OCRL_HUMAN
ID OCRL_HUMAN Reviewed; 901 AA.
AC Q01968; A6NKI1; A8KAP2; B7ZLX2; O60800; Q15684; Q15774; Q4VY09; Q4VY10;
AC Q5JQF1; Q5JQF2; Q9UJG5; Q9UMA5;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Inositol polyphosphate 5-phosphatase OCRL {ECO:0000305};
DE EC=3.1.3.36 {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:15474001, ECO:0000269|PubMed:7761412};
DE EC=3.1.3.56 {ECO:0000269|PubMed:15474001, ECO:0000269|PubMed:7761412};
DE AltName: Full=Inositol polyphosphate 5-phosphatase OCRL-1;
DE Short=OCRL-1 {ECO:0000303|PubMed:8504307};
DE AltName: Full=Lowe oculocerebrorenal syndrome protein;
DE AltName: Full=Phosphatidylinositol 3,4,5-triphosphate 5-phosphatase;
DE EC=3.1.3.86 {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:15474001};
GN Name=OCRL {ECO:0000312|HGNC:HGNC:8108}; Synonyms=OCRL1 {ECO:0000303|Ref.2};
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] (ISOFORM B).
RC TISSUE=Kidney;
RX PubMed=1321346; DOI=10.1038/358239a0;
RA Attree O., Olivos I.M., Okabe I., Bailey L.C., Nelson D.L., Lewis R.A.,
RA McInnes R.R., Nussbaum R.L.;
RT "The Lowe's oculocerebrorenal syndrome gene encodes a protein highly
RT homologous to inositol polyphosphate-5-phosphatase.";
RL Nature 358:239-242(1992).
RN [2]
RP SEQUENCE REVISION TO 585.
RA Attree O., Olivos I.M., Okabe I., Bailey L.C., Nelson D.L., Lewis R.A.,
RA McInnes R.R., Nussbaum R.L.;
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=9048911; DOI=10.1007/s004390050329;
RA Nussbaum R.L., Orrison B.M., Janne P.A., Charnas L.R., Chinault A.C.;
RT "Physical mapping and genomic structure of the Lowe syndrome gene OCRL1.";
RL Hum. Genet. 99:145-150(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Uterus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 814-843.
RX PubMed=8504307; DOI=10.1093/hmg/2.4.461;
RA Leahey A.-M., Charnas L.R., Nussbaum R.L.;
RT "Nonsense mutations in the OCRL-1 gene in patients with the
RT oculocerebrorenal syndrome of Lowe.";
RL Hum. Mol. Genet. 2:461-463(1993).
RN [9]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7761412; DOI=10.1073/pnas.92.11.4853;
RA Zhang X., Jefferson A.B., Auethavekiat V., Majerus P.W.;
RT "The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-
RT bisphosphate 5-phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4853-4856(1995).
RN [10]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=9430698; DOI=10.1074/jbc.273.3.1574;
RA Zhang X., Hartz P.A., Philip E., Racusen L.C., Majerus P.W.;
RT "Cell lines from kidney proximal tubules of a patient with Lowe syndrome
RT lack OCRL inositol polyphosphate 5-phosphatase and accumulate
RT phosphatidylinositol 4,5-bisphosphate.";
RL J. Biol. Chem. 273:1574-1582(1998).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
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 [12]
RP CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=15474001; DOI=10.1016/j.febslet.2004.08.052;
RA Schmid A.C., Wise H.M., Mitchell C.A., Nussbaum R., Woscholski R.;
RT "Type II phosphoinositide 5-phosphatases have unique sensitivities towards
RT fatty acid composition and head group phosphorylation.";
RL FEBS Lett. 576:9-13(2004).
RN [13]
RP INTERACTION WITH APPL1; CLATHRIN; FAM109A AND FAM109B, SUBCELLULAR
RP LOCATION, AND VARIANTS OCRL ASN-768 AND PRO-797.
RX PubMed=20133602; DOI=10.1073/pnas.0914658107;
RA Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.;
RT "Two closely related endocytic proteins that share a common OCRL-binding
RT motif with APPL1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21971085; DOI=10.1038/emboj.2011.354;
RA Vicinanza M., Di Campli A., Polishchuk E., Santoro M., Di Tullio G.,
RA Godi A., Levtchenko E., De Leo M.G., Polishchuk R., Sandoval L.,
RA Marzolo M.P., De Matteis M.A.;
RT "OCRL controls trafficking through early endosomes via PtdIns4,5P(2)-
RT dependent regulation of endosomal actin.";
RL EMBO J. 30:4970-4985(2011).
RN [16]
RP INTERACTION WITH APPL1; FAM109A AND FAM109B, VARIANT OCRL ASN-768, AND
RP CHARACTERIZATION OF VARIANT OCRL ASN-768.
RX PubMed=21233288; DOI=10.1091/mbc.e10-08-0730;
RA Noakes C.J., Lee G., Lowe M.;
RT "The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in
RT the endocytic pathway.";
RL Mol. Biol. Cell 22:606-623(2011).
RN [17]
RP FUNCTION IN CILIA ASSEMBLY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP INTERACTION WITH RAB8A, AND MUTAGENESIS OF ASP-422; ASP-499 AND PHE-668.
RX PubMed=22543976; DOI=10.1093/hmg/dds163;
RA Luo N., West C.C., Murga-Zamalloa C.A., Sun L., Anderson R.M., Wells C.D.,
RA Weinreb R.N., Travers J.B., Khanna H., Sun Y.;
RT "OCRL localizes to the primary cilium: a new role for cilia in Lowe
RT syndrome.";
RL Hum. Mol. Genet. 21:3333-3344(2012).
RN [18]
RP FUNCTION IN CILIOGENESIS.
RX PubMed=22228094; DOI=10.1093/hmg/ddr615;
RA Coon B.G., Hernandez V., Madhivanan K., Mukherjee D., Hanna C.B.,
RA Barinaga-Rementeria Ramirez I., Lowe M., Beales P.L., Aguilar R.C.;
RT "The Lowe syndrome protein OCRL1 is involved in primary cilia assembly.";
RL Hum. Mol. Genet. 21:1835-1847(2012).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22072788; DOI=10.1091/mbc.e11-06-0489;
RA Bohdanowicz M., Balkin D.M., De Camilli P., Grinstein S.;
RT "Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes
RT phosphoinositides and attenuates Akt signaling.";
RL Mol. Biol. Cell 23:176-187(2012).
RN [20]
RP REVIEW.
RX PubMed=22381590; DOI=10.1016/j.tibs.2012.01.002;
RA Pirruccello M., De Camilli P.;
RT "Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL.";
RL Trends Biochem. Sci. 37:134-143(2012).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH INPP5F AND RAB5A.
RX PubMed=25869668; DOI=10.1083/jcb.201409064;
RA Nakatsu F., Messa M., Nandez R., Czapla H., Zou Y., Strittmatter S.M.,
RA De Camilli P.;
RT "Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic
RT pathway.";
RL J. Cell Biol. 209:85-95(2015).
RN [22]
RP STRUCTURE BY NMR OF 1-119, DOMAIN PH, INTERACTION WITH CLATHRIN, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19536138; DOI=10.1038/emboj.2009.155;
RA Mao Y., Balkin D.M., Zoncu R., Erdmann K.S., Tomasini L., Hu F., Jin M.M.,
RA Hodsdon M.E., De Camilli P.;
RT "A PH domain within OCRL bridges clathrin-mediated membrane trafficking to
RT phosphoinositide metabolism.";
RL EMBO J. 28:1831-1842(2009).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 540-678 IN COMPLEX WITH RAB8A.
RX PubMed=21378754; DOI=10.1038/emboj.2011.60;
RA Hou X., Hagemann N., Schoebel S., Blankenfeldt W., Goody R.S.,
RA Erdmann K.S., Itzen A.;
RT "A structural basis for Lowe syndrome caused by mutations in the Rab-
RT binding domain of OCRL1.";
RL EMBO J. 30:1659-1670(2011).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 564-901, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH APPL1.
RX PubMed=17765681; DOI=10.1016/j.devcel.2007.08.004;
RA Erdmann K.S., Mao Y., McCrea H.J., Zoncu R., Lee S., Paradise S.,
RA Modregger J., Biemesderfer D., Toomre D., De Camilli P.;
RT "A role of the Lowe syndrome protein OCRL in early steps of the endocytic
RT pathway.";
RL Dev. Cell 13:377-390(2007).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 536-901 IN COMPLEX WITH FAM109A.
RX PubMed=21666675; DOI=10.1038/nsmb.2071;
RA Pirruccello M., Swan L.E., Folta-Stogniew E., De Camilli P.;
RT "Recognition of the F&H motif by the Lowe syndrome protein OCRL.";
RL Nat. Struct. Mol. Biol. 18:789-795(2011).
RN [26]
RP VARIANTS OCRL THR-367 DEL; GLY-451; SER-463 AND ARG-524.
RX PubMed=9199559; DOI=10.1086/515471;
RA Lin T., Orrison B.M., Leahey A.-M., Suchy S.F., Bernard D.J., Lewis R.A.,
RA Nussbaum R.L.;
RT "Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal
RT syndrome.";
RL Am. J. Hum. Genet. 60:1384-1388(1997).
RN [27]
RP VARIANTS OCRL TYR-375; GLN-500; ASP-508 AND CYS-513.
RX PubMed=9682219; DOI=10.1006/mgme.1998.2687;
RA Lin T., Orrison B.M., Suchy S.F., Lewis R.A., Nussbaum R.L.;
RT "Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe
RT syndrome patients.";
RL Mol. Genet. Metab. 64:58-61(1998).
RN [28]
RP VARIANTS OCRL GLN-500 AND GLN-524.
RX PubMed=9632163;
RX DOI=10.1002/(sici)1096-8628(19980605)77:5<348::aid-ajmg2>3.0.co;2-j;
RA Kawano T., Indo Y., Nakazato H., Shimadzu M., Matsuda I.;
RT "Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene
RT derived from three patients with different phenotypes.";
RL Am. J. Med. Genet. 77:348-355(1998).
RN [29]
RP VARIANT OCRL ARG-522.
RX PubMed=9788721; DOI=10.1111/j.1399-0004.1998.tb04284.x;
RA Kubota T., Sakurai A., Arakawa K., Shimazu M., Wakui K., Furihata K.,
RA Fukushima Y.;
RT "Identification of two novel mutations in the OCRL1 gene in Japanese
RT families with Lowe syndrome.";
RL Clin. Genet. 54:199-202(1998).
