Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is a transmembrane protein that is a structural component of the slit diaphragm.[5] They are present on the tips of the podocytes as an intricate mesh and convey strong negative charges which repel protein from crossing into the Bowman's space.
A defect in the gene for nephrin, NPHS1, is associated with congenital nephrotic syndrome of the Finnish type and causes massive amounts of protein to be leaked into the urine, or proteinuria. Nephrin is also required for cardiovascular development.[6]
^ abcGRCh38: Ensembl release 89: ENSG00000161270 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000006649 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Entrez Gene: NPHS1 nephrosis 1, congenital, Finnish type (nephrin)".
^Wagner N, Morrison H, Pagnotta S, Michiels JF, Schwab Y, Tryggvason K, Schedl A, Wagner KD (2011-03-29). "The podocyte protein nephrin is required for cardiac vessel formation". Human Molecular Genetics. 20 (11): 2182–94. doi:10.1093/hmg/ddr106. PMID 21402589.
^ abcdLehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG (Sep 2004). "Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin". Am. J. Pathol. 165 (3): 923–36. doi:10.1016/S0002-9440(10)63354-8. PMC1618613. PMID 15331416.
^Lahdenperä J, Kilpeläinen P, Liu XL, Pikkarainen T, Reponen P, Ruotsalainen V, Tryggvason K (Aug 2003). "Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases". Kidney Int. 64 (2): 404–13. doi:10.1046/j.1523-1755.2003.00097.x. PMID 12846735.
^Verma R, Wharram B, Kovari I, Kunkel R, Nihalani D, Wary KK, Wiggins RC, Killen P, Holzman LB (Jun 2003). "Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin". J. Biol. Chem. 278 (23): 20716–23. doi:10.1074/jbc.M301689200. PMID 12668668.
^Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS (Jul 2003). "Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability". J. Clin. Invest. 112 (2): 209–21. doi:10.1172/JCI18242. PMC164293. PMID 12865409.
^Gerke P, Huber TB, Sellin L, Benzing T, Walz G (Apr 2003). "Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1". J. Am. Soc. Nephrol. 14 (4): 918–26. doi:10.1097/01.ASN.0000057853.05686.89. PMID 12660326.
^Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P (Dec 2001). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". J. Clin. Invest. 108 (11): 1621–9. doi:10.1172/JCI12849. PMC200981. PMID 11733557.
Further reading
Tryggvason K (2002). "Nephrin: role in normal kidney and in disease". Adv. Nephrol. Necker Hosp. 31: 221–34. PMID 11692461.
Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998). "Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome". Mol. Cell. 1 (4): 575–82. doi:10.1016/S1097-2765(00)80057-X. PMID 9660941.
Lenkkeri U, Männikkö M, McCready P, Lamerdin J, Gribouval O, Niaudet PM, Antignac CK, Kashtan CE, Homberg C, Olsen A, Kestilä M, Tryggvason K (1999). "Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations". Am. J. Hum. Genet. 64 (1): 51–61. doi:10.1086/302182. PMC1377702. PMID 9915943.
Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K (1999). "Nephrin is specifically located at the slit diaphragm of glomerular podocytes". Proc. Natl. Acad. Sci. U.S.A. 96 (14): 7962–7. Bibcode:1999PNAS...96.7962R. doi:10.1073/pnas.96.14.7962. PMC22170. PMID 10393930.
Bolk S, Puffenberger EG, Hudson J, Morton DH, Chakravarti A (2000). "Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome, Finnish type, in the old order Mennonites". Am. J. Hum. Genet. 65 (6): 1785–90. doi:10.1086/302687. PMC1288392. PMID 10577936.
Aya K, Tanaka H, Seino Y (2000). "Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type". Kidney Int. 57 (2): 401–4. doi:10.1046/j.1523-1755.2000.00859.x. PMID 10652016.
Li C, Ruotsalainen V, Tryggvason K, Shaw AS, Miner JH (2000). "CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere". Am. J. Physiol. Renal Physiol. 279 (4): F785–92. doi:10.1152/ajprenal.2000.279.4.F785. PMID 10997929. S2CID 37166239.
Huber TB, Kottgen M, Schilling B, Walz G, Benzing T (2001). "Interaction with podocin facilitates nephrin signaling". J. Biol. Chem. 276 (45): 41543–6. doi:10.1074/jbc.C100452200. PMID 11562357.
