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Q01968 (OCRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inositol polyphosphate 5-phosphatase OCRL-1

EC=3.1.3.36
Alternative name(s):
Lowe oculocerebrorenal syndrome protein
Gene names
Name:OCRL
Synonyms:INPP5F, OCRL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length901 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. Also converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. May function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. Involved in primary cilia assembly. Ref.14 Ref.15

Catalytic activity

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate.

Subunit structure

Interacts with APPL1, FAM109A/SES1 and FAM109B/SES2; APPL1-binding and FAM109A-binding are mutually exclusive. Interacts with clathrin heavy chain. Interacts with several Rab GTPases, at least RAB1B, RAB5A, RAB6A, RAB8A and RAB31; these interactions may play a dual role in targeting OCRL to the specific membranes and stimulating the phosphatase activity. Interaction with RAB8A modulates OCRL recruitment to cilia. Ref.11 Ref.13 Ref.14 Ref.17 Ref.19

Subcellular location

Cytoplasmic vesiclephagosome membrane By similarity. Early endosome membrane. Membraneclathrin-coated pit. Cell projectionciliumphotoreceptor outer segment. Cytoplasmic vesicle By similarity. Endosome By similarity. Golgi apparatustrans-Golgi network By similarity. Note: Also found on macropinosomes. Ref.11 Ref.14 Ref.17 Ref.19

Tissue specificity

Brain, skeletal muscle, heart, kidney, lung, placenta and fibroblasts. Expressed in the retina and the retinal pigment epithelium. Ref.14

Domain

The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature. Ref.17

Involvement in disease

Lowe oculocerebrorenal syndrome (OCRL) [MIM:309000]: X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.13 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.29 Ref.30

Dent disease 2 (DD2) [MIM:300555]: A renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27 Ref.28 Ref.30

Sequence similarities

Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.

Contains 1 PH domain.

Contains 1 Rho-GAP domain.

Caution

It is uncertain whether Met-1, Met-18 or Met-20 is the initiator.

Sequence caution

The sequence AAA59964.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCilium biogenesis/degradation
   Cellular componentCell projection
Cilium
Coated pit
Cytoplasmic vesicle
Endosome
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseCataract
Ciliopathy
Disease mutation
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcilium assembly

Inferred from mutant phenotype Ref.15Ref.14. Source: UniProtKB

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

inositol phosphate metabolic process

Traceable author statement. Source: Reactome

lipid metabolic process

Non-traceable author statement Ref.1. Source: UniProtKB

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol dephosphorylation

Inferred from electronic annotation. Source: Ensembl

phospholipid metabolic process

Traceable author statement. Source: Reactome

positive regulation of Rac GTPase activity

Inferred from direct assay PubMed 12915445. Source: GOC

regulation of Rac GTPase activity

Inferred from direct assay PubMed 12915445. Source: FlyBase

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi stack

Traceable author statement PubMed 1840503. Source: ProtInc

Golgi-associated vesicle

Traceable author statement PubMed 1840503. Source: ProtInc

clathrin-coated vesicle

Inferred from direct assay Ref.13. Source: UniProtKB

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 12915445. Source: FlyBase

cytosol

Traceable author statement. Source: Reactome

early endosome

Inferred from direct assay Ref.13. Source: UniProtKB

early endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 12915445. Source: FlyBase

phagocytic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

photoreceptor outer segment

Inferred from direct assay Ref.14. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 12915445. Source: FlyBase

trans-Golgi network

Inferred from direct assay PubMed 12915445. Source: FlyBase

   Molecular_functionRac GTPase activator activity

Inferred from direct assay PubMed 12915445. Source: FlyBase

Rac GTPase binding

Inferred from physical interaction PubMed 12915445. Source: FlyBase

inositol phosphate phosphatase activity

Non-traceable author statement Ref.1. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity

Traceable author statement Ref.9. Source: ProtInc

protein binding

Inferred from physical interaction Ref.13Ref.14. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: Q01968-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: Q01968-2)

The sequence of this isoform differs from the canonical sequence as follows:
     707-714: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 901901Inositol polyphosphate 5-phosphatase OCRL-1
PRO_0000209721