RN [30]
RP VARIANTS OCRL GLU-357; GLU-421; ASP-424 AND TYR-498.
RX PubMed=10923037;
RX DOI=10.1002/1098-1004(200008)16:2<157::aid-humu8>3.0.co;2-9;
RA Monnier N., Satre V., Lerouge E., Berthoin F., Lunardi J.;
RT "OCRL1 mutation analysis in French Lowe syndrome patients: implications for
RT molecular diagnosis strategy and genetic counseling.";
RL Hum. Mutat. 16:157-165(2000).
RN [31]
RP VARIANTS OCRL LYS-478-479-TYR DEL; GLN-500 AND LEU-526.
RX PubMed=10767176; DOI=10.1006/mgme.1999.2955;
RA Roeschinger W., Muntau A.C., Rudolph G., Roscher A.A., Kammerer S.;
RT "Carrier assessment in families with Lowe oculocerebrorenal syndrome: novel
RT mutations in the OCRL1 gene and correlation of direct DNA diagnosis with
RT ocular examination.";
RL Mol. Genet. Metab. 69:213-222(2000).
RN [32]
RP VARIANTS DENT2 CYS-318 AND CYS-479.
RX PubMed=15627218; DOI=10.1086/427887;
RA Hoopes R.R. Jr., Shrimpton A.E., Knohl S.J., Hueber P., Hoppe B.,
RA Matyus J., Simckes A., Tasic V., Toenshoff B., Suchy S.F., Nussbaum R.L.,
RA Scheinman S.J.;
RT "Dent disease with mutations in OCRL1.";
RL Am. J. Hum. Genet. 76:260-267(2005).
RN [33]
RP VARIANTS DENT2 CYS-318 AND TRP-493.
RX PubMed=17384968; DOI=10.1007/s00467-007-0454-x;
RA Sekine T., Nozu K., Iyengar R., Fu X.J., Matsuo M., Tanaka R., Iijima K.,
RA Matsui E., Harita Y., Inatomi J., Igarashi T.;
RT "OCRL1 mutations in patients with Dent disease phenotype in Japan.";
RL Pediatr. Nephrol. 22:975-980(2007).
RN [34]
RP VARIANT OCRL LYS-591.
RX PubMed=19168822; DOI=10.1177/0883073808321047;
RA Yuksel A., Karaca E., Albayram M.S.;
RT "Magnetic resonance imaging, magnetic resonance spectroscopy, and facial
RT dysmorphism in a case of Lowe syndrome with novel OCRL1 gene mutation.";
RL J. Child Neurol. 24:93-96(2009).
RN [35]
RP VARIANTS OCRL SER-242; THR-274; ARG-277; CYS-318; CYS-337; ILE-361;
RP GLY-372; TYR-373; PHE-374; ARG-414; ASN-451; GLY-457; LYS-468; GLY-468;
RP LEU-495; HIS-499; ARG-503; LYS-591; VAL-742 DEL; PRO-797; LEU-801 AND
RP ARG-891, AND VARIANTS DENT2 HIS-354 AND LEU-799.
RX PubMed=21031565; DOI=10.1002/humu.21391;
RA Hichri H., Rendu J., Monnier N., Coutton C., Dorseuil O., Poussou R.V.,
RA Baujat G., Blanchard A., Nobili F., Ranchin B., Remesy M., Salomon R.,
RA Satre V., Lunardi J.;
RT "From Lowe syndrome to Dent disease: correlations between mutations of the
RT OCRL1 gene and clinical and biochemical phenotypes.";
RL Hum. Mutat. 32:379-388(2011).
CC -!- FUNCTION: Catalyzes the hydrolysis of the 5-position phosphate of
CC phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and
CC phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the
CC greatest catalytic activity towards PtdIns(4,5)P2 (PubMed:7761412,
CC PubMed:15474001, PubMed:9430698, PubMed:10764818). Able also to
CC hydrolyze the 5-phosphate of inositol 1,4,5-trisphosphate and of
CC inositol 1,3,4,5-tetrakisphosphate (PubMed:7761412, PubMed:25869668).
CC Regulates traffic in the endosomal pathway by regulating the specific
CC pool of phosphatidylinositol 4,5-bisphosphate that is associated with
CC endosomes (PubMed:21971085). Involved in primary cilia assembly
CC (PubMed:22228094, PubMed:22543976). Acts as a regulator of
CC phagocytosis, hydrolyzing PtdIns(4,5)P2 to promote phagosome closure,
CC through attenuation of PI3K signaling (PubMed:22072788).
CC {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:15474001,
CC ECO:0000269|PubMed:21971085, ECO:0000269|PubMed:22072788,
CC ECO:0000269|PubMed:22228094, ECO:0000269|PubMed:22543976,
CC ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:7761412,
CC ECO:0000269|PubMed:9430698}.
