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Protein

CD2-associated protein

Gene

CD2AP

Organism
Homo sapiens (Human)
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

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB
  • structural constituent of cytoskeleton Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

BioCyciZFISH:G66-31324-MONOMER.
ReactomeiR-HSA-373753. Nephrin interactions.
SignaLinkiQ9Y5K6.

Names & Taxonomyi

Protein namesi
Recommended name:
CD2-associated protein
Alternative name(s):
Adapter protein CMS
Cas ligand with multiple SH3 domains
Gene namesi
Name:CD2AP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:14258. CD2AP.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: ProtInc
  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: HPA
  • endocytic vesicle Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • filamentous actin Source: UniProtKB
  • nucleolus Source: HPA
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: HPA
  • ruffle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Focal segmental glomerulosclerosis 3 (FSGS3)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
See also OMIM:607832

Organism-specific databases

DisGeNETi23607.
MalaCardsiCD2AP.
MIMi607832. phenotype.
OpenTargetsiENSG00000198087.
Orphaneti93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBiPA26208.

Polymorphism and mutation databases

BioMutaiCD2AP.
DMDMi30172980.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000894351 – 639CD2-associated proteinAdd BLAST639

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki58Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei67PhosphoserineCombined sources1
Modified residuei80PhosphoserineCombined sources1
Modified residuei86PhosphoserineCombined sources1
Modified residuei224PhosphoserineCombined sources1
Modified residuei458PhosphoserineCombined sources1
Modified residuei463PhosphoserineCombined sources1
Modified residuei469PhosphoserineBy similarity1
Modified residuei510PhosphoserineCombined sources1
Modified residuei514PhosphoserineCombined sources1
Modified residuei565PhosphothreonineCombined sources1
Modified residuei582PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-Src.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y5K6.
MaxQBiQ9Y5K6.
PaxDbiQ9Y5K6.
PeptideAtlasiQ9Y5K6.
PRIDEiQ9Y5K6.

PTM databases

iPTMnetiQ9Y5K6.
PhosphoSitePlusiQ9Y5K6.

Expressioni

Tissue specificityi

Widely expressed in fetal and adult tissues.

Gene expression databases

BgeeiENSG00000198087.
CleanExiHS_CD2AP.
GenevisibleiQ9Y5K6. HS.

Organism-specific databases

HPAiCAB004352.
HPA003267.
HPA003326.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
BLNKQ8WV282EBI-298152,EBI-2623522
CBLP226814EBI-298152,EBI-518228
CBLBQ1319111EBI-298152,EBI-744027
CD2P067294EBI-298152,EBI-3912464
GRB2P629933EBI-298152,EBI-401755
IQGAP1P469404EBI-298152,EBI-297509
PDCD6IPQ8WUM42EBI-298152,EBI-310624
TSG101Q998162EBI-298152,EBI-346882

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • SH3 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi117140. 104 interactors.
DIPiDIP-31807N.
IntActiQ9Y5K6. 39 interactors.
MINTiMINT-93491.
STRINGi9606.ENSP00000352264.

Structurei

Secondary structure

1639
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 6Combined sources3
Beta strandi25 – 30Combined sources6
Beta strandi37 – 42Combined sources6
Beta strandi45 – 50Combined sources6
Beta strandi53 – 56Combined sources4
Beta strandi112 – 115Combined sources4
Beta strandi134 – 142Combined sources9
Beta strandi145 – 150Combined sources6
Beta strandi153 – 158Combined sources6
Helixi159 – 161Combined sources3
Beta strandi162 – 164Combined sources3
Helixi489 – 492Combined sources4
Helixi503 – 505Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FEINMR-A111-166[»]
2J6FX-ray1.70A1-62[»]
2J6KX-ray2.78A/B/C/D/E/F/G/H/I/J/K/L1-62[»]
2J6OX-ray2.22A1-62[»]
2J7IX-ray2.90A/B1-62[»]
3AA6X-ray1.90C485-507[»]
3LK4X-ray1.990/3/6/9/C/F/I/L/O/R/U/X475-503[»]
3U23X-ray1.11A109-168[»]
4WCIX-ray1.65A/C/E1-60[»]
4X1VX-ray1.58A109-168[»]
ProteinModelPortaliQ9Y5K6.
SMRiQ9Y5K6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5K6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 59SH3 1; truncatedPROSITE-ProRule annotationAdd BLAST59
Domaini108 – 167SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini269 – 330SH3 3PROSITE-ProRule annotationAdd BLAST62

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 175Interaction with ANLN and localization to the midbody1 PublicationAdd BLAST175

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili577 – 638Sequence analysisAdd BLAST62

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi336 – 352SH3-bindingSequence analysisAdd BLAST17
Motifi378 – 397SH3-bindingSequence analysisAdd BLAST20
Motifi410 – 422SH3-bindingSequence analysisAdd BLAST13

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi336 – 422Pro-richAdd BLAST87

Domaini

The Pro-rich domain may mediate binding to SH3 domains.
Potential homodimerization is mediated by the coiled coil domain.

Sequence similaritiesi

Contains 3 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG4348. Eukaryota.
ENOG410XQBY. LUCA.
GeneTreeiENSGT00530000063594.
HOGENOMiHOG000231405.
HOVERGENiHBG057824.
InParanoidiQ9Y5K6.
KOiK13738.
OMAiVHDDELT.
OrthoDBiEOG091G041Q.
PhylomeDBiQ9Y5K6.
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.

