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FLASH GENE
Symbol OCRL contributors: mct/npt/pgu - updated : 14-06-2016
HGNC name oculocerebrorenal syndrome of Lowe
HGNC id 8108
Corresponding disease
DTD2 Dent disease 2
OCRL oculocerebrorenal syndrome of Lowe
Location Xq25      Physical location : 128.674.251 - 128.726.528
Synonym name
  • Lowe oculocerebrorenal syndrome protein
  • phosphatidylinositol polyphosphate 5-phosphatase
  • phosphatidylinositol-4,5-biphosphate,(PIP2),5-phosphatase
    • Synonym symbol(s) INPP5F, LOCR, PIBPP, OCRL1, NPHL2
    EC.number 3.1.3.36
    DNA
    TYPE functioning gene
    STRUCTURE 52.28 kb     24 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 5165 - 901 - 2009 19211563
  • binds clathrin with higher affinity than isoform b and is significantly more enriched in clathrin-coated trafficking intermediates
  • much less or not involved in the process of endocytosis
    • 23 - 5141 - 893 - 2009 19211563
  • having a second clathrin-binding site that contributes to clathrin binding of both isoforms
  • participating in clathrin-mediated trafficking events such as endocytosis
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Reproductivefemale systemuterus  highly
     male systemtestis   
    Respiratoryrespiratory tractlarynx  highly
    Urinarykidneytubule    Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
     fibroblast Homo sapiens
    Urinaryepithelial cell Homo sapiens
    Urinarytubular cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a phosphoinositide phosphatase domain in the N terminal region
  • a central 5-phosphatase domain, with an important role in its ciliary localization
  • a consensus motif (which we have called a phenylalanine and histidine [F-H] motif) for OCRL binding
  • P85 chimerin (GTP activating protein) homology domain in the C terminal region
  • C-terminal ASH and RhoGAP-like domains, interacting with APPL1, another Rab5 effector that participates in signaling from endocytic membranes
    • HOMOLOGY
    intraspecies homolog to inositol polyphosphate-5-phosphatase type II
    paralog to INPP5B
    Homologene
    FAMILY
  • inositol-1,4,5-trisphosphate 5-phosphatase type 2 family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    text
  • localized to the trans-Golgi network, early endosomes, plasma membrane ruffles, and clathrin-coated trafficking intermediates
  • membrane association requires interaction with Rab GTPases
  • localizes to the primary cilium of retinal pigment epithelial cells, fibroblasts and kidney tubular cells
    • basic FUNCTION
  • signal terminating in the inositol signaling pathway
  • hydrolysis of water-soluble and lipid inositol polyphosphate substrates
  • presumably the adaptation to bind clathrin reflects an important function for OCRL1 in clathrin-coated structure
  • playing a role in clathrin-mediated trafficking of proteins from endosomes to the trans-Golgi network and defects in this pathway might contribute to the Lowe syndrome phenotype
  • role for OCRL in membrane trafficking between the trans-Golgi network and endosomes
  • inositol polyphosphate 5-phosphatase, involved in homeostasis of lenticular metabolism and in actin polymerization
  • membrane-bound protein recruited to membranes via interaction with a variety of Rab proteins
  • role for the phosphatase OCRL in cell division
  • via its 5-phosphatase activity, OCRL controls early endosome (EE) function
  • controls trafficking through early endosomes via PtdIns4,5P&
    • 8322;-dependent regulation of endosomal actin
  • likely participates in vesicle trafficking to the primary cilium
  • also participates in primary cilium-targeting of proteins via the endocytic pathway
  • is a phosphoinositide 5-phosphatase that interacts with small GTPases and is involved in intracellular trafficking
  • role of OCRL in cilia maintenance, suggesting the involvement of ciliary dysfunction in the manifestation of Lowe syndrome
  • partition to the basal body and axoneme of primary cilium in ocular-ciliated cell lines, retinal tissue, kidney tubular cells and fibroblasts
  • OCRL and RAB8A are recruited to the cilia during early ciliogenesis
  • OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network
  • interacts with several members of the rab family of small GTPases (rabs play a dual role in regulation of OCRL, firstly targeting it to the Golgi apparatus and endosomes, and secondly, directly stimulating the 5-phosphatase activity of OCRL after membrane recruitment)
  • FAM109A and FAM109B are two novel OCRL-binding proteins
  • effector of the RAB35 GTPase in cytokinesis abscission
  • interacts with components of the endosomal machinery
  • interact with the GTPase RAB8A which in turn has a crucial role in ciliogenesis
  • partial functional redundancy between INPP5B and OCRL for primary cilia assembly
  • OCRL counteracted accumulation of M6PR in endosomes in an activity-dependent manner
  • phosphatase OCRL, located on macropinosomes, interacts with RAB8A, suggesting that RAB8A may operate on multiple levels to modulate phosphoinositides in macropinosomes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OCRL , DTD2
    related resource Database of the OCRL1 Mutations Causing Lowe Syndrome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS