INP5K_HUMAN
ID INP5K_HUMAN Reviewed; 448 AA.
AC Q9BT40; B2R6I2; B2R750; D3DTH8; Q15733; Q9NPJ5; Q9P2R5;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Inositol polyphosphate 5-phosphatase K {ECO:0000305};
DE EC=3.1.3.56 {ECO:0000269|PubMed:10753883, ECO:0000269|PubMed:28190456, ECO:0000269|PubMed:28190459};
DE AltName: Full=Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase;
DE EC=3.1.3.86 {ECO:0000269|PubMed:10753883, ECO:0000269|PubMed:16824732};
DE AltName: Full=Phosphatidylinositol-4,5-bisphosphate 5-phosphatase;
DE EC=3.1.3.36 {ECO:0000269|PubMed:10753883};
DE AltName: Full=Skeletal muscle and kidney-enriched inositol phosphatase {ECO:0000303|PubMed:10753883};
GN Name=INPP5K {ECO:0000312|HGNC:HGNC:33882};
GN Synonyms=PPS, SKIP {ECO:0000303|PubMed:10753883};
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 {ECO:0000312|EMBL:AAH04362.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION,
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Testis {ECO:0000269|PubMed:10753883};
RX PubMed=10753883; DOI=10.1074/jbc.275.15.10870;
RA Ijuin T., Mochizuki Y., Fukami K., Funaki M., Asano T., Takenawa T.;
RT "Identification and characterization of a novel inositol polyphosphate 5-
RT phosphatase.";
RL J. Biol. Chem. 275:10870-10875(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3] {ECO:0000305}
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye {ECO:0000312|EMBL:AAH04362.1};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 120-448.
RC TISSUE=Brain {ECO:0000312|EMBL:AAB03214.1};
RA Nussbaum R.L.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-349; ASP-361; TRP-362 AND
RP TYR-376.
RX PubMed=12536145; DOI=10.1074/jbc.m209991200;
RA Gurung R., Tan A., Ooms L.M., McGrath M.J., Huysmans R.D., Munday A.D.,
RA Prescott M., Whisstock J.C., Mitchell C.A.;
RT "Identification of a novel domain in two mammalian inositol-polyphosphate
RT 5-phosphatases that mediates membrane ruffle localization. The inositol 5-
RT phosphatase SKIP localizes to the endoplasmic reticulum and translocates to
RT membrane ruffles following epidermal growth factor stimulation.";
RL J. Biol. Chem. 278:11376-11385(2003).
RN [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16824732; DOI=10.1016/j.cellsig.2006.05.010;
RA Vandeput F., Backers K., Villeret V., Pesesse X., Erneux C.;
RT "The influence of anionic lipids on SHIP2 phosphatidylinositol 3,4,5-
RT trisphosphate 5-phosphatase activity.";
RL Cell. Signal. 18:2193-2199(2006).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] PHE-315.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [9]
RP INTERACTION WITH GPR78 AND PAK1, REGION, AND SUBCELLULAR LOCATION.
RX PubMed=26940976; DOI=10.1111/gtc.12353;
RA Ijuin T., Hatano N., Takenawa T.;
RT "Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase
RT SKIP and determines its localization.";
RL Genes Cells 21:457-465(2016).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INVOLVEMENT IN MDCCAID,
RP VARIANTS MDCCAID THR-50; SER-294 DEL; CYS-300 AND THR-363, CHARACTERIZATION
RP OF VARIANTS MDCCAID THR-50; SER-294 DEL; CYS-300 AND THR-363, AND
RP MUTAGENESIS OF ASP-310.
RX PubMed=28190456; DOI=10.1016/j.ajhg.2017.01.024;
RA Wiessner M., Roos A., Munn C.J., Viswanathan R., Whyte T., Cox D.,
RA Schoser B., Sewry C., Roper H., Phadke R., Marini Bettolo C., Barresi R.,
RA Charlton R., Boennemann C.G., Abath Neto O., Reed U.C., Zanoteli E.,
RA Araujo Martins Moreno C., Ertl-Wagner B., Stucka R., De Goede C.,
RA Borges da Silva T., Hathazi D., Dell'Aica M., Zahedi R.P., Thiele S.,
RA Mueller J., Kingston H., Mueller S., Curtis E., Walter M.C., Strom T.M.,
RA Straub V., Bushby K., Muntoni F., Swan L.E., Lochmueller H., Senderek J.;
RT "Mutations in INPP5K, Encoding a Phosphoinositide 5-Phosphatase, Cause
RT Congenital muscular dystrophy with cataracts and mild cognitive
RT impairment.";
RL Am. J. Hum. Genet. 100:523-536(2017).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, VARIANTS MDCCAID MET-23; VAL-93; SER-140 AND
RP ASN-269, CHARACTERIZATION OF VARIANTS MDCCAID MET-23; VAL-93; SER-140 AND
RP ASN-269, AND MUTAGENESIS OF ASP-310.
