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Q9JLQ0 (CD2AP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length637 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation. 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. Ref.6

Subunit structure

Self-associates. Homodimer Potential. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with DDN; interaction is direct. 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. Interacts directly with RET (inactive) and CBLC; upon RET activation by GDNF suggested to dissociate from RET as CBLC:CD2AP complex. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Subcellular location

Cytoplasmcytoskeleton. Cell projectionruffle. 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

Tissue specificity

Expressed in podocytes (at protein level). Ref.12

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 processCell cycle
Cell division
Mitosis
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
   DomainCoiled coil
Repeat
SH3 domain
SH3-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell migration

Inferred from electronic annotation. Source: Ensembl

mitotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of transforming growth factor beta1 production

Inferred from genetic interaction PubMed 21911934. Source: MGI

positive regulation of protein localization to nucleus

Inferred from genetic interaction PubMed 21911934. Source: MGI

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of actin cytoskeleton reorganization

Inferred from genetic interaction PubMed 21911934. Source: MGI

regulation of receptor-mediated endocytosis

Inferred from electronic annotation. Source: Ensembl

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

vesicle organization

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell cortex

Inferred from sequence orthology PubMed 17056598. Source: MGI

cell-cell junction

Inferred from direct assay PubMed 23793062. Source: MGI

cytoplasm

Inferred from direct assay Ref.2. Source: MGI

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle

Inferred from electronic annotation. Source: Ensembl

filamentous actin

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay PubMed 15924139. Source: MGI

ruffle

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction Ref.2. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 637637CD2-associated protein
PRO_0000089436

Regions

Domain1 – 5959SH3 1; truncated
Domain108 – 16760SH3 2
Domain269 – 33062SH3 3
Region1 – 175175Interaction with ANLN and localization to the midbody By similarity
Coiled coil578 – 63659 Potential
Motif336 – 35217SH3-binding Potential
Motif378 – 39720SH3-binding Potential
Motif410 – 42213SH3-binding Potential
Compositional bias336 – 42287Pro-rich

Amino acid modifications

Modified residue2241Phosphoserine By similarity
Modified residue4581Phosphoserine Ref.13
Modified residue5101Phosphoserine By similarity
Modified residue5141Phosphoserine By similarity

Experimental info

Sequence conflict781V → E in AAF73150. Ref.2
Sequence conflict1071Missing in AAC36099. Ref.1
Sequence conflict1101K → Q in AAC36099. Ref.1
Sequence conflict2441P → R in AAC36099. Ref.1
Sequence conflict295 – 2973IIH → LS in AAC36099. Ref.1
Sequence conflict3921P → PTAPTKA in AAC36099. Ref.1
Sequence conflict5451S → P in AAF73150. Ref.2
Sequence conflict5451S → P in CAD30510. Ref.3
Sequence conflict5451S → P in AAH19744. Ref.5
Sequence conflict5781R → K in AAF73150. Ref.2
Sequence conflict5781R → K in CAD30510. Ref.3
Sequence conflict5781R → K in AAH19744. Ref.5

Secondary structure

.................................... 637
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9JLQ0 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 0B618FE82AF12332

FASTA63770,450
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction."
Tsui C.C., Pierchala B.A.
J. Neurosci. 28:8789-8800(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RET, TISSUE SPECIFICITY.
[13]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"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.
CCDSCCDS50114.1.
RefSeqNP_033977.3. NM_009847.3.
UniGeneMm.218637.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JTENMR-A270-329[»]
2KRMNMR-A2-58[»]
2KRNNMR-A111-166[»]
2KRONMR-A270-329[»]
2LZ6NMR-B270-329[»]
2MCNNMR-A2-58[»]
ProteinModelPortalQ9JLQ0.
SMRQ9JLQ0. Positions 2-329, 475-503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198584. 19 interactions.
IntActQ9JLQ0. 20 interactions.
MINTMINT-255809.
STRING10090.ENSMUSP00000024709.

PTM databases

PhosphoSiteQ9JLQ0.

Proteomic databases

MaxQBQ9JLQ0.
PaxDbQ9JLQ0.
PRIDEQ9JLQ0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000024709; ENSMUSP00000024709; ENSMUSG00000061665.
GeneID12488.
KEGGmmu:12488.
UCSCuc008cot.1. mouse.

Organism-specific databases

CTD23607.
MGIMGI:1330281. Cd2ap.

Phylogenomic databases

eggNOGNOG319250.
GeneTreeENSGT00530000063594.
HOGENOMHOG000231405.
HOVERGENHBG057824.
InParanoidQ9JLQ0.
KOK13738.
OMAVHDDELT.
OrthoDBEOG7W41BC.
TreeFamTF350191.

Enzyme and pathway databases

ReactomeREACT_223082. Cell-Cell communication.

Gene expression databases

BgeeQ9JLQ0.
CleanExMM_CD2AP.
GenevestigatorQ9JLQ0.

Family and domain databases

InterProIPR028445. CD2AP.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR14167:SF23. PTHR14167:SF23. 1 hit.
PfamPF00018. SH3_1. 1 hit.
PF14604. SH3_9. 2 hits.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00326. SH3. 3 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 3 hits.
PROSITEPS50002. SH3. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCD2AP. mouse.
EvolutionaryTraceQ9JLQ0.
NextBio281400.
PROQ9JLQ0.
SOURCESearch...

Entry information

Entry nameCD2AP_MOUSE
AccessionPrimary (citable) accession number: Q9JLQ0
Secondary accession number(s): E9QL86 expand/collapse secondary AC list , O88903, Q8K4Z1, Q8VCI9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot