Q01968 (OCRL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
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 + H2O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate.
Subunit structure	Interacts with APPL1, FAM109A and FAM109B; APPL1-binding and FAM109A-binding are mutually exclusive. Interacts with clathrin heavy chain. Ref.10 Ref.12
Subcellular location	Endosome. Note: Also found on macropinosomes. Ref.10
Tissue specificity	Brain, skeletal muscle, heart, kidney, lung, placenta and fibroblasts.
Involvement in disease	Defects in OCRL are the cause of Lowe oculocerebrorenal syndrome (OCRL) [MIM:309000]. It 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. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 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. Ref.19 Ref.20 Ref.22
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.
Sequence caution	The sequence AAA59964.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Endosome
Coding sequence diversity	Alternative splicing
Disease	Cataract Disease mutation
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	inositol or phosphatidylinositol phosphatase activity Traceable author statement Ref.1. Source: ProtInc
Biological process	phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: InterPro regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular component	Golgi 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.12. Source: UniProtKB cytosol Traceable author statement. Source: Reactome early endosome Inferred from direct assay Ref.12. Source: UniProtKB
Molecular function	phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Traceable author statement Ref.8. Source: ProtInc protein binding Inferred from physical interaction Ref.12. 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 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

242

1

F → S in OCRL. Ref.22
Corresponds to variant rs137853828 [ dbSNP | Ensembl ].

VAR_064773

Natural variant

274

1

I → T in OCRL. Ref.22
Corresponds to variant rs137853829 [ dbSNP | Ensembl ].

VAR_064774

Natural variant

277

1

Q → R in OCRL. Ref.22
Corresponds to variant rs137853830 [ dbSNP | Ensembl ].

VAR_064775

Natural variant

318

1

R → C in DD2 and OCRL. Ref.19 Ref.20 Ref.22
Corresponds to variant rs137853263 [ dbSNP | Ensembl ].

VAR_022698

Natural variant

337

1

R → C in OCRL; associated with I-361. Ref.22
Corresponds to variant rs137853831 [ dbSNP | Ensembl ].

VAR_064776

Natural variant

337

1

R → P in OCRL.

VAR_010169

Natural variant

354

1

N → H in DD2. Ref.22
Corresponds to variant rs137853833 [ dbSNP | Ensembl ].

VAR_064777

Natural variant

357

1

G → E in OCRL; uncertain pathological significance. Ref.17
Corresponds to variant rs137853854 [ dbSNP | Ensembl ].

VAR_010170

Natural variant

361

1

R → I in OCRL; associated with C-337. Ref.22
Corresponds to variant rs137853832 [ dbSNP | Ensembl ].

VAR_064778

Natural variant

367

1

Missing in OCRL. Ref.13

VAR_010171

Natural variant

372

1

V → G in OCRL. Ref.22
Corresponds to variant rs137853834 [ dbSNP | Ensembl ].

VAR_010172

Natural variant

373

1

N → Y in OCRL. Ref.22
Corresponds to variant rs137853835 [ dbSNP | Ensembl ].

VAR_064779

Natural variant

374

1

S → F in OCRL. Ref.22
Corresponds to variant rs137853836 [ dbSNP | Ensembl ].

VAR_064780

Natural variant

375

1

H → Y in OCRL. Ref.14
Corresponds to variant rs137853848 [ dbSNP | Ensembl ].

VAR_010173

Natural variant

414

1

H → R in OCRL. Ref.22
Corresponds to variant rs137853837 [ dbSNP | Ensembl ].

VAR_064781

Natural variant

421

1

G → E in OCRL. Ref.17
Corresponds to variant rs137853855 [ dbSNP | Ensembl ].

VAR_010174

Natural variant

424

1

N → D in OCRL. Ref.17
Corresponds to variant rs137853856 [ dbSNP | Ensembl ].

VAR_010175

Natural variant

451

1

D → G in OCRL. Ref.13
Corresponds to variant rs137853850 [ dbSNP | Ensembl ].

VAR_010176

Natural variant

451

1

D → N in OCRL. Ref.22
Corresponds to variant rs137853838 [ dbSNP | Ensembl ].

VAR_064782

Natural variant

457

1

R → G in OCRL. Ref.22
Corresponds to variant rs137853839 [ dbSNP | Ensembl ].

VAR_064783

Natural variant

463

1

F → S in OCRL. Ref.13
Corresponds to variant rs137853851 [ dbSNP | Ensembl ].

VAR_010177

Natural variant

468

1

E → G in OCRL. Ref.22
Corresponds to variant rs137853841 [ dbSNP | Ensembl ].

VAR_064784

Natural variant

468

1

E → K in OCRL. Ref.22
Corresponds to variant rs137853840 [ dbSNP | Ensembl ].

VAR_064785

Natural variant

478 – 479

2

Missing in OCRL.

VAR_023957

Natural variant

479

1

Y → C in DD2. Ref.19
Corresponds to variant rs137853262 [ dbSNP | Ensembl ].

VAR_022699

Natural variant

493

1

R → W in DD2. Ref.20
Corresponds to variant rs137853846 [ dbSNP | Ensembl ].

VAR_064786

Natural variant

495

1

P → L in OCRL. Ref.22

VAR_064787

Natural variant

498

1

C → Y in OCRL. Ref.17
Corresponds to variant rs137853857 [ dbSNP | Ensembl ].

VAR_010178

Natural variant

499

1

D → H in OCRL. Ref.22
Corresponds to variant rs137853842 [ dbSNP | Ensembl ].

VAR_064788

Natural variant

500

1

R → G in OCRL.

VAR_010179

Natural variant

500

1

R → Q in OCRL. Ref.14 Ref.15 Ref.18
Corresponds to variant rs137853260 [ dbSNP | Ensembl ].

VAR_010180

Natural variant

503

1

W → R in OCRL. Ref.22
Corresponds to variant rs137853843 [ dbSNP | Ensembl ].

VAR_064789

Natural variant

508

1

V → D in OCRL. Ref.14
Corresponds to variant rs137853849 [ dbSNP | Ensembl ].

VAR_010181

Natural variant

513

1

Y → C in OCRL. Ref.14
Corresponds to variant rs137853847 [ dbSNP | Ensembl ].

VAR_010182

Natural variant

522

1

S → R in OCRL. Ref.16
Corresponds to variant rs137853853 [ dbSNP | Ensembl ].

VAR_010183

Natural variant

524

1

H → Q in OCRL. Ref.15
Corresponds to variant rs137853261 [ dbSNP | Ensembl ].

VAR_010184

Natural variant

524

1

H → R in OCRL. Ref.13
Corresponds to variant rs137853852 [ dbSNP | Ensembl ].

VAR_010185

Natural variant

526

1

P → L in OCRL. Ref.18
Corresponds to variant rs137853858 [ dbSNP | Ensembl ].

VAR_023958

Natural variant

533

1

I → S in OCRL.

VAR_010187

Natural variant

591

1

N → K in OCRL. Ref.21 Ref.22
Corresponds to variant rs137853844 [ dbSNP | Ensembl ].

VAR_064790

Natural variant

742

1

Missing in OCRL. Ref.22

VAR_064791

Natural variant

768

1

I → N in OCRL; uncertain pathological significance; abolishes FAM109A-binding; does not affect clathrin-binding. Ref.10 Ref.12

VAR_010188

Natural variant

797

1

A → P in OCRL; uncertain pathological significance; abolishes FAM109A-, FAM109B- and APPL1-binding; does not affect clathrin-binding. Ref.10 Ref.22

VAR_010189

Natural variant

799

1

P → L in DD2. Ref.22

VAR_064792

Natural variant

801

1

P → L in OCRL. Ref.22

VAR_064793

Natural variant

891

1

L → R in OCRL. Ref.22
Corresponds to variant rs137853845 [ dbSNP | Ensembl ].

VAR_064794

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	FASTA	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., 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: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. , 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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
[7]	"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: 8504307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 814-843.
[8]	"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: 7761412] [Abstract] Cited for: CHARACTERIZATION.
[9]	"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: 9430698] [Abstract] Cited for: CHARACTERIZATION.
[10]	"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: 20133602] [Abstract] Cited for: INTERACTION WITH APPL1; CLATHRIN; FAM109A AND FAM109B, SUBCELLULAR LOCATION, VARIANTS OCRL ASN-768 AND PRO-797.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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: 21233288] [Abstract] Cited for: INTERACTION WITH APPL1; FAM109A AND FAM109B, VARIANT OCRL ASN-768.
[13]	"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: 9199559] [Abstract] Cited for: VARIANTS OCRL THR-367 DEL; GLY-451; SER-463 AND ARG-524.
[14]	"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: 9682219] [Abstract] Cited for: VARIANTS OCRL TYR-375; GLN-500; ASP-508 AND CYS-513.
[15]	"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: 9632163] [Abstract] Cited for: VARIANTS OCRL GLN-500 AND GLN-524.
[16]	"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: 9788721] [Abstract] Cited for: VARIANT OCRL ARG-522.
[17]	"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: 10923037] [Abstract] Cited for: VARIANTS OCRL GLU-357; GLU-421; ASP-424 AND TYR-498.
[18]	"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: 10767176] [Abstract] Cited for: VARIANTS OCRL LYS-478-479-TYR DEL; GLN-500 AND LEU-526.
[19]	"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: 15627218] [Abstract] Cited for: VARIANTS DD2 CYS-318 AND CYS-479.
[20]	"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: 17384968] [Abstract] Cited for: VARIANTS DD2 CYS-318 AND TRP-493.
[21]	"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: 19168822] [Abstract] Cited for: VARIANT OCRL LYS-591.
[22]	"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: 21031565] [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.

Web resources

Lowe Syndrome mutation database

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M88162 mRNA. Translation: AAA59964.2. Different initiation.
U57627 mRNA. Translation: AAB03839.2.
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.
S62085 mRNA. Translation: AAB26926.1.

IPI

IPI00480049.
IPI00873093.

PIR

S29069.

RefSeq

NP_000267.2. NM_000276.3.
NP_001578.2. NM_001587.3.

UniGene

Hs.126357.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KIE	NMR	-	A	1-119	[»]
2QV2	X-ray	2.40	A	564-901	[»]
3QBT	X-ray	2.00	B/D/F/H	540-678	[»]
3QIS	X-ray	2.30	A	536-901	[»]

ProteinModelPortal

Q01968.

SMR

Q01968. Positions 1-119, 218-898.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-5004450.

STRING

Q01968.

PTM databases

PhosphoSite

Q01968.

Polymorphism databases

DMDM

67477390.

Proteomic databases

PRIDE

Q01968.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371113; ENSP00000360154; ENSG00000122126.

GeneID

4952.

KEGG

hsa:4952.

UCSC

uc004euq.3. human.
uc004eur.3. human.

Organism-specific databases

CTD

4952.

GeneCards

GC0XP128673.

H-InvDB

HIX0056225.

HGNC

HGNC:8108. OCRL.

HPA

HPA012495.

MIM

300535. gene.
300555. phenotype.
309000. phenotype.

neXtProt

NX_Q01968.

Orphanet

93623. Dent disease type 2.
534. Oculocerebrorenal syndrome.

PharmGKB

PA31896.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5411.

GeneTree

ENSGT00620000087599.

HOVERGEN

HBG000070.

InParanoid

Q01968.

KO

K01099.

OMA

TGIHREP.

OrthoDB

EOG4V1703.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000122126-MONOMER.

Reactome

REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

Q01968.

Bgee

Q01968.

CleanEx

HS_INPP5F.

Genevestigator

Q01968.

GermOnline

ENSG00000122126. Homo sapiens.

Family and domain databases

Gene3D

G3DSA:1.10.555.10. RhoGAP. 2 hits.

InterPro

IPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]

Pfam

PF03372. Exo_endo_phos. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]

SMART

SM00128. IPPc. 1 hit.
SM00324. RhoGAP. 1 hit.
[Graphical view]

SUPFAM

SSF56219. Exo_endo_phos. 1 hit.
SSF48350. Rho_GAP. 1 hit.

PROSITE

PS50238. RHOGAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q01968.

NextBio

19074.

SOURCE

Search...

Entry information

Entry name

OCRL_HUMAN

Accession

Primary (citable) accession number: Q01968
Secondary accession number(s): A6NKI1 , 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:	April 18, 2012
This is version 135 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.