Mammalian protein found in Homo sapiens
NPHS1 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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Identifiers |
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Aliases | NPHS1, CNF, NPHN, nephrin, NPHS1 nephrin, nephrin, NPHS1 adhesion molecule, nephrin |
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External IDs | OMIM: 602716; MGI: 1859637; HomoloGene: 20974; GeneCards: NPHS1; OMA:NPHS1 - orthologs |
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Gene location (Human) |
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![Chromosome 19 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/5/54/Ideogram_human_chromosome_19.svg/300px-Ideogram_human_chromosome_19.svg.png) | Chr. | Chromosome 19 (human)[1] |
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| Band | 19q13.12 | Start | 35,825,372 bp[1] |
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End | 35,869,287 bp[1] |
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Gene location (Mouse) |
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![Chromosome 7 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/e/e4/Ideogram_house_mouse_chromosome_7.svg/260px-Ideogram_house_mouse_chromosome_7.svg.png) | Chr. | Chromosome 7 (mouse)[2] |
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| Band | 7|7 B1 | Start | 30,157,740 bp[2] |
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End | 30,186,648 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - buccal mucosa cell
- body of pancreas
- vena cava
- tendon of biceps brachii
- Skeletal muscle tissue of rectus abdominis
- glomerulus
- metanephric glomerulus
- human kidney
- mucosa of pharynx
- nipple
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| Top expressed in | - glomerulus
- embryo
- embryo
- morula
- neural layer of retina
- gastrula
- blastocyst
- dentate gyrus of hippocampal formation granule cell
- right kidney
- pancreas
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - myosin binding
- protein binding
| Cellular component | - integral component of membrane
- cell projection
- membrane
- plasma membrane
- integral component of plasma membrane
- intracellular anatomical structure
- slit diaphragm
- extracellular exosome
- focal adhesion
| Biological process | - excretion
- 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 costimulation
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 19: 35.83 – 35.87 Mb | Chr 7: 30.16 – 30.19 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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] It is present on the tips of the podocytes as an intricate mesh connecting adjacent foot processes. Nephrin contributes to the strong size selectivity of the slit diaphragm,[6][7] however, the relative contribution of the slit diaphragm to exclusion of protein by the glomerulus is debated.[6][8] The extracellular interactions, both homophilic and heterophilic—between nephrin and NEPH1—are not completely understood.[6] In addition to eight immunoglobulin G–like motifs and a fibronectin type 3 repeat, nephrin has a single transmembrane domain and a short intracellular tail.[6][7] Tyrosine phosphorylation at different sites on the intracellular tail contribute to the regulation of slit diaphragm formation during development[7] and repair in pathology affecting podocytes.[6][7] Podocin may interact with nephrin to guide it onto lipid rafts in podocytes, requiring the integrity of an arginine residue of nephrin at position 1160.[7]
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.[9]
Interactions
Nephrin has been shown to interact with:
See also
References
- ^ 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)".
- ^ a b c d e Patrakka J, Tryggvason K (2007). "Nephrin – a unique structural and signaling protein of the kidney filter". Trends in Molecular Medicine. 13 (9): 396–403. doi:10.1016/j.molmed.2007.06.006. PMID 17766183.
- ^ a b c d e Martin CE, Jones N (2018). "Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond". Frontiers in Endocrinology. 9. doi:10.3389/fendo.2018.00302. PMC 5996060. PMID 29922234. Art. No. 302.
- ^ Menzel S, Moeller MJ (2011). "Role of the podocyte in proteinuria". Pediatric Nephrology. 26: 1775–1780. doi:10.1007/s00467-010-1725-5. PMC 3163769. PMID 21184239.
- ^ 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, 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. PMC 1618613. 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. 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
- 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. PMC 1377702. 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. 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.
- 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. 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, 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.
- 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