Al-Gazali L.,
RA Sztriha L., Bayoumi R.A., Zaki M.S., Abdel-Aleem A., Rosti R.O.,
RA Kayserili H., Swistun D., Scott L.C., Bertini E., Boltshauser E., Fazzi E.,
RA Travaglini L., Field S.J., Gayral S., Jacoby M., Schurmans S.,
RA Dallapiccola B., Majerus P.W., Valente E.M., Gleeson J.G.;
RT "Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link
RT phosphatidyl inositol signaling to the ciliopathies.";
RL Nat. Genet. 41:1032-1036(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INTERACTION WITH PDE6D, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-641,
RP METHYLATION AT CYS-641, AND MUTAGENESIS OF CYS-641.
RX PubMed=24166846; DOI=10.1002/humu.22470;
RA Thomas S., Wright K.J., Le Corre S., Micalizzi A., Romani M., Abhyankar A.,
RA Saada J., Perrault I., Amiel J., Litzler J., Filhol E., Elkhartoufi N.,
RA Kwong M., Casanova J.L., Boddaert N., Baehr W., Lyonnet S., Munnich A.,
RA Burglen L., Chassaing N., Encha-Ravazi F., Vekemans M., Gleeson J.G.,
RA Valente E.M., Jackson P.K., Drummond I.A., Saunier S., Attie-Bitach T.;
RT "A homozygous PDE6D mutation in Joubert syndrome impairs targeting of
RT farnesylated INPP5E protein to the primary cilium.";
RL Hum. Mutat. 35:137-146(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 275-623.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human INPP5E.";
RL Submitted (NOV-2010) to the PDB data bank.
RN [12]
RP VARIANTS JBTS1 ARG-286; MET-303; SER-345; ASN-426; GLN-435; ARG-474;
RP ASP-534; HIS-563; CYS-585; GLN-621 AND ARG-641.
RX PubMed=23386033; DOI=10.1038/ejhg.2012.305;
RG International JSRD Study Group;
RA Travaglini L., Brancati F., Silhavy J., Iannicelli M., Nickerson E.,
RA Elkhartoufi N., Scott E., Spencer E., Gabriel S., Thomas S., Ben-Zeev B.,
RA Bertini E., Boltshauser E., Chaouch M., Cilio M.R., de Jong M.M.,
RA Kayserili H., Ogur G., Poretti A., Signorini S., Uziel G., Zaki M.S.,
RA Johnson C., Attie-Bitach T., Gleeson J.G., Valente E.M.;
RT "Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome
RT and related disorders.";
RL Eur. J. Hum. Genet. 21:1074-1078(2013).
RN [13]
RP VARIANT JBTS1 GLN-621, AND INVOLVEMENT IN JBTS1.
RX PubMed=23034536; DOI=10.1038/jhg.2012.117;
RA Tsurusaki Y., Kobayashi Y., Hisano M., Ito S., Doi H., Nakashima M.,
RA Saitsu H., Matsumoto N., Miyake N.;
RT "The diagnostic utility of exome sequencing in Joubert syndrome and related
RT disorders.";
RL J. Hum. Genet. 58:113-115(2013).
RN [14]
RP VARIANT JBTS1 ALA-522.
RX PubMed=29052317; DOI=10.1002/ajmg.a.38376;
RA Hardee I., Soldatos A., Davids M., Vilboux T., Toro C., David K.L.,
RA Ferreira C.R., Nehrebecky M., Snow J., Thurm A., Heller T., Macnamara E.F.,
RA Gunay-Aygun M., Zein W.M., Gahl W.A., Malicdan M.C.V.;
RT "Defective ciliogenesis in INPP5E-related Joubert syndrome.";
RL Am. J. Med. Genet. A 173:3231-3237(2017).