Palmén T, Ahola H, Palgi J, Aaltonen P, Luimula P, Wang S, Jaakkola I, Knip M, Otonkoski T, Holthöfer H (2002). "Nephrin is expressed in the pancreatic beta cells". Diabetologia. 44 (10): 1274–80. doi:10.1007/s001250100641. PMID 11692176.
Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P (2002). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". J. Clin. Invest. 108 (11): 1621–9. doi:10.1172/JCI12849. PMC200981. PMID 11733557.
Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P (2002). "Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration". Hum. Mol. Genet. 11 (4): 379–88. doi:10.1093/hmg/11.4.379. PMID 11854170.
Yan K, Khoshnoodi J, Ruotsalainen V, Tryggvason K (2002). "N-linked glycosylation is critical for the plasma membrane localization of nephrin". J. Am. Soc. Nephrol. 13 (5): 1385–9. doi:10.1097/01.ASN.0000013297.11876.5B. PMID 11961028.
Shimizu J, Tanaka H, Aya K, Ito S, Sado Y, Seino Y (2002). "A missense mutation in the nephrin gene impairs membrane targeting". Am. J. Kidney Dis. 40 (4): 697–703. doi:10.1053/ajkd.2002.35676. PMID 12324903.
Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, Mathieson PW (2002). "Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation". Am. J. Pathol. 161 (4): 1459–66. doi:10.1016/S0002-9440(10)64421-5. PMC1867300. PMID 12368218.
Kim BK, Hong HK, Kim JH, Lee HS (2002). "Differential expression of nephrin in acquired human proteinuric diseases". Am. J. Kidney Dis. 40 (5): 964–73. doi:10.1053/ajkd.2002.36328. PMID 12407641.
Langham RG, Kelly DJ, Cox AJ, Thomson NM, Holthöfer H, Zaoui P, Pinel N, Cordonnier DJ, Gilbert RE (2003). "Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition". Diabetologia. 45 (11): 1572–6. doi:10.1007/s00125-002-0946-y. PMID 12436341.
Gigante M, Monno F, Roberto R, Laforgia N, Assael MB, Livolti S, Caringella A, La Manna A, Masella L, Iolascon A (2003). "Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach". J. Nephrol. 15 (6): 696–702. PMID 12495287.
Pettersson-Fernholm K, Forsblom C, Perola M, Groop PH (2003). "Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients". Kidney Int. 63 (4): 1205–10. doi:10.1046/j.1523-1755.2003.00855.x. PMID 12631336.
Kapodistria K, Tsilibary EP, Politis P, Moustardas P, Charonis A, Kitsiou P (2015). "Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling". Mol. Cell. Endocrinol. 400: 112–28. doi:10.1016/j.mce.2014.11.003. PMID 25448064.
nephrin, protein, necessary, proper, functioning, renal, filtration, barrier, renal, filtration, barrier, consists, fenestrated, endothelial, cells, glomerular, basement, membrane, podocytes, epithelial, cells, transmembrane, protein, that, structural, compone. Nephrin is a protein necessary for the proper functioning of the renal filtration barrier The renal filtration barrier consists of fenestrated endothelial cells the glomerular basement membrane and the podocytes of epithelial cells Nephrin is a transmembrane protein that is a structural component of the slit diaphragm 5 They are present on the tips of the podocytes as an intricate mesh and convey strong negative charges which repel protein from crossing into the Bowman s space NPHS1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4ZRTIdentifiersAliasesNPHS1 CNF NPHN nephrin NPHS1 nephrin nephrin NPHS1 adhesion molecule nephrinExternal IDsOMIM 602716 MGI 1859637 HomoloGene 20974 GeneCards NPHS1Gene location Human Chr Chromosome 19 human 1 Band19q13 12Start35 825 372 bp 1 End35 869 287 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 B1Start30 157 740 bp 2 End30 186 648 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inbody of pancreasvena cavaglomerulusmetanephric glomeruluskidneynipplebody of tonguespermrenal medullacardiaTop expressed inglomerulusmorulablastocystpancreasyolk sackidneysuperior frontal gyrussubmandibular glandrhombic lipstomachMore reference expression dataBioGPSn aGene ontologyMolecular functionmyosin binding protein bindingCellular componentintegral component of membrane cell projection membrane plasma membrane integral component of plasma membrane intracellular anatomical structure slit diaphragm extracellular exosome focal adhesionBiological processexcretion glomerular visceral epithelial cell development positive regulation of actin filament polymerization glomerular basement membrane development muscle organ development regulation of excretion MAPK cascade multicellular organism development JNK cascade cell adhesion myoblast fusion skeletal muscle tissue development protein localization to synapse axon guidance T cell costimulationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez486854631EnsemblENSG00000161270ENSMUSG00000006649UniProtO60500Q9QZS7RefSeq mRNA NM 004646NM 019459RefSeq protein NP 004637NP 062332Location UCSC Chr 19 35 83 35 87 MbChr 7 30 16 30 19 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseA defect in the gene for nephrin NPHS1 is associated with congenital nephrotic syndrome of the Finnish type and causes massive amounts of protein to be leaked into the urine or proteinuria Nephrin is also required for cardiovascular development 6 Contents 1 Interactions 2 See also 3 References 4 Further reading 5 External linksInteractions EditNephrin has been shown to interact with CASK 7 CD2AP 7 CDH3 7 and CTNND1 7 FYN 8 9 KIRREL 10 11 and NPHS2 12 See also EditPodocyteReferences Edit a b c GRCh38 Ensembl release 89 ENSG00000161270 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000006649 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene NPHS1 nephrosis 1 congenital Finnish type nephrin Wagner N Morrison H Pagnotta S Michiels JF Schwab Y Tryggvason K Schedl A Wagner KD 2011 03 29 The podocyte protein nephrin is required for cardiac vessel formation Human Molecular Genetics 20 11 2182 94 doi 10 1093 hmg ddr106 PMID 21402589 a b c d Lehtonen S Lehtonen E Kudlicka K Holthofer H Farquhar MG Sep 2004 Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin Darby canine kidney cells expressing nephrin Am J Pathol 165 3 923 36 doi 10 1016 S0002 9440 10 63354 8 PMC 1618613 PMID 15331416 Lahdenpera J Kilpelainen P Liu XL Pikkarainen T Reponen P Ruotsalainen V Tryggvason K Aug 2003 Clustering induced tyrosine phosphorylation of nephrin by Src family kinases Kidney Int 64 2 404 13 doi 10 1046 j 1523 1755 2003 00097 x PMID 12846735 Verma R Wharram B Kovari I Kunkel R Nihalani D Wary KK Wiggins RC Killen P Holzman LB Jun 2003 Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin J Biol Chem 278 23 20716 23 doi 10 1074 jbc M301689200 PMID 12668668 Liu G Kaw B Kurfis J Rahmanuddin S Kanwar YS Chugh SS Jul 2003 Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability J Clin Invest 112 2 209 21 doi 10 1172 JCI18242 PMC 164293 PMID 12865409 Gerke P Huber TB Sellin L Benzing T Walz G Apr 2003 Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1 J Am Soc Nephrol 14 4 918 26 doi 10 1097 01 ASN 0000057853 05686 89 PMID 12660326 Schwarz K Simons M Reiser J Saleem MA Faul C Kriz W Shaw AS Holzman LB Mundel P Dec 2001 Podocin a raft associated component of the glomerular slit diaphragm interacts with CD2AP and nephrin J Clin Invest 108 11 1621 9 doi 10 1172 JCI12849 PMC 200981 PMID 11733557 Further reading EditTryggvason K 2002 Nephrin role in normal kidney and in disease Adv Nephrol Necker Hosp 31 221 34 PMID 11692461 Kestila M Lenkkeri U Mannikko M Lamerdin J McCready P Putaala H Ruotsalainen V Morita T Nissinen M Herva R Kashtan CE Peltonen L Holmberg C Olsen A Tryggvason K 1998 Positionally cloned gene for a novel glomerular protein nephrin is mutated in congenital nephrotic syndrome Mol Cell 1 4 575 82 doi 10 1016 S1097 2765 00 80057 X PMID 9660941 Lenkkeri U Mannikko M McCready P Lamerdin J Gribouval O Niaudet PM Antignac CK Kashtan CE Homberg C Olsen A Kestila M Tryggvason K 1999 Structure of the gene for congenital nephrotic syndrome