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:15474001,
CC ECO:0000269|PubMed:7761412, ECO:0000269|PubMed:9430698};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765;
CC Evidence={ECO:0000305};
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, ECO:0000269|PubMed:15474001};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000305};
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:15474001, ECO:0000269|PubMed:7761412};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11393;
CC Evidence={ECO:0000305};
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:15474001, ECO:0000269|PubMed:7761412};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19798;
CC Evidence={ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for Ins(1,3,4,5)P4 {ECO:0000269|PubMed:7761412};
CC KM=139 uM for PtdIns(3,4,5)P3 {ECO:0000269|PubMed:15474001};
CC KM=23 uM for PtdIns(4,5)P2 {ECO:0000269|PubMed:15474001};
CC KM=70 uM for Ins(1,4,5)P3 {ECO:0000269|PubMed:7761412};
CC Vmax=1.8 umol/min/mg enzyme with Ins(1,3,4,5)P4 as substrate
CC {ECO:0000269|PubMed:7761412};
CC Vmax=8 umol/min/mg enzyme with Ins(1,4,5)P3 as substrate
CC {ECO:0000269|PubMed:7761412};
CC -!- SUBUNIT: Interacts with APPL1, FAM109A/SES1 and FAM109B/SES2; APPL1-
CC binding and FAM109A-binding are mutually exclusive. Interacts with
CC clathrin heavy chain. Interacts with several Rab GTPases, at least
CC RAB1B, RAB5A, RAB6A, RAB8A and RAB31; these interactions may play a
CC dual role in targeting OCRL to the specific membranes and stimulating
CC the phosphatase activity. Interaction with RAB8A modulates OCRL
CC recruitment to cilia. Interacts with INPP5F (PubMed:25869668).
CC {ECO:0000269|PubMed:17765681, ECO:0000269|PubMed:19536138,
CC ECO:0000269|PubMed:20133602, ECO:0000269|PubMed:21233288,
CC ECO:0000269|PubMed:21378754, ECO:0000269|PubMed:21666675,
CC ECO:0000269|PubMed:22543976, ECO:0000269|PubMed:25869668}.
CC -!- INTERACTION:
CC Q01968; Q00610: CLTC; NbExp=10; IntAct=EBI-6148898, EBI-354967;
CC Q01968; P61106: RAB14; NbExp=3; IntAct=EBI-6148898, EBI-1056404;
CC Q01968; P62820: RAB1A; NbExp=8; IntAct=EBI-6148898, EBI-716845;
CC Q01968; Q9H0U4: RAB1B; NbExp=3; IntAct=EBI-6148898, EBI-1045214;
CC Q01968; P20339: RAB5A; NbExp=11; IntAct=EBI-6148898, EBI-399437;
CC Q01968; P20340: RAB6A; NbExp=12; IntAct=EBI-6148898, EBI-1052826;
CC Q01968; P61006: RAB8A; NbExp=15; IntAct=EBI-6148898, EBI-722293;
CC Q01968; P63000: RAC1; NbExp=3; IntAct=EBI-6148898, EBI-413628;
CC Q01968; Q9Y5X1: SNX9; NbExp=5; IntAct=EBI-6148898, EBI-77848;
CC Q01968; P11442: Cltc; Xeno; NbExp=5; IntAct=EBI-6148898, EBI-397997;
CC Q01968; Q68FD5: Cltc; Xeno; NbExp=2; IntAct=EBI-6148898, EBI-769168;
CC Q01968; Q91VH2: Snx9; Xeno; NbExp=2; IntAct=EBI-6148898, EBI-8429356;
CC Q01968-2; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-11749425, EBI-12039345;
CC Q01968-2; Q8N4B1-4: PHETA1; NbExp=3; IntAct=EBI-11749425, EBI-14131832;
CC Q01968-2; Q6ICB4: PHETA2; NbExp=6; IntAct=EBI-11749425, EBI-11081747;
CC Q01968-2; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-11749425, EBI-14065960;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:D3ZGS3}. Early endosome membrane
CC {ECO:0000269|PubMed:21971085, ECO:0000269|PubMed:25869668}. Membrane,
CC clathrin-coated pit {ECO:0000269|PubMed:25869668}. Cell projection,
CC cilium, photoreceptor outer segment {ECO:0000269|PubMed:22543976}. Cell
CC projection, cilium {ECO:0000269|PubMed:22543976}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:D3ZGS3}. Endosome {ECO:0000269|PubMed:21971085,
CC ECO:0000269|PubMed:25869668}. Golgi apparatus, trans-Golgi network
CC {ECO:0000250|UniProtKB:D3ZGS3}. Lysosome {ECO:0000269|PubMed:9430698}.
CC Note=Also found on macropinosomes (PubMed:25869668). Colocalized with
CC APPL1 on phagosomes (PubMed:22072788). {ECO:0000269|PubMed:22072788,
CC ECO:0000269|PubMed:25869668}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q01968-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q01968-2; Sequence=VSP_002681;
CC -!- TISSUE SPECIFICITY: Brain, skeletal muscle, heart, kidney, lung,
CC placenta and fibroblasts. Expressed in the retina and the retinal
CC pigment epithelium. {ECO:0000269|PubMed:22543976}.
CC -!- DOMAIN: The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating)
CC domains form a single folding module. The ASH domain has an
CC immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic
CC arginine and is catalytically inactive. The ASH-RhoGAP module regulates
CC the majority of the protein-protein interactions currently described.
CC The ASH domain mediates association with membrane-targeting Rab
CC GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1,
CC which is then displaced by FAM109A and FAM109B as endosomes mature.
CC {ECO:0000269|PubMed:19536138}.
