OCRL_RAT
ID OCRL_RAT Reviewed; 902 AA.
AC D3ZGS3;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Inositol polyphosphate 5-phosphatase OCRL {ECO:0000305};
DE EC=3.1.3.36 {ECO:0000250|UniProtKB:Q01968};
DE EC=3.1.3.56 {ECO:0000250|UniProtKB:Q01968};
DE AltName: Full=Inositol polyphosphate 5-phosphatase OCRL-1;
DE Short=OCRL-1 {ECO:0000303|PubMed:19795375};
DE AltName: Full=Phosphatidylinositol 3,4,5-triphosphate 5-phosphatase;
DE EC=3.1.3.86 {ECO:0000250|UniProtKB:Q01968};
GN Name=Ocrl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP INTERACTION WITH RAB31, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19795375; DOI=10.1002/jnr.22236;
RA Rodriguez-Gabin A.G., Ortiz E., Demoliner K., Si Q., Almazan G.,
RA Larocca J.N.;
RT "Interaction of Rab31 and OCRL-1 in oligodendrocytes: its role in transport
RT of mannose 6-phosphate receptors.";
RL J. Neurosci. Res. 88:589-604(2010).
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. Able also to
CC hydrolyze the 5-phosphate of inositol 1,4,5-trisphosphate and of
CC inositol 1,3,4,5-tetrakisphosphate. Regulates traffic in the endosomal
CC pathway by regulating the specific pool of phosphatidylinositol 4,5-
CC bisphosphate that is associated with endosomes. Involved in primary
CC cilia assembly. Acts as a regulator of phagocytosis, hydrolyzing
CC PtdIns(4,5)P2 to promote phagosome closure, through attenuation of PI3K
CC signaling. {ECO:0000250|UniProtKB:Q01968}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC ChEBI:CHEBI:58456; EC=3.1.3.36;
CC Evidence={ECO:0000250|UniProtKB:Q01968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765;
CC Evidence={ECO:0000250|UniProtKB:Q01968};
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:0000250|UniProtKB:Q01968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529;
CC Evidence={ECO:0000250|UniProtKB:Q01968};
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:0000250|UniProtKB:Q01968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11393;
CC Evidence={ECO:0000250|UniProtKB:Q01968};
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:0000250|UniProtKB:Q01968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19798;
CC Evidence={ECO:0000250|UniProtKB:Q01968};
CC -!- SUBUNIT: Interacts with APPL1, PHETA1/SES1 and PHETA2/SES2; APPL1-
CC binding and PHETA1-binding are mutually exclusive. Interacts with
CC clathrin heavy chain. Interacts with several Rab GTPases, at least
CC RAB1B, RAB5A, RAB6A and RAB8A; these interactions may play a dual role
CC in targeting OCRL to the specific membranes and stimulating the
CC phosphatase activity. Interaction with RAB8A modulates OCRL recruitment
CC to cilia (By similarity). Interacts with RAB31 (PubMed:19795375).
CC Interacts with INPP5F (By similarity). {ECO:0000250|UniProtKB:Q01968,
CC ECO:0000269|PubMed:19795375}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:Q01968}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q01968}. Membrane, clathrin-coated pit
CC {ECO:0000250|UniProtKB:Q01968}. Cell projection, cilium, photoreceptor
CC outer segment {ECO:0000250|UniProtKB:Q01968}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q01968}. Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:19795375}. Endosome {ECO:0000269|PubMed:19795375}.
CC Cytoplasmic vesicle {ECO:0000269|PubMed:19795375}. Note=Also found on
CC macropinosomes. {ECO:0000250|UniProtKB:Q01968}.
CC -!- TISSUE SPECIFICITY: Detected in brain oligodendrocytes (at protein
CC level). Detected in brain oligodendrocytes.
CC {ECO:0000269|PubMed:19795375}.
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 PHETA1 and PHETA2 as endosomes mature (By
CC similarity). {ECO:0000250|UniProtKB:Q01968}.
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC type II family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AABR06108328; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; D3ZGS3; -.
DR SMR; D3ZGS3; -.
DR IntAct; D3ZGS3; 1.
DR MINT; D3ZGS3; -.
DR STRING; 10116.ENSRNOP00000005267; -.