Regions

Domain1 – 119119PH
Domain721 – 901181Rho-GAP
Region237 – 5633275-phosphatase
Region564 – 678115ASH
Motif73 – 775Clathrin box 1
Motif702 – 7065Clathrin box 2

Natural variations

Alternative sequence707 – 7148Missing in isoform B.
VSP_002681
Natural variant2421F → S in OCRL. Ref.30
Corresponds to variant rs137853828 [ dbSNP | Ensembl ].
VAR_064773
Natural variant2741I → T in OCRL. Ref.30
Corresponds to variant rs137853829 [ dbSNP | Ensembl ].
VAR_064774
Natural variant2771Q → R in OCRL. Ref.30
Corresponds to variant rs137853830 [ dbSNP | Ensembl ].
VAR_064775
Natural variant3181R → C in DD2 and OCRL. Ref.27 Ref.28 Ref.30
Corresponds to variant rs137853263 [ dbSNP | Ensembl ].
VAR_022698
Natural variant3371R → C in OCRL; associated with I-361. Ref.30
Corresponds to variant rs137853831 [ dbSNP | Ensembl ].
VAR_064776
Natural variant3371R → P in OCRL.
VAR_010169
Natural variant3541N → H in DD2. Ref.30
Corresponds to variant rs137853833 [ dbSNP | Ensembl ].
VAR_064777
Natural variant3571G → E in OCRL; uncertain pathological significance. Ref.25
Corresponds to variant rs137853854 [ dbSNP | Ensembl ].
VAR_010170
Natural variant3611R → I in OCRL; associated with C-337. Ref.30
Corresponds to variant rs137853832 [ dbSNP | Ensembl ].
VAR_064778
Natural variant3671Missing in OCRL. Ref.21
VAR_010171
Natural variant3721V → G in OCRL. Ref.30
Corresponds to variant rs137853834 [ dbSNP | Ensembl ].
VAR_010172
Natural variant3731N → Y in OCRL. Ref.30
Corresponds to variant rs137853835 [ dbSNP | Ensembl ].
VAR_064779
Natural variant3741S → F in OCRL. Ref.30
Corresponds to variant rs137853836 [ dbSNP | Ensembl ].
VAR_064780
Natural variant3751H → Y in OCRL. Ref.22
Corresponds to variant rs137853848 [ dbSNP | Ensembl ].
VAR_010173
Natural variant4141H → R in OCRL. Ref.30
Corresponds to variant rs137853837 [ dbSNP | Ensembl ].
VAR_064781
Natural variant4211G → E in OCRL. Ref.25
Corresponds to variant rs137853855 [ dbSNP | Ensembl ].
VAR_010174
Natural variant4241N → D in OCRL. Ref.25
Corresponds to variant rs137853856 [ dbSNP | Ensembl ].
VAR_010175
Natural variant4511D → G in OCRL. Ref.21
Corresponds to variant rs137853850 [ dbSNP | Ensembl ].
VAR_010176
Natural variant4511D → N in OCRL. Ref.30
Corresponds to variant rs137853838 [ dbSNP | Ensembl ].
VAR_064782
Natural variant4571R → G in OCRL. Ref.30
Corresponds to variant rs137853839 [ dbSNP | Ensembl ].
VAR_064783
Natural variant4631F → S in OCRL. Ref.21
Corresponds to variant rs137853851 [ dbSNP | Ensembl ].
VAR_010177
Natural variant4681E → G in OCRL. Ref.30
Corresponds to variant rs137853841 [ dbSNP | Ensembl ].
VAR_064784
Natural variant4681E → K in OCRL. Ref.30
Corresponds to variant rs137853840 [ dbSNP | Ensembl ].
VAR_064785
Natural variant478 – 4792Missing in OCRL.
VAR_023957
Natural variant4791Y → C in DD2. Ref.27
Corresponds to variant rs137853262 [ dbSNP | Ensembl ].
VAR_022699
Natural variant4931R → W in DD2. Ref.28
Corresponds to variant rs137853846 [ dbSNP | Ensembl ].
VAR_064786
Natural variant4951P → L in OCRL. Ref.30
VAR_064787
Natural variant4981C → Y in OCRL. Ref.25
Corresponds to variant rs137853857 [ dbSNP | Ensembl ].
VAR_010178
Natural variant4991D → H in OCRL. Ref.30
Corresponds to variant rs137853842 [ dbSNP | Ensembl ].
VAR_064788
Natural variant5001R → G in OCRL.
VAR_010179
Natural variant5001R → Q in OCRL. Ref.22 Ref.23 Ref.26
Corresponds to variant rs137853260 [ dbSNP | Ensembl ].
VAR_010180
Natural variant5031W → R in OCRL. Ref.30
Corresponds to variant rs137853843 [ dbSNP | Ensembl ].
VAR_064789
Natural variant5081V → D in OCRL. Ref.22
Corresponds to variant rs137853849 [ dbSNP | Ensembl ].
VAR_010181
Natural variant5131Y → C in OCRL. Ref.22
Corresponds to variant rs137853847 [ dbSNP | Ensembl ].
VAR_010182
Natural variant5221S → R in OCRL. Ref.24
Corresponds to variant rs137853853 [ dbSNP | Ensembl ].
VAR_010183
Natural variant5241H → Q in OCRL. Ref.23
Corresponds to variant rs137853261 [ dbSNP | Ensembl ].
VAR_010184
Natural variant5241H → R in OCRL. Ref.21
Corresponds to variant rs137853852 [ dbSNP | Ensembl ].
VAR_010185
Natural variant5261P → L in OCRL. Ref.26
Corresponds to variant rs137853858 [ dbSNP | Ensembl ].
VAR_023958
Natural variant5331I → S in OCRL.
VAR_010187
Natural variant5911N → K in OCRL. Ref.29 Ref.30
Corresponds to variant rs137853844 [ dbSNP | Ensembl ].
VAR_064790
Natural variant7421Missing in OCRL. Ref.30
VAR_064791
Natural variant7681I → N in OCRL; uncertain pathological significance; abolishes FAM109A-binding; does not affect clathrin-binding. Ref.11 Ref.13
VAR_010188
Natural variant7971A → P in OCRL; uncertain pathological significance; abolishes FAM109A-, FAM109B- and APPL1-binding; does not affect clathrin-binding. Ref.11 Ref.30
VAR_010189
Natural variant7991P → L in DD2. Ref.30
VAR_064792
Natural variant8011P → L in OCRL. Ref.30
VAR_064793
Natural variant8911L → R in OCRL. Ref.30
Corresponds to variant rs137853845 [ dbSNP | Ensembl ].
VAR_064794

