CD2AP
CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.[1][2]
This gene encodes a scaffolding molecule that regulates the actin cytoskeleton. The protein directly interacts with filamentous actin and a variety of cell membrane proteins through multiple actin binding sites, SH3 domains, and a proline-rich region containing binding sites for SH3 domains. The cytoplasmic protein localizes to membrane ruffles, lipid rafts, and the leading edges of cells. It is implicated in dynamic actin remodeling and membrane trafficking that occurs during receptor endocytosis and cytokinesis. Haploinsufficiency of this gene is implicated in susceptibility to glomerular disease.[2]
See also
Interactions
CD2AP has been shown to interact with NPHS2,[3] Nephrin,[4] Cbl gene[5][6][7] and RAB4A.[7]
References
- ^ Kirsch KH, Georgescu MM, Ishimaru S, Hanafusa H (Jun 1999). "CMS: An adapter molecule involved in cytoskeletal rearrangements". Proc Natl Acad Sci USA 96 (11): 6211–6. doi:10.1073/pnas.96.11.6211. PMC 26861. PMID 10339567. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26861.
- ^ a b "Entrez Gene: CD2AP CD2-associated protein". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23607.
- ^ Schwarz, K; Simons M, Reiser J, Saleem M A, Faul C, Kriz W, Shaw A S, Holzman L B, Mundel P (Dec. 2001). "Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin". J. Clin. Invest. (United States) 108 (11): 1621–9. doi:10.1172/JCI12849. ISSN 0021-9738. PMC 200981. PMID 11733557. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=200981.
- ^ Lehtonen, Sanna; Lehtonen Eero, Kudlicka Krystyna, Holthöfer Harry, Farquhar Marilyn G (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. (United States) 165 (3): 923–36. doi:10.1016/S0002-9440(10)63354-8. ISSN 0002-9440. PMC 1618613. PMID 15331416. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1618613.
- ^ Haglund, Kaisa; Ivankovic-Dikic Inga, Shimokawa Noriaki, Kruh Gary D, Dikic Ivan (May. 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell. Sci. (England) 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. ISSN 0021-9533. PMID 15128873.
- ^ Kirsch, K H; Georgescu M M, Shishido T, Langdon W Y, Birge R B, Hanafusa H (Feb. 2001). "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction". J. Biol. Chem. (United States) 276 (7): 4957–63. doi:10.1074/jbc.M005784200. ISSN 0021-9258. PMID 11067845.
- ^ a b Cormont, Mireille; Metón Isidoro, Mari Muriel, Monzo Pascale, Keslair Frédérique, Gaskin Chantell, McGraw Timothy E, Le Marchand-Brustel Yannick (Feb. 2003). "CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl". Traffic (Denmark) 4 (2): 97–112. doi:10.1034/j.1600-0854.2003.40205.x. ISSN 1398-9219. PMID 12559036.
Further reading
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Dustin ML, Olszowy MW, Holdorf AD, et al. (1998). "A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts". Cell 94 (5): 667–77. doi:10.1016/S0092-8674(00)81608-6. PMID 9741631.
- Lehtonen S, Ora A, Olkkonen VM, et al. (2000). "In vivo interaction of the adapter protein CD2-associated protein with the type 2 polycystic kidney disease protein, polycystin-2". J. Biol. Chem. 275 (42): 32888–93. doi:10.1074/jbc.M006624200. PMID 10913159.
- Li C, Ruotsalainen V, Tryggvason K, et al. (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. PMID 10997929.
- Kirsch KH, Georgescu MM, Shishido T, et al. (2001). "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction". J. Biol. Chem. 276 (7): 4957–63. doi:10.1074/jbc.M005784200. PMID 11067845.
- Schwarz K, Simons M, Reiser J, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=200981.
- Scott MP, Zappacosta F, Kim EY, et al. (2002). "Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1". J. Biol. Chem. 277 (31): 28238–46. doi:10.1074/jbc.M202783200. PMID 12029088.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Badour K, Zhang J, Shi F, et al. (2003). "The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse". Immunity 18 (1): 141–54. doi:10.1016/S1074-7613(02)00516-2. PMID 12530983.
- Cormont M, Metón I, Mari M, et al. (2003). "CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl". Traffic 4 (2): 97–112. doi:10.1034/j.1600-0854.2003.40205.x. PMID 12559036.
- Lynch DK, Winata SC, Lyons RJ, et al. (2003). "A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton". J. Biol. Chem. 278 (24): 21805–13. doi:10.1074/jbc.M211407200. PMID 12672817.
- Hutchings NJ, Clarkson N, Chalkley R, et al. (2003). "Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85". J. Biol. Chem. 278 (25): 22396–403. doi:10.1074/jbc.M302540200. PMID 12690097.
- Kim JM, Wu H, Green G, et al. (2003). "CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility". Science 300 (5623): 1298–300. doi:10.1126/science.1081068. PMID 12764198.
- Schulze WX, Mann M (2004). "A novel proteomic screen for peptide-protein interactions". J. Biol. Chem. 279 (11): 10756–64. doi:10.1074/jbc.M309909200. PMID 14679214.
- Haglund K, Ivankovic-Dikic I, Shimokawa N, et al. (2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell. Sci. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873.
- Lehtonen S, Lehtonen E, Kudlicka K, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1618613.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Rush J, Moritz A, Lee KA, et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
- Coward RJ, Foster RR, Patton D, et al. (2005). "Nephrotic plasma alters slit diaphragm-dependent signaling and translocates nephrin, Podocin, and CD2 associated protein in cultured human podocytes". J. Am. Soc. Nephrol. 16 (3): 629–37. doi:10.1681/ASN.2004030172. PMID 15659563.
PDB gallery
|
|
|
2j6f: N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG) BOUND TO CBL-B PEPTIDE
|
|
2j6k: N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG)
|
|
2j6o: ATYPICAL POLYPROLINE RECOGNITION BY THE CMS N-TERMINAL SH3 DOMAIN. CMS:CD2 HETEROTRIMER
|
|
2j7i: ATYPICAL POLYPROLINE RECOGNITION BY THE CMS N-TERMINAL SH3 DOMAIN. CMS:CD2 HETERODIMER
|
|
|
|