CD2AP explained

CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.^{[1] [2]}

Function

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]

Interactions

CD2AP has been shown to interact with:

• Cbl gene,^{[3] [4] [5]}
• NPHS2,^[6]
• Nephrin,^[7] and
• RAB4A.^[5]

See also

• Focal segmental glomerulosclerosis

Further reading

• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS . A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts . Cell . 94 . 5 . 667–77 . 1998 . 9741631 . 10.1016/S0092-8674(00)81608-6. 18042803 . free .
• Lehtonen S, Ora A, Olkkonen VM, Geng L, Zerial M, Somlo S, Lehtonen E . 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 . 2000 . 10913159 . 10.1074/jbc.M006624200 . free .
• Li C, Ruotsalainen V, Tryggvason K, Shaw AS, Miner JH . 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 . 2000 . 10997929 . 10.1152/ajprenal.2000.279.4.F785. 37166239 . free .
• Kirsch KH, Georgescu MM, Shishido T, Langdon WY, Birge RB, Hanafusa H . 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 . 2001 . 11067845 . 10.1074/jbc.M005784200 . free .
• Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P . Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin . J. Clin. Invest. . 108 . 11 . 1621–9 . 2002 . 11733557 . 200981 . 10.1172/JCI12849 .
• Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT . 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 . 2002 . 12029088 . 10.1074/jbc.M202783200 . free .
• Badour K, Zhang J, Shi F, McGavin MK, Rampersad V, Hardy LA, Field D, Siminovitch KA . 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 . 2003 . 12530983 . 10.1016/S1074-7613(02)00516-2 . free .
• Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y . CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl . Traffic . 4 . 2 . 97–112 . 2003 . 12559036 . 10.1034/j.1600-0854.2003.40205.x . 38612642 .
• Lynch DK, Winata SC, Lyons RJ, Hughes WE, Lehrbach GM, Wasinger V, Corthals G, Cordwell S, Daly RJ . 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 . 2003 . 12672817 . 10.1074/jbc.M211407200 . free .
• Hutchings NJ, Clarkson N, Chalkley R, Barclay AN, Brown MH . Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85 . J. Biol. Chem. . 278 . 25 . 22396–403 . 2003 . 12690097 . 10.1074/jbc.M302540200 . free .
• 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 . 300 . 5623 . 1298–300 . 2003 . 12764198 . 10.1126/science.1081068 . 2003Sci...300.1298K . 7106967 .
• Schulze WX, Mann M . A novel proteomic screen for peptide-protein interactions . J. Biol. Chem. . 279 . 11 . 10756–64 . 2004 . 14679214 . 10.1074/jbc.M309909200 . free .
• Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . 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 . 2004 . 15128873 . 10.1242/jcs.01148 . 14083271 .
• Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG . 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 . 2004 . 15331416 . 1618613 . 10.1016/S0002-9440(10)63354-8 .
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nat. Biotechnol. . 23 . 1 . 94–101 . 2005 . 15592455 . 10.1038/nbt1046 . 7200157 .
• Coward RJ, Foster RR, Patton D, Ni L, Lennon R, Bates DO, Harper SJ, Mathieson PW, Saleem MA . 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 . 2005 . 15659563 . 10.1681/ASN.2004030172 . free .

Notes and References

1. Kirsch KH, Georgescu MM, Ishimaru S, Hanafusa H . CMS: An adapter molecule involved in cytoskeletal rearrangements . Proc Natl Acad Sci USA . 96 . 11 . 6211–6 . Jun 1999 . 10339567 . 26861 . 10.1073/pnas.96.11.6211 . 1999PNAS...96.6211K . free .
2. Web site: Entrez Gene: CD2AP CD2-associated protein.
3. Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I . 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 . May 2004 . 15128873 . 10.1242/jcs.01148 . 14083271 .
4. Kirsch KH, Georgescu MM, Shishido T, Langdon WY, Birge RB, Hanafusa H . 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 . Feb 2001 . 11067845 . 10.1074/jbc.M005784200 . free .
5. Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y . CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl . Traffic . 4 . 2 . 97–112 . Feb 2003 . 12559036 . 10.1034/j.1600-0854.2003.40205.x. 38612642 .
6. Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P . Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin . J. Clin. Invest. . 108 . 11 . 1621–9 . Dec 2001 . 11733557 . 200981 . 10.1172/JCI12849 .
7. Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG . 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 . Sep 2004 . 15331416 . 1618613 . 10.1016/S0002-9440(10)63354-8 .