Experimental info

Mutagenesis4221D → A: Does not affect interaction with RAB8A. Ref.14
Mutagenesis4991D → A: Does not affect interaction with RAB8A. Ref.14
Mutagenesis6681F → V: Does not interact with RAB8A. Does not localize to cilia. Ref.14
Sequence conflict1801P → L in BAF85796. Ref.4
Sequence conflict3211G → E in AAI44107. Ref.7

Secondary structure

............................................................................................................................... 901
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified June 7, 2005. Version 3.
Checksum: 476BFCCC3655C1FE

FASTA901104,205
        10         20         30         40         50         60 
MEPPLPVGAQ PLATVEGMEM KGPLREPCAL TLAQRNGQYE LIIQLHEKEQ HVQDIIPINS 

        70         80         90        100        110        120 
HFRCVQEAEE TLLIDIASNS GCKIRVQGDW IRERRFEIPD EEHCLKFLSA VLAAQKAQSQ 

       130        140        150        160        170        180 
LLVPEQKDSS SWYQKLDTKD KPSVFSGLLG FEDNFSSMNL DKKINSQNQP TGIHREPPPP 

       190        200        210        220        230        240 
PFSVNKMLPR EKEASNKEQP KVTNTMRKLF VPNTQSGQRE GLIKHILAKR EKEYVNIQTF 

       250        260        270        280        290        300 
RFFVGTWNVN GQSPDSGLEP WLNCDPNPPD IYCIGFQELD LSTEAFFYFE SVKEQEWSMA 

       310        320        330        340        350        360 
VERGLHSKAK YKKVQLVRLV GMMLLIFARK DQCRYIRDIA TETVGTGIMG KMGNKGGVAV 

       370        380        390        400        410        420 
RFVFHNTTFC IVNSHLAAHV EDFERRNQDY KDICARMSFV VPNQTLPQLN IMKHEVVIWL 

