DAB2_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DAB2_RAT
• UniProt AC: O88797
• Protein Name: Disabled homolog 2
• Gene Name: Dab2
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 768
• Subcellular Localization: Cytoplasm. Cytoplasmic vesicle, clathrin-coated vesicle membrane. Membrane, clathrin-coated pit. Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane a
• Protein 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 containing 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. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. 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. May act as a tumor suppressor..
• Protein Sequence: MSNEVETSTTNGQPDQQAAPKAPSKKEKKKGSEKTDEYLLARFKGDGVKYKAKLIGIDDVPDARGDKMSQDSMMKLKGMAAAGRSQGQHKQRIWVNISLSGIKIIDEKTGVIEHEHPVNKISFIARDVTDNRAFGYVCGGEGQHQFFAIKTGQQAEPLVVDLKDLFQVIYNVKKKEEEKKKVEEANKAEENGSEALMTLDDQANKLKLGVDQMDLFGDMSTPPDLNNPTESRDILLVDLNSEIDTNQNSLRENPFLTNGVTSCSLPRPKPQASFLPESAFSANLNFFPTPNPDPFRDDPFAQPDQSAPSSFHSLTSADQKKANPGSLSTPQSKGPLNGDTDYFGQQFDQISNRTGKQEAQGGPWPYPSSQTQQAVRTQNGVSEKEQNGFHIKSSPNPFVGSPPKGLSVPNGVKQDLESSVQSSAHDSIAIIPPPQSTKPGRGRRTAKSSANDLLASDIFASEPPGQMSPTGQPAVPQANFMDLFKTSAPAPMGSGPLVGLGTVPVTPPQAGPWTPVVFTPSTTVVPGAIISGQPSGFGQPLVFGTTPAVQVWNQPSSFATAASPPPPAVWCPTTSVAPNTWSSTSPLGNPFQSSNIFPPSTISTQSFPQPMMSSVLVTPPQPPPRNGPLKDTLSDAFTGLDPLGDKEVKEVKEMFKDFQLRQPPLVPSRKGETPSSGTSSAFSSYFNNKVGIPQEHVDHDDFDANQLLNKINEPPKPAPRQGVLSGTKSADNSLENPFSKGFSSTNPSVVSQPASSDAHRSPFGNPFA

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSNEVETST ------CCCCCCCCC	41.52	-
2	Phosphorylation	------MSNEVETST ------CCCCCCCCC	41.52	22673903
24	Phosphorylation	QAAPKAPSKKEKKKG CCCCCCCCHHHHCCC	62.31	11812785
32	Phosphorylation	KKEKKKGSEKTDEYL HHHHCCCCCCCCHHH	44.81	25575281
35	Phosphorylation	KKKGSEKTDEYLLAR HCCCCCCCCHHHHHH	29.97	25575281
44	Acetylation	EYLLARFKGDGVKYK HHHHHHHCCCCCEEE	51.00	22902405
108	Acetylation	GIKIIDEKTGVIEHE CEEEEECCCCCEECC	47.00	22902405
170	Phosphorylation	KDLFQVIYNVKKKEE HHHHHHHHHCCCHHH	18.29	-
193	Phosphorylation	NKAEENGSEALMTLD HHHHHHHCHHCCCHH	31.14	22673903
221	Phosphorylation	DLFGDMSTPPDLNNP HHCCCCCCCCCCCCC	32.00	25532521
326	Phosphorylation	QKKANPGSLSTPQSK HHHCCCCCCCCCCCC	22.02	25575281
328	Phosphorylation	KANPGSLSTPQSKGP HCCCCCCCCCCCCCC	39.47	25532521
329	Phosphorylation	ANPGSLSTPQSKGPL CCCCCCCCCCCCCCC	30.55	30181290
332	Phosphorylation	GSLSTPQSKGPLNGD CCCCCCCCCCCCCCC	40.56	30181290
393	Phosphorylation	QNGFHIKSSPNPFVG HCCEECCCCCCCCCC	50.88	25575281
394	Phosphorylation	NGFHIKSSPNPFVGS CCEECCCCCCCCCCC	24.56	25532521
401	Phosphorylation	SPNPFVGSPPKGLSV CCCCCCCCCCCCCCC	32.50	27097102
468	Phosphorylation	SEPPGQMSPTGQPAV CCCCCCCCCCCCCCC	16.06	22668510
618	Phosphorylation	MMSSVLVTPPQPPPR CEEEEEECCCCCCCC	25.70	-
652	Acetylation	DKEVKEVKEMFKDFQ CHHHHHHHHHHHHCC	44.55	22902405
673	Phosphorylation	VPSRKGETPSSGTSS CCCCCCCCCCCCCHH	36.82	-
675	Phosphorylation	SRKGETPSSGTSSAF CCCCCCCCCCCHHHH	49.14	-
725	Phosphorylation	APRQGVLSGTKSADN CCCCCCCCCCCCCCC	41.85	25575281
727	Phosphorylation	RQGVLSGTKSADNSL CCCCCCCCCCCCCCC	20.60	25575281
729	Phosphorylation	GVLSGTKSADNSLEN CCCCCCCCCCCCCCC	40.47	29779826
733	Phosphorylation	GTKSADNSLENPFSK CCCCCCCCCCCCCCC	37.29	25575281
739	Phosphorylation	NSLENPFSKGFSSTN CCCCCCCCCCCCCCC	32.88	25575281
751	Phosphorylation	STNPSVVSQPASSDA CCCCCHHCCCCCCCC	28.43	23984901
755	Phosphorylation	SVVSQPASSDAHRSP CHHCCCCCCCCCCCC	35.12	23984901
756	Phosphorylation	VVSQPASSDAHRSPF HHCCCCCCCCCCCCC	40.71	23984901
761	Phosphorylation	ASSDAHRSPFGNPFA CCCCCCCCCCCCCCC	18.08	23984901

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
24	S	Phosphorylation	Kinase	PRKCA	P17252	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of DAB2_RAT !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of DAB2_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of DAB2_RAT !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.