Full text data of CD2AP
CD2AP
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
CD2-associated protein (Adapter protein CMS; Cas ligand with multiple SH3 domains)
CD2-associated protein (Adapter protein CMS; Cas ligand with multiple SH3 domains)
UniProt
Q9Y5K6
ID CD2AP_HUMAN Reviewed; 639 AA.
AC Q9Y5K6; A6NL34; Q5VYA3; Q9UG97;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 127.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, AND INTERACTION WITH
RP BCAR1.
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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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
RT protein c-Cbl through a tyrosine phosphorylation-regulated Src
RT homology 3 domain interaction.";
RL J. Biol. Chem. 276:4957-4963(2001).
RN [8]
RP GLOMERULAR DISEASE SUSCEPTIBILITY.
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
RT disease susceptibility.";
RL Science 300:1298-1300(2003).
RN [9]
RP FUNCTION, INTERACTION WITH ANLN, SUBCELLULAR LOCATION, AND
RP 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.,
RA Taniguchi H.;
RT "CFBP is a novel tyrosine-phosphorylated protein that might function
RT as a 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.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and 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
RT regulation of ret signal transduction.";
RL J. Neurosci. 28:8789-8800(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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 MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RP AND SER-514, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-62 IN COMPLEXES WITH CD2
RP AND 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 [23]
RP STRUCTURE BY NMR OF 111-166, AND 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 [24]
RP X-RAY CRYSTALLOGRAPHY (1.11 ANGSTROMS) OF 109-168 IN COMPLEX WITH
RP RIN3.
RG Structural genomics consortium (SGC);
RT "Atomic resolution crystal structure of the 2nd SH3 domain from human
RT CD2AP (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
CC proteins and the actin cytoskeleton. In collaboration with CBLC,
CC 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
CC promoter of RET degradation. May play a role in receptor
CC clustering and cytoskeletal polarity in the junction between T-
CC cell and antigen-presenting cell. May anchor the podocyte slit
CC diaphragm to the actin cytoskeleton in renal glomerolus. Also
CC required for cytokinesis.
CC -!- SUBUNIT: Self-associates. Homodimer (Potential). Interacts with F-
CC actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with
CC DDN; interaction is direct. Interacts (via SH3 2 domain) with CBL
CC (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via
CC SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with
CC ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts
CC with RIN3. Interacts directly with RET (inactive) and CBLC; upon
CC RET activation by GDNF suggested to dissociate from RET as
CC CBLC:CD2AP complex.
CC -!- INTERACTION:
CC Q8WV28:BLNK; NbExp=2; IntAct=EBI-298152, EBI-2623522;
CC P22681:CBL; NbExp=3; IntAct=EBI-298152, EBI-518228;
CC Q13191:CBLB; NbExp=11; IntAct=EBI-298152, EBI-744027;
CC P06729:CD2; NbExp=4; IntAct=EBI-298152, EBI-3912464;
CC P62993:GRB2; NbExp=3; IntAct=EBI-298152, EBI-401755;
CC P46940:IQGAP1; NbExp=4; IntAct=EBI-298152, EBI-297509;
CC Q8WUM4:PDCD6IP; NbExp=2; IntAct=EBI-298152, EBI-310624;
CC Q99816:TSG101; NbExp=2; IntAct=EBI-298152, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cell projection, ruffle (By similarity). Note=Colocalizes with F-
CC actin and BCAR1/p130Cas in membrane ruffles. Located at podocyte
CC slit diaphragm between podocyte foot processes (By similarity).
CC During late anaphase and telophase, concentrates in the vicinity
CC of the midzone microtubules and in the midbody in late telophase.
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.
CC -!- PTM: Phosphorylated on tyrosine residues; probably by c-Abl, Fyn
CC and c-Src.
CC -!- DISEASE: Focal segmental glomerulosclerosis 3 (FSGS3)
CC [MIM:607832]: A renal pathology defined by the presence of
CC segmental sclerosis in glomeruli and resulting in proteinuria,
CC reduced glomerular filtration rate and progressive decline in
CC renal function. Renal insufficiency often progresses to end-stage
CC renal disease, a highly morbid state requiring either dialysis
CC therapy or kidney transplantation. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Contains 3 SH3 domains.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CD2AP";
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DR EMBL; AF146277; AAD34595.1; -; mRNA.
DR EMBL; AF164377; AAF80495.1; -; mRNA.
DR EMBL; AL355353; CAH73238.1; -; Genomic_DNA.
DR EMBL; AL358178; CAH73238.1; JOINED; Genomic_DNA.
DR EMBL; AL358178; CAI16839.1; -; Genomic_DNA.
DR EMBL; AL355353; CAI16839.1; JOINED; Genomic_DNA.
DR EMBL; CH471081; EAX04319.1; -; Genomic_DNA.
DR EMBL; BC069444; AAH69444.1; -; mRNA.
DR EMBL; AL050105; CAB43274.1; -; mRNA.
DR PIR; T13151; T13151.
DR RefSeq; NP_036252.1; NM_012120.2.
DR UniGene; Hs.485518; -.
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 PDBsum; 2FEI; -.
DR PDBsum; 2J6F; -.
DR PDBsum; 2J6K; -.
DR PDBsum; 2J6O; -.
DR PDBsum; 2J7I; -.
DR PDBsum; 3AA6; -.
DR PDBsum; 3LK4; -.
DR PDBsum; 3U23; -.
DR ProteinModelPortal; Q9Y5K6; -.
DR SMR; Q9Y5K6; 2-329, 475-503.
DR DIP; DIP-31807N; -.
DR IntAct; Q9Y5K6; 30.
DR MINT; MINT-93491; -.
DR STRING; 9606.ENSP00000352264; -.
DR PhosphoSite; Q9Y5K6; -.
DR DMDM; 30172980; -.
DR PaxDb; Q9Y5K6; -.
DR PRIDE; Q9Y5K6; -.
DR Ensembl; ENST00000359314; ENSP00000352264; ENSG00000198087.
DR GeneID; 23607; -.
DR KEGG; hsa:23607; -.
DR UCSC; uc003oyw.3; human.
DR CTD; 23607; -.
DR GeneCards; GC06P047445; -.
DR HGNC; HGNC:14258; CD2AP.
DR HPA; CAB004352; -.
DR HPA; HPA003267; -.
DR HPA; HPA003326; -.
DR MIM; 604241; gene.
DR MIM; 607832; phenotype.
DR neXtProt; NX_Q9Y5K6; -.
DR Orphanet; 93213; Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
DR PharmGKB; PA26208; -.
DR eggNOG; NOG319250; -.
DR HOGENOM; HOG000231405; -.
DR HOVERGEN; HBG057824; -.
DR InParanoid; Q9Y5K6; -.
DR KO; K13738; -.
DR OMA; VHDDELT; -.
DR OrthoDB; EOG7W41BC; -.
DR PhylomeDB; Q9Y5K6; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR SignaLink; Q9Y5K6; -.
DR ChiTaRS; CD2AP; human.
DR EvolutionaryTrace; Q9Y5K6; -.
DR GeneWiki; CD2AP; -.
DR GenomeRNAi; 23607; -.
DR NextBio; 46304; -.
DR PRO; PR:Q9Y5K6; -.
DR Bgee; Q9Y5K6; -.
DR CleanEx; HS_CD2AP; -.
DR Genevestigator; Q9Y5K6; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0031941; C:filamentous actin; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; TAS:ProtInc.
DR InterPro; IPR028445; CD2AP.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR14167:SF7; PTHR14167:SF7; 1.
DR Pfam; PF00018; SH3_1; 1.
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 projection; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Mitosis; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; SH3 domain; SH3-binding.
FT CHAIN 1 639 CD2-associated protein.
FT /FTId=PRO_0000089435.
FT DOMAIN 1 59 SH3 1; truncated.
FT DOMAIN 108 167 SH3 2.
FT DOMAIN 269 330 SH3 3.
FT REGION 1 175 Interaction with ANLN and localization to
FT the midbody.
FT COILED 577 638 Potential.
FT MOTIF 336 352 SH3-binding (Potential).
FT MOTIF 378 397 SH3-binding (Potential).
FT MOTIF 410 422 SH3-binding (Potential).
FT COMPBIAS 336 422 Pro-rich.
FT MOD_RES 224 224 Phosphoserine.
FT MOD_RES 458 458 Phosphoserine.
FT MOD_RES 510 510 Phosphoserine.
FT MOD_RES 514 514 Phosphoserine.
FT VARIANT 581 581 N -> K (in dbSNP:rs34069459).
FT /FTId=VAR_033672.
FT STRAND 4 6
FT STRAND 25 31
FT STRAND 37 42
FT STRAND 45 50
FT HELIX 51 53
FT STRAND 54 56
FT STRAND 112 115
FT STRAND 134 142
FT STRAND 145 150
FT STRAND 153 158
FT HELIX 159 161
FT STRAND 162 164
FT HELIX 489 492
FT HELIX 503 505
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
//
ID CD2AP_HUMAN Reviewed; 639 AA.
AC Q9Y5K6; A6NL34; Q5VYA3; Q9UG97;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 127.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, AND INTERACTION WITH
RP BCAR1.
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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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
RT protein c-Cbl through a tyrosine phosphorylation-regulated Src
RT homology 3 domain interaction.";
RL J. Biol. Chem. 276:4957-4963(2001).
RN [8]
RP GLOMERULAR DISEASE SUSCEPTIBILITY.
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
RT disease susceptibility.";
RL Science 300:1298-1300(2003).
RN [9]
RP FUNCTION, INTERACTION WITH ANLN, SUBCELLULAR LOCATION, AND
RP 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.,
RA Taniguchi H.;
RT "CFBP is a novel tyrosine-phosphorylated protein that might function
RT as a 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.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and 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
RT regulation of ret signal transduction.";
RL J. Neurosci. 28:8789-8800(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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 MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RP AND SER-514, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-62 IN COMPLEXES WITH CD2
RP AND 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 [23]
RP STRUCTURE BY NMR OF 111-166, AND 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 [24]
RP X-RAY CRYSTALLOGRAPHY (1.11 ANGSTROMS) OF 109-168 IN COMPLEX WITH
RP RIN3.
RG Structural genomics consortium (SGC);
RT "Atomic resolution crystal structure of the 2nd SH3 domain from human
RT CD2AP (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
CC proteins and the actin cytoskeleton. In collaboration with CBLC,
CC 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
CC promoter of RET degradation. May play a role in receptor
CC clustering and cytoskeletal polarity in the junction between T-
CC cell and antigen-presenting cell. May anchor the podocyte slit
CC diaphragm to the actin cytoskeleton in renal glomerolus. Also
CC required for cytokinesis.
CC -!- SUBUNIT: Self-associates. Homodimer (Potential). Interacts with F-
CC actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with
CC DDN; interaction is direct. Interacts (via SH3 2 domain) with CBL
CC (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via
CC SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with
CC ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts
CC with RIN3. Interacts directly with RET (inactive) and CBLC; upon
CC RET activation by GDNF suggested to dissociate from RET as
CC CBLC:CD2AP complex.
CC -!- INTERACTION:
CC Q8WV28:BLNK; NbExp=2; IntAct=EBI-298152, EBI-2623522;
CC P22681:CBL; NbExp=3; IntAct=EBI-298152, EBI-518228;
CC Q13191:CBLB; NbExp=11; IntAct=EBI-298152, EBI-744027;
CC P06729:CD2; NbExp=4; IntAct=EBI-298152, EBI-3912464;
CC P62993:GRB2; NbExp=3; IntAct=EBI-298152, EBI-401755;
CC P46940:IQGAP1; NbExp=4; IntAct=EBI-298152, EBI-297509;
CC Q8WUM4:PDCD6IP; NbExp=2; IntAct=EBI-298152, EBI-310624;
CC Q99816:TSG101; NbExp=2; IntAct=EBI-298152, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Cell projection, ruffle (By similarity). Note=Colocalizes with F-
CC actin and BCAR1/p130Cas in membrane ruffles. Located at podocyte
CC slit diaphragm between podocyte foot processes (By similarity).
CC During late anaphase and telophase, concentrates in the vicinity
CC of the midzone microtubules and in the midbody in late telophase.
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.
CC -!- PTM: Phosphorylated on tyrosine residues; probably by c-Abl, Fyn
CC and c-Src.
CC -!- DISEASE: Focal segmental glomerulosclerosis 3 (FSGS3)
CC [MIM:607832]: A renal pathology defined by the presence of
CC segmental sclerosis in glomeruli and resulting in proteinuria,
CC reduced glomerular filtration rate and progressive decline in
CC renal function. Renal insufficiency often progresses to end-stage
CC renal disease, a highly morbid state requiring either dialysis
CC therapy or kidney transplantation. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Contains 3 SH3 domains.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CD2AP";
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DR EMBL; AF146277; AAD34595.1; -; mRNA.
DR EMBL; AF164377; AAF80495.1; -; mRNA.
DR EMBL; AL355353; CAH73238.1; -; Genomic_DNA.
DR EMBL; AL358178; CAH73238.1; JOINED; Genomic_DNA.
DR EMBL; AL358178; CAI16839.1; -; Genomic_DNA.
DR EMBL; AL355353; CAI16839.1; JOINED; Genomic_DNA.
DR EMBL; CH471081; EAX04319.1; -; Genomic_DNA.
DR EMBL; BC069444; AAH69444.1; -; mRNA.
DR EMBL; AL050105; CAB43274.1; -; mRNA.
DR PIR; T13151; T13151.
DR RefSeq; NP_036252.1; NM_012120.2.
DR UniGene; Hs.485518; -.
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 PDBsum; 2FEI; -.
DR PDBsum; 2J6F; -.
DR PDBsum; 2J6K; -.
DR PDBsum; 2J6O; -.
DR PDBsum; 2J7I; -.
DR PDBsum; 3AA6; -.
DR PDBsum; 3LK4; -.
DR PDBsum; 3U23; -.
DR ProteinModelPortal; Q9Y5K6; -.
DR SMR; Q9Y5K6; 2-329, 475-503.
DR DIP; DIP-31807N; -.
DR IntAct; Q9Y5K6; 30.
DR MINT; MINT-93491; -.
DR STRING; 9606.ENSP00000352264; -.
DR PhosphoSite; Q9Y5K6; -.
DR DMDM; 30172980; -.
DR PaxDb; Q9Y5K6; -.
DR PRIDE; Q9Y5K6; -.
DR Ensembl; ENST00000359314; ENSP00000352264; ENSG00000198087.
DR GeneID; 23607; -.
DR KEGG; hsa:23607; -.
DR UCSC; uc003oyw.3; human.
DR CTD; 23607; -.
DR GeneCards; GC06P047445; -.
DR HGNC; HGNC:14258; CD2AP.
DR HPA; CAB004352; -.
DR HPA; HPA003267; -.
DR HPA; HPA003326; -.
DR MIM; 604241; gene.
DR MIM; 607832; phenotype.
DR neXtProt; NX_Q9Y5K6; -.
DR Orphanet; 93213; Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
DR PharmGKB; PA26208; -.
DR eggNOG; NOG319250; -.
DR HOGENOM; HOG000231405; -.
DR HOVERGEN; HBG057824; -.
DR InParanoid; Q9Y5K6; -.
DR KO; K13738; -.
DR OMA; VHDDELT; -.
DR OrthoDB; EOG7W41BC; -.
DR PhylomeDB; Q9Y5K6; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR SignaLink; Q9Y5K6; -.
DR ChiTaRS; CD2AP; human.
DR EvolutionaryTrace; Q9Y5K6; -.
DR GeneWiki; CD2AP; -.
DR GenomeRNAi; 23607; -.
DR NextBio; 46304; -.
DR PRO; PR:Q9Y5K6; -.
