Reviewed, UniProtKB/Swiss-Prot Q9Y5K6 (CD2AP_HUMAN)

Names and origin

Protein names

Recommended name:
    CD2-associated protein
Alternative name(s):
    Cas ligand with multiple SH3 domains
    Adapter protein CMS

Gene names

Name:

CD2AP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	639 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.
Subunit structure	Homodimer. Interacts through its second SH3 domain with the phosphorylated CBL C-terminus. Interacts with BCAR1/p130Cas SH3 domain. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP By similarity. Interacts with FAM125A and ARHGAP17. Interacts with ANLN, CD2 and CBLB.
Subcellular location	Cytoplasm › cytoskeletonBy similarity. Cell projection › ruffleBy similarity. Note= Colocalizes with F-actin and BCAR1/p130Cas in membrane ruffles. Located at podocyte slit diaphragm between podocyte foot processes By similarity. During late anaphase and telophase, concentrates in the vicinity of the midzone microtubules and in the midbody in late telophase.
Tissue specificity	Widely expressed in fetal and adult tissues.
Domain	The Pro-rich domain may mediate binding to SH3 domains. Potential homodimerization is mediated by the coiled coil domain.
Post-translational modification	Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-Src.
Involvement in disease	Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]. FSGS3 is a common renal lesion characterized by increased urinary protein excretion and decreasing kidney function. Renal insufficiency often progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS is defined by the presence of segmental sclerosis in glomeruli, and is seen in all ethnic groups, although it is particularly common in individuals of African descent. FSGS occurs as an isolated primary condition or secondary to disorders as HIV infection, obesity, hypertension and diabetes. FSGS may also be inherited as a mendelian trait.
Sequence similarities	Contains 3 SH3 domains.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat SH3 domain SH3-binding
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein complex assembly Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Non-traceable author statement. Source: ProtInc substrate-bound cell migration, cell extension Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Ref.1 Traceable author statement. Source: ProtInc filamentous actin Ref.1 Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA ruffle Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	SH3 domain binding Ref.1 Inferred from direct assay. Source: UniProtKB structural constituent of cytoskeleton Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-298152,EBI-375543
FYN	P06241	1	EBI-298152,EBI-515315
HCK	P08631	1	EBI-298152,EBI-346340
SOS1	Q07889	1	EBI-298152,EBI-297487
SOS2	Q07890	1	EBI-298152,EBI-298181

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 639

639

CD2-associated protein

PRO_0000089435

Regions

Domain

1 – 59

59

SH3 1; truncated

Domain

108 – 167

60

SH3 2

Domain

269 – 330

62

SH3 3

Region

1 – 175

175

Interaction with ANLN and localization to the midbody

Coiled coil

577 – 638

62

Potential

Motif

336 – 352

17

SH3-binding Potential

Motif

378 – 397

20

SH3-binding Potential

Motif

410 – 422

13

SH3-binding Potential

Compositional bias

336 – 422

87

Pro-rich

Amino acid modifications

Modified residue

88

1

Phosphotyrosine

Modified residue

458

1

Phosphoserine

Modified residue

510

1

Phosphoserine

Natural variations

Natural variant

581

1

N → K: dbSNP rs34069459.

