SHIP2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SHIP2_MOUSE
• UniProt AC: Q6P549
• Protein Name: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
• Gene Name: Inppl1
• Organism: Mus musculus (Mouse).
• Sequence Length: 1257
• Subcellular Localization: Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Membrane; Peripheral membrane protein. Cell projection, filopodium. Cell projection, lamellipodium. Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms de
• Protein Description: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (By similarity). Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (By similarity)..
• Protein Sequence: MASVCGTPSPGGALGSPAPAWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEGEREPDPPDDRDASDVEDEKPPLPPRSGSTSISAPVGPSSPLPTPETPTTPAAESTPNGLSTVSHEYLKGSYGLDLEAVRGGASNLPHLTRTLVTSCRRLHSEVDKVLSGLEILSKVFDQQSSPMVTRLLQQQSLPQTGEQELESLVLKLSVLKDFLSGIQKKALKALQDMSSTAPPAPLQPSIRKAKTIPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNRHSKQDEPDMISVFIGTWNMGSVPPPKNVTSWFTSKGLGKALDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTTRRNQNYLDILRLLSLGDRQLSAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRREFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDDTGAKSKVPSVSRGSQEHRSGSRKPASTETSCPLSKLFEEPEKPPPTGRPPAPPRAVPREEPLNPRLKSEGTSEQEGVAAPPPKNSFNNPAYYVLEGVPHQLLPLEPPSLARAPLPPATKNKVAITVPAPQLGRHRTPRVGEGSSSDEDSGGTLPPPDFPPPPLPDSAIFLPPNLDPLSMPVVRGRSGGEARGPPPPKAHPRPPLPPGTSPASTFLGEVASGDDRSCSVLQMAKTLSEVDYAPGPGRSALLPNPLELQPPRGPSDYGRPLSFPPPRIRESIQEDLAEEAPCPQGGRASGLGEAGMGAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK

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
3	Phosphorylation	-----MASVCGTPSP -----CCCCCCCCCC	29.78	26745281
7	Phosphorylation	-MASVCGTPSPGGAL -CCCCCCCCCCCCCC	18.57	26745281
9	Phosphorylation	ASVCGTPSPGGALGS CCCCCCCCCCCCCCC	35.69	26745281
16	Phosphorylation	SPGGALGSPAPAWYH CCCCCCCCCCCHHHC	20.81	23984901
43	Phosphorylation	ARAGRDGSFLVRDSE HHCCCCCCEEECCCC	21.50	29176673
132	Phosphorylation	PPDDRDASDVEDEKP CCCCCCHHHCCCCCC	46.61	25521595
145	Phosphorylation	KPPLPPRSGSTSISA CCCCCCCCCCCEEEC	42.75	26643407
147	Phosphorylation	PLPPRSGSTSISAPV CCCCCCCCCEEECCC	21.89	26643407
148	Phosphorylation	LPPRSGSTSISAPVG CCCCCCCCEEECCCC	33.34	26643407
149	Phosphorylation	PPRSGSTSISAPVGP CCCCCCCEEECCCCC	19.08	26643407
151	Phosphorylation	RSGSTSISAPVGPSS CCCCCEEECCCCCCC	26.70	26643407
157	Phosphorylation	ISAPVGPSSPLPTPE EECCCCCCCCCCCCC	38.36	26643407
158	Phosphorylation	SAPVGPSSPLPTPET ECCCCCCCCCCCCCC	33.32	26643407
162	Phosphorylation	GPSSPLPTPETPTTP CCCCCCCCCCCCCCC	41.25	26643407
165	Phosphorylation	SPLPTPETPTTPAAE CCCCCCCCCCCCCCC	27.43	26643407
167	Phosphorylation	LPTPETPTTPAAEST CCCCCCCCCCCCCCC	53.48	26643407
168	Phosphorylation	PTPETPTTPAAESTP CCCCCCCCCCCCCCC	16.48	26643407
173	Phosphorylation	PTTPAAESTPNGLST CCCCCCCCCCCCCCC	44.42	25777480
174	Phosphorylation	TTPAAESTPNGLSTV CCCCCCCCCCCCCCC	16.57	25777480
179	Phosphorylation	ESTPNGLSTVSHEYL CCCCCCCCCCCHHHH	28.32	25777480
180	Phosphorylation	STPNGLSTVSHEYLK CCCCCCCCCCHHHHC	30.94	25777480
182	Phosphorylation	PNGLSTVSHEYLKGS CCCCCCCCHHHHCCC	15.64	25777480
185	Phosphorylation	LSTVSHEYLKGSYGL CCCCCHHHHCCCCCC	14.32	25777480
189	Phosphorylation	SHEYLKGSYGLDLEA CHHHHCCCCCCCHHH	17.91	25367039