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) (PubMed:10764818) (By similarity). Specific for lipid
CC substrates, inactive towards water soluble inositol phosphates
CC (PubMed:10764818). Plays an essential role in the primary cilium by
CC controlling ciliary growth and phosphoinositide 3-kinase (PI3K)
CC signaling and stability (By similarity). {ECO:0000250|UniProtKB:Q9JII1,
CC ECO:0000269|PubMed:10764818}.
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:0000269|PubMed:10764818, ECO:0000269|PubMed:19668216};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765;
CC Evidence={ECO:0000305|PubMed:10764818, ECO:0000305|PubMed:19668216};
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:10764818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305|PubMed:10764818};
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:0000250|UniProtKB:Q9JII1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32956;
CC Evidence={ECO:0000250|UniProtKB:Q9JII1};
CC -!- ACTIVITY REGULATION: Active in the presence of octyl-glucoside or
CC Triton X-100, but completely inhibited by CTAB.
CC {ECO:0000269|PubMed:10764818}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.65 uM for phosphatidylinositol-3,4,5-trisphosphate
CC {ECO:0000269|PubMed:10764818};
CC Vmax=0.1145 umol/min/mg enzyme with phosphatidylinositol-3,4,5-
CC trisphosphate as substrate {ECO:0000269|PubMed:10764818};
CC -!- SUBUNIT: Interacts (when prenylated) with PDE6D; this is important for
CC normal location in cilia. {ECO:0000269|PubMed:24166846}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000269|PubMed:19668215, ECO:0000269|PubMed:19668216,
CC ECO:0000269|PubMed:24166846}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q9JII1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9JII1}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9JII1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9WVR1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9WVR1}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9WVR1}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q9WVR1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9WVR1}. Nucleus {ECO:0000250|UniProtKB:Q9JII1}.
CC Note=Peripheral membrane protein associated with Golgi stacks.
CC {ECO:0000250|UniProtKB:Q9JII1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NRR6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NRR6-2; Sequence=VSP_009799;
CC -!- TISSUE SPECIFICITY: Detected in brain, heart, pancreas, testis and
CC spleen. {ECO:0000269|PubMed:10764818}.
CC -!- DISEASE: Joubert syndrome 1 (JBTS1) [MIM:213300]: A disorder presenting
CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal
CC breathing abnormalities and psychomotor delay. Neuroradiologically, it
CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened
CC and reoriented superior cerebellar peduncles, and an abnormally large
CC interpeduncular fossa, giving the appearance of a molar tooth on
CC transaxial slices (molar tooth sign). Additional variable features
CC include retinal dystrophy and renal disease.
CC {ECO:0000269|PubMed:19668216, ECO:0000269|PubMed:23034536,
CC ECO:0000269|PubMed:23386033, ECO:0000269|PubMed:29052317}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Intellectual disability, truncal obesity, retinal dystrophy,
CC and micropenis (MORMS) [MIM:610156]: An autosomal recessive disorder
CC characterized by moderate intellectual disability, truncal obesity,
CC congenital non-progressive retinal dystrophy, and micropenis in males.
CC The phenotype is similar to Bardet-Biedl syndrome and Cohen syndrome
CC Distinguishing features are the age of onset, the non-progressive
CC nature of the visual impairment, lack of dysmorphic facies, skin or
CC gingival infection, microcephaly, mottled retina, polydactyly, and
CC testicular anomalies. {ECO:0000269|PubMed:19668215}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC type IV family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB03215.1; Type=Miscellaneous discrepancy; Note=Several sequencing problems.; Evidence={ECO:0000305};
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DR EMBL; AF187891; AAF81404.1; -; mRNA.
DR EMBL; AL592301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88234.1; -; Genomic_DNA.
DR EMBL; BC028032; AAH28032.1; -; mRNA.
DR EMBL; U45974; AAB03215.1; ALT_SEQ; mRNA.
DR CCDS; CCDS7000.1; -. [Q9NRR6-1]
DR RefSeq; NP_001305431.1; NM_001318502.1.