RX PubMed=28190459; DOI=10.1016/j.ajhg.2017.01.019;
RA Osborn D.P., Pond H.L., Mazaheri N., Dejardin J., Munn C.J., Mushref K.,
RA Cauley E.S., Moroni I., Pasanisi M.B., Sellars E.A., Hill R.S.,
RA Partlow J.N., Willaert R.K., Bharj J., Malamiri R.A., Galehdari H.,
RA Shariati G., Maroofian R., Mora M., Swan L.E., Voit T., Conti F.J.,
RA Jamshidi Y., Manzini M.C.;
RT "Mutations in INPP5K cause a form of Congenital Muscular Dystrophy
RT overlapping Marinesco-Sjoegren Syndrome and dystroglycanopathy.";
RL Am. J. Hum. Genet. 100:537-545(2017).
CC -!- FUNCTION: Inositol 5-phosphatase which acts on inositol 1,4,5-
CC trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol
CC 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate
CC (PubMed:10753883, PubMed:16824732). Has 6-fold higher affinity for
CC phosphatidylinositol 4,5-bisphosphate than for inositol 1,4,5-
CC trisphosphate (PubMed:10753883). Negatively regulates assembly of the
CC actin cytoskeleton. Controls insulin-dependent glucose uptake among
CC inositol 3,4,5-trisphosphate phosphatases; therefore, is the specific
CC regulator for insulin signaling in skeletal muscle (By similarity).
CC {ECO:0000250|UniProtKB:Q8C5L6, ECO:0000269|PubMed:10753883,
CC ECO:0000269|PubMed:16824732, ECO:0000269|PubMed:28190456,
CC ECO:0000269|PubMed:28190459}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,4,5-trisphosphate + H2O = 1D-myo-inositol
CC 1,4-bisphosphate + phosphate; Xref=Rhea:RHEA:19797,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58282,
CC ChEBI:CHEBI:203600; EC=3.1.3.56;
CC Evidence={ECO:0000269|PubMed:10753883, ECO:0000269|PubMed:28190456,
CC ECO:0000269|PubMed:28190459};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19798;
CC Evidence={ECO:0000305|PubMed:10753883, ECO:0000305|PubMed:28190456,
CC ECO:0000305|PubMed:28190459};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,3,4-trisphosphate + phosphate; Xref=Rhea:RHEA:11392,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414; EC=3.1.3.56;
CC Evidence={ECO:0000269|PubMed:10753883};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11393;
CC Evidence={ECO:0000305|PubMed:10753883};
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:10753883};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765;
CC Evidence={ECO:0000305|PubMed:10753883};
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:10753883, ECO:0000269|PubMed:16824732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305|PubMed:10753883};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-
CC trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43548,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416,
CC ChEBI:CHEBI:83417; Evidence={ECO:0000269|PubMed:10753883,
CC ECO:0000269|PubMed:16824732};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43550;
CC Evidence={ECO:0000305|PubMed:16824732};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=180 uM for phosphatidylinositol 4,5-bisphosphate
CC {ECO:0000269|PubMed:10753883};
CC KM=1.15 mM for phosphatidylinositol 3,4,5-trisphosphate
CC {ECO:0000269|PubMed:10753883};
CC -!- SUBUNIT: Interacts with GPR78; necessary for INPP5K localization at the
CC endoplasmic reticulum. Interacts with PAK1; competes with GPR78.
CC {ECO:0000269|PubMed:26940976}.