DR Bgee; Q9Y5K6; -.
DR CleanEx; HS_CD2AP; -.
DR Genevestigator; Q9Y5K6; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0031941; C:filamentous actin; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0006461; P:protein complex assembly; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; TAS:ProtInc.
DR InterPro; IPR028445; CD2AP.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR14167:SF7; PTHR14167:SF7; 1.
DR Pfam; PF00018; SH3_1; 1.
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 projection; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Mitosis; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; SH3 domain; SH3-binding.
FT CHAIN 1 639 CD2-associated protein.
FT /FTId=PRO_0000089435.
FT DOMAIN 1 59 SH3 1; truncated.
FT DOMAIN 108 167 SH3 2.
FT DOMAIN 269 330 SH3 3.
FT REGION 1 175 Interaction with ANLN and localization to
FT the midbody.
FT COILED 577 638 Potential.
FT MOTIF 336 352 SH3-binding (Potential).
FT MOTIF 378 397 SH3-binding (Potential).
FT MOTIF 410 422 SH3-binding (Potential).
FT COMPBIAS 336 422 Pro-rich.
FT MOD_RES 224 224 Phosphoserine.
FT MOD_RES 458 458 Phosphoserine.
FT MOD_RES 510 510 Phosphoserine.
FT MOD_RES 514 514 Phosphoserine.
FT VARIANT 581 581 N -> K (in dbSNP:rs34069459).
FT /FTId=VAR_033672.
FT STRAND 4 6
FT STRAND 25 31
FT STRAND 37 42
FT STRAND 45 50
FT HELIX 51 53
FT STRAND 54 56
FT STRAND 112 115
FT STRAND 134 142
FT STRAND 145 150
FT STRAND 153 158
FT HELIX 159 161
FT STRAND 162 164
FT HELIX 489 492
FT HELIX 503 505
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
//
MIM
604241
*RECORD*
*FIELD* NO
604241
*FIELD* TI
*604241 CD2-ASSOCIATED PROTEIN; CD2AP
;;CAS LIGAND WITH MULTIPLE SH3 DOMAINS; CMS
*FIELD* TX
read more
CLONING
P130(Cas) (602941) is a docking protein that is tyrosine-phosphorylated
in response to a variety of extracellular stimuli, such as growth
factors, cell-cell interaction, and cell-matrix interaction, and appears
to play a critical role in the integrin-linked formation of focal
complexes. To understand the growth regulatory pathway of p130(Cas),
Kirsch et al. (1999) used the yeast 2-hybrid system to search for
interacting molecules. They identified a human protein, which they
called CMS for p130(Cas) ligand with multiple SH3 domains, as a direct
binding protein of p130(Cas). CMS is a multifunctional adapter-type
molecule, which is localized in the cytoplasm, membrane ruffles, and
leading edges of cells. Its structure and colocalization with F-actin
(see 102610) and p130(Cas) suggested a function as a scaffolding protein
involved in the dynamic regulation of the actin cytoskeleton. The cDNA
corresponding to CMS encodes a protein of 639 amino acids with a deduced
molecular mass of approximately 70 kD. Amino acid analysis revealed that
CMS contains in its N terminus 3 SH3 domains followed by a proline-rich
region containing binding sites for SH3 domains. Putative actin-binding
sites and a coiled-coil domain are located at the C terminus of the
protein, which also contains a putative leucine zipper motif. CMS mRNA
is ubiquitously expressed in adult and fetal human tissues as an
approximately 5.4-kb transcript, as detected by Northern blot analysis.
Dustin et al. (1998) cloned the mouse homolog of CMS, which they called
CD2AP, that binds the cytoplasmic tail of the adhesion molecule CD2
(186990). Kirsch et al. (1999) stated that the mouse CD2AP protein is
86% identical to human CMS.
GENE FUNCTION
Kirsch et al. (1999) demonstrated that CMS induces vesicle formation and
colocalizes with p130(Cas) and F-actin to membrane ruffles. It also
associates with and is phosphorylated by tyrosine kinases. CMS is able
to homodimerize through the coiled-coil domain located in its C
terminus. There was no evidence for intermolecular or intramolecular
binding via the SH3 domains and PXXP binding.
Dustin et al. (1998) demonstrated that ligand engagement of the adhesion
molecule CD2 initiates the process of protein segregation, CD2
clustering, and cytoskeletal polarization. Although protein segregation
was not dependent on the cytoplasmic domain of CD2, CD2 clustering and
cytoskeletal polarization required an interaction with the CD2
cytoplasmic domain with a novel SH3-containing protein.
MOLECULAR GENETICS
Kim et al. (2003) found the same mutation (604241.0001) in the CD2AP
gene in 2 African Americans with primary focal segmental
glomerulosclerosis (FSGS3; 607832). The mutation affects the splice
acceptor of exon 7 on one allele, replacing 2 nucleotides, GC, with CT.
No stable truncated protein was produced from the alternatively spliced
transcript. Kim et al. (2003) suggested that haploinsufficiency for
CD2AP is a determinant of human susceptibility to glomerular disease.
In a boy with severe early-onset nephrotic syndrome associated with
focal segmental glomerulosclerosis, Lowik et al. (2007) identified a
homozygous mutation in the CD2AP gene (R612X; 604241.0002). There was no
expression of the mutant protein in patient lymphocytes, consistent with
a complete loss of function. Each unaffected parent was heterozygous for
the mutation, indicating that heterozygosity for this mutation does not
result in renal disease.
ANIMAL MODEL
Shih et al. (1999) generated mice lacking CD2AP by targeted disruption.
In Cd2ap-deficient mice, immune function was compromised, but the mice
died from renal failure at 6 to 7 weeks of age. In the kidney, Cd2ap was
expressed primarily in glomerular epithelial cells. Knockout mice
exhibited defects in epithelial cell foot processes, accompanied by
mesangial cell hyperplasia and extracellular matrix deposition. CD2AP
associated with nephrin (602716), which is the primary component of the
slit diaphragm. This observation supports a role for CD2AP in this
specialized cell junction.
Kim et al. (2003) studied Cd2ap heterozygous mice because they exhibit
reduced Cd2ap protein levels. Mice with Cd2ap haploinsufficiency
developed glomerular changes at 9 months of age and had increased
susceptibility to glomerular injury by nephrotoxic antibodies or immune
complexes. Electron microscopic analysis of podocytes revealed defects
in the formation of multivesicular bodies, suggesting an impairment of
the intracellular degradation pathway.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CD2AP
gene to chromosome 6 (TMAP WI-17603).
*FIELD* AV
.0001
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3
CD2AP, IVS6, GC-CT, -1
In 2 patients with primary focal segmental glomerulosclerosis (FSGS3;
607832), Kim et al. (2003) identified a heterozygous splice site
mutation in the splice acceptor of exon 7 on one allele of the CD2AP
gene in which 2 nucleotides, GC, were replaced with CT. CD2AP expression
was lower in these 2 patients compared with control samples. Neither of
2 antibodies used recognized other protein products, suggesting that a
stable truncated CD2AP protein was not generated from mRNA carrying this
exon 7 splice site mutation.
.0002
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3
CD2AP, ARG612TER
In a boy with nephrotic syndrome associated with focal segmental
glomerulosclerosis (607832), Lowik et al. (2007) identified a homozygous
1834C-T transition in exon 18 of the CD2AP gene, resulting in an
arg612-to-ter (R612X) substitution at the C terminus. The mutation
occurred in the second putative actin-binding site in the supercoiled
domain and yielded a protein truncated by only 4%. The boy was born of
consanguineous parents of Mediterranean ancestry, each of whom was
unaffected and carried the mutation in heterozygous state, indicating
that heterozygosity for this mutation does not result in kidney disease.
At age 10 months, he showed failure to thrive and proteinuria associated
with FSGS, mesangial matrix expansion, and mild effacement of the
podocyte processes. There was no expression of the mutant protein in
patient lymphocytes, consistent with a complete loss of function. In
vitro functional expression studies showed that the mutant protein had
significantly decreased F-actin binding efficiency compared to wildtype
(6% of wildtype binding).
*FIELD* RF
1. Dustin, M. L.; Olszowy, M. W.; Holdorf, A. D.; Li, J.; Bromley,
S.; Desai, N.; Widder, P.; Rosenberger, F.; van der Merwe, P. A.;
Allen, P. M.; Shaw, A. S.: A novel adaptor protein orchestrates receptor
patterning and cytoskeletal polarity in T-cell contacts. Cell 94:
667-677, 1998.
2. Kim, J. M.; Wu, H.; Green, G.; Winkler, C. A.; Kopp, J. B.; Miner,
J. H.; Unanue, E. R.; Shaw, A. S.: CD2-associated protein haploinsufficiency
is linked to glomerular disease susceptibility. Science 300: 1298-1300,
2003.
3. Kirsch, K. H.; Georgescu, M.-M.; Ishimaru, S.; Hanafusa, H.: CMS:
an adapter molecule involved in cytoskeletal rearrangements. Proc.
Nat. Acad. Sci. 96: 6211-6216, 1999.
4. Lowik, M. M.; Groenen, P. J. T. A.; Pronk, I.; Lilien, M. R.; Goldschmeding,
R.; Dijkman, H. B.; Levtchenko, E. N.; Monnens, L. A.; van den Heuvel,
L. P.: Focal segmental glomerulosclerosis in a patient homozygous
for a CD2AP mutation. Kidney Int. 72: 1198-1203, 2007.
