CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010708
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Disabled homolog 2 
Protein Synonyms/Alias
 DOC-2; Mitogen-responsive phosphoprotein 
Gene Name
 Dab2 
Gene Synonyms/Alias
 Doc2 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
53DGVKYKAKLIGIDDVubiquitination[1]
67VPDARGDKMSQDSMMubiquitination[1]
173FQVIYNVKKKEEDKKubiquitination[1]
205TLDDQANKLKLGVDQubiquitination[1]
647PLGDKEVKEVKEMFKubiquitination[1]
650DKEVKEVKEMFKDFQubiquitination[1]
654KEVKEMFKDFQLRQPubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containg non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Isoform p96 is involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Isoform p67 is not involved in LDL receptor endocytosis. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta- catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF- 1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. Isoform p67 may be involved in transcriptional regulation. May act as a tumor suppressor. 
Sequence Annotation
 DOMAIN 45 196 PID.
 REGION 230 447 Required for localization to clathrin-
 REGION 600 730 Sufficient for interaction with GRB2.
 REGION 617 625 Required for interaction with CSK (By
 REGION 647 766 Required for interaction with MYO6.
 REGION 661 669 Required for interaction with GRB2 and
 REGION 707 723 Sufficient for interaction with SH3KBP1
 MOTIF 293 295 DPF 1.
 MOTIF 298 300 DPF 2.
 MOD_RES 2 2 N-acetylserine (By similarity).
 MOD_RES 323 323 Phosphoserine.
 MOD_RES 326 326 Phosphoserine; in mitosis (By
 MOD_RES 328 328 Phosphoserine; in mitosis (By
 MOD_RES 342 342 Phosphotyrosine.
 MOD_RES 401 401 Phosphoserine.
 MOD_RES 727 727 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; Coated pit; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Developmental protein; Differentiation; Endocytosis; Membrane; Nucleus; Phosphoprotein; Protein transport; Reference proteome; Transport; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 766 AA 
Protein Sequence
MSNEVETSTT NGQPDQQAAP KAPSKKEKKK GSEKTDEYLL ARFKGDGVKY KAKLIGIDDV 60
PDARGDKMSQ DSMMKLKGMA AAGRSQGQHK QRIWVNISLS GIKIIDEKTG VIEHEHPVNK 120
ISFIARDVTD NRAFGYVCGG EGQHQFFAIK TGQQAEPLVV DLKDLFQVIY NVKKKEEDKK 180
KVEEANKAEE NGSEALMTLD DQANKLKLGV DQMDLFGDMS TPPDLNSPTE SKDILLVDLN 240
SEIDTNQNSL RENPFLTNGV TSCSLPRPKP QASFLPENAF SANLNFFPTP NPDPFRDDPF 300
AQPDQSAPSS FDSLTSPDQK KASLSSSSTP QSKGPLNGDT DYFGQQFDQL SNRTGKPEAQ 360
GGPWPYPSSQ TQQAVRTQNG VSEREQNGFH IKSSPNPFVG SPPKGLSVPN GVKQDLESSV 420
QSSAHDSIAI IPPPQSTKPG RGRRTAKSSA NDLLASDIFA SEPPGQMSPT GQPAVPQSNF 480
LDLFKGNAPA PVGPLVGLGT VPVTPPQAGP WTPVVYSPST TVVPGAIISG QPPSFRQPLV 540
FGTTPAVQVW NQSPSFATPA SPPPPTVWCP TTSVAPNAWS STSPLGNPFQ SNNIFPPPTM 600
STQSSPQPMM SSVLATPPQP PPRNGPLKDI PSDAFTGLDP LGDKEVKEVK EMFKDFQLRQ 660
PPLVPSRKGE TPPSGTSSAF SSYFNNKVGI PQEHVDHDDF DANQLLNKIN EPPKPAPRQG 720
VLLGTKSADN SLENPFSKGF SSSNPSVVSQ PASSDPHRSP FGNPFA 766 
Gene Ontology
 GO:0016324; C:apical plasma membrane; IDA:MGI.
 GO:0030132; C:clathrin coat of coated pit; IDA:UniProtKB.
 GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0005634; C:nucleus; IDA:MGI.
 GO:0070022; C:transforming growth factor beta receptor homodimeric complex; IEA:Compara.
 GO:0035612; F:AP-2 adaptor complex binding; IDA:UniProtKB.
 GO:0038024; F:cargo receptor activity; IDA:UniProtKB.
 GO:0035615; F:clathrin adaptor activity; IDA:UniProtKB.
 GO:0005178; F:integrin binding; IMP:UniProtKB.
 GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
 GO:0007257; P:activation of JUN kinase activity; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0000904; P:cell morphogenesis involved in differentiation; IMP:MGI.
 GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:UniProtKB.
 GO:0048268; P:clathrin coat assembly; IDA:UniProtKB.
 GO:0007492; P:endoderm development; IMP:MGI.
 GO:0007588; P:excretion; IMP:MGI.
 GO:0001701; P:in utero embryonic development; IMP:MGI.
 GO:0030099; P:myeloid cell differentiation; IEP:UniProtKB.
 GO:0060766; P:negative regulation of androgen receptor signaling pathway; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IEA:Compara.
 GO:0032091; P:negative regulation of protein binding; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0006907; P:pinocytosis; IMP:MGI.
 GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
 GO:2000370; P:positive regulation of clathrin-mediated endocytosis; IDA:UniProtKB.
 GO:2000643; P:positive regulation of early endosome to late endosome transport; IEA:Compara.
 GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB.
 GO:2001046; P:positive regulation of integrin-mediated signaling pathway; IMP:UniProtKB.
 GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:UniProtKB.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Compara.
 GO:0001921; P:positive regulation of receptor recycling; IMP:UniProtKB.
 GO:0060391; P:positive regulation of SMAD protein import into nucleus; IEA:Compara.
 GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IEA:Compara.
 GO:2000096; P:positive regulation of Wnt receptor signaling pathway, planar cell polarity pathway; IEA:Compara.
 GO:0015031; P:protein transport; IEA:UniProtKB-KW.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
Interpro
 IPR011993; PH_like_dom.
 IPR006020; PTyr_interaction_dom. 
Pfam
 PF00640; PID 
SMART
 SM00462; PTB 
PROSITE
 PS01179; PID 
PRINTS