CC -!- INTERACTION:
CC Q9BT40; Q15041: ARL6IP1; NbExp=5; IntAct=EBI-749162, EBI-714543;
CC Q9BT40; P18859: ATP5PF; NbExp=3; IntAct=EBI-749162, EBI-2606700;
CC Q9BT40; Q8N9I5: FADS6; NbExp=3; IntAct=EBI-749162, EBI-3943864;
CC Q9BT40; Q969F0: FATE1; NbExp=7; IntAct=EBI-749162, EBI-743099;
CC Q9BT40; Q9Y3E0: GOLT1B; NbExp=3; IntAct=EBI-749162, EBI-4402607;
CC Q9BT40; Q92876: KLK6; NbExp=3; IntAct=EBI-749162, EBI-2432309;
CC Q9BT40; Q15323: KRT31; NbExp=6; IntAct=EBI-749162, EBI-948001;
CC Q9BT40; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-749162, EBI-739832;
CC Q9BT40; Q15013: MAD2L1BP; NbExp=11; IntAct=EBI-749162, EBI-712181;
CC Q9BT40; Q96AL5: PBX3; NbExp=3; IntAct=EBI-749162, EBI-741171;
CC Q9BT40; O95562: SFT2D2; NbExp=3; IntAct=EBI-749162, EBI-4402330;
CC Q9BT40; Q9UBN6: TNFRSF10D; NbExp=3; IntAct=EBI-749162, EBI-1044859;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:12536145, ECO:0000269|PubMed:26940976,
CC ECO:0000269|PubMed:28190456}. Cytoplasm {ECO:0000269|PubMed:10753883}.
CC Note=Following stimulation with EGF, translocates to membrane ruffles
CC (PubMed:12536145, PubMed:26940976). Concentrated at the periphery of
CC the nucleus (PubMed:10753883). {ECO:0000269|PubMed:10753883,
CC ECO:0000269|PubMed:12536145, ECO:0000269|PubMed:26940976}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:10753883};
CC IsoId=Q9BT40-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:10753883};
CC IsoId=Q9BT40-2; Sequence=VSP_050612;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC skeletal muscle, heart and kidney. {ECO:0000269|PubMed:10753883}.
CC -!- DISEASE: Muscular dystrophy, congenital, with cataracts and
CC intellectual disability (MDCCAID) [MIM:617404]: An autosomal recessive
CC form of muscular dystrophy with onset in early childhood and
CC characterized by progressive muscle weakness. Almost all patients also
CC have early-onset cataracts and intellectual disability of varying
CC severity. Some patients have seizures. {ECO:0000269|PubMed:28190456,
CC ECO:0000269|PubMed:28190459}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC type II family. {ECO:0000305}.
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DR EMBL; AB036829; BAA92340.1; -; mRNA.
DR EMBL; AB036830; BAA92341.1; -; mRNA.
DR EMBL; AB036831; BAA92342.1; -; Genomic_DNA.
DR EMBL; AK312585; BAG35479.1; -; mRNA.
DR EMBL; AK312844; BAG35697.1; -; mRNA.
DR EMBL; CH471108; EAW90614.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90615.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90618.1; -; Genomic_DNA.
DR EMBL; BC004362; AAH04362.1; -; mRNA.
DR EMBL; U45973; AAB03214.1; -; mRNA.
DR CCDS; CCDS11004.1; -. [Q9BT40-1]
DR CCDS; CCDS11005.1; -. [Q9BT40-2]
DR RefSeq; NP_001129114.1; NM_001135642.1. [Q9BT40-2]
DR RefSeq; NP_057616.2; NM_016532.3. [Q9BT40-1]
DR RefSeq; NP_570122.1; NM_130766.2. [Q9BT40-2]
DR RefSeq; XP_005256740.1; XM_005256683.2. [Q9BT40-2]
DR RefSeq; XP_011522236.1; XM_011523934.1. [Q9BT40-2]
DR RefSeq; XP_016880244.1; XM_017024755.1.
DR RefSeq; XP_016880245.1; XM_017024756.1. [Q9BT40-2]
DR AlphaFoldDB; Q9BT40; -.
DR SMR; Q9BT40; -.
DR BioGRID; 119720; 60.
DR CORUM; Q9BT40; -.
DR IntAct; Q9BT40; 39.
DR MINT; Q9BT40; -.
DR STRING; 9606.ENSP00000413937; -.
DR SwissLipids; SLP:000000957; -.
DR DEPOD; INPP5K; -.
DR iPTMnet; Q9BT40; -.
DR PhosphoSitePlus; Q9BT40; -.
DR BioMuta; INPP5K; -.
DR DMDM; 116242791; -.
DR EPD; Q9BT40; -.
DR jPOST; Q9BT40; -.
DR MassIVE; Q9BT40; -.
DR MaxQB; Q9BT40; -.
DR PaxDb; Q9BT40; -.
DR PeptideAtlas; Q9BT40; -.
DR PRIDE; Q9BT40; -.
DR ProteomicsDB; 78948; -. [Q9BT40-1]
DR ProteomicsDB; 78949; -. [Q9BT40-2]
DR Antibodypedia; 22714; 146 antibodies from 25 providers.
DR DNASU; 51763; -.
DR Ensembl; ENST00000320345.10; ENSP00000318476.6; ENSG00000132376.20. [Q9BT40-2]
DR Ensembl; ENST00000406424.8; ENSP00000385177.4; ENSG00000132376.20. [Q9BT40-2]
DR Ensembl; ENST00000421807.7; ENSP00000413937.2; ENSG00000132376.20. [Q9BT40-1]
DR GeneID; 51763; -.
DR KEGG; hsa:51763; -.
DR MANE-Select; ENST00000421807.7; ENSP00000413937.2; NM_016532.4; NP_057616.2.
DR UCSC; uc002fsr.4; human. [Q9BT40-1]
DR CTD; 51763; -.
DR DisGeNET; 51763; -.
DR GeneCards; INPP5K; -.
DR HGNC; HGNC:33882; INPP5K.
DR HPA; ENSG00000132376; Low tissue specificity.
DR MalaCards; INPP5K; -.
DR MIM; 607875; gene.
DR MIM; 617404; phenotype.
DR neXtProt; NX_Q9BT40; -.
DR OpenTargets; ENSG00000132376; -.
DR Orphanet; 559; Marinesco-Sjoegren syndrome.
DR PharmGKB; PA164720951; -.
DR VEuPathDB; HostDB:ENSG00000132376; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000156538; -.
DR InParanoid; Q9BT40; -.
DR OMA; EHFRCIM; -.
DR OrthoDB; 772410at2759; -.
DR PhylomeDB; Q9BT40; -.
DR TreeFam; TF317034; -.
DR BioCyc; MetaCyc:HS05626-MON; -.
DR BRENDA; 3.1.3.56; 2681.
DR PathwayCommons; Q9BT40; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR SignaLink; Q9BT40; -.
DR BioGRID-ORCS; 51763; 35 hits in 1081 CRISPR screens.
DR ChiTaRS; INPP5K; human.
DR GeneWiki; SKIP; -.
DR GenomeRNAi; 51763; -.
DR Pharos; Q9BT40; Tbio.
DR PRO; PR:Q9BT40; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BT40; protein.
DR Bgee; ENSG00000132376; Expressed in pigmented layer of retina and 206 other tissues.
DR ExpressionAtlas; Q9BT40; baseline and differential.
DR Genevisible; Q9BT40; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:MGI.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0016312; F:inositol bisphosphate phosphatase activity; IDA:MGI.
DR GO; GO:0046030; F:inositol trisphosphate phosphatase activity; IDA:MGI.
DR GO; GO:0052659; F:inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0042577; F:lipid phosphatase activity; NAS:UniProtKB.
DR GO; GO:0034595; F:phosphatidylinositol phosphate 5-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0034594; F:phosphatidylinositol trisphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0005000; F:vasopressin receptor activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IDA:MGI.
DR GO; GO:0043922; P:negative regulation by host of viral transcription; IDA:UniProtKB.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:0035305; P:negative regulation of dephosphorylation; ISS:UniProtKB.
DR GO; GO:0010829; P:negative regulation of glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:2000466; P:negative regulation of glycogen (starch) synthase activity; ISS:UniProtKB.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0090315; P:negative regulation of protein targeting to membrane; IDA:UniProtKB.
DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IDA:UniProtKB.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR GO; GO:2001153; P:positive regulation of renal water transport; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0035810; P:positive regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0097178; P:ruffle assembly; IDA:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR041611; SKICH.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF17751; SKICH; 1.
DR SMART; SM00128; IPPc; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Congenital muscular dystrophy; Cytoplasm;
KW Disease variant; Endoplasmic reticulum; Hydrolase; Intellectual disability;
KW Lipid metabolism; Reference proteome.
