Recombinant Human Na (+)/H (+) exchange regulatory cofactor NHE-RF3 (PDZK1)
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Description
Functional Roles
PDZK1 regulates multiple processes through its scaffolding activity:
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Ion Transport: Modulates proximal tubular Na+-dependent phosphate cotransport and CFTR chloride channel activity .
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Cholesterol Metabolism: Connects SCARB1 (scavenger receptor) with intracellular cholesterol transport machinery .
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Drug Resistance: Interacts with ABCC2 (multidrug resistance protein 2) and PDZK1IP1 to influence cellular drug efflux .
Key Interaction Partners
PDZK1 forms complexes with:
Additional interactors include AKAP10, CLCN3, and SLK .
Experimental Use
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Antibody Validation: The recombinant fragment (aa 1–96) serves as a control for antibody specificity (e.g., Thermo Fisher PA5-52261) .
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Blocking Protocol: Recommended 100x molar excess of PDZK1 fragment pre-incubated with antibodies for 30 minutes .
Disease Relevance
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Osteoarthritis: PDZK1 protects against mechanical overload-induced chondrocyte senescence by preserving mitochondrial function .
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Kidney Disorders: Dysregulation contributes to phosphate homeostasis defects .
Research Findings
Product Specs
Form
Lyophilized powder
Note: We will prioritize shipping the format currently in stock. However, if you have any specific requirements for the format, please specify them in the order notes. We will fulfill your request to the best of our ability.
Note: We will prioritize shipping the format currently in stock. However, if you have any specific requirements for the format, please specify them in the order notes. We will fulfill your request to the best of our ability.
Lead Time
Delivery time
may vary depending on the purchasing method or location. Please consult your local distributors
for specific delivery timelines.
Note: All our proteins are shipped with standard blue ice packs. If you require dry ice shipping, please communicate with us beforehand as additional fees will apply.
Note: All our proteins are shipped with standard blue ice packs. If you require dry ice shipping, please communicate with us beforehand as additional fees will apply.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
We recommend briefly centrifuging the vial before opening to ensure the contents are at the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. We recommend adding 5-50% glycerol (final concentration) and aliquoting for long-term storage at -20°C/-80°C. Our standard final concentration of glycerol is 50%, which can be used as a reference.
Shelf Life
Shelf life is influenced by various factors, including storage conditions, buffer composition, storage temperature, and protein stability.
Generally, the shelf life for liquid form is 6 months at -20°C/-80°C. The shelf life for lyophilized form is 12 months at -20°C/-80°C.
Generally, the shelf life for liquid form is 6 months at -20°C/-80°C. The shelf life for lyophilized form is 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquoting is essential for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag type will be determined during the manufacturing process.
The tag type is determined during the production process. If you have a specific tag type requirement, please inform us, and we will prioritize development of the specified tag.
Synonyms
1700023D20Rik; 2610507N21Rik; 4921513F16Rik; AI267131; AI314638; AL022680; C terminal linking and modulating protein; CAP70; CFTR associated protein of 70 kDa ; CFTR associated protein; 70-KD; CFTR-associated protein of 70 kDa; CLAMP; D3Ertd537e; Dietary Pi-regulated RNA-1; Diphor-1; mPDZK1; Na(+)/H(+) exchange regulatory cofactor NHE-RF3; Na(+)/H(+) exchanger regulatory factor 3; Na/Pi cotransporter C-terminal-associated protein 1; Na/Pi cotransporter C-terminal-associated protein; NaPi Cap1; NaPi-Cap1; NaPiCap1; NHERF 3; NHERF-3; NHERF3; NHRF3_HUMAN; OTTHUMP00000015572 ; PDZ domain containing 1; PDZ domain containing protein 1; PDZ domain-containing protein 1; PDZD1; PDZK1; Sodium hydrogen exchanger regulatory factor 3; Sodium-hydrogen exchanger regulatory factor 3
Buffer Before Lyophilization
Tris/PBS-based buffer, 6%
Trehalose.
Datasheet
Please contact us to get it.
Expression Region
1-519
Protein Length
full length protein
Purity
>85% (SDS-PAGE)
Species
Homo sapiens (Human)
Target Names
Target Protein Sequence
MTSTFNPREC KLSKQEGQNY GFFLRIEKDT EGHLVRVVEK CSPAEKAGLQ DGDRVLRING
VFVDKEEHMQ VVDLVRKSGN SVTLLVLDGD SYEKAVKTRV DLKELGQSQK EQGLSDNILS
PVMNGGVQTW TQPRLCYLVK EGGSYGFSLK TVQGKKGVYM TDITPQGVAM RAGVLADDHL
IEVNGENVED ASHEEVVEKV KKSGSRVMFL LVDKETDKRH VEQKIQFKRE TASLKLLPHQ
PRIVEMKKGS NGYGFYLRAG SEQKGQIIKD IDSGSPAEEA GLKNNDLVVA VNGESVETLD
HDSVVEMIRK GGDQTSLLVV DKETDNMYRL AHFSPFLYYQ SQELPNGSVK EAPAPTPTSL
EVSSPPDTTE EVDHKPKLCR LAKGENGYGF HLNAIRGLPG SFIKEVQKGG PADLAGLEDE
DVIIEVNGVN VLDEPYEKVV DRIQSSGKNV TLLVCGKKAY DYFQAKKIPI VSSLADPLDT
PPDSKEGIVV ESNHDSHMAK ERAHSTASHS SSNSEDTEM
Uniprot No.
Target Background
Function
PDZK1, a scaffold protein, connects plasma membrane proteins and regulatory components, influencing their surface expression in the apical domains of epithelial cells. It plays a crucial role in regulating diverse processes related to ion transport and second messenger cascades. In complex with SLC9A3R1, it may cluster functionally interdependent proteins, modulating the trafficking and activity of associated membrane proteins. PDZK1 might be involved in cellular mechanisms related to multidrug resistance through its interaction with ABCC2 and PDZK1IP1. It may enhance CFTR chloride channel activity. PDZK1 is essential for normal cell surface expression of SCARB1, contributing to the maintenance of normal plasma cholesterol levels through its effects on SCARB1. It plays a role in the correct localization and function of the chloride-anion exchanger SLC26A6 at the plasma membrane in the brush border of the proximal tubule in the kidney. PDZK1 might be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport, consequently playing a significant role in tubule function.
Gene References Into Functions
- PDZK1 directly interacts with OATP2B1, leading to a change in the amount of transporter in the membrane, resulting in enhanced transport function. PMID: 29752999
- Research indicates a negative correlation between PDZK1 expression and SHP-1 activation, along with poor clinical outcomes in clear cell renal cell carcinoma (ccRCC). PDZK1 has been identified as a novel tumor suppressor in ccRCC by inhibiting SHP-1 activity. PMID: 28692056
- HNF1alpha, previously recognized as a modulator of various transporters in the renal transportosome, also plays a key role in PDZK1 transcription. PMID: 28724612
- A single nucleotide polymorphism (SNP) in PDZK1, rs12129861, was found to be significantly associated with gout susceptibility (meta-analysis). PMID: 27720648
- PDZK1 has been identified as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Low levels of PDZK1 might predict poor clinical outcomes in patients with ccRCC. PMID: 27993630
- Loss of PDZK1 expression due to inflammation might contribute to the observed NHE3 dysfunction in the inflamed intestine. PMID: 25271043
- PARP regulates estradiol-mediated cell growth by controlling the ER/IGF-1R/PDZK1 axis. PMID: 26183824
- The PDZK1 adaptor protein gene, associated with urate transporters, is not linked to gout. PMID: 25362723
- PDZK1 negatively regulates 5-HT2AR endocytosis and has no effect on 5-HT2AR-mediated ERK1/2 phosphorylation. PMID: 25562428
- A study has described the structure of D-AKAP2 in complex with two interacting partners, revealing the precise mechanism by which a disordered segment forms an alpha-helix to PKA and a beta-strand to PDZK1. PMID: 25348485
- PDZK1 and NHERF1 regulate the transport function of OATP1A2 by modulating protein internalization via a clathrin-dependent pathway and enhancing protein stability. PMID: 24728453
- A correlation between PDZK1, Cdc37, Akt, and breast cancer malignancy suggests that PDZK1 plays a role in cell growth through Akt stabilization by increasing and interacting with Cdc37. PMID: 24869908
- IRF3 activation by innate antiviral signaling represses TGF-beta-induced growth inhibition, gene regulation, and epithelial-mesenchymal transition, as well as the generation of Treg effector lymphocytes from naive CD4(+) lymphocytes. PMID: 25526531
- NHERF3 is a key regulator of organic transport in the kidney, particularly MRP4-mediated clearance of drug molecules. PMID: 24436471
- Research suggests a direct relationship between ER-alpha and PDZK1, and identifies a novel oncogenic activity for PDZK1 in breast cancer. PMID: 23821363
- Antibody screening identified three candidate prognostic markers in breast cancer: Anillin (ANLN), PDZ-Binding Kinase (PBK), and PDZ-Domain Containing 1 (PDZK1). PMID: 23547718
- Upregulation of PDZK1 could play a significant role in the development of melasma in association with estrogen through NHE, CFTR, and SLC26A3. PMID: 22696060
- PDZ domain-containing 1 (PDZK1) protein regulates phospholipase C-beta3 (PLC-beta3)-specific activation of somatostatin by forming a ternary complex with PLC-beta3 and somatostatin receptors. PMID: 22528496
- The human prostacyclin receptor interacts with the PDZ adapter protein PDZK1. This interaction plays a crucial role in endothelial cell migration and angiogenesis. PMID: 21653824
- While PDZK1 binding is essential for optimal cell surface expression of oatp1a1, phosphorylation provides a mechanism for rapid regulation of the distribution of oatp1a1 between the cell surface and intracellular vesicular pools. PMID: 21183661
- The SR-BI partner PDZK1 facilitates hepatitis C virus entry. PMID: 20949066
- Data suggests that PDZK1/EBP50/ezrin forms a regulated ternary complex in vitro and in vivo. PMID: 20237154