CC -!- DISEASE: Lowe oculocerebrorenal syndrome (OCRL) [MIM:309000]: X-linked
CC multisystem disorder affecting eyes, nervous system, and kidney. It is
CC characterized by hydrophthalmia, cataract, intellectual disability,
CC vitamin D-resistant rickets, aminoaciduria, and reduced ammonia
CC production by the kidney. Ocular abnormalities include cataract,
CC glaucoma, microphthalmos, and decreased visual acuity. Developmental
CC delay, hypotonia, behavior abnormalities, and areflexia are also
CC present. Renal tubular involvement is characterized by impaired
CC reabsorption of bicarbonate, amino acids, and phosphate.
CC Musculoskeletal abnormalities such as joint hypermobility, dislocated
CC hips, and fractures may develop as consequences of renal tubular
CC acidosis and hypophosphatemia. Cataract is the only significant
CC manifestation in carriers and is detected by slit-lamp examination.
CC {ECO:0000269|PubMed:10767176, ECO:0000269|PubMed:10923037,
CC ECO:0000269|PubMed:19168822, ECO:0000269|PubMed:20133602,
CC ECO:0000269|PubMed:21031565, ECO:0000269|PubMed:21233288,
CC ECO:0000269|PubMed:9199559, ECO:0000269|PubMed:9632163,
CC ECO:0000269|PubMed:9682219, ECO:0000269|PubMed:9788721}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Dent disease 2 (DENT2) [MIM:300555]: An X-linked renal disease
CC belonging to the 'Dent disease complex', a group of disorders
CC characterized by proximal renal tubular defect, hypercalciuria,
CC nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic
CC features is remarkably similar in the various disorders, except for
CC differences in the severity of bone deformities and renal impairment.
CC Characteristic abnormalities include low-molecular-weight proteinuria
CC and other features of Fanconi syndrome, such as glycosuria,
CC aminoaciduria, and phosphaturia, but typically do not include proximal
CC renal tubular acidosis. Progressive renal failure is common, as are
CC nephrocalcinosis and kidney stones. {ECO:0000269|PubMed:15627218,
CC ECO:0000269|PubMed:17384968, ECO:0000269|PubMed:21031565}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC type II family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1, Met-18 or Met-20 is the
CC initiator. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA59964.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Lowe Syndrome mutation database;
CC URL="http://research.nhgri.nih.gov/lowe/";
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DR EMBL; M88162; AAA59964.2; ALT_INIT; mRNA.
DR EMBL; U57627; AAB03839.2; -; mRNA.
DR EMBL; AK293107; BAF85796.1; -; mRNA.
DR EMBL; AL022162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z73496; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471107; EAX11831.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11832.1; -; Genomic_DNA.
DR EMBL; BC130612; AAI30613.1; -; mRNA.
DR EMBL; BC144106; AAI44107.1; -; mRNA.
DR EMBL; S62085; AAB26926.1; -; mRNA.
DR CCDS; CCDS35393.1; -. [Q01968-1]
DR CCDS; CCDS35394.1; -. [Q01968-2]
DR PIR; S29069; S29069.
DR RefSeq; NP_000267.2; NM_000276.3. [Q01968-1]
DR RefSeq; NP_001578.2; NM_001587.3. [Q01968-2]
DR PDB; 2KIE; NMR; -; A=1-119.
DR PDB; 2QV2; X-ray; 2.40 A; A=564-901.
DR PDB; 3QBT; X-ray; 2.00 A; B/D/F/H=540-678.
DR PDB; 3QIS; X-ray; 2.30 A; A=536-901.
DR PDB; 4CMN; X-ray; 3.13 A; A=215-560.
DR PDBsum; 2KIE; -.
DR PDBsum; 2QV2; -.
DR PDBsum; 3QBT; -.
DR PDBsum; 3QIS; -.
DR PDBsum; 4CMN; -.
DR AlphaFoldDB; Q01968; -.
DR SMR; Q01968; -.
DR BioGRID; 111006; 141.
DR DIP; DIP-45092N; -.
DR IntAct; Q01968; 204.
DR MINT; Q01968; -.
DR STRING; 9606.ENSP00000360154; -.
DR SwissLipids; SLP:000001182; -.
DR DEPOD; OCRL; -.
DR iPTMnet; Q01968; -.
DR MetOSite; Q01968; -.
DR PhosphoSitePlus; Q01968; -.
DR BioMuta; OCRL; -.
DR DMDM; 67477390; -.
DR EPD; Q01968; -.
DR jPOST; Q01968; -.
DR MassIVE; Q01968; -.
DR MaxQB; Q01968; -.
DR PaxDb; Q01968; -.
DR PeptideAtlas; Q01968; -.
DR PRIDE; Q01968; -.
DR ProteomicsDB; 58022; -. [Q01968-1]
DR ProteomicsDB; 58023; -. [Q01968-2]
DR TopDownProteomics; Q01968-2; -. [Q01968-2]
DR ABCD; Q01968; 1 sequenced antibody.
DR Antibodypedia; 509; 361 antibodies from 34 providers.
DR DNASU; 4952; -.
DR Ensembl; ENST00000357121.5; ENSP00000349635.5; ENSG00000122126.18. [Q01968-2]
DR Ensembl; ENST00000371113.9; ENSP00000360154.4; ENSG00000122126.18. [Q01968-1]
DR GeneID; 4952; -.
DR KEGG; hsa:4952; -.
