Reviewed, UniProtKB/Swiss-Prot Q01968 (OCRL_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	901 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 diversity	Alternative splicing
Disease	Cataract Disease mutation
Molecular function	Hydrolase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	lipid metabolic process Ref.1 Ref.8 Traceable author statement. Source: ProtInc signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi stack Traceable author statement. Source: ProtInc Golgi-associated vesicle Traceable author statement. Source: ProtInc
Molecular function	phosphatidylinositol-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 901

901

Inositol polyphosphate 5-phosphatase OCRL-1

PRO_0000209721

Regions

Domain

721 – 901

181

Rho-GAP

Natural variations

Alternative sequence

707 – 714

8

Missing in isoform B.

VSP_002681

Natural variant

318

1

R → C in DD2.

VAR_022698

Natural variant

337

1

R → P in Lowe syndrome.

VAR_010169

Natural variant

357

1

G → E in Lowe syndrome; could be a rare polymorphism.

VAR_010170

Natural variant

367

1

Missing in Lowe syndrome.

VAR_010171

Natural variant

372

1

V → G in Lowe syndrome.

VAR_010172

Natural variant

375

1

H → Y in Lowe syndrome.

VAR_010173

Natural variant

421

1

G → E in Lowe syndrome.

VAR_010174

Natural variant

424

1

N → D in Lowe syndrome.

VAR_010175

Natural variant

451

1

D → G in Lowe syndrome.

VAR_010176

Natural variant

463

1

F → S in Lowe syndrome.

VAR_010177

Natural variant

478 – 479

2

Missing in Lowe syndrome.

VAR_023957

Natural variant

479

1

Y → C in DD2.

VAR_022699

Natural variant

498

1

C → Y in Lowe syndrome.

VAR_010178

Natural variant

500

1

R → G in Lowe syndrome.

VAR_010179

Natural variant

500

1

R → Q in Lowe syndrome.

VAR_010180

Natural variant

508

1

V → D in Lowe syndrome.

VAR_010181

Natural variant

513

1

Y → C in Lowe syndrome.

VAR_010182

Natural variant

522

1

S → R in Lowe syndrome.

VAR_010183

Natural variant

524

1

H → Q in Lowe syndrome.

VAR_010184

Natural variant

524

1

H → R in Lowe syndrome.

VAR_010185

Natural variant

526

1

P → L in Lowe syndrome.

VAR_023958

Natural variant

533

1

I → S in Lowe syndrome.

VAR_010187

Natural variant

768

1

I → N in Lowe syndrome; could be a rare polymorphism.

VAR_010188

Natural variant

797

1

A → P in Lowe syndrome; could be a rare polymorphism.

VAR_010189

Secondary structure

1

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901

Helix Strand Turn

Details...

Beta strand

571 – 577

7

Turn

607 – 609

3

Beta strand

615 – 619

5

Beta strand

633 – 636

4

Turn

640 – 642

3

Helix

643 – 648

6

Beta strand

649 – 651

3

Beta strand

655 – 657

3

Beta strand

669 – 675

7

Helix

684 – 687

4

Helix

700 – 702

3

Beta strand

732 – 734

3

Helix

736 – 748

13

Turn

753 – 757

5

Helix

762 – 774

13

Helix

784 – 797

14

Helix

805 – 807

3

Helix

808 – 814

7

Helix

818 – 826

9

Helix

830 – 847

18

Helix

850 – 853

4

Helix

857 – 868

12

Helix

873 – 875

3

Helix

881 – 896

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified June 7, 2005. Version 3. Checksum: 476BFCCC3655C1FE	FASTA	901	104,205
	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
	Isoform B [UniParc]. Checksum: E61E59C6AD0AC650		893	103,227
	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 KLIDLEKSLL QMVPLDEGAS 730 740 750 760 770 780 ERPLQVPKEI WLLVDHLFKY ACHQEDLFQT PGMQEELQQI IDCLDTSIPE TIPGSNHSVA 790 800 810 820 830 840 EALLIFLEAL PEPVICYELY QRCLDSAYDP RICRQVISQL PRCHRNVFRY LMAFLRELLK 850 860 870 880 890 FSEYNSVNAN MIATLFTSLL LRPPPNLMAR QTPSDRQRAI QFLLGFLLGS EED

References

	« Hide 'large scale' referencesShow '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. , 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.,