ID CD2AP_HUMAN Reviewed; 639 AA. AC Q9Y5K6; A6NL34; Q5VYA3; Q9UG97; DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 207. DE RecName: Full=CD2-associated protein; DE AltName: Full=Adapter protein CMS; DE AltName: Full=Cas ligand with multiple SH3 domains; GN Name=CD2AP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, HOMODIMERIZATION, INTERACTION WITH RP BCAR1, SUBCELLULAR LOCATION, DOMAIN, AND PHOSPHORYLATION. RX PubMed=10339567; DOI=10.1073/pnas.96.11.6211; RA Kirsch K.H., Georgescu M.M., Ishimaru S., Hanafusa H.; RT "CMS: an adapter molecule involved in cytoskeletal rearrangements."; RL Proc. Natl. Acad. Sci. U.S.A. 96:6211-6216(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Ora A., Toppinen M., Lehtonen E.; RT "Human homolog of CD2AP."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 548-639. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP PHOSPHORYLATION, INTERACTION WITH CBL, AND HOMODIMERIZATION. RX PubMed=11067845; DOI=10.1074/jbc.m005784200; RA Kirsch K.H., Georgescu M.M., Shishido T., Langdon W.Y., Birge R.B., RA Hanafusa H.; RT "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c- RT Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain RT interaction."; RL J. Biol. Chem. 276:4957-4963(2001). RN [8] RP INVOLVEMENT IN SUSCEPTIBILITY TO FSGS3. RX PubMed=12764198; DOI=10.1126/science.1081068; RA Kim J.M., Wu H., Green G., Winkler C.A., Kopp J.B., Miner J.H., RA Unanue E.R., Shaw A.S.; RT "CD2-associated protein haploinsufficiency is linked to glomerular disease RT susceptibility."; RL Science 300:1298-1300(2003). RN [9] RP FUNCTION, INTERACTION WITH ANLN, SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=15800069; DOI=10.1091/mbc.e04-09-0773; RA Monzo P., Gauthier N.C., Keslair F., Loubat A., Field C.M., RA Le Marchand-Brustel Y., Cormont M.; RT "Clues to CD2-associated protein involvement in cytokinesis."; RL Mol. Biol. Cell 16:2891-2902(2005). RN [10] RP INTERACTION WITH ARHGAP17. RX PubMed=16678097; DOI=10.1016/j.cell.2006.02.045; RA Wells C.D., Fawcett J.P., Traweger A., Yamanaka Y., Goudreault M., RA Elder K., Kulkarni S., Gish G., Virag C., Lim C., Colwill K., RA Starostine A., Metalnikov P., Pawson T.; RT "A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity RT proteins in epithelial cells."; RL Cell 125:535-548(2006). RN [11] RP INTERACTION WITH MVB12A. RX PubMed=16895919; DOI=10.1074/jbc.m605693200; RA Konishi H., Tashiro K., Murata Y., Nabeshi H., Yamauchi E., Taniguchi H.; RT "CFBP is a novel tyrosine-phosphorylated protein that might function as a RT regulator of CIN85/CD2AP."; RL J. Biol. Chem. 281:28919-28931(2006). RN [12] RP INTERACTION WITH PDCD6IP AND TSG101. RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850; RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K., RA Sundquist W.I.; RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and RT function in cytokinesis."; RL EMBO J. 26:4215-4227(2007). RN [13] RP INTERACTION WITH RET. RX PubMed=18753381; DOI=10.1523/jneurosci.2738-08.2008; RA Tsui C.C., Pierchala B.A.; RT "CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation RT of ret signal transduction."; RL J. Neurosci. 28:8789-8800(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-510, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224; SER-458; SER-510 AND RP SER-514, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] RP FUNCTION, INTERACTION WITH CAPZA1; CGNL1 AND SH3BP1, AND SUBCELLULAR RP LOCATION. RX PubMed=22891260; DOI=10.1083/jcb.201202094; RA Elbediwy A., Zihni C., Terry S.J., Clark P., Matter K., Balda M.S.; RT "Epithelial junction formation requires confinement of Cdc42 activity by a RT novel SH3BP1 complex."; RL J. Cell Biol. 198:677-693(2012). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67; SER-80; SER-86; SER-224; RP SER-458; SER-463; SER-510; SER-514; THR-565 AND SER-582, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-463, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [25] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-58, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-523, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [27] RP INTERACTION WITH CHIKUNGUNYA VIRUS NON-STRUCTURAL PROTEIN 3 (MICROBIAL RP INFECTION). RX PubMed=31493651; DOI=10.1016/j.virol.2019.08.022; RA Agback P., Dominguez F., Pustovalova Y., Lukash T., Shiliaev N., RA Orekhov V.Y., Frolov I., Agback T., Frolova E.I.; RT "Structural characterization and biological function of bivalent binding of RT CD2AP to intrinsically disordered domain of chikungunya virus nsP3 RT protein."; RL Virology 537:130-142(2019). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-62 IN COMPLEXES WITH CD2 AND RP CBLB, AND SUBUNIT. RX PubMed=17020880; DOI=10.1074/jbc.m606411200; RA Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I., RA Bravo J.; RT "Atypical polyproline recognition by the CMS N-terminal Src homology 3 RT domain."; RL J. Biol. Chem. 281:38845-38853(2006). RN [29] RP STRUCTURE BY NMR OF 111-166, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17188587; DOI=10.1016/j.bbapap.2006.09.018; RA Yao B., Zhang J., Dai H., Sun J., Jiao Y., Tang Y., Wu J., Shi Y.; RT "Solution structure of the second SH3 domain of human CMS and a newly RT identified binding site at the C-terminus of c-Cbl."; RL Biochim. Biophys. Acta 1774:35-43(2007). RN [30] RP X-RAY CRYSTALLOGRAPHY (1.11 ANGSTROMS) OF 109-168 IN COMPLEX WITH RIN3. RG Structural genomics consortium (SGC); RT "Atomic resolution crystal structure of the 2nd SH3 domain from human CD2AP RT (CMS) in complex with a proline-rich peptide from human RIN3."; RL Submitted (DEC-2011) to the PDB data bank. RN [31] RP VARIANTS MET-301 AND ALA-374. RX PubMed=23595123; DOI=10.1038/jhg.2013.27; RA Al-Hamed M.H., Al-Sabban E., Al-Mojalli H., Al-Harbi N., Faqeih E., RA Al Shaya H., Alhasan K., Al-Hissi S., Rajab M., Edwards N., Al-Abbad A., RA Al-Hassoun I., Sayer J.A., Meyer B.F.; RT "A molecular genetic analysis of childhood nephrotic syndrome in a cohort RT of Saudi Arabian families."; RL J. Hum. Genet. 58:480-489(2013). CC -!- FUNCTION: Seems to act as an adapter protein between membrane proteins CC and the actin cytoskeleton (PubMed:10339567). In collaboration with CC CBLC, modulates the rate of RET turnover and may act as regulatory CC checkpoint that limits the potency of GDNF on neuronal survival. CC Controls CBLC function, converting it from an inhibitor to a promoter CC of RET degradation (By similarity). May play a role in receptor CC clustering and cytoskeletal polarity in the junction between T-cell and CC antigen-presenting cell (By similarity). May anchor the podocyte slit CC diaphragm to the actin cytoskeleton in renal glomerolus. Also required CC for cytokinesis (PubMed:15800069). Plays a role in epithelial cell CC junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, CC ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, CC ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}. CC -!- SUBUNIT: Homodimer. Interacts with F-actin, PKD2, NPHS1 and NPHS2. CC Interacts with WTIP. Interacts with DDN; interaction is direct. CC Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus). CC Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A CC and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP CC and TSG101. Interacts with RIN3. Interacts directly with RET (inactive) CC and CBLC; upon RET activation by GDNF suggested to dissociate from RET CC as CBLC:CD2AP complex (Probable) (PubMed:10339567, PubMed:11067845, CC PubMed:15800069, PubMed:16678097, PubMed:16895919, PubMed:17020880, CC PubMed:17853893, PubMed:18753381, Ref.30). Interacts with CGNL1 and CC SH3BP1; probably part of a complex at cell junctions (PubMed:22891260). CC Interacts with CAPZA1 (PubMed:22891260). {ECO:0000269|PubMed:10339567, CC ECO:0000269|PubMed:11067845, ECO:0000269|PubMed:15800069, CC ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:16895919, CC ECO:0000269|PubMed:17020880, ECO:0000269|PubMed:17853893, CC ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:22891260, CC ECO:0000269|Ref.30, ECO:0000305}. CC -!- SUBUNIT: (Microbial infection) Interacts (via SH3 domains) with CC Chikungunya virus non-structural protein 3 (via C-terminus); this CC interaction plays a role in initiation of viral replication. CC {ECO:0000269|PubMed:31493651}. CC -!- INTERACTION: CC Q9Y5K6; Q8WV28: BLNK; NbExp=2; IntAct=EBI-298152, EBI-2623522; CC Q9Y5K6; P22681: CBL; NbExp=4; IntAct=EBI-298152, EBI-518228; CC Q9Y5K6; Q13191: CBLB; NbExp=11; IntAct=EBI-298152, EBI-744027; CC Q9Y5K6; P06729: CD2; NbExp=4; IntAct=EBI-298152, EBI-3912464; CC Q9Y5K6; Q9Y5K6: CD2AP; NbExp=3; IntAct=EBI-298152, EBI-298152; CC Q9Y5K6; P06241: FYN; NbExp=2; IntAct=EBI-298152, EBI-515315; CC Q9Y5K6; P62993: GRB2; NbExp=3; IntAct=EBI-298152, EBI-401755; CC Q9Y5K6; P46940: IQGAP1; NbExp=4; IntAct=EBI-298152, EBI-297509; CC Q9Y5K6; Q8WUM4: PDCD6IP; NbExp=3; IntAct=EBI-298152, EBI-310624; CC Q9Y5K6; Q8TB24: RIN3; NbExp=3; IntAct=EBI-298152, EBI-1570523; CC Q9Y5K6; Q96B97: SH3KBP1; NbExp=4; IntAct=EBI-298152, EBI-346595; CC Q9Y5K6; Q99816: TSG101; NbExp=2; IntAct=EBI-298152, EBI-346882; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:15800069}. Cell projection, ruffle CC {ECO:0000269|PubMed:10339567}. Cell junction CC {ECO:0000269|PubMed:22891260}. Note=Colocalizes with F-actin and CC BCAR1/p130Cas in membrane ruffles (PubMed:10339567). Located at CC podocyte slit diaphragm between podocyte foot processes (By CC similarity). During late anaphase and telophase, concentrates in the CC vicinity of the midzone microtubules and in the midbody in late CC telophase (PubMed:15800069). {ECO:0000250|UniProtKB:Q9JLQ0, CC ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069}. CC -!- TISSUE SPECIFICITY: Widely expressed in fetal and adult tissues. CC -!- DOMAIN: The Pro-rich domain may mediate binding to SH3 domains. CC -!- DOMAIN: Potential homodimerization is mediated by the coiled coil CC domain. {ECO:0000269|PubMed:10339567}. CC -!- PTM: Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c- CC Src. {ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:11067845, CC ECO:0000269|PubMed:15800069}. CC -!- DISEASE: Focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]: A CC renal pathology defined by the presence of segmental sclerosis in CC glomeruli and resulting in proteinuria, reduced glomerular filtration CC rate and progressive decline in renal function. Renal insufficiency CC often progresses to end-stage renal disease, a highly morbid state CC requiring either dialysis therapy or kidney transplantation. CC {ECO:0000269|PubMed:12764198}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF146277; AAD34595.1; -; mRNA. DR EMBL; AF164377; AAF80495.1; -; mRNA. DR EMBL; AL355353; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358178; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX04319.1; -; Genomic_DNA. DR EMBL; BC069444; AAH69444.1; -; mRNA. DR EMBL; AL050105; CAB43274.1; -; mRNA. DR CCDS; CCDS34472.1; -. DR PIR; T13151; T13151. DR RefSeq; NP_036252.1; NM_012120.2. DR PDB; 2FEI; NMR; -; A=111-166. DR PDB; 2J6F; X-ray; 1.70 A; A=1-62. DR PDB; 2J6K; X-ray; 2.78 A; A/B/C/D/E/F/G/H/I/J/K/L=1-62. DR PDB; 2J6O; X-ray; 2.22 A; A=1-62. DR PDB; 2J7I; X-ray; 2.90 A; A/B=1-62. DR PDB; 3AA6; X-ray; 1.90 A; C=485-507. DR PDB; 3LK4; X-ray; 1.99 A; 0/3/6/9/C/F/I/L/O/R/U/X=475-503. DR PDB; 3U23; X-ray; 1.11 A; A=109-168. DR PDB; 4WCI; X-ray; 1.65 A; A/C/E=1-60. DR PDB; 4X1V; X-ray; 1.58 A; A=109-168. DR PDB; 7DS6; X-ray; 1.69 A; C=496-507. DR PDB; 7DS8; X-ray; 1.95 A; C=485-495. DR PDBsum; 2FEI; -. DR PDBsum; 2J6F; -. DR PDBsum; 2J6K; -. DR PDBsum; 2J6O; -. DR PDBsum; 2J7I; -. DR PDBsum; 3AA6; -. DR PDBsum; 3LK4; -. DR PDBsum; 3U23; -. DR PDBsum; 4WCI; -. DR PDBsum; 4X1V; -. DR PDBsum; 7DS6; -. DR PDBsum; 7DS8; -. DR AlphaFoldDB; Q9Y5K6; -. DR SMR; Q9Y5K6; -. DR BioGRID; 117140; 205. DR CORUM; Q9Y5K6; -. DR DIP; DIP-31807N; -. DR IntAct; Q9Y5K6; 82. DR MINT; Q9Y5K6; -. DR STRING; 9606.ENSP00000352264; -. DR TCDB; 8.A.34.1.5; the endophilin (endophilin) family. DR GlyGen; Q9Y5K6; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9Y5K6; -. DR MetOSite; Q9Y5K6; -. DR PhosphoSitePlus; Q9Y5K6; -. DR BioMuta; CD2AP; -. DR DMDM; 30172980; -. DR EPD; Q9Y5K6; -. DR jPOST; Q9Y5K6; -. DR MassIVE; Q9Y5K6; -. DR MaxQB; Q9Y5K6; -. DR PaxDb; 9606-ENSP00000352264; -. DR PeptideAtlas; Q9Y5K6; -. DR ProteomicsDB; 86434; -. DR Pumba; Q9Y5K6; -. DR ABCD; Q9Y5K6; 9 sequenced antibodies. DR Antibodypedia; 1016; 217 antibodies from 33 providers. DR DNASU; 23607; -. DR Ensembl; ENST00000359314.5; ENSP00000352264.5; ENSG00000198087.7. DR GeneID; 23607; -. DR KEGG; hsa:23607; -. DR MANE-Select; ENST00000359314.5; ENSP00000352264.5; NM_012120.3; NP_036252.1. DR UCSC; uc003oyw.4; human. DR AGR; HGNC:14258; -. DR CTD; 23607; -. DR DisGeNET; 23607; -. DR GeneCards; CD2AP; -. DR HGNC; HGNC:14258; CD2AP. DR HPA; ENSG00000198087; Low tissue specificity. DR MalaCards; CD2AP; -. DR MIM; 604241; gene. DR MIM; 607832; phenotype. DR neXtProt; NX_Q9Y5K6; -. DR NIAGADS; ENSG00000198087; -. DR OpenTargets; ENSG00000198087; -. DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome. DR PharmGKB; PA26208; -. DR VEuPathDB; HostDB:ENSG00000198087; -. DR eggNOG; KOG4348; Eukaryota. DR GeneTree; ENSGT00940000157566; -. DR HOGENOM; CLU_024255_2_0_1; -. DR InParanoid; Q9Y5K6; -. DR OMA; XEIKRET; -. DR OrthoDB; 2972088at2759; -. DR PhylomeDB; Q9Y5K6; -. DR TreeFam; TF350191; -. DR PathwayCommons; Q9Y5K6; -. DR Reactome; R-HSA-373753; Nephrin family interactions. DR SignaLink; Q9Y5K6; -. DR SIGNOR; Q9Y5K6; -. DR BioGRID-ORCS; 23607; 17 hits in 1163 CRISPR screens. DR ChiTaRS; CD2AP; human. DR EvolutionaryTrace; Q9Y5K6; -. DR GeneWiki; CD2AP; -. DR GenomeRNAi; 23607; -. DR Pharos; Q9Y5K6; Tbio. DR PRO; PR:Q9Y5K6; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9Y5K6; Protein. DR Bgee; ENSG00000198087; Expressed in jejunal mucosa and 196 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc. DR GO; GO:0030424; C:axon; ISS:ARUK-UCL. DR GO; GO:0031252; C:cell leading edge; IBA:GO_Central. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0034451; C:centriolar satellite; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0031941; C:filamentous actin; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; IEA:Ensembl. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0002102; C:podosome; IEA:Ensembl. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0031982; C:vesicle; IBA:GO_Central. DR GO; GO:0051015; F:actin filament binding; IEA:Ensembl. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB. DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc. DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0001771; P:immunological synapse formation; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0051058; P:negative regulation of small GTPase mediated signal transduction; IMP:UniProtKB. DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IEA:Ensembl. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl. DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0071559; P:response to transforming growth factor beta; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR GO; GO:0051403; P:stress-activated MAPK cascade; IEA:Ensembl. DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; TAS:ProtInc. DR GO; GO:0050808; P:synapse organization; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0032905; P:transforming growth factor beta1 production; IEA:Ensembl. DR CDD; cd12053; SH3_CD2AP_1; 1. DR CDD; cd12054; SH3_CD2AP_2; 1. DR CDD; cd12056; SH3_CD2AP_3; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 3. DR InterPro; IPR035775; CD2AP_SH3_1. DR InterPro; IPR035777; CD2AP_SH3_3. DR InterPro; IPR035776; CD2AP_SH_2. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR14167:SF92; CIN85 AND CD2AP RELATED, ISOFORM J; 1. DR PANTHER; PTHR14167; SH3 DOMAIN-CONTAINING; 1. DR Pfam; PF00018; SH3_1; 1. DR Pfam; PF14604; SH3_9; 2. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00326; SH3; 3. DR SUPFAM; SSF50044; SH3-domain; 3. DR PROSITE; PS50002; SH3; 3. DR Genevisible; Q9Y5K6; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cell division; Cell junction; Cell projection; KW Coiled coil; Cytoplasm; Cytoskeleton; Host-virus interaction; KW Isopeptide bond; Mitosis; Phosphoprotein; Reference proteome; Repeat; KW SH3 domain; SH3-binding; Ubl conjugation. FT CHAIN 1..639 FT /note="CD2-associated protein" FT /id="PRO_0000089435" FT DOMAIN 1..59 FT /note="SH3 1; truncated" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 108..167 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 269..330 FT /note="SH3 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 1..175 FT /note="Interaction with ANLN and localization to the FT midbody" FT /evidence="ECO:0000269|PubMed:15800069" FT REGION 168..209 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 227..256 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 333..428 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 577..638 FT /evidence="ECO:0000255" FT MOTIF 336..352 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT MOTIF 378..397 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT MOTIF 410..422 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 182..207 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 358..377 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 67 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 80 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 86 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 224 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 458 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 469 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:F1LRS8" FT MOD_RES 510 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 514 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 565 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 582 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 58 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT CROSSLNK 523 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 301 FT /note="K -> M (found in patients with steroid-resistant FT nephrotic syndrome; uncertain significance; FT dbSNP:rs141778404)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087609" FT VARIANT 374 FT /note="T -> A (in dbSNP:rs138727736)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087610" FT VARIANT 581 FT /note="N -> K (in dbSNP:rs34069459)" FT /id="VAR_033672" FT STRAND 4..6 FT /evidence="ECO:0007829|PDB:4WCI" FT STRAND 25..30 FT /evidence="ECO:0007829|PDB:4WCI" FT STRAND 37..42 FT /evidence="ECO:0007829|PDB:4WCI" FT STRAND 45..50 FT /evidence="ECO:0007829|PDB:4WCI" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:4WCI" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:3U23" FT STRAND 134..142 FT /evidence="ECO:0007829|PDB:3U23" FT STRAND 145..150 FT /evidence="ECO:0007829|PDB:3U23" FT STRAND 153..158 FT /evidence="ECO:0007829|PDB:3U23" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:3U23" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:3U23" FT HELIX 489..492 FT /evidence="ECO:0007829|PDB:3AA6" FT HELIX 503..505 FT /evidence="ECO:0007829|PDB:3AA6" SQ SEQUENCE 639 AA; 71451 MW; 7576509C7ED5B343 CRC64; MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP DNFVKEIKRE TEFKDDSLPI KRERHGNVAS LVQRISTYGL PAGGIQPHPQ TKNIKKKTKK RQCKVLFEYI PQNEDELELK VGDIIDINEE VEEGWWSGTL NNKLGLFPSN FVKELEVTDD GETHEAQDDS ETVLAGPTSP IPSLGNVSET ASGSVTQPKK IRGIGFGDIF KEGSVKLRTR TSSSETEEKK PEKPLILQSL GPKTQSVEIT KTDTEGKIKA KEYCRTLFAY EGTNEDELTF KEGEIIHLIS KETGEAGWWR GELNGKEGVF PDNFAVQINE LDKDFPKPKK PPPPAKAPAP KPELIAAEKK YFSLKPEEKD EKSTLEQKPS KPAAPQVPPK KPTPPTKASN LLRSSGTVYP KRPEKPVPPP PPIAKINGEV SSISSKFETE PVSKLKLDSE QLPLRPKSVD FDSLTVRTSK ETDVVNFDDI ASSENLLHLT ANRPKMPGRR LPGRFNGGHS PTHSPEKILK LPKEEDSANL KPSELKKDTC YSPKPSVYLS TPSSASKANT TAFLTPLEIK AKVETDDVKK NSLDELRAQI IELLCIVEAL KKDHGKELEK LRKDLEEEKT MRSNLEMEIE KLKKAVLSS //