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Reviewed, UniProtKB/Swiss-Prot Q01968 (OCRL_HUMAN)

Last modified November 25, 2008. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length901 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

Catalytic activity

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate.

Tissue specificity

Brain, skeletal muscle, heart, kidney, lung, placenta and fibroblasts.

Involvement in disease

Defects in OCRL are the cause of Lowe syndrome [MIM:309000]; also known as Lowe oculocerebrorenal syndrome. The Lowe syndrome is an 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.

Defects in OCRL are the cause of Dent disease type 2 (DD2) [MIM:300555]. DD2 is 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.

Sequence similarities

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

Contains 1 Rho-GAP domain.

Caution

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

Ontologies

Keywords

   Coding sequence diversityAlternative splicing
   DiseaseCataract
Disease mutation
   Molecular functionHydrolase
   Technical term3D-structure

Gene Ontology (GO)

   Biological processlipid metabolic process Ref.1 Ref.8

Traceable author statement. Source: ProtInc

signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular componentGolgi stack

Traceable author statement. Source: ProtInc

Golgi-associated vesicle

Traceable author statement. Source: ProtInc

   Molecular functionphosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Ref.8

Traceable author statement. Source: ProtInc

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

Domain721 – 901181Rho-GAP

Natural variations

Alternative sequence707 – 7148Missing in isoform B.
VSP_002681
Natural variant3181R → C in DD2.
VAR_022698
Natural variant3371R → P in Lowe syndrome.
VAR_010169
Natural variant3571G → E in Lowe syndrome; could be a rare polymorphism.
VAR_010170
Natural variant3671Missing in Lowe syndrome.
VAR_010171
Natural variant3721V → G in Lowe syndrome.
VAR_010172
Natural variant3751H → Y in Lowe syndrome.
VAR_010173
Natural variant4211G → E in Lowe syndrome.
VAR_010174
Natural variant4241N → D in Lowe syndrome.
VAR_010175
Natural variant4511D → G in Lowe syndrome.
VAR_010176
Natural variant4631F → S in Lowe syndrome.
VAR_010177
Natural variant478 – 4792Missing in Lowe syndrome.
VAR_023957
Natural variant4791Y → C in DD2.
VAR_022699
Natural variant4981C → Y in Lowe syndrome.
VAR_010178
Natural variant5001R → G in Lowe syndrome.
VAR_010179
Natural variant5001R → Q in Lowe syndrome.
VAR_010180
Natural variant5081V → D in Lowe syndrome.
VAR_010181
Natural variant5131Y → C in Lowe syndrome.
VAR_010182
Natural variant5221S → R in Lowe syndrome.
VAR_010183
Natural variant5241H → Q in Lowe syndrome.
VAR_010184
Natural variant5241H → R in Lowe syndrome.
VAR_010185
Natural variant5261P → L in Lowe syndrome.
VAR_023958
Natural variant5331I → S in Lowe syndrome.
VAR_010187
Natural variant7681I → N in Lowe syndrome; could be a rare polymorphism.
VAR_010188
Natural variant7971A → P in Lowe syndrome; could be a rare polymorphism.
VAR_010189

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 »

893103,227

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: 1321346] [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: 9048911] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
Tissue: Brain.
[4]"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.,