DR RefSeq; NP_063945.2; NM_019892.5. [Q9NRR6-1]
DR PDB; 2XSW; X-ray; 1.90 A; A/B=275-623.
DR PDBsum; 2XSW; -.
DR AlphaFoldDB; Q9NRR6; -.
DR SMR; Q9NRR6; -.
DR BioGRID; 121159; 68.
DR CORUM; Q9NRR6; -.
DR IntAct; Q9NRR6; 6.
DR STRING; 9606.ENSP00000360777; -.
DR SwissLipids; SLP:000001180; -.
DR DEPOD; INPP5E; -.
DR GlyGen; Q9NRR6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NRR6; -.
DR PhosphoSitePlus; Q9NRR6; -.
DR BioMuta; INPP5E; -.
DR DMDM; 212276439; -.
DR EPD; Q9NRR6; -.
DR jPOST; Q9NRR6; -.
DR MassIVE; Q9NRR6; -.
DR MaxQB; Q9NRR6; -.
DR PaxDb; Q9NRR6; -.
DR PeptideAtlas; Q9NRR6; -.
DR PRIDE; Q9NRR6; -.
DR ProteomicsDB; 82414; -. [Q9NRR6-1]
DR ProteomicsDB; 82415; -. [Q9NRR6-2]
DR Antibodypedia; 32176; 99 antibodies from 24 providers.
DR DNASU; 56623; -.
DR Ensembl; ENST00000371712.4; ENSP00000360777.3; ENSG00000148384.14. [Q9NRR6-1]
DR Ensembl; ENST00000676019.1; ENSP00000501984.1; ENSG00000148384.14. [Q9NRR6-2]
DR GeneID; 56623; -.
DR KEGG; hsa:56623; -.
DR MANE-Select; ENST00000371712.4; ENSP00000360777.3; NM_019892.6; NP_063945.2.
DR UCSC; uc004cho.4; human. [Q9NRR6-1]
DR CTD; 56623; -.
DR DisGeNET; 56623; -.
DR GeneCards; INPP5E; -.
DR GeneReviews; INPP5E; -.
DR HGNC; HGNC:21474; INPP5E.
DR HPA; ENSG00000148384; Low tissue specificity.
DR MalaCards; INPP5E; -.
DR MIM; 213300; phenotype.
DR MIM; 610156; phenotype.
DR MIM; 613037; gene.
DR neXtProt; NX_Q9NRR6; -.
DR OpenTargets; ENSG00000148384; -.
DR Orphanet; 475; Joubert syndrome.
DR Orphanet; 1454; Joubert syndrome with hepatic defect.
DR Orphanet; 220493; Joubert syndrome with ocular defect.
DR Orphanet; 75858; MORM syndrome.
DR PharmGKB; PA164741785; -.
DR VEuPathDB; HostDB:ENSG00000148384; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000158199; -.
DR HOGENOM; CLU_011711_5_5_1; -.
DR InParanoid; Q9NRR6; -.
DR OMA; HADYKLR; -.
DR OrthoDB; 885595at2759; -.
DR PhylomeDB; Q9NRR6; -.
DR TreeFam; TF323475; -.
DR BioCyc; MetaCyc:HS09270-MON; -.
DR BRENDA; 3.1.3.36; 2681.
DR PathwayCommons; Q9NRR6; -.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-5624958; ARL13B-mediated ciliary trafficking of INPP5E.
DR SignaLink; Q9NRR6; -.
DR BioGRID-ORCS; 56623; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; INPP5E; human.
DR GenomeRNAi; 56623; -.
DR Pharos; Q9NRR6; Tbio.
DR PRO; PR:Q9NRR6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9NRR6; protein.
DR Bgee; ENSG00000148384; Expressed in right uterine tube and 192 other tissues.
DR ExpressionAtlas; Q9NRR6; baseline and differential.
DR Genevisible; Q9NRR6; HS.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; TAS:UniProtKB.
DR GO; GO:0016314; F:phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity; IEA:Ensembl.
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; IBA:GO_Central.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IEA:Ensembl.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:1903565; P:negative regulation of protein localization to cilium; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IEA:Ensembl.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
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 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Ciliopathy; Cilium; Cytoplasm; Cytoskeleton; Disease variant;
KW Golgi apparatus; Hydrolase; Intellectual disability; Joubert syndrome;
KW Lipid metabolism; Lipoprotein; Membrane; Methylation; Nucleus; Obesity;
KW Phosphoprotein; Prenylation; Reference proteome; Repeat.
FT CHAIN 1..641
FT /note="Phosphatidylinositol polyphosphate 5-phosphatase
FT type IV"
FT /evidence="ECO:0000305|PubMed:24166846"
FT /id="PRO_0000209747"
FT PROPEP 642..644
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:24166846"
FT /id="PRO_0000431688"
FT REPEAT 10..13
FT /note="1"
FT REPEAT 15..18
FT /note="2"
FT REPEAT 28..31
FT /note="3"
FT REPEAT 39..42
FT /note="4"
FT REPEAT 55..58
FT /note="5"
FT REPEAT 69..71
FT /note="6"
FT REPEAT 72..74
FT /note="7"
FT REPEAT 75..78
FT /note="8"
FT REPEAT 121..124
FT /note="9"
FT REPEAT 169..172
FT /note="10"
FT REPEAT 183..185
FT /note="11"
FT REPEAT 190..193
FT /note="12"
FT REPEAT 236..239
FT /note="13"
FT REGION 1..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 10..242
FT /note="13 X 4 AA repeats of P-X-X-P"
FT COMPBIAS 80..102
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 103..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..169
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVR1"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JII1"
FT MOD_RES 641
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305|PubMed:24166846"
FT LIPID 641
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000305|PubMed:24166846"
FT VAR_SEQ 346..379
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10764818"
FT /id="VSP_009799"
FT VARIANT 201
FT /note="I -> M (in dbSNP:rs36064831)"
FT /id="VAR_047078"
FT VARIANT 286
FT /note="G -> R (in JBTS1; dbSNP:rs757936530)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077247"
FT VARIANT 303
FT /note="V -> M (in JBTS1; dbSNP:rs746212325)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077248"
FT VARIANT 345
FT /note="R -> S (in JBTS1)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077249"
FT VARIANT 378
FT /note="R -> C (in JBTS1; slightly reduced
FT phosphatidylinositol-4,5-bisphosphate 5-phosphatase
FT activity; dbSNP:rs121918130)"
FT /evidence="ECO:0000269|PubMed:19668216"
FT /id="VAR_063012"
FT VARIANT 426
FT /note="T -> N (in JBTS1)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077250"
FT VARIANT 435
FT /note="R -> Q (in JBTS1; severe reduction of
FT phosphatidylinositol-4,5-bisphosphate 5-phosphatase
FT activity; dbSNP:rs121918129)"
FT /evidence="ECO:0000269|PubMed:19668216,
FT ECO:0000269|PubMed:23386033"
FT /id="VAR_063013"
FT VARIANT 474
FT /note="W -> R (in JBTS1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077251"
FT VARIANT 512
FT /note="R -> W (in JBTS1; associated with W-515; severe
FT reduction of phosphatidylinositol-4,5-bisphosphate 5-
FT phosphatase activity; dbSNP:rs374152018)"
FT /evidence="ECO:0000269|PubMed:19668216"
FT /id="VAR_063014"
FT VARIANT 515
FT /note="R -> W (in JBTS1; associated with W-512; severe
FT reduction of phosphatidylinositol-4,5-bisphosphate 5-
FT phosphatase activity; dbSNP:rs13297509)"
FT /evidence="ECO:0000269|PubMed:19668216"
