CD2AP

CD2AP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FEI, 2J6F, 2J6K, 2J6O, 2J7I, 3AA6, 3LK4, 3U23, 4WCI, 4X1V
Identifiers
Aliases	CD2AP, CMS, CD2-associated protein
External IDs	MGI: 1330281 HomoloGene: 7663 GeneCards: CD2AP
Genetically Related Diseases
Alzheimer's disease[1]
Gene ontology Molecular function • beta-catenin binding • SH3 domain binding • protein complex binding • cadherin binding • structural constituent of cytoskeleton • protein C-terminus binding • protein binding • vascular endothelial growth factor receptor binding • cadherin binding involved in cell-cell adhesion Cellular component • cytoplasm • filamentous actin • cell projection • cell-cell junction • ruffle • plasma membrane • endocytic vesicle • protein complex • nucleolus • cell leading edge • actin cytoskeleton • perinuclear region of cytoplasm • extracellular exosome • cytoskeleton • cell-cell adherens junction Biological process • single organismal cell-cell adhesion • regulation of actin cytoskeleton reorganization • mitotic nuclear division • negative regulation of transforming growth factor beta1 production • protein complex assembly • vesicle organization • substrate-dependent cell migration, cell extension • cell division • cell cycle • cell migration • regulation of receptor-mediated endocytosis • signal transduction • proteasome-mediated ubiquitin-dependent protein catabolic process • positive regulation of protein localization to nucleus • cytoskeleton organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23607	12488
Ensembl	ENSG00000198087	ENSMUSG00000061665
UniProt	Q9Y5K6	Q9JLQ0
RefSeq (mRNA)	NM_012120	NM_009847
RefSeq (protein)	NP_036252.1	NP_033977.3
Location (UCSC)	Chr 6: 47.48 – 47.63 Mb	Chr 17: 42.79 – 42.88 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

CD2-associated protein is a protein that in humans is encoded by the CD2AP gene.^[4][5]

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.^[5]

Interactions

CD2AP has been shown to interact with:

• Cbl gene,^[6][7][8]
• NPHS2,^[9]
• Nephrin,^[10] and
• RAB4A.^[8]

See also

• Focal segmental glomerulosclerosis

References

1. "Diseases that are genetically associated with CD2AP view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. 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.
5. "Entrez Gene: CD2AP CD2-associated protein".
6. Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I (May 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.
7. Kirsch KH, Georgescu MM, Shishido T, Langdon WY, Birge RB, 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. 276 (7): 4957–63. doi:10.1074/jbc.M005784200. PMID 11067845.
8. Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y (Feb 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.
9. 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.
10. 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.

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, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS (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, Geng L, Zerial M, Somlo S, Lehtonen E (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, 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. PMID 10997929.
• Kirsch KH, Georgescu MM, Shishido T, Langdon WY, Birge RB, Hanafusa H (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, 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.
• Scott MP, Zappacosta F, Kim EY, Annan RS, Miller WT (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.
• Badour K, Zhang J, Shi F, McGavin MK, Rampersad V, Hardy LA, Field D, Siminovitch KA (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, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y (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, Hughes WE, Lehrbach GM, Wasinger V, Corthals G, Cordwell S, Daly RJ (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, Barclay AN, Brown MH (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, Winkler CA, Kopp JB, Miner JH, Unanue ER, Shaw AS (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, Kruh GD, Dikic I (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, Holthöfer H, Farquhar MG (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.
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (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, Ni L, Lennon R, Bates DO, Harper SJ, Mathieson PW, Saleem MA (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.