FT CHAIN 1..448
FT /note="Inositol polyphosphate 5-phosphatase K"
FT /id="PRO_0000209727"
FT REGION 16..318
FT /note="Catalytic"
FT /evidence="ECO:0000255"
FT REGION 318..448
FT /note="Required for interaction with GPR78 and PAK1"
FT /evidence="ECO:0000269|PubMed:26940976"
FT REGION 321..448
FT /note="Required for ruffle localization"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10753883,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_050612"
FT VARIANT 23
FT /note="V -> M (in MDCCAID; decreased phosphatidylinositol-
FT 4,5-bisphosphate 5-phosphatase activity;
FT dbSNP:rs750781027)"
FT /evidence="ECO:0000269|PubMed:28190459"
FT /id="VAR_078998"
FT VARIANT 50
FT /note="I -> T (in MDCCAID; decreased phosphatidylinositol-
FT 4,5-bisphosphate 5-phosphatase activity; shows normal
FT localization indistinguishable from the wild-type;
FT dbSNP:rs1060505038)"
FT /evidence="ECO:0000269|PubMed:28190456"
FT /id="VAR_078999"
FT VARIANT 93
FT /note="M -> V (in MDCCAID; decreased phosphatidylinositol-
FT 4,5-bisphosphate 5-phosphatase activity;
FT dbSNP:rs1060505039)"
FT /evidence="ECO:0000269|PubMed:28190459"
FT /id="VAR_079000"
FT VARIANT 140
FT /note="G -> S (in MDCCAID; no phosphatidylinositol-4,5-
FT bisphosphate 5-phosphatase activity; dbSNP:rs749383757)"
FT /evidence="ECO:0000269|PubMed:28190459"
FT /id="VAR_079001"
FT VARIANT 269
FT /note="D -> N (in MDCCAID; no phosphatidylinositol-4,5-
FT bisphosphate 5-phosphatase activity; dbSNP:rs761612652)"
FT /evidence="ECO:0000269|PubMed:28190459"
FT /id="VAR_079002"
FT VARIANT 294
FT /note="Missing (in MDCCAID; decreased phosphatidylinositol-
FT 4,5-bisphosphate 5-phosphatase activity; shows normal
FT localization indistinguishable from the wild-type)"
FT /evidence="ECO:0000269|PubMed:28190456"
FT /id="VAR_079003"
FT VARIANT 300
FT /note="Y -> C (in MDCCAID; no phosphatidylinositol-4,5-
FT bisphosphate 5-phosphatase activity; shows normal
FT localization indistinguishable from the wild-type;
FT dbSNP:rs766046008)"
FT /evidence="ECO:0000269|PubMed:28190456"
FT /id="VAR_079004"
FT VARIANT 315
FT /note="S -> F (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036497"
FT VARIANT 363
FT /note="I -> T (in MDCCAID; shows a diffuse perinuclear
FT mislocalization; dbSNP:rs993849342)"
FT /evidence="ECO:0000269|PubMed:28190456"
FT /id="VAR_079005"
FT MUTAGEN 310
FT /note="D->G: No phosphatidylinositol-4,5-bisphosphate 5-
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:28190456,
FT ECO:0000269|PubMed:28190459"
FT MUTAGEN 349
FT /note="Y->A,F: No effect on EGF-induced ruffle
FT localization."
FT /evidence="ECO:0000269|PubMed:12536145"
FT MUTAGEN 361
FT /note="D->A: Significant decrease in EGF-induced ruffle
FT localization."
FT /evidence="ECO:0000269|PubMed:12536145"
FT MUTAGEN 362
FT /note="W->A: Significant decrease in EGF-induced ruffle
FT localization."
FT /evidence="ECO:0000269|PubMed:12536145"
FT MUTAGEN 376
FT /note="Y->A,F: No effect on EGF-induced ruffle
FT localization."
FT /evidence="ECO:0000269|PubMed:12536145"
FT CONFLICT 120
FT /note="T -> A (in Ref. 5; AAB03214)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="S -> R (in Ref. 1; BAA92340/BAA92341/BAA92342 and 5;
FT AAB03214)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="S -> R (in Ref. 1; BAA92340/BAA92341/BAA92342 and 5;
FT AAB03214)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 51090 MW; 46FAA48C6E2EEAD4 CRC64;
MSSRKLSGPK GRRLSIHVVT WNVASAAPPL DLSDLLQLNN RNLNLDIYVI GLQELNSGII
SLLSDAAFND SWSSFLMDVL SPLSFIKVSH VRMQGILLLV FAKYQHLPYI QILSTKSTPT
GLFGYWGNKG GVNICLKLYG YYVSIINCHL PPHISNNYQR LEHFDRILEM QNCEGRDIPN
ILDHDLIIWF GDMNFRIEDF GLHFVRESIK NRCYGGLWEK DQLSIAKKHD PLLREFQEGR
LLFPPTYKFD RNSNDYDTSE KKRKPAWTDR ILWRLKRQPC AGPDTPIPPA SHFSLSLRGY
SSHMTYGISD HKPVSGTFDL ELKPLVSAPL IVLMPEDLWT VENDMMVSYS STSDFPSSPW
DWIGLYKVGL RDVNDYVSYA WVGDSKVSCS DNLNQVYIDI SNIPTTEDEF LLCYYSNSLR
SVVGISRPFQ IPPGSLREDP LGEAQPQI