DR MANE-Select; ENST00000371113.9; ENSP00000360154.4; NM_000276.4; NP_000267.2.
DR UCSC; uc004euq.4; human. [Q01968-1]
DR CTD; 4952; -.
DR DisGeNET; 4952; -.
DR GeneCards; OCRL; -.
DR GeneReviews; OCRL; -.
DR HGNC; HGNC:8108; OCRL.
DR HPA; ENSG00000122126; Low tissue specificity.
DR MalaCards; OCRL; -.
DR MIM; 300535; gene.
DR MIM; 300555; phenotype.
DR MIM; 309000; phenotype.
DR neXtProt; NX_Q01968; -.
DR OpenTargets; ENSG00000122126; -.
DR Orphanet; 93623; Dent disease type 2.
DR Orphanet; 534; Oculocerebrorenal syndrome of Lowe.
DR PharmGKB; PA31896; -.
DR VEuPathDB; HostDB:ENSG00000122126; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000157996; -.
DR HOGENOM; CLU_006779_3_1_1; -.
DR InParanoid; Q01968; -.
DR OMA; SDHDHIF; -.
DR PhylomeDB; Q01968; -.
DR TreeFam; TF317034; -.
DR BioCyc; MetaCyc:HS04546-MON; -.
DR BRENDA; 3.1.3.36; 2681.
DR PathwayCommons; Q01968; -.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q01968; -.
DR BioGRID-ORCS; 4952; 9 hits in 706 CRISPR screens.
DR ChiTaRS; OCRL; human.
DR EvolutionaryTrace; Q01968; -.
DR GeneWiki; OCRL; -.
DR GenomeRNAi; 4952; -.
DR Pharos; Q01968; Tbio.
DR PRO; PR:Q01968; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q01968; protein.
DR Bgee; ENSG00000122126; Expressed in endometrium epithelium and 141 other tissues.
DR ExpressionAtlas; Q01968; baseline and differential.
DR Genevisible; Q01968; HS.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; TAS:ProtInc.
DR GO; GO:0005798; C:Golgi-associated vesicle; TAS:ProtInc.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0005802; C:trans-Golgi network; IDA:FlyBase.
DR GO; GO:0005096; F:GTPase activator activity; IDA:FlyBase.
DR GO; GO:0052745; F:inositol phosphate phosphatase activity; IDA:UniProtKB.
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; TAS:Reactome.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0034596; F:phosphatidylinositol phosphate 4-phosphatase activity; TAS:Reactome.
DR GO; GO:0034485; F:phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity; IEA:RHEA.
DR GO; GO:0043813; F:phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity; TAS:Reactome.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IPI:FlyBase.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IBA:GO_Central.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IBA:GO_Central.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:FlyBase.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd09093; INPP5c_INPP5B; 1.
DR CDD; cd13382; PH_OCRL1; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR037793; OCRL1/INPP5B_INPP5c.
DR InterPro; IPR037787; OCRL1_PH.
DR InterPro; IPR031995; OCRL_clath-bd.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF16726; OCRL_clath_bd; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cataract; Cell projection; Ciliopathy;
KW Cilium; Cilium biogenesis/degradation; Coated pit; Cytoplasmic vesicle;
KW Disease variant; Endosome; Golgi apparatus; Hydrolase; Lipid metabolism;
KW Lysosome; Membrane; Reference proteome.
FT CHAIN 1..901
FT /note="Inositol polyphosphate 5-phosphatase OCRL"
FT /id="PRO_0000209721"
FT DOMAIN 1..119
FT /note="PH"
FT DOMAIN 721..901
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 164..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..563
FT /note="5-phosphatase"
FT REGION 564..678
FT /note="ASH"
FT MOTIF 73..77
FT /note="Clathrin box 1"
FT MOTIF 702..706
FT /note="Clathrin box 2"
FT VAR_SEQ 707..714
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:1321346,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_002681"
FT VARIANT 242
FT /note="F -> S (in OCRL; dbSNP:rs137853828)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064773"
FT VARIANT 274
FT /note="I -> T (in OCRL; dbSNP:rs137853829)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064774"
FT VARIANT 277
FT /note="Q -> R (in OCRL; dbSNP:rs137853830)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064775"
FT VARIANT 318
FT /note="R -> C (in DENT2 and OCRL; dbSNP:rs137853263)"
FT /evidence="ECO:0000269|PubMed:15627218,
FT ECO:0000269|PubMed:17384968, ECO:0000269|PubMed:21031565"
FT /id="VAR_022698"
FT VARIANT 337
FT /note="R -> C (in OCRL; associated with I-361;
FT dbSNP:rs137853831)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064776"
FT VARIANT 337
FT /note="R -> P (in OCRL)"
FT /id="VAR_010169"
FT VARIANT 354
FT /note="N -> H (in DENT2; dbSNP:rs137853833)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064777"
FT VARIANT 357
FT /note="G -> E (in OCRL; uncertain pathological
FT significance; dbSNP:rs137853854)"
FT /evidence="ECO:0000269|PubMed:10923037"
FT /id="VAR_010170"
FT VARIANT 361
FT /note="R -> I (in OCRL; associated with C-337;
