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, CD2 associated protein
External IDs	OMIM: 604241 MGI: 1330281 HomoloGene: 7663 GeneCards: CD2AP
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p12.3 Start 47,477,789 bp [1] End 47,627,263 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17|17 B3 Start 43,103,842 bp [2] End 43,187,556 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa duodenum rectum glomerulus amniotic fluid metanephric glomerulus cavity of mouth germinal epithelium caput epididymis corpus epididymis Top expressed in gastric mucosa mucous cell of stomach renal corpuscle epithelium of stomach medullary collecting duct urothelium aortic valve secondary oocyte left colon ascending aorta More reference expression data BioGPS n/a
Gene ontology Molecular function beta-catenin binding SH3 domain binding protein-containing complex binding structural constituent of cytoskeleton protein C-terminus binding protein binding vascular endothelial growth factor receptor binding cadherin binding Cellular component filamentous actin cell projection cell-cell junction ruffle endocytic vesicle cell leading edge actin cytoskeleton perinuclear region of cytoplasm extracellular exosome cytoskeleton cytoplasm plasma membrane cell junction protein-containing complex Biological process regulation of actin cytoskeleton reorganization negative regulation of transforming growth factor beta1 production 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 actin filament organization negative regulation of small GTPase mediated signal transduction cell-cell adhesion protein-containing complex assembly positive regulation of protein secretion 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 NP_033977 Location (UCSC) Chr 6: 47.48 – 47.63 Mb Chr 17: 43.1 – 43.19 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

CD2-associated protein is a protein that in humans is encoded by the CD2AP gene. ^{[5] [6]}

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. ^[6]

Interactions

CD2AP has been shown to interact with:

• Cbl gene, ^{[7] [8] [9]}
• NPHS2, ^[10]
• Nephrin, ^[11] and
• RAB4A. ^[9]

See also

• Focal segmental glomerulosclerosis

References

1. GRCh38: Ensembl release 89: ENSG00000198087 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061665 - 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. 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. Bibcode:1999PNAS...96.6211K. doi: 10.1073/pnas.96.11.6211 . PMC   26861 . PMID   10339567.
6. "Entrez Gene: CD2AP CD2-associated protein".
7. 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.
8. 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.
9. 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. S2CID   38612642.
10. 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.
11. 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. S2CID   18042803.
• 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. doi: 10.1152/ajprenal.2000.279.4.F785 . PMID   10997929. S2CID   37166239.
• 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. S2CID   38612642.
• 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. Bibcode:2003Sci...300.1298K. doi:10.1126/science.1081068. PMID   12764198. S2CID   7106967.
• 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. S2CID   7200157.
• 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.

External links

• Human CD2AP genome location and CD2AP gene details page in the UCSC Genome Browser .