dbPTM

DAB2P_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DAB2P_MOUSE
UniProt AC	Q3UHC7
Protein Name	Disabled homolog 2-interacting protein
Gene Name	Dab2ip
Organism	Mus musculus (Mouse).
Sequence Length	1189
Subcellular Localization	Cytoplasm. Cell membrane Peripheral membrane protein . Cell projection, dendrite. Colocalizes with TIRAP at the plasma membrane. Colocalizes with ARF6 at the plasma membrane and endocytic vesicles. Translocates from the plasma membrane to the cytop
Protein Description	Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to proinflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively..
Protein Sequence	MSAGGNARKSTGRPSYYYRLLRRPRLQRQRSRSRSRTRPARESPQERPGSRRSLPGSMSEKNPSMEPSASTPFRVTGFLSRRLKGSIKRTKSQPKLDRNHSFRHILPGFRSAAAAAADNERSHLMPRLKESRSHESLLSPSSAVEALDLSMEEEVIIKPVHSSILGQDYCFEVTTSSGSKCFSCRSAAERDKWMENLRRAVHPNKDNSRRVEHILKLWVIEAKDLPAKKKYLCELCLDDVLYARTTSKLKTDNVFWGEHFEFHNLPPLRTVTVHLYRETDKKKKKERNSYLGLVSLPAASVAGRQFVEKWYPVVTPNPKGGKGPGPMIRIKARYQTVSILPMEMYKEFAEHITNHYLGLCAALEPILSAKTKEEMASALVHILQSTGKVKDFLTDLMMSEVDRCGDNEHLIFRENTLATKAIEEYLKLVGQKYLQDALGEFIKALYESDENCEVDPSKCSSADLPEHQGNLKMCCELAFCKIINSYCVFPRELKEVFASWRQECSSRGRPDISERLISASLFLRFLCPAIMSPSLFNLLQEYPDDRTARTLTLIAKVTQNLANFAKFGSKEEYMSFMNQFLEHEWTNMQRFLLEISNPETLSNTAGFEGYIDLGRELSSLHSLLWEAVSQLDQSVVSKLGPLPRILRDVHTALSTPGSGQLPGTNDLASTPGSGSSSVSAGLQKMVIENDLSGLIDFTRLPSPTPENKDLFFVTRSSGVQPSPARSSSYSEANEPDLQMANGSKSLSMVDLQDARTLDGEAGSPVGPDALPADGQVPATQLLAGWPARAAPVSLAGLATVRRAVPTPTTPGTSEGAPGRPQLLAPLSFQNPVYQMAAGLPLSPRGLGDSGSEGHSSLSSHSNSEELAAAAKLGSFSTAAEELARRPGELARRQMSLTEKGGQPTVPRQNSAGPQRRIDQPPPPPPPPPPAPRGRTPPTLLSTLQYPRPSSGTLASASPDWAGPGTRLRQQSSSSKGDSPELKPRAMHKQGPSPVSPNALDRTAAWLLTMNAQLLEDEGLGPDPPHRDRLRSKEELSQAEKDLAVLQDKLRISTKKLEEYETLFKCQEETTQKLVLEYQARLEEGEERLRRQQEDKDIQMKGIISRLMSVEEELKKDHAEMQAAVDSKQKIIDAQEKRIASLDAANARLMSALTQLKERYSMQARNGVSPTNPTKLQITENGEFRNSSNC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
35	Phosphorylation	RQRSRSRSRTRPARE HHHHHHCCCCCCCCC	38.97	23737553
37	Phosphorylation	RSRSRSRTRPARESP HHHHCCCCCCCCCCC	42.10	23737553
43	Phosphorylation	RTRPARESPQERPGS CCCCCCCCCCCCCCC	26.74	29899451
53	Phosphorylation	ERPGSRRSLPGSMSE CCCCCCCCCCCCCCC	37.49	25293948
57	Phosphorylation	SRRSLPGSMSEKNPS CCCCCCCCCCCCCCC	19.73	25293948
59	Phosphorylation	RSLPGSMSEKNPSME CCCCCCCCCCCCCCC	47.30	25293948
64	Phosphorylation	SMSEKNPSMEPSAST CCCCCCCCCCCCCCC	45.21	25293948
76	Phosphorylation	ASTPFRVTGFLSRRL CCCCCHHHHHHHHHH	20.26	-
86	Phosphorylation	LSRRLKGSIKRTKSQ HHHHHCCCHHCCCCC	24.29	28066266
92	Phosphorylation	GSIKRTKSQPKLDRN CCHHCCCCCCCCCCC	51.61	28382018
101	Phosphorylation	PKLDRNHSFRHILPG CCCCCCCCHHHHCHH	27.76	26824392
174	Phosphorylation	QDYCFEVTTSSGSKC CCEEEEEECCCCCCE	17.48	21189417
175	Phosphorylation	DYCFEVTTSSGSKCF CEEEEEECCCCCCEE	26.52	21189417
176	Phosphorylation	YCFEVTTSSGSKCFS EEEEEECCCCCCEEE	24.28	21189417
177	Phosphorylation	CFEVTTSSGSKCFSC EEEEECCCCCCEEEC	45.02	21189417
179	Phosphorylation	EVTTSSGSKCFSCRS EEECCCCCCEEECCC	28.35	21189417
183	Phosphorylation	SSGSKCFSCRSAAER CCCCCEEECCCHHHH	20.35	21189417
289	Phosphorylation	KKKKERNSYLGLVSL CCHHHCCCCCCCHHH	28.14	26824392
290	Phosphorylation	KKKERNSYLGLVSLP CHHHCCCCCCCHHHC	14.34	23984901
334	Phosphorylation	MIRIKARYQTVSILP CEEEEEEEEEEEEEE	17.25	25293948
336	Phosphorylation	RIKARYQTVSILPME EEEEEEEEEEEEEHH	13.79	25293948
338	Phosphorylation	KARYQTVSILPMEMY EEEEEEEEEEEHHHH	23.07	25293948
345	Phosphorylation	SILPMEMYKEFAEHI EEEEHHHHHHHHHHH	8.28	25293948
499	Phosphorylation	ELKEVFASWRQECSS HHHHHHHHHHHHHHH	16.01	22817900
618	Phosphorylation	IDLGRELSSLHSLLW HHHHHHHHHHHHHHH	26.54	22871156
619	Phosphorylation	DLGRELSSLHSLLWE HHHHHHHHHHHHHHH	42.60	22871156
622	Phosphorylation	RELSSLHSLLWEAVS HHHHHHHHHHHHHHH	30.37	22871156
664	Phosphorylation	GSGQLPGTNDLASTP CCCCCCCCCCCCCCC	24.50	29899451
669	Phosphorylation	PGTNDLASTPGSGSS CCCCCCCCCCCCCCC	42.29	25293948
670	Phosphorylation	GTNDLASTPGSGSSS CCCCCCCCCCCCCCH	26.51	22817900
673	Phosphorylation	DLASTPGSGSSSVSA CCCCCCCCCCCHHHH	36.38	25293948
675	Phosphorylation	ASTPGSGSSSVSAGL CCCCCCCCCHHHHHH	22.57	22817900
676	Phosphorylation	STPGSGSSSVSAGLQ CCCCCCCCHHHHHHH	37.98	25293948
677	Phosphorylation	TPGSGSSSVSAGLQK CCCCCCCHHHHHHHH	23.07	25293948
679	Phosphorylation	GSGSSSVSAGLQKMV CCCCCHHHHHHHHHH	20.68	25293948
692	Phosphorylation	MVIENDLSGLIDFTR HHEECCCCCCCCCCC	34.12	26160508
698	Phosphorylation	LSGLIDFTRLPSPTP CCCCCCCCCCCCCCC	27.78	23984901
702	Phosphorylation	IDFTRLPSPTPENKD CCCCCCCCCCCCCCC	46.10	25521595
704	Phosphorylation	FTRLPSPTPENKDLF CCCCCCCCCCCCCCE	47.80	22324799
714	Phosphorylation	NKDLFFVTRSSGVQP CCCCEEEECCCCCCC	21.48	26160508
722	Phosphorylation	RSSGVQPSPARSSSY CCCCCCCCCCCCCCC	17.69	23684622
726	Phosphorylation	VQPSPARSSSYSEAN CCCCCCCCCCCCCCC	26.24	27087446
727	Phosphorylation	QPSPARSSSYSEANE CCCCCCCCCCCCCCC	27.95	27087446
728	Phosphorylation	PSPARSSSYSEANEP CCCCCCCCCCCCCCC	33.65	25521595
729	Phosphorylation	SPARSSSYSEANEPD CCCCCCCCCCCCCCC	16.69	25521595
730	Phosphorylation	PARSSSYSEANEPDL CCCCCCCCCCCCCCH	31.98	23984901
745	Phosphorylation	QMANGSKSLSMVDLQ HCCCCCCCCCCEEHH	27.63	29899451
747	Phosphorylation	ANGSKSLSMVDLQDA CCCCCCCCCEEHHCC	24.69	25521595
756	Phosphorylation	VDLQDARTLDGEAGS EEHHCCCCCCCCCCC	30.81	25521595
763	Phosphorylation	TLDGEAGSPVGPDAL CCCCCCCCCCCCCCC	24.38	22817900
793	O-linked_Glycosylation	PARAAPVSLAGLATV CCCCCCCCHHCHHHH	16.08	55411701
799	Phosphorylation	VSLAGLATVRRAVPT CCHHCHHHHHHCCCC	21.42	26824392
827	Phosphorylation	PQLLAPLSFQNPVYQ CCEECCCCCCCHHHH	24.59	-
833	Phosphorylation	LSFQNPVYQMAAGLP CCCCCHHHHHHCCCC	8.20	20116462
842	Phosphorylation	MAAGLPLSPRGLGDS HHCCCCCCCCCCCCC	15.60	26824392
849	Phosphorylation	SPRGLGDSGSEGHSS CCCCCCCCCCCCCCC	42.28	25338131
851	Phosphorylation	RGLGDSGSEGHSSLS CCCCCCCCCCCCCCC	44.34	25338131
855	Phosphorylation	DSGSEGHSSLSSHSN CCCCCCCCCCCCCCC	43.78	25338131
861	Phosphorylation	HSSLSSHSNSEELAA CCCCCCCCCHHHHHH	43.96	25338131
874	Phosphorylation	AAAAKLGSFSTAAEE HHHHHHCCHHHHHHH	26.85	26239621
876	Phosphorylation	AAKLGSFSTAAEELA HHHHCCHHHHHHHHH	20.87	29899451
895	Phosphorylation	ELARRQMSLTEKGGQ HHHHHHHHHHHCCCC	24.65	22324799
897	Phosphorylation	ARRQMSLTEKGGQPT HHHHHHHHHCCCCCC	28.48	22324799
910	Phosphorylation	PTVPRQNSAGPQRRI CCCCCCCCCCCCCCC	26.68	29514104
935	Phosphorylation	PPAPRGRTPPTLLST CCCCCCCCCCCHHHC	36.12	25293948
938	Phosphorylation	PRGRTPPTLLSTLQY CCCCCCCCHHHCCCC	41.35	25293948
941	Phosphorylation	RTPPTLLSTLQYPRP CCCCCHHHCCCCCCC	30.13	25293948
950	Phosphorylation	LQYPRPSSGTLASAS CCCCCCCCCCCCCCC	38.18	25338131
955	Phosphorylation	PSSGTLASASPDWAG CCCCCCCCCCCCCCC	32.18	28066266
957	Phosphorylation	SGTLASASPDWAGPG CCCCCCCCCCCCCCC	22.39	28066266
965	Phosphorylation	PDWAGPGTRLRQQSS CCCCCCCCCCCCCCC	29.66	28066266
971	Phosphorylation	GTRLRQQSSSSKGDS CCCCCCCCCCCCCCC	24.69	29899451
972	Phosphorylation	TRLRQQSSSSKGDSP CCCCCCCCCCCCCCC	34.00	29895711
973	Phosphorylation	RLRQQSSSSKGDSPE CCCCCCCCCCCCCCC	41.12	21454597
974	Phosphorylation	LRQQSSSSKGDSPEL CCCCCCCCCCCCCCC	42.48	20415495
978	Phosphorylation	SSSSKGDSPELKPRA CCCCCCCCCCCCHHH	29.01	25521595
992	Phosphorylation	AMHKQGPSPVSPNAL HHHCCCCCCCCCCHH	44.77	26824392
995	Phosphorylation	KQGPSPVSPNALDRT CCCCCCCCCCHHHHH	18.80	23527152
1031	Phosphorylation	PHRDRLRSKEELSQA CCHHHHCCHHHHHHH	49.35	25266776
1036	Phosphorylation	LRSKEELSQAEKDLA HCCHHHHHHHHHHHH	30.53	28066266
1052	Phosphorylation	LQDKLRISTKKLEEY HHHHHHHCHHHHHHH	27.95	30387612
1108	Phosphorylation	GIISRLMSVEEELKK HHHHHHHCHHHHHHH	30.85	25521595
1140	Phosphorylation	AQEKRIASLDAANAR HHHHHHHHHHHHHHH	25.14	27180971
1150	Phosphorylation	AANARLMSALTQLKE HHHHHHHHHHHHHHH	25.39	24759943
1153	Phosphorylation	ARLMSALTQLKERYS HHHHHHHHHHHHHHH	31.41	24759943
1159	Phosphorylation	LTQLKERYSMQARNG HHHHHHHHHHHCCCC	15.02	30635358
1160	Phosphorylation	TQLKERYSMQARNGV HHHHHHHHHHCCCCC	15.61	30635358
1168	Phosphorylation	MQARNGVSPTNPTKL HHCCCCCCCCCCCCE	27.66	25521595
1170	Phosphorylation	ARNGVSPTNPTKLQI CCCCCCCCCCCCEEE	46.45	25263469
1173	Phosphorylation	GVSPTNPTKLQITEN CCCCCCCCCEEECCC	46.59	30635358

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
728	S	Phosphorylation	Kinase	MAP3K5	O35099	Uniprot
728	S	Phosphorylation	Kinase	RIPK1	Q60855	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
728	S	Phosphorylation		-
In response to TNF-alpha-induction, phosphorylated at Ser-728; phosphorylation leads to a conformational change, and thus, increases its association with 14-3-3 proteins, MAP3K5, RIPK1 and TRAF2 in endothelial cells; also stimulates regulatory p85 subunit sequestring and PI3K-p85 complex activity inhibition.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of DAB2P_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of DAB2P_MOUSE !!

Drug and Disease Associations

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

Regulatory Network of DAB2P_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-978, AND MASSSPECTROMETRY.	19367708 [Abstract]
"Qualitative and quantitative analyses of protein phosphorylation innaive and stimulated mouse synaptosomal preparations."; Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,Gerrits B., Panse C., Schlapbach R., Mansuy I.M.; Mol. Cell. Proteomics 6:283-293(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-702, AND MASSSPECTROMETRY.	17114649 [Abstract]

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