FT /id="VAR_063015"
FT VARIANT 522
FT /note="G -> A (in JBTS1; reduced levels of protein in
FT patients' fibroblasts; significant number of cells from
FT patients have shorter or no cilia; dbSNP:rs771866500)"
FT /evidence="ECO:0000269|PubMed:29052317"
FT /id="VAR_081790"
FT VARIANT 534
FT /note="Y -> D (in JBTS1)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077252"
FT VARIANT 563
FT /note="R -> H (in JBTS1; slightly reduced
FT phosphatidylinositol-4,5-bisphosphate 5-phosphatase
FT activity; dbSNP:rs121918128)"
FT /evidence="ECO:0000269|PubMed:19668216,
FT ECO:0000269|PubMed:23386033"
FT /id="VAR_063016"
FT VARIANT 580
FT /note="K -> E (in JBTS1; severe reduction of
FT phosphatidylinositol-4,5-bisphosphate 5-phosphatase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19668216"
FT /id="VAR_063017"
FT VARIANT 585
FT /note="R -> C (in JBTS1; dbSNP:rs763992407)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077253"
FT VARIANT 621
FT /note="R -> Q (in JBTS1; dbSNP:rs1588830568)"
FT /evidence="ECO:0000269|PubMed:23034536,
FT ECO:0000269|PubMed:23386033"
FT /id="VAR_076892"
FT VARIANT 641
FT /note="C -> R (in JBTS1)"
FT /evidence="ECO:0000269|PubMed:23386033"
FT /id="VAR_077254"
FT MUTAGEN 641
FT /note="C->A: Abolishes farnesylation-dependent interaction
FT with PDE6D."
FT /evidence="ECO:0000269|PubMed:24166846"
FT CONFLICT 345
FT /note="R -> T (in Ref. 1; AAF81404)"
FT /evidence="ECO:0000305"
FT HELIX 287..293
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 298..307
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 319..322
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 332..340
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 345..356
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 360..368
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 371..378
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 379..384
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 389..399
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 402..413
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 416..424
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 432..445
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 465..467
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 468..477
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 486..493
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 501..505
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 509..515
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 540..543
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 556..564
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 567..575
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 581..584
FT /evidence="ECO:0007829|PDB:2XSW"
FT STRAND 587..594
FT /evidence="ECO:0007829|PDB:2XSW"
FT HELIX 611..623
FT /evidence="ECO:0007829|PDB:2XSW"
SQ SEQUENCE 644 AA; 70205 MW; 5B6CFB75CD0ADC9A CRC64;
MPSKAENLRP SEPAPQPPEG RTLQGQLPGA PPAQRAGSPP DAPGSESPAL ACSTPATPSG
EDPPARAAPI APRPPARPRL ERALSLDDKG WRRRRFRGSQ EDLEARNGTS PSRGSVQSEG
PGAPAHSCSP PCLSTSLQEI PKSRGVLSSE RGSPSSGGNP LSGVASSSPN LPHRDAAVAG
SSPRLPSLLP PRPPPALSLD IASDSLRTAN KVDSDLADYK LRAQPLLVRA HSSLGPGRPR
SPLACDDCSL RSAKSSFSLL APIRSKDVRS RSYLEGSLLA SGALLGADEL ARYFPDRNVA
LFVATWNMQG QKELPPSLDE FLLPAEADYA QDLYVIGVQE GCSDRREWET RLQETLGPHY
VLLSSAAHGV LYMSLFIRRD LIWFCSEVEC STVTTRIVSQ IKTKGALGIS FTFFGTSFLF
ITSHFTSGDG KVAERLLDYT RTVQALVLPR NVPDTNPYRS SAADVTTRFD EVFWFGDFNF
RLSGGRTVVD ALLCQGLVVD VPALLQHDQL IREMRKGSIF KGFQEPDIHF LPSYKFDIGK
DTYDSTSKQR TPSYTDRVLY RSRHKGDICP VSYSSCPGIK TSDHRPVYGL FRVKVRPGRD
NIPLAAGKFD RELYLLGIKR RISKEIQRQQ ALQSQNSSTI CSVS