FT dbSNP:rs137853832)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064778"
FT VARIANT 367
FT /note="Missing (in OCRL)"
FT /evidence="ECO:0000269|PubMed:9199559"
FT /id="VAR_010171"
FT VARIANT 372
FT /note="V -> G (in OCRL; dbSNP:rs137853834)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_010172"
FT VARIANT 373
FT /note="N -> Y (in OCRL; dbSNP:rs137853835)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064779"
FT VARIANT 374
FT /note="S -> F (in OCRL; dbSNP:rs137853836)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064780"
FT VARIANT 375
FT /note="H -> Y (in OCRL; dbSNP:rs137853848)"
FT /evidence="ECO:0000269|PubMed:9682219"
FT /id="VAR_010173"
FT VARIANT 414
FT /note="H -> R (in OCRL; dbSNP:rs137853837)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064781"
FT VARIANT 421
FT /note="G -> E (in OCRL; dbSNP:rs137853855)"
FT /evidence="ECO:0000269|PubMed:10923037"
FT /id="VAR_010174"
FT VARIANT 424
FT /note="N -> D (in OCRL; dbSNP:rs137853856)"
FT /evidence="ECO:0000269|PubMed:10923037"
FT /id="VAR_010175"
FT VARIANT 451
FT /note="D -> G (in OCRL; dbSNP:rs137853850)"
FT /evidence="ECO:0000269|PubMed:9199559"
FT /id="VAR_010176"
FT VARIANT 451
FT /note="D -> N (in OCRL; dbSNP:rs137853838)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064782"
FT VARIANT 457
FT /note="R -> G (in OCRL; dbSNP:rs137853839)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064783"
FT VARIANT 463
FT /note="F -> S (in OCRL; dbSNP:rs137853851)"
FT /evidence="ECO:0000269|PubMed:9199559"
FT /id="VAR_010177"
FT VARIANT 468
FT /note="E -> G (in OCRL; dbSNP:rs137853841)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064784"
FT VARIANT 468
FT /note="E -> K (in OCRL; dbSNP:rs137853840)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064785"
FT VARIANT 478..479
FT /note="Missing (in OCRL)"
FT /id="VAR_023957"
FT VARIANT 479
FT /note="Y -> C (in DENT2; dbSNP:rs137853262)"
FT /evidence="ECO:0000269|PubMed:15627218"
FT /id="VAR_022699"
FT VARIANT 493
FT /note="R -> W (in DENT2; dbSNP:rs137853846)"
FT /evidence="ECO:0000269|PubMed:17384968"
FT /id="VAR_064786"
FT VARIANT 495
FT /note="P -> L (in OCRL)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064787"
FT VARIANT 498
FT /note="C -> Y (in OCRL; dbSNP:rs137853857)"
FT /evidence="ECO:0000269|PubMed:10923037"
FT /id="VAR_010178"
FT VARIANT 499
FT /note="D -> H (in OCRL; dbSNP:rs137853842)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064788"
FT VARIANT 500
FT /note="R -> G (in OCRL; dbSNP:rs398123287)"
FT /id="VAR_010179"
FT VARIANT 500
FT /note="R -> Q (in OCRL; dbSNP:rs137853260)"
FT /evidence="ECO:0000269|PubMed:10767176,
FT ECO:0000269|PubMed:9632163, ECO:0000269|PubMed:9682219"
FT /id="VAR_010180"
FT VARIANT 503
FT /note="W -> R (in OCRL; dbSNP:rs137853843)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064789"
FT VARIANT 508
FT /note="V -> D (in OCRL; dbSNP:rs137853849)"
FT /evidence="ECO:0000269|PubMed:9682219"
FT /id="VAR_010181"
FT VARIANT 513
FT /note="Y -> C (in OCRL; dbSNP:rs137853847)"
FT /evidence="ECO:0000269|PubMed:9682219"
FT /id="VAR_010182"
FT VARIANT 522
FT /note="S -> R (in OCRL; dbSNP:rs137853853)"
FT /evidence="ECO:0000269|PubMed:9788721"
FT /id="VAR_010183"
FT VARIANT 524
FT /note="H -> Q (in OCRL; dbSNP:rs137853261)"
FT /evidence="ECO:0000269|PubMed:9632163"
FT /id="VAR_010184"
FT VARIANT 524
FT /note="H -> R (in OCRL; dbSNP:rs137853852)"
FT /evidence="ECO:0000269|PubMed:9199559"
FT /id="VAR_010185"
FT VARIANT 526
FT /note="P -> L (in OCRL; dbSNP:rs137853858)"
FT /evidence="ECO:0000269|PubMed:10767176"
FT /id="VAR_023958"
FT VARIANT 533
FT /note="I -> S (in OCRL)"
FT /id="VAR_010187"
FT VARIANT 591
FT /note="N -> K (in OCRL; dbSNP:rs137853844)"
FT /evidence="ECO:0000269|PubMed:19168822,
FT ECO:0000269|PubMed:21031565"
FT /id="VAR_064790"
FT VARIANT 742
FT /note="Missing (in OCRL)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064791"
FT VARIANT 768
FT /note="I -> N (in OCRL; uncertain pathological
FT significance; abolishes FAM109A-, FAM109B- and APPL1-
FT binding)"
FT /evidence="ECO:0000269|PubMed:20133602,
FT ECO:0000269|PubMed:21233288"
FT /id="VAR_010188"
FT VARIANT 797
FT /note="A -> P (in OCRL; uncertain pathological
FT significance; dbSNP:rs935956958)"
FT /evidence="ECO:0000269|PubMed:20133602,
FT ECO:0000269|PubMed:21031565"
FT /id="VAR_010189"
FT VARIANT 799
FT /note="P -> L (in DENT2)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064792"
FT VARIANT 801
FT /note="P -> L (in OCRL)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064793"
FT VARIANT 891
FT /note="L -> R (in OCRL; dbSNP:rs137853845)"
FT /evidence="ECO:0000269|PubMed:21031565"
FT /id="VAR_064794"
FT MUTAGEN 422
FT /note="D->A: Does not affect interaction with RAB8A."
