NHERF4 / TRP channels
Name: Na(+)/H(+) exchange regulatory cofactor NHE-RF4
(NHERF4)
Official Symbol: PDZD3
provided by HGNC
Function:
Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation. Stimulates SLC9A3 activity in the presence of elevated calcium ions.
Source: Reorganizing the protein space at the Universal Protein Resource (UniProt)
Nucleic Acids Res. 40: D71-D75 (2012).
Species |
External DB
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Entrez Gene | UniprotKB | DIP | IntAct | MINT | BioGRID | STRING | IUPHAR-DB | KEGG | OMIM | |
Human
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79849![]() |
Q86UT5![]() |
DIP-41141N![]() |
MINT-1773252![]() |
122940![]() |
Q86UT5![]() |
hsa:79849![]() |
607146![]() |
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Mouse
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170761![]() |
Q99MJ6![]() |
DIP-41892N![]() |
MINT-152467![]() |
228423![]() |
Q99MJ6![]() |
mmu:170761![]() |
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Rat
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500986![]() |
D4A7C5![]() |
272293![]() |
rno:500986![]() |
Biological Process:
- GO:0019934
: cGMP-mediated signaling
- GO:0006811
: ion transport
- GO:0030827
: negative regulation of cGMP biosynthetic process
- GO:0007168
: receptor guanylyl cyclase signaling pathway
- GO:0009636
: response to toxin
- GO:0006833
: water transport
Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/
World Wide Web URL: http://www.geneontology.org/
Disease:
No information in OMIM
Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine,
Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/
World Wide Web URL: http://omim.org/
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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPV4 |
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NHERF4 | Inference | Prediction | 16565876 | |||||
TRPV5 |
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NHERF4 | Yeast two-hybrid | Mouse | C-terminus | Mouse | Kidney | cDNA library | 16565876 | |
TRPV6 |
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NHERF4 | Yeast two-hybrid | Mouse | 575-727 | Mouse | Kidney | cDNA library | 17645868 | |
TRPV6 |
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NHERF4 | Yeast two-hybrid | Mouse | C-terminus | Mouse | Kidney | cDNA library | 16565876 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Validation: In vitro validation
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Assay with recombinant proteins | Reference | |||||||||
TRP channel construct | Interactor construct | |||||||||
TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
TRPV4 |
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NHERF4 | Fusion protein-pull down assay | Mouse | C-terminus | E. coli | Mouse | Full-length | In vitro translation | 16565876 |
TRPV5 |
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NHERF4 | Fusion protein-pull down assay | Mouse | C-terminus | E. coli | Mouse | Full-length | In vitro translation | 16565876 |
TRPV6 |
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NHERF4 | Fusion protein-pull down assay | Mouse | 575-727 | E. coli | Mouse | Full-length | In vitro translation | 17645868 |
TRPV6 |
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NHERF4 | Fusion protein-pull down assay | Mouse | C-terminus | E. coli | Mouse | Full-length | In vitro translation | 16565876 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vivo validation
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPV5 |
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NHERF4 | Co-immunofluorescence staining | Xenopus oocyte | Mouse | Full-length | Mouse | Full-length | 16565876 | |
TRPV5 |
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NHERF4 | Co-immunofluorescence staining | Mouse kidney section | 16565876 | |||||
TRPV5 |
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NHERF4 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Mouse | Full-length | 16565876 | |
TRPV6 |
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NHERF4 | Co-immunoprecipitation | HEK293 | Mouse | Full-length | Mouse | Full-length | 16565876 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Characterization
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Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPV5 |
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NHERF4 | Fusion protein-pull down assay | Mouse | 579-617 | Mouse | Not determined | 16565876 | ||
TRPV6 |
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NHERF4 | Fusion protein-pull down assay | Mouse | 724-727 | Mouse | Not determined | 17645868 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Functional consequence
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPV6 |
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NHERF4 | Patch clamp | Activation | 17645868 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