of the finnish type NPHS1 and characterization of mutations Am J Hum Genet 64 1 51 61 doi 10 1086 302182 PMC 1377702 PMID 9915943 Ruotsalainen V Ljungberg P Wartiovaara J Lenkkeri U Kestila M Jalanko H Holmberg C Tryggvason K 1999 Nephrin is specifically located at the slit diaphragm of glomerular podocytes Proc Natl Acad Sci U S A 96 14 7962 7 Bibcode 1999PNAS 96 7962R doi 10 1073 pnas 96 14 7962 PMC 22170 PMID 10393930 Bolk S Puffenberger EG Hudson J Morton DH Chakravarti A 2000 Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome Finnish type in the old order Mennonites Am J Hum Genet 65 6 1785 90 doi 10 1086 302687 PMC 1288392 PMID 10577936 Aya K Tanaka H Seino Y 2000 Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type Kidney Int 57 2 401 4 doi 10 1046 j 1523 1755 2000 00859 x PMID 10652016 Li C Ruotsalainen V Tryggvason K Shaw AS Miner JH 2000 CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere Am J Physiol Renal Physiol 279 4 F785 92 doi 10 1152 ajprenal 2000 279 4 F785 PMID 10997929 S2CID 37166239 Huber TB Kottgen M Schilling B Walz G Benzing T 2001 Interaction with podocin facilitates nephrin signaling J Biol Chem 276 45 41543 6 doi 10 1074 jbc C100452200 PMID 11562357 Palmen T Ahola H Palgi J Aaltonen P Luimula P Wang S Jaakkola I Knip M Otonkoski T Holthofer H 2002 Nephrin is expressed in the pancreatic beta cells Diabetologia 44 10 1274 80 doi 10 1007 s001250100641 PMID 11692176 Schwarz K Simons M Reiser J Saleem MA Faul C Kriz W Shaw AS Holzman LB Mundel P 2002 Podocin a raft associated component of the glomerular slit diaphragm interacts with CD2AP and nephrin J Clin Invest 108 11 1621 9 doi 10 1172 JCI12849 PMC 200981 PMID 11733557 Koziell A Grech V Hussain S Lee G Lenkkeri U Tryggvason K Scambler P 2002 Genotype phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter relationship in glomerular filtration Hum Mol Genet 11 4 379 88 doi 10 1093 hmg 11 4 379 PMID 11854170 Yan K Khoshnoodi J Ruotsalainen V Tryggvason K 2002 N linked glycosylation is critical for the plasma membrane localization of nephrin J Am Soc Nephrol 13 5 1385 9 doi 10 1097 01 ASN 0000013297 11876 5B PMID 11961028 Shimizu J Tanaka H Aya K Ito S Sado Y Seino Y 2002 A missense mutation in the nephrin gene impairs membrane targeting Am J Kidney Dis 40 4 697 703 doi 10 1053 ajkd 2002 35676 PMID 12324903 Saleem MA Ni L Witherden I Tryggvason K Ruotsalainen V Mundel P Mathieson PW 2002 Co localization of nephrin podocin and the actin cytoskeleton evidence for a role in podocyte foot process formation Am J Pathol 161 4 1459 66 doi 10 1016 S0002 9440 10 64421 5 PMC 1867300 PMID 12368218 Kim BK Hong HK Kim JH Lee HS 2002 Differential expression of nephrin in acquired human proteinuric diseases Am J Kidney Dis 40 5 964 73 doi 10 1053 ajkd 2002 36328 PMID 12407641 Langham RG Kelly DJ Cox AJ Thomson NM Holthofer H Zaoui P Pinel N Cordonnier DJ Gilbert RE 2003 Proteinuria and the expression of the podocyte slit diaphragm protein nephrin in diabetic nephropathy effects of angiotensin converting enzyme inhibition Diabetologia 45 11 1572 6 doi 10 1007 s00125 002 0946 y PMID 12436341 Gigante M Monno F Roberto R Laforgia N Assael MB Livolti S Caringella A La Manna A Masella L Iolascon A 2003 Congenital nephrotic syndrome of the Finnish type in Italy a molecular approach J Nephrol 15 6 696 702 PMID 12495287 Pettersson Fernholm K Forsblom C Perola M Groop PH 2003 Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients Kidney Int 63 4 1205 10 doi 10 1046 j 1523 1755 2003 00855 x PMID 12631336 Kapodistria K Tsilibary EP Politis P Moustardas P Charonis A Kitsiou P 2015 Nephrin a transmembrane protein is involved in pancreatic beta cell survival signaling Mol Cell Endocrinol 400 112 28 doi 10 1016 j mce 2014 11 003 PMID 25448064 External links Editnephrin at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Nephrin amp oldid 1152773482, wikipedia, wiki, book, books, library,
