Nephrin interactions (Homo sapiens)

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Description

Nephrin is a member of the Super-IgG-Molecule family and is most prominently expressed in kidney podocytes. It is a major if not the most important structural component of the slit diaphragm, a modified adherens junction in between these cells. Nephrin is composed of an extracellular domain with eight distal IgG like domains and one proximal fibronectin type III domain, a transmembrane domain and a short intracellular domain. Nephrin molecules show both homophilic and heterophilic interactions. Among heterophilic interaction partners slit diaphragm proteins such as NEPH1, NEPH2 and NEPH3 were shown to stabilize the slit diaphragm structure. Intracellularly Podocin, CD2 associated protein (CD2AP) and adherins junction associated proteins like IQGAP, MAGI, CASK and spectrins were all shown to interact with nephrin. Hence nephrin seems to play a major role in organizing the molecular structure of the slit diaphragm itself and via its binding partners links it to the actin cytoskeleton. Nephrin does not only fulfill static properties within the slit diaphragm but by tyrosine phosphorylation of its cytoplasmic tail by the Src kinase Fyn it initiates the PI3K AKT signaling cascade which seems to promote antiapoptotic signals.

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CompareRevisionActionTimeUserComment
42085view21:55, 4 March 2011MaintBotAutomatic update
39893view05:55, 21 January 2011MaintBotNew pathway

External references

View all 26...

Name Type Database reference
Podocin:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24571 (Reactome)
Nephrin dimer:

IQGAP1

ComplexREACT_24686 (Reactome)
Nephrin dimer ComplexREACT_24735 (Reactome)
PI3K:CD2AP:p-

Nephrin:Fyn:NEPH1

ComplexREACT_24519 (Reactome)
NEPH1 ProteinQ96J84 (UniProt)
Nephrin ProteinO60500-1 (UniProt)
Nephrin dimer:

NEPH1

ComplexREACT_24342 (Reactome)
CD2AP:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24742 (Reactome)
Nephrin dimer:

NEPH2/NEPH3

ComplexREACT_24383 (Reactome)
Nephrin dimer:CASK ComplexREACT_24544 (Reactome)
FYN ProteinP06241 (UniProt)
Nephrin dimer:

adherins junction- associated proteins

ComplexREACT_24676 (Reactome)
ATP Metabolite15422 (ChEBI)
Podocin oligomer UnknownREACT_24198 (Reactome)
NEPH1:p-Nephrin:

Fyn

ComplexREACT_24538 (Reactome)
CD2AP ProteinQ9Y5K6 (UniProt)
ADP Metabolite16761 (ChEBI)
PI3K ComplexREACT_4240 (Reactome)
NCK ProteinREACT_17190 (Reactome)
CASK ProteinO14936 (UniProt)
NEPH1:p-Nephrin:

Fyn:NCK

ComplexREACT_24581 (Reactome)
IQGAP1 ProteinP46940 (UniProt)
N-WASP ProteinO00401 (UniProt)
adherens junction-

associated proteins

ProteinREACT_24771 (Reactome)
NEPH1:p-Nephrin:

Fyn:NCK:N-WASP

ComplexREACT_24683 (Reactome)
NEPH2/NEPH3 ProteinREACT_24799 (Reactome)
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