FT /evidence="ECO:0000269|PubMed:22543976"
FT MUTAGEN 499
FT /note="D->A: Does not affect interaction with RAB8A."
FT /evidence="ECO:0000269|PubMed:22543976"
FT MUTAGEN 668
FT /note="F->V: Does not interact with RAB8A. Does not
FT localize to cilia."
FT /evidence="ECO:0000269|PubMed:22543976"
FT CONFLICT 180
FT /note="P -> L (in Ref. 4; BAF85796)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="G -> E (in Ref. 7; AAI44107)"
FT /evidence="ECO:0000305"
FT STRAND 10..21
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 24..35
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 38..45
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:2KIE"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 80..90
FT /evidence="ECO:0007829|PDB:2KIE"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:2KIE"
FT HELIX 101..118
FT /evidence="ECO:0007829|PDB:2KIE"
FT HELIX 222..229
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 235..248
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 292..304
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 311..319
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 322..329
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 332..335
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 336..345
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 355..364
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 367..375
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 383..396
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 414..422
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 432..440
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 444..448
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 452..458
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 483..486
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 489..491
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 499..504
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 506..510
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:4CMN"
FT STRAND 527..538
FT /evidence="ECO:0007829|PDB:4CMN"
FT HELIX 541..548
FT /evidence="ECO:0007829|PDB:3QBT"
FT HELIX 553..560
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 565..568
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 571..577
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 583..591
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 597..602
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 608..611
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 615..619
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 621..624
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 629..636
FT /evidence="ECO:0007829|PDB:3QBT"
FT HELIX 640..648
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 649..651
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 655..661
FT /evidence="ECO:0007829|PDB:3QBT"
FT STRAND 666..675
FT /evidence="ECO:0007829|PDB:3QBT"
FT HELIX 684..689
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 700..702
FT /evidence="ECO:0007829|PDB:2QV2"
FT HELIX 736..748
FT /evidence="ECO:0007829|PDB:3QIS"
FT TURN 753..757
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 762..774
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 784..797
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 805..814
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 818..826
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 830..847
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 850..853
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 857..868
FT /evidence="ECO:0007829|PDB:3QIS"
FT HELIX 873..875
FT /evidence="ECO:0007829|PDB:2QV2"
FT HELIX 883..895
FT /evidence="ECO:0007829|PDB:3QIS"
SQ SEQUENCE 901 AA; 104205 MW; 476BFCCC3655C1FE CRC64;
MEPPLPVGAQ PLATVEGMEM KGPLREPCAL TLAQRNGQYE LIIQLHEKEQ HVQDIIPINS
HFRCVQEAEE TLLIDIASNS GCKIRVQGDW IRERRFEIPD EEHCLKFLSA VLAAQKAQSQ
LLVPEQKDSS SWYQKLDTKD KPSVFSGLLG FEDNFSSMNL DKKINSQNQP TGIHREPPPP
PFSVNKMLPR EKEASNKEQP KVTNTMRKLF VPNTQSGQRE GLIKHILAKR EKEYVNIQTF
RFFVGTWNVN GQSPDSGLEP WLNCDPNPPD IYCIGFQELD LSTEAFFYFE SVKEQEWSMA
VERGLHSKAK YKKVQLVRLV GMMLLIFARK DQCRYIRDIA TETVGTGIMG KMGNKGGVAV
RFVFHNTTFC IVNSHLAAHV EDFERRNQDY KDICARMSFV VPNQTLPQLN IMKHEVVIWL
GDLNYRLCMP DANEVKSLIN KKDLQRLLKF DQLNIQRTQK KAFVDFNEGE IKFIPTYKYD
SKTDRWDSSG KCRVPAWCDR ILWRGTNVNQ LNYRSHMELK TSDHKPVSAL FHIGVKVVDE
RRYRKVFEDS VRIMDRMEND FLPSLELSRR EFVFENVKFR QLQKEKFQIS NNGQVPCHFS
FIPKLNDSQY CKPWLRAEPF EGYLEPNETV DISLDVYVSK DSVTILNSGE DKIEDILVLH
LDRGKDYFLT ISGNYLPSCF GTSLEALCRM KRPIREVPVT KLIDLEEDSF LEKEKSLLQM
VPLDEGASER PLQVPKEIWL LVDHLFKYAC HQEDLFQTPG MQEELQQIID CLDTSIPETI
PGSNHSVAEA LLIFLEALPE PVICYELYQR CLDSAYDPRI CRQVISQLPR CHRNVFRYLM
AFLRELLKFS EYNSVNANMI ATLFTSLLLR PPPNLMARQT PSDRQRAIQF LLGFLLGSEE
D
