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Protein

CD2-associated protein

Gene

Cd2ap

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiREACT_293748. Nephrin interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
CD2-associated protein
Alternative name(s):
Mesenchyme-to-epithelium transition protein with SH3 domains 1
Short name:
METS-1
Gene namesi
Name:Cd2ap
Synonyms:Mets1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1330281. Cd2ap.

Subcellular locationi

  • 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.By similarity

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cell cortex Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: Reactome
  • endocytic vesicle Source: Ensembl
  • extracellular exosome Source: MGI
  • filamentous actin Source: MGI
  • nucleolus Source: MGI
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: MGI
  • ruffle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 637637CD2-associated proteinPRO_0000089436Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei224 – 2241PhosphoserineBy similarity
Modified residuei458 – 4581Phosphoserine1 Publication
Modified residuei510 – 5101PhosphoserineBy similarity
Modified residuei514 – 5141PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-Src.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9JLQ0.
PaxDbiQ9JLQ0.
PRIDEiQ9JLQ0.

PTM databases

PhosphoSiteiQ9JLQ0.

Expressioni

Tissue specificityi

Expressed in podocytes (at protein level).1 Publication

Gene expression databases

BgeeiQ9JLQ0.
CleanExiMM_CD2AP.
GenevisibleiQ9JLQ0. MM.

Interactioni

Subunit structurei

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.Curated9 Publications

Protein-protein interaction databases

BioGridi198584. 19 interactions.
IntActiQ9JLQ0. 21 interactions.
MINTiMINT-255809.
STRINGi10090.ENSMUSP00000024709.

Structurei

Secondary structure

1
637
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 63Combined sources
Beta strandi8 – 103Combined sources
Beta strandi14 – 174Combined sources
Beta strandi25 – 317Combined sources
Beta strandi37 – 426Combined sources
Beta strandi45 – 506Combined sources
Helixi51 – 533Combined sources
Beta strandi54 – 563Combined sources
Beta strandi113 – 1153Combined sources
Beta strandi134 – 1429Combined sources
Beta strandi145 – 1506Combined sources
Beta strandi153 – 1586Combined sources
Turni159 – 1613Combined sources
Beta strandi270 – 2789Combined sources
Beta strandi283 – 2875Combined sources
Beta strandi295 – 3017Combined sources
Beta strandi303 – 31311Combined sources
Beta strandi316 – 3216Combined sources
Helixi322 – 3243Combined sources
Beta strandi325 – 3295Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JTENMR-A270-329[»]
2KRMNMR-A2-58[»]
2KRNNMR-A111-166[»]
2KRONMR-A270-329[»]
2LZ6NMR-B270-329[»]
2MCNNMR-A2-58[»]
ProteinModelPortaliQ9JLQ0.
SMRiQ9JLQ0. Positions 2-329, 475-503.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9JLQ0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 5959SH3 1; truncatedPROSITE-ProRule annotationAdd
BLAST
Domaini108 – 16760SH3 2PROSITE-ProRule annotationAdd
BLAST
Domaini269 – 33062SH3 3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 175175Interaction with ANLN and localization to the midbodyBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili578 – 63659Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi336 – 35217SH3-bindingSequence AnalysisAdd
BLAST
Motifi378 – 39720SH3-bindingSequence AnalysisAdd
BLAST
Motifi410 – 42213SH3-bindingSequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi336 – 42287Pro-richAdd
BLAST

Domaini

Potential homodimerization is mediated by the coiled coil domain.By similarity

Sequence similaritiesi

Contains 3 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiNOG319250.
GeneTreeiENSGT00530000063594.
HOGENOMiHOG000231405.
HOVERGENiHBG057824.
InParanoidiQ9JLQ0.
KOiK13738.
OMAiVHDDELT.
OrthoDBiEOG7W41BC.
TreeFamiTF350191.

Family and domain databases

InterProiIPR028445. CD2AP.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR14167:SF23. PTHR14167:SF23. 1 hit.
PfamiPF00018. SH3_1. 1 hit.
PF14604. SH3_9. 2 hits.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
PROSITEiPS50002. SH3. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JLQ0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP
60 70 80 90 100
DNFVKEIKRE TEPKDDNLPI KRERQGNVAS LVQRISTYGL PAGGIQPHPQ
110 120 130 140 150
TKAIKKKTKK RQCKVLFDYS PQNEDELELI VGDVIDVIEE VEEGWWSGTL
160 170 180 190 200
NNKLGLFPSN FVKELESTED GETHNAQEES EVPLTGPTSP LPSPGNGSEP
210 220 230 240 250
APGSVAQPKK IRGIGFGDIF KEGSVKLRTR TSSSETEEKK TEKPLILQPL
260 270 280 290 300
GSRTQNVEVT KPDVDGKIKA KEYCRTLFPY TGTNEDELTF REGEIIHLIS
310 320 330 340 350
KETGEAGWWK GELNGKEGVF PDNFAVQISE LDKDFPKPKK PPPPAKGPAP
360 370 380 390 400
KPDLSAAEKK AFPLKAEEKD EKSLLEQKPS KPAAPQVPPK KPTAPTKASN
410 420 430 440 450
LLRSPGAVYP KRPEKPVPPP PPAAKINGEV SIISSKIDTE PVSKPKLDPE
460 470 480 490 500
QLPVRPKSVD LDAFVARNSK ETDDVNFDDI ASSENLLHLT ANRPKMPGRR
510 520 530 540 550
LPGRFNGGHS PTQSPEKTLK LPKEDDSGNL KPLEFKKDAS YSSKSSLSTP
560 570 580 590 600
SSASKVNTAA FLTPLELKAK AEADDGKRNS VDELRAQIIE LLCIVDALKK
610 620 630
DHGKELEKLR KELEEEKAMR SNLEVEIAKL KKAVLLS
Length:637
Mass (Da):70,450
Last modified:July 27, 2011 - v3
Checksum:i0B618FE82AF12332
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti78 – 781V → E in AAF73150 (PubMed:10913159).Curated
Sequence conflicti107 – 1071Missing in AAC36099 (PubMed:9741631).Curated
Sequence conflicti110 – 1101K → Q in AAC36099 (PubMed:9741631).Curated
Sequence conflicti244 – 2441P → R in AAC36099 (PubMed:9741631).Curated
Sequence conflicti295 – 2973IIH → LS in AAC36099 (PubMed:9741631).Curated
Sequence conflicti392 – 3921P → PTAPTKA in AAC36099 (PubMed:9741631).Curated
Sequence conflicti545 – 5451S → P in AAF73150 (PubMed:10913159).Curated
Sequence conflicti545 – 5451S → P in CAD30510 (Ref. 3) Curated
Sequence conflicti545 – 5451S → P in AAH19744 (PubMed:15489334).Curated
Sequence conflicti578 – 5781R → K in AAF73150 (PubMed:10913159).Curated
Sequence conflicti578 – 5781R → K in CAD30510 (Ref. 3) Curated
Sequence conflicti578 – 5781R → K in AAH19744 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS50114.1.
RefSeqiNP_033977.3. NM_009847.3.
UniGeneiMm.218637.

Genome annotation databases

EnsembliENSMUST00000024709; ENSMUSP00000024709; ENSMUSG00000061665.
GeneIDi12488.
KEGGimmu:12488.
UCSCiuc008cot.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS50114.1.
RefSeqiNP_033977.3. NM_009847.3.
UniGeneiMm.218637.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JTENMR-A270-329[»]
2KRMNMR-A2-58[»]
2KRNNMR-A111-166[»]
2KRONMR-A270-329[»]
2LZ6NMR-B270-329[»]
2MCNNMR-A2-58[»]
ProteinModelPortaliQ9JLQ0.
SMRiQ9JLQ0. Positions 2-329, 475-503.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198584. 19 interactions.
IntActiQ9JLQ0. 21 interactions.
MINTiMINT-255809.
STRINGi10090.ENSMUSP00000024709.

PTM databases

PhosphoSiteiQ9JLQ0.

Proteomic databases

MaxQBiQ9JLQ0.
PaxDbiQ9JLQ0.
PRIDEiQ9JLQ0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024709; ENSMUSP00000024709; ENSMUSG00000061665.
GeneIDi12488.
KEGGimmu:12488.
UCSCiuc008cot.1. mouse.

Organism-specific databases

CTDi23607.
MGIiMGI:1330281. Cd2ap.

Phylogenomic databases

eggNOGiNOG319250.
GeneTreeiENSGT00530000063594.
HOGENOMiHOG000231405.
HOVERGENiHBG057824.
InParanoidiQ9JLQ0.
KOiK13738.
OMAiVHDDELT.
OrthoDBiEOG7W41BC.
TreeFamiTF350191.

Enzyme and pathway databases

ReactomeiREACT_293748. Nephrin interactions.

Miscellaneous databases

ChiTaRSiCd2ap. mouse.
EvolutionaryTraceiQ9JLQ0.
NextBioi281400.
PROiQ9JLQ0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JLQ0.
CleanExiMM_CD2AP.
GenevisibleiQ9JLQ0. MM.

Family and domain databases

InterProiIPR028445. CD2AP.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR14167:SF23. PTHR14167:SF23. 1 hit.
PfamiPF00018. SH3_1. 1 hit.
PF14604. SH3_9. 2 hits.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
PROSITEiPS50002. SH3. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. Cited for: STRUCTURE BY NMR OF 270-329.

Entry informationi

Entry nameiCD2AP_MOUSE
AccessioniPrimary (citable) accession number: Q9JLQ0
Secondary accession number(s): E9QL86
, O88903, Q8K4Z1, Q8VCI9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: July 27, 2011
Last modified: July 22, 2015
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.