       430        440        450        460        470        480 
GDLNYRLCMP DANEVKSLIN KKDLQRLLKF DQLNIQRTQK KAFVDFNEGE IKFIPTYKYD 

       490        500        510        520        530        540 
SKTDRWDSSG KCRVPAWCDR ILWRGTNVNQ LNYRSHMELK TSDHKPVSAL FHIGVKVVDE 

       550        560        570        580        590        600 
RRYRKVFEDS VRIMDRMEND FLPSLELSRR EFVFENVKFR QLQKEKFQIS NNGQVPCHFS 

       610        620        630        640        650        660 
FIPKLNDSQY CKPWLRAEPF EGYLEPNETV DISLDVYVSK DSVTILNSGE DKIEDILVLH 

       670        680        690        700        710        720 
LDRGKDYFLT ISGNYLPSCF GTSLEALCRM KRPIREVPVT KLIDLEEDSF LEKEKSLLQM 

       730        740        750        760        770        780 
VPLDEGASER PLQVPKEIWL LVDHLFKYAC HQEDLFQTPG MQEELQQIID CLDTSIPETI 

       790        800        810        820        830        840 
PGSNHSVAEA LLIFLEALPE PVICYELYQR CLDSAYDPRI CRQVISQLPR CHRNVFRYLM 

       850        860        870        880        890        900 
AFLRELLKFS EYNSVNANMI ATLFTSLLLR PPPNLMARQT PSDRQRAIQF LLGFLLGSEE 


D 

« Hide

Isoform B [UniParc].

Checksum: E61E59C6AD0AC650
Show »

FASTA893103,227

References

« Hide 'large scale' references
[1]"The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase."
Attree O., Olivos I.M., Okabe I., Bailey L.C., Nelson D.L., Lewis R.A., McInnes R.R., Nussbaum R.L.
Nature 358:239-242(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Kidney.
[2]Attree O., Olivos I.M., Okabe I., Bailey L.C., Nelson D.L., Lewis R.A., McInnes R.R., Nussbaum R.L.
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 585.
[3]"Physical mapping and genomic structure of the Lowe syndrome gene OCRL1."
Nussbaum R.L., Orrison B.M., Janne P.A., Charnas L.R., Chinault A.C.
Hum. Genet. 99:145-150(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Uterus.
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
[8]"Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe."
Leahey A.-M., Charnas L.R., Nussbaum R.L.
Hum. Mol. Genet. 2:461-463(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 814-843.
[9]"The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase."
Zhang X., Jefferson A.B., Auethavekiat V., Majerus P.W.
Proc. Natl. Acad. Sci. U.S.A. 92:4853-4856(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[10]"Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate."
Zhang X., Hartz P.A., Philip E., Racusen L.C., Majerus P.W.
J. Biol. Chem. 273:1574-1582(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[11]"Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1."
Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.
Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APPL1; CLATHRIN; FAM109A AND FAM109B, SUBCELLULAR LOCATION, VARIANTS OCRL ASN-768 AND PRO-797.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway."
Noakes C.J., Lee G., Lowe M.
Mol. Biol. Cell 22:606-623(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APPL1; FAM109A AND FAM109B, VARIANT OCRL ASN-768.
[14]"OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome."
Luo N., West C.C., Murga-Zamalloa C.A., Sun L., Anderson R.M., Wells C.D., Weinreb R.N., Travers J.B., Khanna H., Sun Y.
Hum. Mol. Genet. 21:3333-3344(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CILIA ASSEMBLY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH RAB8A, MUTAGENESIS OF ASP-422; ASP-499 AND PHE-668.
[15]"The Lowe syndrome protein OCRL1 is involved in primary cilia assembly."
Coon B.G., Hernandez V., Madhivanan K., Mukherjee D., Hanna C.B., Barinaga-Rementeria Ramirez I., Lowe M., Beales P.L., Aguilar R.C.
Hum. Mol. Genet. 21:1835-1847(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CILIOGENESIS.
[16]"Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL."
Pirruccello M., De Camilli P.
Trends Biochem. Sci. 37:134-143(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism."
Mao Y., Balkin D.M., Zoncu R., Erdmann K.S., Tomasini L., Hu F., Jin M.M., Hodsdon M.E., De Camilli P.
EMBO J. 28:1831-1842(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-119, DOMAIN PH, INTERACTION WITH CLATHRIN, SUBCELLULAR LOCATION.
[18]"A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1."
Hou X., Hagemann N., Schoebel S., Blankenfeldt W., Goody R.S., Erdmann K.S., Itzen A.
EMBO J. 30:1659-1670(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 540-678 IN COMPLEX WITH RAB8A.
[19]"A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway."
Erdmann K.S., Mao Y., McCrea H.J., Zoncu R., Lee S., Paradise S., Modregger J., Biemesderfer D., Toomre D., De Camilli P.
Dev. Cell 13:377-390(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 564-901, SUBCELLULAR LOCATION, INTERACTION WITH APPL1.
[20]"Recognition of the F&H motif by the Lowe syndrome protein OCRL."
Pirruccello M., Swan L.E., Folta-Stogniew E., De Camilli P.
Nat. Struct. Mol. Biol. 18:789-795(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 536-901 IN COMPLEX WITH FAM109A.
[21]"Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome."
Lin T., Orrison B.M., Leahey A.-M., Suchy S.F., Bernard D.J., Lewis R.A., Nussbaum R.L.
Am. J. Hum. Genet. 60:1384-1388(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL THR-367 DEL; GLY-451; SER-463 AND ARG-524.
[22]"Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients."
Lin T., Orrison B.M., Suchy S.F., Lewis R.A., Nussbaum R.L.
Mol. Genet. Metab. 64:58-61(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL TYR-375; GLN-500; ASP-508 AND CYS-513.
[23]"Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes."
Kawano T., Indo Y., Nakazato H., Shimadzu M., Matsuda I.
Am. J. Med. Genet. 77:348-355(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL GLN-500 AND GLN-524.
[24]"Identification of two novel mutations in the OCRL1 gene in Japanese families with Lowe syndrome."
Kubota T., Sakurai A., Arakawa K., Shimazu M., Wakui K., Furihata K., Fukushima Y.
Clin. Genet. 54:199-202(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OCRL ARG-522.
[25]"OCRL1 mutation analysis in French Lowe syndrome patients: implications for molecular diagnosis strategy and genetic counseling."
Monnier N., Satre V., Lerouge E., Berthoin F., Lunardi J.
Hum. Mutat. 16:157-165(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL GLU-357; GLU-421; ASP-424 AND TYR-498.
[26]"Carrier assessment in families with Lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination."
Roeschinger W., Muntau A.C., Rudolph G., Roscher A.A., Kammerer S.
Mol. Genet. Metab. 69:213-222(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL LYS-478-479-TYR DEL; GLN-500 AND LEU-526.
[27]"Dent disease with mutations in OCRL1."
Hoopes R.R. Jr., Shrimpton A.E., Knohl S.J., Hueber P., Hoppe B., Matyus J., Simckes A., Tasic V., Toenshoff B., Suchy S.F., Nussbaum R.L., Scheinman S.J.
Am. J. Hum. Genet. 76:260-267(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DD2 CYS-318 AND CYS-479.
[28]"OCRL1 mutations in patients with Dent disease phenotype in Japan."
Sekine T., Nozu K., Iyengar R., Fu X.J., Matsuo M., Tanaka R., Iijima K., Matsui E., Harita Y., Inatomi J., Igarashi T.
Pediatr. Nephrol. 22:975-980(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DD2 CYS-318 AND TRP-493.
[29]"Magnetic resonance imaging, magnetic resonance spectroscopy, and facial dysmorphism in a case of Lowe syndrome with novel OCRL1 gene mutation."
Yuksel A., Karaca E., Albayram M.S.
J. Child Neurol. 24:93-96(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OCRL LYS-591.
[30]"From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes."
Hichri H., Rendu J., Monnier N., Coutton C., Dorseuil O., Poussou R.V., Baujat G., Blanchard A., Nobili F., Ranchin B., Remesy M., Salomon R., Satre V., Lunardi J.
Hum. Mutat. 32:379-388(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OCRL SER-242; THR-274; ARG-277; CYS-318; CYS-337; ILE-361; GLY-372; TYR-373; PHE-374; ARG-414; ASN-451; GLY-457; LYS-468; GLY-468; LEU-495; HIS-499; ARG-503; LYS-591; VAL-742 DEL; PRO-797; LEU-801 AND ARG-891, VARIANTS DD2 HIS-354 AND LEU-799.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M88162 mRNA. Translation: AAA59964.2. Different initiation.
U57627 mRNA. Translation: AAB03839.2.
AK293107 mRNA. Translation: BAF85796.1.
AL022162, AL138745, AL662877 Genomic DNA. Translation: CAI95695.1.
AL022162, AL138745, AL662877 Genomic DNA. Translation: CAI95696.1.
AL138745, AL022162, AL662877 Genomic DNA. Translation: CAI42615.1.
AL138745, AL022162, AL662877 Genomic DNA. Translation: CAI42616.1.
AL662877, AL022162, AL138745 Genomic DNA. Translation: CAI41087.1.
AL662877, AL022162, AL138745 Genomic DNA. Translation: CAI41088.1.
Z73496 Genomic DNA. No translation available.
CH471107 Genomic DNA. Translation: EAX11831.1.
CH471107 Genomic DNA. Translation: EAX11832.1.
BC130612 mRNA. Translation: AAI30613.1.
BC144106 mRNA. Translation: AAI44107.1.
S62085 mRNA. Translation: AAB26926.1.
CCDSCCDS35393.1. [Q01968-1]
CCDS35394.1. [Q01968-2]
PIRS29069.
RefSeqNP_000267.2. NM_000276.3. [Q01968-1]
NP_001578.2. NM_001587.3. [Q01968-2]
UniGeneHs.126357.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KIENMR-A1-119[»]
2QV2X-ray2.40A564-901[»]
3QBTX-ray2.00B/D/F/H540-678[»]
3QISX-ray2.30A536-901[»]
4CMNX-ray3.13A215-560[»]
ProteinModelPortalQ01968.
SMRQ01968. Positions 1-119, 234-538, 540-898.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111006. 6 interactions.
IntActQ01968. 21 interactions.
MINTMINT-5004450.

PTM databases

PhosphoSiteQ01968.

Polymorphism databases

DMDM67477390.

Proteomic databases

MaxQBQ01968.
PaxDbQ01968.
PRIDEQ01968.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357121; ENSP00000349635; ENSG00000122126. [Q01968-2]
ENST00000371113; ENSP00000360154; ENSG00000122126. [Q01968-1]
GeneID4952.
KEGGhsa:4952.
UCSCuc004euq.3. human. [Q01968-1]
uc004eur.3. human. [Q01968-2]

Organism-specific databases

CTD4952.
GeneCardsGC0XP128673.
GeneReviewsOCRL.
HGNCHGNC:8108. OCRL.
HPAHPA012495.
MIM300535. gene.
300555. phenotype.
309000. phenotype.
neXtProtNX_Q01968.
Orphanet93623. Dent disease type 2.
534. Oculocerebrorenal syndrome.
PharmGKBPA31896.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5411.
HOVERGENHBG000070.
InParanoidQ01968.
KOK01099.
OMAAKYKKVQ.
OrthoDBEOG7J4465.
PhylomeDBQ01968.
TreeFamTF317034.

Enzyme and pathway databases

BioCycMetaCyc:HS04546-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.
SignaLinkQ01968.

Gene expression databases

BgeeQ01968.
CleanExHS_INPP5F.
GenevestigatorQ01968.

Family and domain databases

Gene3D1.10.555.10. 2 hits.
3.60.10.10. 1 hit.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]
SMARTSM00128. IPPc. 1 hit.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 2 hits.
SSF56219. SSF56219. 1 hit.
PROSITEPS50238. RHOGAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ01968.
GeneWikiOCRL.
GenomeRNAi4952.
NextBio19074.
PROQ01968.
SOURCESearch...

Entry information

Entry nameOCRL_HUMAN
AccessionPrimary (citable) accession number: Q01968
Secondary accession number(s): A6NKI1 expand/collapse secondary AC list , A8KAP2, B7ZLX2, O60800, Q15684, Q15774, Q4VY09, Q4VY10, Q5JQF1, Q5JQF2, Q9UJG5, Q9UMA5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: June 7, 2005
Last modified: July 9, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM