CD2AP_HUMAN
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 03-AUG-2022, entry version 198.
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.
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.
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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; 156.
DR CORUM; Q9Y5K6; -.
DR DIP; DIP-31807N; -.
DR IntAct; Q9Y5K6; 75.
DR MINT; Q9Y5K6; -.
DR STRING; 9606.ENSP00000352264; -.
DR TCDB; 8.A.34.1.5; the endophilin (endophilin) family.
DR GlyGen; Q9Y5K6; 1 site, 1 O-linked glycan (1 site).
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; Q9Y5K6; -.
DR PeptideAtlas; Q9Y5K6; -.
DR PRIDE; Q9Y5K6; -.
DR ProteomicsDB; 86434; -.
DR ABCD; Q9Y5K6; 9 sequenced antibodies.
DR Antibodypedia; 1016; 190 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 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; RSPGTIY; -.
DR OrthoDB; 1577081at2759; -.
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; 16 hits in 1087 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 194 other tissues.
DR Genevisible; Q9Y5K6; HS.
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:0030139; C:endocytic vesicle; IEA:Ensembl.
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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0008013; F:beta-catenin 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:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0005172; F:vascular endothelial growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
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:0098609; P:cell-cell adhesion; 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: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:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IEA:Ensembl.
DR GO; GO:0048259; P:regulation of receptor-mediated endocytosis; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; TAS:ProtInc.
DR GO; GO:0032905; P:transforming growth factor beta1 production; IEA:Ensembl.
DR GO; GO:0016050; P:vesicle organization; IEA:Ensembl.
DR CDD; cd12053; SH3_CD2AP_1; 1.
DR CDD; cd12054; SH3_CD2AP_2; 1.
DR CDD; cd12056; SH3_CD2AP_3; 1.
DR InterPro; IPR028445; CD2AP.
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:SF23; PTHR14167:SF23; 2.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF14604; SH3_9; 2.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 3.
DR SUPFAM; SSF50044; SSF50044; 3.
DR PROSITE; PS50002; SH3; 3.
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 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
