Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol PDZK1 contributors: mct/shn - updated : 15-07-2015
HGNC name PDZ domain containing 1
HGNC id 8821
DNA
TYPE functioning gene
STRUCTURE 36.54 kb     10 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   HRE
MAPPING cloned Y linked   status provisional
Map cen - D1S2344 - D1S442 - PDZK1 - D1S2612 - D1S3466 - qter
Authors White (98)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 2301 - 519 - Malmberg (2008)
9 - 2230 - 519 - -
7 - 1897 - 408 - -
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   highly
Digestiveintestinesmall intestine  highly Rattus norvegicus
 liver   highly
Urinarykidneytubuleconvoluted tubuleproximal tubulehighly
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
Digestiveenterocyte Rattus norvegicus
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • four PDZ (PSD95/disc large/ZO-1) domains(the first for the association with SCARB1), which bind to the C-termini of a number of membrane transporter proteins, including ion channels CFTR) and cell surface receptors
  • C-terminal domain required for the activation of SCARB1, and the tail interacts with the PDZ domains of SLC9A3R1, and this interaction is negatively regulated by the intramolecular association of PDZK1
  • HOMOLOGY
    interspecies ortholog to Pdzk1, Mus musculus
    ortholog to Pdzk1, Rattus norvegicus
    ortholog to pdzk1, Danio rerio
    ortholog to PDZK1, Pan troglodytes
    Homologene
    FAMILY
    CATEGORY adaptor , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • localized at the apical membrane of renal proximal tubules
  • colocalizes plasma membrane
  • basic FUNCTION
  • playing a role in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules
  • plays a specific role in stabilizing Muc3 in the apical membrane of small intestinal enterocytes
  • major scaffolder in brush borders of proximal tubular cells
  • multi-PDZ domain-containing adaptor protein that binds to the C terminus of the high density lipoprotein receptor, scavenger receptor, class B, type I (SCARB1), and controls the posttranscriptional, tissue-specific expression of this lipoprotein receptor
  • required for HDL activation of endothelial nitric oxide synthase and cell migration (Zhu 2008)
  • uniquely required for HDL/SCARB1 signaling in endothelium, and through these mechanisms, it is critically involved in the maintenance of endothelial monolayer integrity (Zhu 2008)
  • member of the family of proteins that is instrumental in preventing cardiovascular disease by maintaining normal lipoprotein metabolism
  • NHERF1, NHERF2, and PDZK1, modulate CFTR membrane retention, conductivity, and interactions with other transporters
  • reconstitutes calcium inhibition of SLC9A3 activity by anchoring SLC9A3 basally and releasing it with elevated Ca(2+)
  • by entering into the ternary complex, PDZK1 can both enhance the scaffolding at the apical membrane as well as augment SLC9A3R1 role in microvilli formation
  • indirect involvement of PDZK1 in HCV (hepatitis C virus) entry via its ability to interact with SCARB1 and enhance its activity as an HCV entry factor
  • plays a role in the stabilization/retention of SLC34A3 in the microvilli more than in the trafficking of the transporter to the apical membrane
  • plays an important role in the adaptation of SLC34A3 to low Pi conditions
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • carboxy-terminal portion of cMOAT (MRP2)
  • Scavenger receptor B, type I, SRBI
  • ClC-3B
  • membrane-associated protein of 17 kD, MAP17; NaPi-IIa, solute carrier SLC17A1; Na+/H+ exchanger NHE-3; organic cation transporter OCTN1; chloride-formate exchanger, CFEX; and urate-anion exchanger,URAT1
  • high density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI)
  • as a functional regulator of OCTN2 through direct interaction with the C terminus
  • PEPT2
  • somatostatin receptor subtype 5, SSTR5
  • OAT4
  • SLC9A3
  • SLC9A3R1
  • SCARB1
  • SLC34A3
  • PTGIR
  • PDZK1 expression was indirectly regulated by ESR1 stimulation, requiring insulinlike growth factor 1 receptor (IGF1R) expression and function
  • PDZK1 and SLC9A3R1 regulate the transport function of SLCO1A2 by modulating protein internalization via a clathrin-dependent pathway and by enhancing protein stability
  • interactions of SLC5A1 with the scaffold protein PDZK1
  • cell & other
    REGULATION
    Other upregulated by a restricted phosphate diet which shares homology to the NaYH exchanger regulatory factor
    regulated by DD96 (regulating PDZK1 turnover)
    regulated by PPARA via the peroxisome proliferator responsive element (PPRE)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in estrogen-responsive breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • PDZK1-deficient mice developed normally, did not display any gross phenotypic abnormalities, and were fecund, lack of PDZK1 resulted in modulation of expression of selective ion channels in the kidney, as well as increased serum cholesterol levels
  • SR-BI protein expression in PDZK1 knock-out (KO) mice was reduced by 95% in the liver, 50% in the proximal intestine, and not affected in steroidogenic organs
  • the ratio of unesterified to total plasma cholesterol was normal, females were fertile, and cholesteryl ester stores in steroidogenic organs were essentially unaffected in PDZK1 KO mice
  • inactivation of the Pdzk1 gene promotes the development of aortic root atherosclerosis in apolipoprotein E KO mice fed with a high fat/high cholesterol diet
  • Pdzk1-/- mice adapted to chronic low Pi diets showed an increased expression of SLC34A1 protein in the apical membrane of proximal tubules but impaired up-regulation of SLC34A3