Q9Y5K6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVDYIVEYDY DAVHDDELTI RVGEIIRNVK KLQEEGWLEG ELNGRRGMFP
60 70 80 90 100
DNFVKEIKRE TEFKDDSLPI KRERHGNVAS LVQRISTYGL PAGGIQPHPQ
110 120 130 140 150
TKNIKKKTKK RQCKVLFEYI PQNEDELELK VGDIIDINEE VEEGWWSGTL
160 170 180 190 200
NNKLGLFPSN FVKELEVTDD GETHEAQDDS ETVLAGPTSP IPSLGNVSET
210 220 230 240 250
ASGSVTQPKK IRGIGFGDIF KEGSVKLRTR TSSSETEEKK PEKPLILQSL
260 270 280 290 300
GPKTQSVEIT KTDTEGKIKA KEYCRTLFAY EGTNEDELTF KEGEIIHLIS
310 320 330 340 350
KETGEAGWWR GELNGKEGVF PDNFAVQINE LDKDFPKPKK PPPPAKAPAP
360 370 380 390 400
KPELIAAEKK YFSLKPEEKD EKSTLEQKPS KPAAPQVPPK KPTPPTKASN
410 420 430 440 450
LLRSSGTVYP KRPEKPVPPP PPIAKINGEV SSISSKFETE PVSKLKLDSE
460 470 480 490 500
QLPLRPKSVD FDSLTVRTSK ETDVVNFDDI ASSENLLHLT ANRPKMPGRR
510 520 530 540 550
LPGRFNGGHS PTHSPEKILK LPKEEDSANL KPSELKKDTC YSPKPSVYLS
560 570 580 590 600
TPSSASKANT TAFLTPLEIK AKVETDDVKK NSLDELRAQI IELLCIVEAL
610 620 630
KKDHGKELEK LRKDLEEEKT MRSNLEMEIE KLKKAVLSS
Length:639
Mass (Da):71,451
Last modified:November 1, 1999 - v1
Checksum:i7576509C7ED5B343
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033672581N → K.Corresponds to variant rs34069459dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34472.1.
PIRiT13151.
RefSeqiNP_036252.1. NM_012120.2.
UniGeneiHs.485518.

Genome annotation databases

EnsembliENST00000359314; ENSP00000352264; ENSG00000198087.
GeneIDi23607.
KEGGihsa:23607.
UCSCiuc003oyw.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34472.1.
PIRiT13151.
RefSeqiNP_036252.1. NM_012120.2.
UniGeneiHs.485518.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FEINMR-A111-166[»]
2J6FX-ray1.70A1-62[»]
2J6KX-ray2.78A/B/C/D/E/F/G/H/I/J/K/L1-62[»]
2J6OX-ray2.22A1-62[»]
2J7IX-ray2.90A/B1-62[»]
3AA6X-ray1.90C485-507[»]
3LK4X-ray1.990/3/6/9/C/F/I/L/O/R/U/X475-503[»]
3U23X-ray1.11A109-168[»]
4WCIX-ray1.65A/C/E1-60[»]
4X1VX-ray1.58A109-168[»]
ProteinModelPortaliQ9Y5K6.
SMRiQ9Y5K6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117140. 104 interactors.
DIPiDIP-31807N.
IntActiQ9Y5K6. 39 interactors.
MINTiMINT-93491.
STRINGi9606.ENSP00000352264.

PTM databases

iPTMnetiQ9Y5K6.
PhosphoSitePlusiQ9Y5K6.

Polymorphism and mutation databases

BioMutaiCD2AP.
DMDMi30172980.

Proteomic databases

EPDiQ9Y5K6.
MaxQBiQ9Y5K6.
PaxDbiQ9Y5K6.
PeptideAtlasiQ9Y5K6.
PRIDEiQ9Y5K6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359314; ENSP00000352264; ENSG00000198087.
GeneIDi23607.
KEGGihsa:23607.
UCSCiuc003oyw.4. human.

Organism-specific databases

CTDi23607.
DisGeNETi23607.
GeneCardsiCD2AP.
HGNCiHGNC:14258. CD2AP.
HPAiCAB004352.
HPA003267.
HPA003326.
MalaCardsiCD2AP.
MIMi604241. gene.
607832. phenotype.
neXtProtiNX_Q9Y5K6.
OpenTargetsiENSG00000198087.
Orphaneti93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBiPA26208.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4348. Eukaryota.
ENOG410XQBY. LUCA.
GeneTreeiENSGT00530000063594.
HOGENOMiHOG000231405.
HOVERGENiHBG057824.
InParanoidiQ9Y5K6.
KOiK13738.
OMAiVHDDELT.
OrthoDBiEOG091G041Q.
PhylomeDBiQ9Y5K6.
TreeFamiTF350191.

Enzyme and pathway databases

BioCyciZFISH:G66-31324-MONOMER.
ReactomeiR-HSA-373753. Nephrin interactions.
SignaLinkiQ9Y5K6.

Miscellaneous databases

ChiTaRSiCD2AP. human.
EvolutionaryTraceiQ9Y5K6.
GeneWikiiCD2AP.
GenomeRNAii23607.
PROiQ9Y5K6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198087.
CleanExiHS_CD2AP.
GenevisibleiQ9Y5K6. HS.

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...

Entry informationi

Entry nameiCD2AP_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5K6
Secondary accession number(s): A6NL34, Q5VYA3, Q9UG97
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.