Nephrin family interactions (Homo sapiens)

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1-826-2817-2122, 257, 29-3111, 13-1522-2415, 162, 3, 9-12cytosolNephrin dimerNEPH1:p-Nephrin:Fyn:NCKPI3KNEPH1:p-Nephrin:FynPI3K:CD2AP:p-Nephrin:Fyn:NEPH1N-WASPPodocin:p-Nephrin:Fyn:NEPH1CD2APADPCD2AP:p-Nephrin:Fyn:NEPH1Nephrin dimer:NEPH2/NEPH3Podocin oligomerNephrinNEPH1:p-Nephrin:Fyn:NCK:N-WASPCASKNEPH1NEPH2/NEPH3ATPadherens junction-associated proteinsNCKNephrin dimer:NEPH1Nephrin dimer:CASKFYNNephrin dimer:IQGAP1Nephrin dimer:adherins junction-associated proteinsIQGAP1


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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Bibliography

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  2. Garg P, Verma R, Nihalani D, Johnstone DB, Holzman LB.; ''Neph1 cooperates with nephrin to transduce a signal that induces actin polymerization.''; PubMed Europe PMC Scholia
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  13. Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ.; ''Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway.''; PubMed Europe PMC Scholia
  14. Verma R, Kovari I, Soofi A, Nihalani D, Patrie K, Holzman LB.; ''Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization.''; PubMed Europe PMC Scholia
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  17. Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, Egger L, Lecha RL, Borner C, Pavenstädt H, Shaw AS, Walz G, Benzing T.; ''Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
114888view16:40, 25 January 2021ReactomeTeamReactome version 75
113334view11:40, 2 November 2020ReactomeTeamReactome version 74
112545view15:51, 9 October 2020ReactomeTeamReactome version 73
101459view11:32, 1 November 2018ReactomeTeamreactome version 66
100997view21:11, 31 October 2018ReactomeTeamreactome version 65
100533view19:45, 31 October 2018ReactomeTeamreactome version 64
100080view16:30, 31 October 2018ReactomeTeamreactome version 63
99631view15:01, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99237view12:44, 31 October 2018ReactomeTeamreactome version 62
94496view09:02, 14 September 2017Mkutmonreactome version 61
88033view13:34, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86623view09:22, 11 July 2016ReactomeTeamreactome version 56
83128view10:03, 18 November 2015ReactomeTeamVersion54
81468view13:00, 21 August 2015ReactomeTeamVersion53
76942view08:21, 17 July 2014ReactomeTeamFixed remaining interactions
76647view12:01, 16 July 2014ReactomeTeamFixed remaining interactions
75977view10:03, 11 June 2014ReactomeTeamRe-fixing comment source
75680view11:00, 10 June 2014ReactomeTeamReactome 48 Update
75035view13:54, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74679view08:44, 30 April 2014ReactomeTeamReactome46
42085view21:55, 4 March 2011MaintBotAutomatic update
39893view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
CASK ProteinO14936 (UniProt)
CD2AP ProteinQ9Y5K6 (UniProt)
CD2AP:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24742 (Reactome)
FYN ProteinP06241 (UniProt)
IQGAP1 ProteinP46940 (UniProt)
N-WASP ProteinO00401 (UniProt)
NCK ProteinREACT_17190 (Reactome)
NEPH1 ProteinQ96J84 (UniProt)
NEPH1:p-Nephrin:

Fyn

ComplexREACT_24538 (Reactome)
NEPH1:p-Nephrin:

Fyn:NCK

ComplexREACT_24581 (Reactome)
NEPH1:p-Nephrin:

Fyn:NCK:N-WASP

ComplexREACT_24683 (Reactome)
NEPH2/NEPH3 ProteinREACT_24799 (Reactome)
Nephrin ProteinO60500-1 (UniProt)
Nephrin dimer ComplexREACT_24735 (Reactome)
Nephrin dimer:

IQGAP1

ComplexREACT_24686 (Reactome)
Nephrin dimer:

NEPH1

ComplexREACT_24342 (Reactome)
Nephrin dimer:

NEPH2/NEPH3

ComplexREACT_24383 (Reactome)
Nephrin dimer:

adherins junction- associated proteins

ComplexREACT_24676 (Reactome)
Nephrin dimer:CASK ComplexREACT_24544 (Reactome)
PI3K ComplexREACT_4240 (Reactome)
PI3K:CD2AP:p-

Nephrin:Fyn:NEPH1

ComplexREACT_24519 (Reactome)
Podocin oligomer UnknownREACT_24198 (Reactome)
Podocin:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24571 (Reactome)
adherens junction-

associated proteins

ProteinREACT_24771 (Reactome)

Annotated Interactions

No annotated interactions

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