VAR_033672

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

639

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Beta strand

25 – 31

7

Beta strand

37 – 42

6

Beta strand

45 – 50

6

Helix

51 – 53

3

Beta strand

54 – 56

3

Beta strand

112 – 114

3

Beta strand

134 – 136

3

Beta strand

141 – 152

12

Beta strand

154 – 158

5

Turn

159 – 161

3

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5K6-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 7576509C7ED5B343	FASTA	639	71,451
	10 20 30 40 50 60 MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP DNFVKEIKRE 70 80 90 100 110 120 TEFKDDSLPI KRERHGNVAS LVQRISTYGL PAGGIQPHPQ TKNIKKKTKK RQCKVLFEYI 130 140 150 160 170 180 PQNEDELELK VGDIIDINEE VEEGWWSGTL NNKLGLFPSN FVKELEVTDD GETHEAQDDS 190 200 210 220 230 240 ETVLAGPTSP IPSLGNVSET ASGSVTQPKK IRGIGFGDIF KEGSVKLRTR TSSSETEEKK 250 260 270 280 290 300 PEKPLILQSL GPKTQSVEIT KTDTEGKIKA KEYCRTLFAY EGTNEDELTF KEGEIIHLIS 310 320 330 340 350 360 KETGEAGWWR GELNGKEGVF PDNFAVQINE LDKDFPKPKK PPPPAKAPAP KPELIAAEKK 370 380 390 400 410 420 YFSLKPEEKD EKSTLEQKPS KPAAPQVPPK KPTPPTKASN LLRSSGTVYP KRPEKPVPPP 430 440 450 460 470 480 PPIAKINGEV SSISSKFETE PVSKLKLDSE QLPLRPKSVD FDSLTVRTSK ETDVVNFDDI 490 500 510 520 530 540 ASSENLLHLT ANRPKMPGRR LPGRFNGGHS PTHSPEKILK LPKEEDSANL KPSELKKDTC 550 560 570 580 590 600 YSPKPSVYLS TPSSASKANT TAFLTPLEIK AKVETDDVKK NSLDELRAQI IELLCIVEAL 610 620 630 KKDHGKELEK LRKDLEEEKT MRSNLEMEIE KLKKAVLSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CMS: an adapter molecule involved in cytoskeletal rearrangements." Kirsch K.H., Georgescu M.M., Ishimaru S., Hanafusa H. Proc. Natl. Acad. Sci. U.S.A. 96:6211-6216(1999) [PubMed: 10339567] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, INTERACTION WITH BCAR1.
[2]	"Human homolog of CD2AP." Ora A., Toppinen M., Lehtonen E. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	The German cDNA consortium Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 548-639. Tissue: Uterus.
[7]	"The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction." Kirsch K.H., Georgescu M.M., Shishido T., Langdon W.Y., Birge R.B., Hanafusa H. J. Biol. Chem. 276:4957-4963(2001) [PubMed: 11067845] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH CBL, HOMODIMERIZATION.
[8]	"CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility." Kim J.M., Wu H., Green G., Winkler C.A., Kopp J.B., Miner J.H., Unanue E.R., Shaw A.S. Science 300:1298-1300(2003) [PubMed: 12764198] [Abstract] Cited for: GLOMERULAR DISEASE SUSCEPTIBILITY.
[9]	"Clues to CD2-associated protein involvement in cytokinesis." Monzo P., Gauthier N.C., Keslair F., Loubat A., Field C.M., Le Marchand-Brustel Y., Cormont M. Mol. Biol. Cell 16:2891-2902(2005) [PubMed: 15800069] [Abstract] Cited for: FUNCTION, INTERACTION WITH ANLN, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-88, MASS SPECTROMETRY.
[11]	"A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells." Wells C.D., Fawcett J.P., Traweger A., Yamanaka Y., Goudreault M., Elder K., Kulkarni S., Gish G., Virag C., Lim C., Colwill K., Starostine A., Metalnikov P., Pawson T. Cell 125:535-548(2006) [PubMed: 16678097] [Abstract] Cited for: INTERACTION WITH ARHGAP17.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-510, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP." Konishi H., Tashiro K., Murata Y., Nabeshi H., Yamauchi E., Taniguchi H. J. Biol. Chem. 281:28919-28931(2006) [PubMed: 16895919] [Abstract] Cited for: INTERACTION WITH FAM125A.
[14]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, MASS SPECTROMETRY. Tissue: Platelet.
[15]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, MASS SPECTROMETRY.
[16]	"Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain." Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I., Bravo J. J. Biol. Chem. 281:38845-38853(2006) [PubMed: 17020880] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-62 IN COMPLEXES WITH CD2 AND CBLB, SUBUNIT.
[17]	"Solution structure of the second SH3 domain of human CMS and a newly identified binding site at the C-terminus of c-Cbl." Yao B., Zhang J., Dai H., Sun J., Jiao Y., Tang Y., Wu J., Shi Y. Biochim. Biophys. Acta 1774:35-43(2007) [PubMed: 17188587] [Abstract] Cited for: STRUCTURE BY NMR OF 111-166, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF146277 mRNA. Translation: AAD34595.1.
AF164377 mRNA. Translation: AAF80495.1.
AL355353, AL358178 Genomic DNA. Translation: CAH73238.1.
AL358178, AL355353 Genomic DNA. Translation: CAI16839.1.
CH471081 Genomic DNA. Translation: EAX04319.1.
BC069444 mRNA. Translation: AAH69444.1.
AL050105 mRNA. Translation: CAB43274.1.

PIR

T13151.

RefSeq

NP_036252.1.

UniGene

Hs.485518

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FEI	NMR	-	A	111-166	[»]
2J6F	X-ray	1.70	A	1-62	[»]
2J6K	X-ray	2.77	A/B/C/D/E/F/G/H/I/J/K/L	1-62	[»]
2J6O	X-ray	2.23	A	1-62	[»]
2J7I	X-ray	2.90	A/B	1-62	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y5K6.

PTM databases

PhosphoSite

Q9Y5K6.

Genome annotation databases

Ensembl

ENSG00000198087. Homo sapiens. [Contig view]

GeneID

23607.

KEGG

hsa:23607.

Organism-specific databases

H-InvDB

HIX0005942.

HGNC

HGNC:14258. CD2AP.

HPA

CAB004352.
HPA003267.
HPA003326.

MIM

604241. gene.
607832. phenotype.

PharmGKB

PA26208.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

Q9Y5K6.

Gene expression databases

ArrayExpress

Q9Y5K6.

CleanEx

HS_CD2AP.

GermOnline

ENSG00000198087. Homo sapiens.

Family and domain databases

InterPro

IPR000108. Neu_cyt_fact_2.
IPR001452. SH3.
[Graphical view]

Pfam

PF00018. SH3_1. 3 hits.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

ProDom

PD000066. SH3. 3 hits.
[