5. Shih, N.-Y.; Li, J.; Karpitskii, V.; Nguyen, A.; Dustin, M. L.;
Kanagawa, O.; Miner, J. H.; Shaw, A. S.: Congenital nephrotic syndrome
in mice lacking CD2-associated protein. Science 286: 312-315, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/22/2010
Victor A. McKusick - updated: 6/27/2005
Ada Hamosh - updated: 5/27/2003
*FIELD* CD
Ada Hamosh: 10/19/1999
*FIELD* ED
carol: 10/25/2010
ckniffin: 10/22/2010
alopez: 1/29/2010
carol: 2/27/2007
alopez: 7/6/2005
terry: 7/5/2005
terry: 6/27/2005
alopez: 5/28/2003
terry: 5/27/2003
carol: 12/14/2000
alopez: 10/20/1999
*RECORD*
*FIELD* NO
604241
*FIELD* TI
*604241 CD2-ASSOCIATED PROTEIN; CD2AP
;;CAS LIGAND WITH MULTIPLE SH3 DOMAINS; CMS
*FIELD* TX
read more
CLONING
P130(Cas) (602941) is a docking protein that is tyrosine-phosphorylated
in response to a variety of extracellular stimuli, such as growth
factors, cell-cell interaction, and cell-matrix interaction, and appears
to play a critical role in the integrin-linked formation of focal
complexes. To understand the growth regulatory pathway of p130(Cas),
Kirsch et al. (1999) used the yeast 2-hybrid system to search for
interacting molecules. They identified a human protein, which they
called CMS for p130(Cas) ligand with multiple SH3 domains, as a direct
binding protein of p130(Cas). CMS is a multifunctional adapter-type
molecule, which is localized in the cytoplasm, membrane ruffles, and
leading edges of cells. Its structure and colocalization with F-actin
(see 102610) and p130(Cas) suggested a function as a scaffolding protein
involved in the dynamic regulation of the actin cytoskeleton. The cDNA
corresponding to CMS encodes a protein of 639 amino acids with a deduced
molecular mass of approximately 70 kD. Amino acid analysis revealed that
CMS contains in its N terminus 3 SH3 domains followed by a proline-rich
region containing binding sites for SH3 domains. Putative actin-binding
sites and a coiled-coil domain are located at the C terminus of the
protein, which also contains a putative leucine zipper motif. CMS mRNA
is ubiquitously expressed in adult and fetal human tissues as an
approximately 5.4-kb transcript, as detected by Northern blot analysis.
Dustin et al. (1998) cloned the mouse homolog of CMS, which they called
CD2AP, that binds the cytoplasmic tail of the adhesion molecule CD2
(186990). Kirsch et al. (1999) stated that the mouse CD2AP protein is
86% identical to human CMS.
GENE FUNCTION
Kirsch et al. (1999) demonstrated that CMS induces vesicle formation and
colocalizes with p130(Cas) and F-actin to membrane ruffles. It also
associates with and is phosphorylated by tyrosine kinases. CMS is able
to homodimerize through the coiled-coil domain located in its C
terminus. There was no evidence for intermolecular or intramolecular
binding via the SH3 domains and PXXP binding.
Dustin et al. (1998) demonstrated that ligand engagement of the adhesion
molecule CD2 initiates the process of protein segregation, CD2
clustering, and cytoskeletal polarization. Although protein segregation
was not dependent on the cytoplasmic domain of CD2, CD2 clustering and
cytoskeletal polarization required an interaction with the CD2
cytoplasmic domain with a novel SH3-containing protein.
MOLECULAR GENETICS
Kim et al. (2003) found the same mutation (604241.0001) in the CD2AP
gene in 2 African Americans with primary focal segmental
glomerulosclerosis (FSGS3; 607832). The mutation affects the splice
acceptor of exon 7 on one allele, replacing 2 nucleotides, GC, with CT.
No stable truncated protein was produced from the alternatively spliced
transcript. Kim et al. (2003) suggested that haploinsufficiency for
CD2AP is a determinant of human susceptibility to glomerular disease.
In a boy with severe early-onset nephrotic syndrome associated with
focal segmental glomerulosclerosis, Lowik et al. (2007) identified a
homozygous mutation in the CD2AP gene (R612X; 604241.0002). There was no
expression of the mutant protein in patient lymphocytes, consistent with
a complete loss of function. Each unaffected parent was heterozygous for
the mutation, indicating that heterozygosity for this mutation does not
result in renal disease.
ANIMAL MODEL
Shih et al. (1999) generated mice lacking CD2AP by targeted disruption.
In Cd2ap-deficient mice, immune function was compromised, but the mice
died from renal failure at 6 to 7 weeks of age. In the kidney, Cd2ap was
expressed primarily in glomerular epithelial cells. Knockout mice
exhibited defects in epithelial cell foot processes, accompanied by
mesangial cell hyperplasia and extracellular matrix deposition. CD2AP
associated with nephrin (602716), which is the primary component of the
slit diaphragm. This observation supports a role for CD2AP in this
specialized cell junction.
Kim et al. (2003) studied Cd2ap heterozygous mice because they exhibit
reduced Cd2ap protein levels. Mice with Cd2ap haploinsufficiency
developed glomerular changes at 9 months of age and had increased
susceptibility to glomerular injury by nephrotoxic antibodies or immune
complexes. Electron microscopic analysis of podocytes revealed defects
in the formation of multivesicular bodies, suggesting an impairment of
the intracellular degradation pathway.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the CD2AP
gene to chromosome 6 (TMAP WI-17603).
*FIELD* AV
.0001
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3
CD2AP, IVS6, GC-CT, -1
In 2 patients with primary focal segmental glomerulosclerosis (FSGS3;
607832), Kim et al. (2003) identified a heterozygous splice site
mutation in the splice acceptor of exon 7 on one allele of the CD2AP
gene in which 2 nucleotides, GC, were replaced with CT. CD2AP expression
was lower in these 2 patients compared with control samples. Neither of
2 antibodies used recognized other protein products, suggesting that a
stable truncated CD2AP protein was not generated from mRNA carrying this
exon 7 splice site mutation.
.0002
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3
CD2AP, ARG612TER
In a boy with nephrotic syndrome associated with focal segmental
glomerulosclerosis (607832), Lowik et al. (2007) identified a homozygous
1834C-T transition in exon 18 of the CD2AP gene, resulting in an
arg612-to-ter (R612X) substitution at the C terminus. The mutation
occurred in the second putative actin-binding site in the supercoiled
domain and yielded a protein truncated by only 4%. The boy was born of
consanguineous parents of Mediterranean ancestry, each of whom was
unaffected and carried the mutation in heterozygous state, indicating
that heterozygosity for this mutation does not result in kidney disease.
At age 10 months, he showed failure to thrive and proteinuria associated
with FSGS, mesangial matrix expansion, and mild effacement of the
podocyte processes. There was no expression of the mutant protein in
patient lymphocytes, consistent with a complete loss of function. In
vitro functional expression studies showed that the mutant protein had
significantly decreased F-actin binding efficiency compared to wildtype
(6% of wildtype binding).
*FIELD* RF
1. Dustin, M. L.; Olszowy, M. W.; Holdorf, A. D.; Li, J.; Bromley,
S.; Desai, N.; Widder, P.; Rosenberger, F.; van der Merwe, P. A.;
Allen, P. M.; Shaw, A. S.: A novel adaptor protein orchestrates receptor
patterning and cytoskeletal polarity in T-cell contacts. Cell 94:
667-677, 1998.
2. Kim, J. M.; Wu, H.; Green, G.; Winkler, C. A.; Kopp, J. B.; Miner,
J. H.; Unanue, E. R.; Shaw, A. S.: CD2-associated protein haploinsufficiency
is linked to glomerular disease susceptibility. Science 300: 1298-1300,
2003.
3. Kirsch, K. H.; Georgescu, M.-M.; Ishimaru, S.; Hanafusa, H.: CMS:
an adapter molecule involved in cytoskeletal rearrangements. Proc.
Nat. Acad. Sci. 96: 6211-6216, 1999.
4. Lowik, M. M.; Groenen, P. J. T. A.; Pronk, I.; Lilien, M. R.; Goldschmeding,
R.; Dijkman, H. B.; Levtchenko, E. N.; Monnens, L. A.; van den Heuvel,
L. P.: Focal segmental glomerulosclerosis in a patient homozygous
for a CD2AP mutation. Kidney Int. 72: 1198-1203, 2007.
5. Shih, N.-Y.; Li, J.; Karpitskii, V.; Nguyen, A.; Dustin, M. L.;
Kanagawa, O.; Miner, J. H.; Shaw, A. S.: Congenital nephrotic syndrome
in mice lacking CD2-associated protein. Science 286: 312-315, 1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 10/22/2010
Victor A. McKusick - updated: 6/27/2005
Ada Hamosh - updated: 5/27/2003
*FIELD* CD
Ada Hamosh: 10/19/1999
*FIELD* ED
carol: 10/25/2010
ckniffin: 10/22/2010
alopez: 1/29/2010
carol: 2/27/2007
alopez: 7/6/2005
terry: 7/5/2005
terry: 6/27/2005
alopez: 5/28/2003
terry: 5/27/2003
carol: 12/14/2000
alopez: 10/20/1999
MIM
607832
*RECORD*
*FIELD* NO
607832
*FIELD* TI
#607832 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3, SUSCEPTIBILITY TO; FSGS3
;;GLOMERULOSCLEROSIS, FOCAL SEGMENTAL, 3, SUSCEPTIBILITY TO
read more*FIELD* TX
A number sign (#) is used with this entry because susceptibility to this
form of hereditary renal disease, referred to here as focal segmental
glomerulosclerosis-3 (FSGS3), is conferred by haploinsufficiency for
CD2-associated protein (CD2AP; 604241) on chromosome 6p12.
DESCRIPTION
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity
associated clinically with proteinuria, the nephrotic syndrome (NPHS),
and progressive loss of renal function. It is a common cause of
end-stage renal disease (ESRD) (Meyrier, 2005).
For a general phenotypic description and a discussion of genetic
heterogeneity of focal segmental glomerulosclerosis and nephrotic
syndrome, see FSGS1 (603278).
CLINICAL FEATURES
Lowik et al. (2007) reported a boy with severe early-onset nephrotic
syndrome associated with FSGS who was born of consanguineous parents of
Mediterranean ancestry. At age 10 months, he showed failure to thrive,
proteinuria, microscopic hematuria, and anemia. Renal biopsy showed
focal segmental glomerulosclerosis with mesangial matrix expansion and
mild effacement of the podocyte processes. The disease progressed, and
he had successful renal transplant at age 5 years.
MOLECULAR GENETICS
Kim et al. (2003) found that mice with haploinsufficiency for CD2AP
exhibit a phenotype similar to human FSGS. They screened a study
population of 30 African Americans with idiopathic FSGS as well as 15
African Americans with HIV-associated FSGS. As a normal control group,
they selected 45 African Americans who had had HIV infection for at
least 8 years with normal kidney function. Kim et al. (2003) detected 6
distinct DNA variants in 10 of 45 patients that were not present in any
of the control subjects. One nucleotide variant, detected in 2 patients
with primary FSGS, was predicted to alter the expression of CD2AP. This
2-bp substitution altered the exon 7 splice acceptor site (604241.0001).
In a boy with nephrotic syndrome associated with focal segmental
glomerulosclerosis, Lowik et al. (2007) identified a homozygous mutation
in the CD2AP gene (R612X; 604241.0002). There was no expression of the
mutant protein in patient lymphocytes, consistent with a complete loss
of function. Each unaffected parent was heterozygous for the mutation,
indicating that heterozygosity for this mutation does not result in
renal disease.
NOMENCLATURE
In the literature, the clinical term 'nephrotic syndrome' (NPHS) and the
pathologic term 'focal segmental glomerulosclerosis' (FSGS) have often
been used to refer to the same disease entity. In OMIM, these disorders
are classified as NPHS or FSGS according to how they were first
designated in the literature.
*FIELD* RF
1. Kim, J. M.; Wu, H.; Green, G.; Winkler, C. A.; Kopp, J. B.; Miner,
J. H.; Unanue, E. R.; Shaw, A. S.: CD2-associated protein haploinsufficiency
is linked to glomerular disease susceptibility. Science 300: 1298-1300,
2003.
2. Lowik, M. M.; Groenen, P. J. T. A.; Pronk, I.; Lilien, M. R.; Goldschmeding,
R.; Dijkman, H. B.; Levtchenko, E. N.; Monnens, L. A.; van den Heuvel,
L. P.: Focal segmental glomerulosclerosis in a patient homozygous
for a CD2AP mutation. Kidney Int. 72: 1198-1203, 2007.
3. Meyrier, A.: Mechanisms of disease: focal segmental glomerulosclerosis. Nature
Clin. Prac.:Nephrol. 1: 44-54, 2005.
*FIELD* CD
Ada Hamosh: 5/28/2003
*FIELD* ED
carol: 10/25/2010
ckniffin: 10/8/2010
alopez: 1/22/2009
alopez: 5/28/2003
*RECORD*
*FIELD* NO
607832
*FIELD* TI
#607832 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3, SUSCEPTIBILITY TO; FSGS3
;;GLOMERULOSCLEROSIS, FOCAL SEGMENTAL, 3, SUSCEPTIBILITY TO
read more*FIELD* TX
A number sign (#) is used with this entry because susceptibility to this
form of hereditary renal disease, referred to here as focal segmental
glomerulosclerosis-3 (FSGS3), is conferred by haploinsufficiency for
CD2-associated protein (CD2AP; 604241) on chromosome 6p12.
DESCRIPTION
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity
associated clinically with proteinuria, the nephrotic syndrome (NPHS),
and progressive loss of renal function. It is a common cause of
end-stage renal disease (ESRD) (Meyrier, 2005).
For a general phenotypic description and a discussion of genetic
heterogeneity of focal segmental glomerulosclerosis and nephrotic
syndrome, see FSGS1 (603278).
CLINICAL FEATURES
Lowik et al. (2007) reported a boy with severe early-onset nephrotic
syndrome associated with FSGS who was born of consanguineous parents of
Mediterranean ancestry. At age 10 months, he showed failure to thrive,
proteinuria, microscopic hematuria, and anemia. Renal biopsy showed
focal segmental glomerulosclerosis with mesangial matrix expansion and
mild effacement of the podocyte processes. The disease progressed, and
he had successful renal transplant at age 5 years.
MOLECULAR GENETICS
Kim et al. (2003) found that mice with haploinsufficiency for CD2AP
exhibit a phenotype similar to human FSGS. They screened a study
population of 30 African Americans with idiopathic FSGS as well as 15
African Americans with HIV-associated FSGS. As a normal control group,
they selected 45 African Americans who had had HIV infection for at
least 8 years with normal kidney function. Kim et al. (2003) detected 6
distinct DNA variants in 10 of 45 patients that were not present in any
of the control subjects. One nucleotide variant, detected in 2 patients
with primary FSGS, was predicted to alter the expression of CD2AP. This
2-bp substitution altered the exon 7 splice acceptor site (604241.0001).
In a boy with nephrotic syndrome associated with focal segmental
glomerulosclerosis, Lowik et al. (2007) identified a homozygous mutation
in the CD2AP gene (R612X; 604241.0002). There was no expression of the
mutant protein in patient lymphocytes, consistent with a complete loss
of function. Each unaffected parent was heterozygous for the mutation,
indicating that heterozygosity for this mutation does not result in
renal disease.
NOMENCLATURE
In the literature, the clinical term 'nephrotic syndrome' (NPHS) and the
pathologic term 'focal segmental glomerulosclerosis' (FSGS) have often
been used to refer to the same disease entity. In OMIM, these disorders
are classified as NPHS or FSGS according to how they were first
designated in the literature.
*FIELD* RF
1. Kim, J. M.; Wu, H.; Green, G.; Winkler, C. A.; Kopp, J. B.; Miner,
J. H.; Unanue, E. R.; Shaw, A. S.: CD2-associated protein haploinsufficiency
is linked to glomerular disease susceptibility. Science 300: 1298-1300,
2003.
2. Lowik, M. M.; Groenen, P. J. T. A.; Pronk, I.; Lilien, M. R.; Goldschmeding,
R.; Dijkman, H. B.; Levtchenko, E. N.; Monnens, L. A.; van den Heuvel,
L. P.: Focal segmental glomerulosclerosis in a patient homozygous
for a CD2AP mutation. Kidney Int. 72: 1198-1203, 2007.
3. Meyrier, A.: Mechanisms of disease: focal segmental glomerulosclerosis. Nature
Clin. Prac.:Nephrol. 1: 44-54, 2005.
*FIELD* CD
Ada Hamosh: 5/28/2003
*FIELD* ED
carol: 10/25/2010
ckniffin: 10/8/2010
alopez: 1/22/2009
alopez: 5/28/2003