3u23

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Template:STRUCTURE 3u23

Contents

Atomic resolution crystal structure of the 2nd SH3 domain from human CD2AP (CMS) in complex with a proline-rich peptide from human RIN3

Disease

[CD2AP_HUMAN] Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:607832]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.[1]

Function

[CD2AP_HUMAN] Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.[2] [RIN3_HUMAN] Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function.[3][4]

About this Structure

3u23 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003 May 23;300(5623):1298-300. PMID:12764198 doi:10.1126/science.1081068
  2. Monzo P, Gauthier NC, Keslair F, Loubat A, Field CM, Le Marchand-Brustel Y, Cormont M. Clues to CD2-associated protein involvement in cytokinesis. Mol Biol Cell. 2005 Jun;16(6):2891-902. Epub 2005 Mar 30. PMID:15800069 doi:E04-09-0773
  3. Kajiho H, Saito K, Tsujita K, Kontani K, Araki Y, Kurosu H, Katada T. RIN3: a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway. J Cell Sci. 2003 Oct 15;116(Pt 20):4159-68. PMID:12972505 doi:http://dx.doi.org/10.1242/jcs.00718
  4. Kajiho H, Sakurai K, Minoda T, Yoshikawa M, Nakagawa S, Fukushima S, Kontani K, Katada T. Characterization of RIN3 as a guanine nucleotide exchange factor for the Rab5 subfamily GTPase Rab31. J Biol Chem. 2011 Jul 8;286(27):24364-73. doi: 10.1074/jbc.M110.172445. Epub 2011, May 17. PMID:21586568 doi:10.1074/jbc.M110.172445

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