Q9JLQ0 (CD2AP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CD2-associated protein

Alternative name(s):
Mesenchyme-to-epithelium transition protein with SH3 domains 1
Short name=METS-1

Gene names

Name:	Cd2ap
Synonyms:	Mets1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	637 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for cytokinesis By similarity. 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. Ref.6
Subunit structure	Self-associates. Homodimer Potential. Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts with RIN3 By similarity. Interacts with DDN; interaction is direct. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Cytoplasm › cytoskeleton. Cell projection › ruffle. Note: During late anaphase and telophase, concentrates in the vicinity of the midzone microtubules and in the midbody in late telophase By similarity. Located at podocyte slit diaphragm between podocyte foot processes. Ref.6 Ref.7
Domain	Potential homodimerization is mediated by the coiled coil domain By similarity.
Post-translational modification	Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-Src By similarity.
Disruption phenotype	Death at 6 to 7 weeks of age from renal failure. Mice show defects in epithelial foot processes, accompanied by mesangial cell hyperplasia and extracellular matrix deposition. Ref.6
Sequence similarities	Contains 3 SH3 domains.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cell projection Cytoplasm Cytoskeleton
Domain	Coiled coil Repeat SH3 domain SH3-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell cortex Inferred from sequence orthology PubMed 17056598. Source: MGI cytosol Traceable author statement. Source: Reactome filamentous actin Inferred from electronic annotation. Source: Compara nucleolus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay PubMed 15924139. Source: MGI ruffle Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 637

637

CD2-associated protein

PRO_0000089436

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 By similarity

Coiled coil

578 – 636

59

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

224

1

Phosphoserine By similarity

Modified residue

458

1

Phosphoserine Ref.12

Modified residue

510

1

Phosphoserine By similarity

Modified residue

514

1

Phosphoserine By similarity

Experimental info

Sequence conflict

78

1

V → E in AAF73150. Ref.2

Sequence conflict

107

1

Missing in AAC36099. Ref.1

Sequence conflict

110

1

K → Q in AAC36099. Ref.1

Sequence conflict

244

1

P → R in AAC36099. Ref.1

Sequence conflict

295 – 297

3

IIH → LS in AAC36099. Ref.1

Sequence conflict

392

1

P → PTAPTKA in AAC36099. Ref.1

Sequence conflict

545

1

S → P in AAF73150. Ref.2

Sequence conflict

545

1

S → P in CAD30510. Ref.3

Sequence conflict

545

1

S → P in AAH19744. Ref.5

Sequence conflict

578

1

R → K in AAF73150. Ref.2

Sequence conflict

578

1

R → K in CAD30510. Ref.3

Sequence conflict

578

1

R → K in AAH19744. Ref.5

Secondary structure

1

.

