Reviewed,
UniProtKB/Swiss-Prot Q01968 (OCRL_HUMAN)
Last modified
July 7, 2009.
Version 105.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| 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 + H2O = 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. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 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.17 |
| 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 Complete proteome |
| Gene Ontology (GO) | |
| Biological process | lipid metabolic process Ref.1 Ref.8 Traceable author statement. Source: ProtInc signal transductionInferred from electronic annotation. Source: InterPro |
| Cellular component | Golgi stack Traceable author statement. Source: ProtInc Golgi-associated vesicleTraceable 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. Ref.17 | 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. Ref.17 | 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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
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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. 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. 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] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [11] | "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 LOWE SYNDROME THR-367 DEL; GLY-451; SER-463 AND ARG-524. |
| [12] | "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 LOWE SYNDROME TYR-375; GLN-500; ASP-508 AND CYS-513. |
| [13] | "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 LOWE SYNDROME GLN-500 AND GLN-524. |
| [14] | "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 LOWE SYNDROME ARG-522. |
| [15] | "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 LOWE SYNDROME GLU-357; GLU-421; ASP-424 AND TYR-498. |
| [16] | "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 LOWE SYNDROME LYS-478-479-TYR DEL; GLN-500 AND LEU-526. |
| [17] | "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. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M88162 mRNA. Translation: AAA59964.2. Different initiation. U57627 mRNA. Translation: AAB03839.2. 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. BC130612 mRNA. Translation: AAI30613.1. S62085 mRNA. Translation: AAB26926.1. | |||||||||||||
| IPI | IPI00480049. IPI00873093. | ||||||||||||
| PIR | S29069. | ||||||||||||
| RefSeq | NP_000267.2. NP_001578.2. | ||||||||||||
| UniGene | Hs.126357 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| ModBase | Search... | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q01968. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q01968. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000122126. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 4952. | ||||||||||||
| KEGG | hsa:4952. | ||||||||||||
| UCSC | uc004euq.1. human. uc004eur.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC0XP128501. | ||||||||||||
| H-InvDB | HIX0056225. | ||||||||||||
| HGNC | HGNC:8108. OCRL. | ||||||||||||
| HPA | HPA012495. | ||||||||||||
| MIM | 300535. gene. 300555. phenotype. 309000. phenotype. | ||||||||||||
| Orphanet | 1652. Dent syndrome. 534. Lowe syndrome. | ||||||||||||
| PharmGKB | PA31896. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOVERGEN | Q01968. | ||||||||||||
| OMA | Q01968. TGIHREP. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 3.1.3.36. 247. | ||||||||||||
| Reactome | REACT_11044. Signaling by Rho GTPases. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q01968. | ||||||||||||
| Bgee | Q01968. | ||||||||||||
| CleanEx | HS_INPP5F. | ||||||||||||
| GermOnline | ENSG00000122126. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR005135. Endo/exonuclease/phosphatase. IPR000300. IPPc. IPR000198. RhoGAP. [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] | ||||||||||||
| PROSITE | PS50238. RHOGAP. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 19074. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | OCRL_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q01968 Secondary accession number(s): A6NKI1 Q9UMA5 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome X Human chromosome X: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