- Overexpression of PDZK1 is associated with a drug-resistance phenotype in multiple myeloma. PMID: 15215163
- PDZK1 plays a role in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules. PMID: 15304510
- Research has investigated the ability of Bcr to interact with other epithelial PDZ proteins, identifying specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3. PMID: 15494376
- Co-transfection of OCTN2 with PDZK1, an intestinal and kidney-enriched PDZ protein, stimulated the uptake of its endogenous substrate carnitine by OCTN2. PMID: 15523054
- Oligomerization of Oatp1a1 with PDZK1 is crucial for its proper subcellular localization and function. PMID: 15994332
- Intracellular sorting of the somatostatin receptor subtype 5 is regulated by interactions with PDZ domain proteins PIST/GOPC and PDZK1. PMID: 16012170
- The interaction of PEPT2 and PDZK1 plays a vital physiological role in both oligopeptide handling and peptide-like drug transport in the human kidney. PMID: 16738539
- The interaction of PDZ proteins with hOAT4 might be cell-specific. In the placenta, a distinct set of interacting proteins, different from PDZK1 and NHERF1, might be necessary to modulate hOAT4 activity. PMID: 17602283
- Pdzk1 plays a specific role in stabilizing Muc17 at the apical membrane of small intestinal enterocytes. PMID: 17990980
- A mouse model has been developed to study human reverse cholesterol transport by expressing CLA-1, human PDZK1, and human apoA-I genes. PMID: 18403724
- Endogenous PPARalpha regulates PDZK1 expression. PMID: 18955051
- While forskolin increases OCTN2 protein expression, the increase in uptake capacity might be offset by a decrease in the expression of PDZK1, NHERF1, or NHERF2. PMID: 19091402
- The tail of PDZK1 interacts with the PDZ domains of EBP50. This interaction is negatively regulated by the intramolecular association of the tail of PDZK1 with its first PDZ domain. PMID: 19173579
- Research suggests that genetic variations in PDZK1 (PDZK1_i33968C > T) might be associated with an elevated risk of metabolic syndrome. PMID: 19321583
- In HEK cells, which express low levels of PDZK1, additional transfection of PDZK1 was required for UTP to inhibit DRA. PMID: 19447883
- NHERF3 colocalizes and directly binds NHE3 at the plasma membrane under basal conditions. PMID: 19535329
Database Links
Protein Families
NHER family
Subcellular Location
Membrane; Peripheral membrane protein. Cell membrane.
Tissue Specificity
Expression is limited to epithelial cells. Expressed in the kidney (brush border of proximal tubule), pancreas, liver, and small intestine. Expressed at a lower level in the adrenal cortex, testis and stomach. Overexpressed in breast, renal and lung carci
Q&A
Basic Research Questions
What experimental approaches confirm direct NHERF3-NHE3 interactions in recombinant systems?
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Methodological answer: Use in vitro overlay assays with NHE3 C-terminal fragments (aa 475–832) to map binding regions. For example:
How do PDZ domains of NHERF3 regulate NHE3 activity?
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Key findings:
Advanced Research Questions
How to resolve contradictions in NHERF dimerization mechanisms for NHE3 regulation?
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Data conflict: NHERF2/NHERF3 heterodimerization is critical for carbachol inhibition , while NHERF1 homodimerization involves PDZ2/CT interactions .
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Resolution strategy:
What methodologies quantify Ca²⁺-dependent NHERF3-NHE3 dissociation kinetics?
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Approach:
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Time-lapse FRET: Measure energy transfer between Cy3-NHE3 and Cy5-NHERF3 at 0.5-μm plasma membrane sections under basal vs. Ca²⁺-elevated conditions .
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Key result: FRET efficiency drops by 50% within 15 min post-Ca²⁺ elevation .
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Validation: Parallel assays with NHERF1/2 to rule out compensatory interactions .
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How does PDZK1 scaffold GPCR-PLC-β3 signaling in recombinant models?
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Mechanistic insight:
Methodological Best Practices
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Protein interaction mapping: Prioritize truncation mutants (e.g., F1-F4 NHE3 fragments ) over yeast two-hybrid for direct binding validation.
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Dynamic studies: Combine FRET with Ca²⁺ chelators (BAPTA-AM) to isolate NHERF3-specific effects .
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Recombinant system selection: Use PS120 fibroblasts for reduced endogenous NHERF interference vs. Caco-2 for polarized epithelial contexts .
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