DR PaxDb; D3ZGS3; -.
DR PeptideAtlas; D3ZGS3; -.
DR ABCD; D3ZGS3; 1 sequenced antibody.
DR RGD; 1594526; Ocrl.
DR VEuPathDB; HostDB:ENSRNOG00000003875; -.
DR eggNOG; KOG0565; Eukaryota.
DR InParanoid; D3ZGS3; -.
DR OMA; SDHDHIF; -.
DR TreeFam; TF317034; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-RNO-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR Reactome; R-RNO-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR PRO; PR:D3ZGS3; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003875; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; D3ZGS3; baseline and differential.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0005096; F:GTPase activator activity; ISO:RGD.
DR GO; GO:0052745; F:inositol phosphate phosphatase activity; ISS: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; IEA:UniProtKB-EC.
DR GO; GO:0004445; F:inositol-polyphosphate 5-phosphatase activity; IEA:UniProtKB-EC.
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; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0060271; P:cilium assembly; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IBA:GO_Central.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; ISO:RGD.
DR GO; GO:0043087; P:regulation of GTPase activity; ISO:RGD.
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 Cell projection; Cilium; Cilium biogenesis/degradation; Coated pit;
KW Cytoplasmic vesicle; Endosome; Golgi apparatus; Hydrolase;
KW Lipid metabolism; Membrane; Reference proteome.
FT CHAIN 1..902
FT /note="Inositol polyphosphate 5-phosphatase OCRL"
FT /id="PRO_0000421565"
FT DOMAIN 1..122
FT /note="PH"
FT DOMAIN 722..902
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 163..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..564
FT /note="5-phosphatase"
FT /evidence="ECO:0000250"
FT REGION 565..679
FT /note="ASH"
FT /evidence="ECO:0000250"
FT MOTIF 76..80
FT /note="Clathrin box 1"
FT MOTIF 703..707
FT /note="Clathrin box 2"
SQ SEQUENCE 902 AA; 104407 MW; 5780A6E949F4C94B CRC64;
MEPRLPIGAQ PLACLHMVAG LEMKGPLREP CVLTLARRNG QYELIIQLHG KEQHVQDIIP
INSHFRCVQE AEETLLIDIA SNSGCKIRVQ GDWTRERHFE IPDEERCLKF LSEVLAAQEA
QSQLLVPEQK DSSNWYQKLD TKDKPAYSGL LGFEDNFSSM NLDKKMNTQN PPTGIHREPP
PPPSSNRMLP REKEALNKEQ PKVTNTMRKL FAPNSQSGQR EGLIKHILAK REKEYVNIQS
FRFFVGTWNV NGQSPDSSLE PWLNCDPNPP DIYCIGFQEL DLSTEAFFYF ESVKEQEWAM
AVERGLPSKA KYKKVQLVRL VGMMLLVFAK KDQCQYIRDI ATETVGTGIM GKMGNKGGVA
MRFVFHNTTF CIVNSHLAAH VEEFERRNQD YKDICARMSF SVPNQTLPQV NIMKHDVVIW
LGDLNYRLCM PDANEVKSLI NKNELQKLLK FDQLNIQRTQ KKAFVDFNEG EIKFIPTYKY
DSKTDRWDSS GKCRVPAWCD RILWRGINVN QLHYRSHMEL KTSDHKPVSA LFHIGVKVVD
ERRYRKVFED IVRIMDRMEN DFLPSLDLSR REFMFENVKF RQLQKEKFQI SNNGQVPCHF
SFIPKLNDTQ YCKPWLRAEP FEGYLEPNET IDISLDVYVS KDSVTILNSG EDKIEDILVL
HLDRGKDYFL TISGNYLPSC FGTSLEALCR MKRPIREVPV TKLIDLEEDS FLEKEKSLLQ
MVPLDEGTSE RPLQVPKEIW LLVDHLFKYA CHQEDLFQTP GMQEELQQII DCLDTSIPET
IPGSNHSVAE ALLIFLEALP EPVICYELYQ RCLDSAHDPR ICKQVISQLP RCHRNVFRYL
MAFLRELLKF SDYNNVSTNM IATLFTSLLL RPPPNLMARQ TPSDRQRAIQ FLLVFLLGSE
ED
