Podocin

NPHS2
Identifiers
Aliases	NPHS2 , PDCN, SRN1, NPHS2 podocin, podocin, NPHS2 stomatin family member, podocin
External IDs	OMIM: 604766; MGI: 2157018; GeneCards: NPHS2
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q25.2 Start 179,550,539 bp [1] End 179,575,952 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1|1 G3 Start 156,138,297 bp [2] End 156,155,605 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in glomerulus metanephric glomerulus human kidney testicle kidney tubule sperm gonad renal medulla right testis left testis Top expressed in glomerulus Bowman's capsule right kidney parietal layer of glomerular capsule human kidney morula thymus embryo embryo medullary collecting duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component extracellular exosome slit diaphragm membrane raft plasma membrane membrane intrinsic component of the cytoplasmic side of the plasma membrane cell-cell junction endoplasmic reticulum integral component of plasma membrane protein-containing complex Biological process actin cytoskeleton reorganization metanephric glomerular visceral epithelial cell development excretion Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 7827 170484 Ensembl ENSG00000116218 ENSMUSG00000026602 UniProt Q9NP85 Q91X05 RefSeq (mRNA) NM_001297575 NM_014625 NM_130456 RefSeq (protein) NP_001284504 NP_055440 NP_569723 Location (UCSC) Chr 1: 179.55 – 179.58 Mb Chr 1: 156.14 – 156.16 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Podocin is a protein that in humans is encoded by the gene NPHS2 (from "nephrosis 2"). ^{[5] [6] [7]} It is a component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. ^[8] Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). ^[9] Symptoms may develop in the first few months of life (congenital nephrotic syndrome) or later in childhood. ^[10]

Structure

Podocin is a membrane protein of the band-7-stomatin family, consisting of 383 amino acids. It has a transmembrane domain forming a hairpin structure, with two cytoplasmic ends at the N- and C-terminus, the latter of which interacts with the cytosolic tail of nephrin, with CD2AP serving as an adaptor. ^[11]

Function

Podocin is localized on the membranes of podocyte foot processes (pedicels) where it oligomerizes in lipid rafts together with nephrin to form the filtration slits. ^{[11] [12]}

Interactions

NPHS2 has been shown to interact with Nephrin ^[13] and CD2AP. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000116218 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026602 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Fuchshuber A, Jean G, Gribouval O, Gubler MC, Broyer M, Beckmann JS, Niaudet P, Antignac C (Mar 1996). "Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis". Hum Mol Genet. 4 (11): 2155–8. doi:10.1093/hmg/4.11.2155. PMID   8589695.
6. Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C (May 2000). "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome". Nat Genet. 24 (4): 349–54. doi:10.1038/74166. PMID   10742096. S2CID   20737871.
7. "Entrez Gene: NPHS2 Nephrosis 2, idiopathic, steroid-resistant (podocin)".
8. Jarad G, Miner JH (May 2009). "Update on the glomerular filtration barrier". Current Opinion in Nephrology and Hypertension. 18 (3): 226–32. doi:10.1097/mnh.0b013e3283296044. PMC   2895306 . PMID   19374010.
9. Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, Kitzis D, Dallman MJ, Bugeon L, Hubner N, Gubler MC, Antignac C, Esquivel EL (October 2009). "Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome". Journal of the American Society of Nephrology. 20 (10): 2181–9. doi:10.1681/ASN.2009040379. PMC   2754108 . PMID   19713307.
10. Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Emma F, Goldstein SL (2016). Pediatric Nephrology. Springer. ISBN   9783662435960. OCLC   1050008865.
11. Tabassum A, Rajeshwari T, Soni N, Raju DS, Yadav M, Nayarisseri A, Jahan P (March 2014). "Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach". Interdisciplinary Sciences: Computational Life Sciences . 6 (1): 32–9. doi:10.1007/s12539-014-0190-4. PMID   24464702. S2CID   17163784.
12. Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, Mathieson PW (October 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.
13. 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

• Caridi G, Perfumo F, Ghiggeri GM (2005). "NPHS2 (Podocin) mutations in nephrotic syndrome. Clinical spectrum and fine mechanisms". Pediatr. Res. 57 (5 Pt 2): 54R–61R. doi: 10.1203/01.PDR.0000160446.01907.B1 . PMID   15817495.
• "Correction to "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome"". Nature Genetics. 25 (1): 125. 2000. doi: 10.1038/75526 . PMID   10802674. S2CID   40951671.
• 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.
• Caridi G, Bertelli R, Carrea A, Di Duca M, Catarsi P, Artero M, Carraro M, Zennaro C, Candiano G, Musante L, Seri M, Ginevri F, Perfumo F, Ghiggeri GM (2002). "Prevalence, genetics, and clinical features of patients carrying podocin mutations in steroid-resistant nonfamilial focal segmental glomerulosclerosis". J. Am. Soc. Nephrol. 12 (12): 2742–6. doi: 10.1681/ASN.V12122742 . PMID   11729243.
• 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.
• Karle SM, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A (2002). "Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome". J. Am. Soc. Nephrol. 13 (2): 388–93. doi: 10.1681/ASN.V132388 . PMID   11805166.
• 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.
• Boute N, Roselli S, Gribouval O, Niaudet P, Gubler MC, Antignac C (2002). "[Characterization of the NPH2 gene, coding for the glomerular protein podocin, implicated in a familial form of cortico-resistant nephrotic syndrome transmitted as an autosomal recessive]". Néphrologie. 23 (1): 35–6. PMID   11908478.
• Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R, Zennaro C, Musante L, Candiano G, Perfumo F, Ghiggeri GM (2002). "Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome". J. Am. Soc. Nephrol. 13 (7): 1946–52. doi: 10.1097/01.ASN.0000016445.29513.AB . PMID   12089392.
• 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.
• Sellin L, Huber TB, Gerke P, Quack I, Pavenstädt H, Walz G (2003). "NEPH1 defines a novel family of podocin interacting proteins". FASEB J. 17 (1): 115–7. doi: 10.1096/fj.02-0242fje . PMID   12424224. S2CID   17732086.
• Tsukaguchi H, Sudhakar A, Le TC, Nguyen T, Yao J, Schwimmer JA, Schachter AD, Poch E, Abreu PF, Appel GB, Pereira AB, Kalluri R, Pollak MR (2003). "NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele". J. Clin. Invest. 110 (11): 1659–66. doi:10.1172/JCI16242. PMC   151634 . PMID   12464671.
• Komatsuda A, Wakui H, Maki N, Kigawa A, Goto H, Ohtani H, Hamai K, Oyama Y, Makoto H, Sawada K, Imai H (2003). "Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis". Renal Failure. 25 (1): 87–93. doi:10.1081/JDI-120017471. PMID   12617336. S2CID   22531807.
• Ohashi T, Uchida K, Uchida S, Sasaki S, Nihei H (2004). "Intracellular mislocalization of mutant podocin and correction by chemical chaperones". Histochem. Cell Biol. 119 (3): 257–64. doi:10.1007/s00418-003-0511-x. PMID   12649741. S2CID   24927819.
• Maruyama K, Iijima K, Ikeda M, Kitamura A, Tsukaguchi H, Yoshiya K, Hoshii S, Wada N, Uemura O, Satomura K, Honda M, Yoshikawa N (2004). "NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children". Pediatr. Nephrol. 18 (5): 412–6. doi:10.1007/s00467-003-1120-6. PMID   12687458. S2CID   2093444.
• Caridi G, Bertelli R, Di Duca M, Dagnino M, Emma F, Onetti Muda A, Scolari F, Miglietti N, Mazzucco G, Murer L, Carrea A, Massella L, Rizzoni G, Perfumo F, Ghiggeri GM (2003). "Broadening the spectrum of diseases related to podocin mutations". J. Am. Soc. Nephrol. 14 (5): 1278–86. doi: 10.1097/01.ASN.0000060578.79050.E0 . PMID   12707396.
• Guan N, Ding J, Zhang J, Yang J (2004). "Expression of nephrin, podocin, alpha-actinin, and WT1 in children with nephrotic syndrome". Pediatr. Nephrol. 18 (11): 1122–7. doi:10.1007/s00467-003-1240-z. PMID   12961083. S2CID   39927513.