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637

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Beta strand

14 – 17

4

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

113 – 115

3

Beta strand

134 – 142

9

Beta strand

145 – 150

6

Beta strand

153 – 158

6

Turn

159 – 161

3

Beta strand

270 – 278

9

Beta strand

283 – 287

5

Beta strand

295 – 301

7

Beta strand

303 – 313

11

Beta strand

316 – 321

6

Helix

322 – 324

3

Beta strand

325 – 329

5

Sequences

	Sequence		Length	Mass (Da)
	Q9JLQ0 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 0B618FE82AF12332	FASTA	637	70,450
	10 20 30 40 50 60 MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP DNFVKEIKRE 70 80 90 100 110 120 TEPKDDNLPI KRERQGNVAS LVQRISTYGL PAGGIQPHPQ TKAIKKKTKK RQCKVLFDYS 130 140 150 160 170 180 PQNEDELELI VGDVIDVIEE VEEGWWSGTL NNKLGLFPSN FVKELESTED GETHNAQEES 190 200 210 220 230 240 EVPLTGPTSP LPSPGNGSEP APGSVAQPKK IRGIGFGDIF KEGSVKLRTR TSSSETEEKK 250 260 270 280 290 300 TEKPLILQPL GSRTQNVEVT KPDVDGKIKA KEYCRTLFPY TGTNEDELTF REGEIIHLIS 310 320 330 340 350 360 KETGEAGWWK GELNGKEGVF PDNFAVQISE LDKDFPKPKK PPPPAKGPAP KPDLSAAEKK 370 380 390 400 410 420 AFPLKAEEKD EKSLLEQKPS KPAAPQVPPK KPTAPTKASN LLRSPGAVYP KRPEKPVPPP 430 440 450 460 470 480 PPAAKINGEV SIISSKIDTE PVSKPKLDPE QLPVRPKSVD LDAFVARNSK ETDDVNFDDI 490 500 510 520 530 540 ASSENLLHLT ANRPKMPGRR LPGRFNGGHS PTQSPEKTLK LPKEDDSGNL KPLEFKKDAS 550 560 570 580 590 600 YSSKSSLSTP SSASKVNTAA FLTPLELKAK AEADDGKRNS VDELRAQIIE LLCIVDALKK 610 620 630 DHGKELEKLR KELEEEKAMR SNLEVEIAKL KKAVLLS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts." 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. Cell 94:667-677(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CD2.
[2]	"In vivo interaction of the adapter protein CD2-associated protein with the type 2 polycystic kidney disease protein, polycystin-2." Lehtonen S., Ora A., Olkkonen V.M., Geng L., Zerial M., Somlo S., Lehtonen E. J. Biol. Chem. 275:32888-32893(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PKD2.
[3]	"Role of the interaction between CD2AP and c-Cbl." Meton I., Le Marchand-Brustel Y., Cormont M. Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 394-637. Tissue: Mammary tumor.
[6]	"Congenital nephrotic syndrome in mice lacking CD2-associated protein." Shih N.Y., Li J., Karpitskii V., Nguyen A., Dustin M.L., Kanagawa O., Miner J.H., Shaw A.S. Science 286:312-315(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NPHS1, DISRUPTION PHENOTYPE.
[7]	"CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain." Shih N.Y., Li J., Cotran R., Mundel P., Miner J.H., Shaw A.S. Am. J. Pathol. 159:2303-2308(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NPHS1.
[8]	"Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin." Schwarz K., Simons M., Reiser J., Saleem M.A., Faul C., Kriz W., Shaw A.S., Holzman L.B., Mundel P. J. Clin. Invest. 108:1621-1629(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPHS1 AND NPHS2.
[9]	"CD2-associated protein directly interacts with the actin cytoskeleton." Lehtonen S., Zhao F., Lehtonen E. Am. J. Physiol. 283:F734-F743(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH F-ACTIN.
[10]	"A WT1 co-regulator controls podocyte phenotype by shuttling between adhesion structures and nucleus." Srichai M.B., Konieczkowski M., Padiyar A., Konieczkowski D.J., Mukherjee A., Hayden P.S., Kamat S., El-Meanawy M.A., Khan S., Mundel P., Lee S.B., Bruggeman L.A., Schelling J.R., Sedor J.R. J. Biol. Chem. 279:14398-14408(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WTIP.
[11]	"Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes." Asanuma K., Campbell K.N., Kim K., Faul C., Mundel P. Proc. Natl. Acad. Sci. U.S.A. 104:10134-10139(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDN.
[12]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, MASS SPECTROMETRY. Tissue: Macrophage.
[13]	"The high resolution NMR structure of the third SH3 domain of CD2AP." Ortega Roldan J.L., Romero Romero M.L., Ora A., Ab E., Lopez Mayorga O., Azuaga A.I., van Nuland N.A. J. Biomol. NMR 39:331-336(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 270-329.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF077003 mRNA. Translation: AAC36099.1.
AF149092 mRNA. Translation: AAF73150.1.
AJ459109 mRNA. Translation: CAD30510.1.
AC111082 Genomic DNA. No translation available.
BC019744 mRNA. Translation: AAH19744.1.

IPI

IPI00268688.

RefSeq

NP_033977.3. NM_009847.3.

UniGene

Mm.218637.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JTE	NMR	-	A	270-329	[»]
2KRM	NMR	-	A	2-58	[»]
2KRN	NMR	-	A	111-166	[»]
2KRO	NMR	-	A	270-329	[»]

ProteinModelPortal

Q9JLQ0.

SMR

Q9JLQ0. Positions 2-329, 475-503.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9JLQ0. 15 interactions.

MINT

MINT-255809.

STRING

10090.ENSMUSP00000024709.

PTM databases

PhosphoSite

Q9JLQ0.

Proteomic databases

PaxDb

Q9JLQ0.

PRIDE

Q9JLQ0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000024709; ENSMUSP00000024709; ENSMUSG00000061665.

GeneID

12488.

KEGG

mmu:12488.

Organism-specific databases

CTD

23607.

MGI

MGI:1330281. Cd2ap.

Phylogenomic databases

eggNOG

NOG319250.

GeneTree

ENSGT00530000063594.

HOGENOM

HOG000231405.

HOVERGEN

HBG057824.

InParanoid

Q9JLQ0.

KO

K13738.

OMA

FAVQINE.

OrthoDB

EOG4GMTWW.

Enzyme and pathway databases

Reactome

REACT_137402. Cell-Cell communication.

Gene expression databases

Bgee

Q9JLQ0.

CleanEx

MM_CD2AP.

Genevestigator

Q9JLQ0.

GermOnline

ENSMUSG00000061665. Mus musculus.

Family and domain databases

InterPro

IPR000108. p67phox.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00018. SH3_1. 3 hits.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

SMART

SM00326. SH3. 3 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 3 hits.

PROSITE

PS50002. SH3. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CD2AP. mouse.

EvolutionaryTrace

Q9JLQ0.

NextBio

281400.

SOURCE

Search...

Entry information

Entry name

CD2AP_MOUSE

Accession

Primary (citable) accession number: Q9JLQ0
Secondary accession number(s): E9QL86 , O88903, Q8K4Z1, Q8VCI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program