190	Phosphorylation	HEYLKGSYGLDLEAV HHHHCCCCCCCHHHH	30.31	25367039
220	Phosphorylation	TSCRRLHSEVDKVLS HHHHHHHHHHHHHHH	43.86	30387612
240	Phosphorylation	SKVFDQQSSPMVTRL HHHHCCCCCHHHHHH	30.67	30635358
241	Phosphorylation	KVFDQQSSPMVTRLL HHHCCCCCHHHHHHH	16.81	25521595
245	Phosphorylation	QQSSPMVTRLLQQQS CCCCHHHHHHHHHCC	14.89	30635358
252	Phosphorylation	TRLLQQQSLPQTGEQ HHHHHHCCCCCCCHH	37.36	27841257
290	Phosphorylation	LKALQDMSSTAPPAP HHHHHHHHCCCCCCC	32.59	24759943
301	Phosphorylation	PPAPLQPSIRKAKTI CCCCCCCCCCCCCCC	23.28	25159016
307	Phosphorylation	PSIRKAKTIPVQAFE CCCCCCCCCCEEEEE	35.06	22817900
332	Ubiquitination	TKIGKSQKFTLSVDV EEECCCCCEEEEEEE	47.62	22790023
353	Phosphorylation	LLRRQRDSQEDWTTF EEEECCCCCCCCCCC	37.34	25338131
426	Phosphorylation	QDEPDMISVFIGTWN CCCCCCEEEEEEEEC	12.34	22871156
524	Phosphorylation	PEHENRISHVSTSSV HHHCCCCCEECHHHC	18.01	25777480
527	Phosphorylation	ENRISHVSTSSVKTG CCCCCEECHHHCHHC	19.69	25777480
528	Phosphorylation	NRISHVSTSSVKTGI CCCCEECHHHCHHCC	24.75	25777480
529	Phosphorylation	RISHVSTSSVKTGIA CCCEECHHHCHHCCC	26.15	25777480
530	Phosphorylation	ISHVSTSSVKTGIAN CCEECHHHCHHCCCC	27.93	25777480
538	Phosphorylation	VKTGIANTLGNKGAV CHHCCCCCCCCCCCE	27.33	28833060
662	Phosphorylation	EISFPPTYRYERGSR HHCCCCCCCCCCCCC	19.57	22817900
671	Phosphorylation	YERGSRDTYAWHKQK CCCCCCCCCCCCCCC	17.65	25367039
672	Phosphorylation	ERGSRDTYAWHKQKP CCCCCCCCCCCCCCC	16.39	22817900
882	Phosphorylation	VPTERLGTRERLYEW CCCCCCCCCHHHHHH	33.67	29514104
887	Phosphorylation	LGTRERLYEWISIDK CCCCHHHHHHEECCC	18.55	22499769
891	Phosphorylation	ERLYEWISIDKDDTG HHHHHHEECCCCCCC	26.30	22499769
897	Phosphorylation	ISIDKDDTGAKSKVP EECCCCCCCCCCCCC	49.53	25367039
902	Acetylation	DDTGAKSKVPSVSRG CCCCCCCCCCCCCCC	58.41	19847677
905	Phosphorylation	GAKSKVPSVSRGSQE CCCCCCCCCCCCCCC	35.39	22942356
907	Phosphorylation	KSKVPSVSRGSQEHR CCCCCCCCCCCCCCC	34.95	29514104
910	Phosphorylation	VPSVSRGSQEHRSGS CCCCCCCCCCCCCCC	31.14	29514104
915	Phosphorylation	RGSQEHRSGSRKPAS CCCCCCCCCCCCCCC	42.92	29514104
917	Phosphorylation	SQEHRSGSRKPASTE CCCCCCCCCCCCCCC	38.08	29514104
922	Phosphorylation	SGSRKPASTETSCPL CCCCCCCCCCCCCCH	34.99	29514104
925	Phosphorylation	RKPASTETSCPLSKL CCCCCCCCCCCHHHH	35.40	29514104
926	Phosphorylation	KPASTETSCPLSKLF CCCCCCCCCCHHHHC	13.91	29514104
927	Glutathionylation	PASTETSCPLSKLFE CCCCCCCCCHHHHCC	5.26	24333276
964	Phosphorylation	PLNPRLKSEGTSEQE CCCHHHCCCCCCCCC	45.94	25367039
967	Phosphorylation	PRLKSEGTSEQEGVA HHHCCCCCCCCCCCC	25.66	26026062
968	Phosphorylation	RLKSEGTSEQEGVAA HHCCCCCCCCCCCCC	48.41	30635358
981	Phosphorylation	AAPPPKNSFNNPAYY CCCCCCCCCCCCCEE	35.16	22499769
987	Phosphorylation	NSFNNPAYYVLEGVP CCCCCCCEEEECCCC	8.72	26824392
988	Phosphorylation	SFNNPAYYVLEGVPH CCCCCCEEEECCCCC	10.72	18515860
1004	Phosphorylation	LLPLEPPSLARAPLP CCCCCCCHHHCCCCC	45.43	22499769
1082	Phosphorylation	MPVVRGRSGGEARGP CCEEECCCCCCCCCC	54.71	27717184
1104	Phosphorylation	RPPLPPGTSPASTFL CCCCCCCCCCCHHHH	36.99	29514104
1130	Phosphorylation	SVLQMAKTLSEVDYA HHHHHHHCHHHCCCC	26.44	29514104
1132	Phosphorylation	LQMAKTLSEVDYAPG HHHHHCHHHCCCCCC	40.58	22499769
1136	Phosphorylation	KTLSEVDYAPGPGRS HCHHHCCCCCCCCCC	21.63	22499769
1159	Phosphorylation	LQPPRGPSDYGRPLS CCCCCCCCCCCCCCC	46.41	29514104
1161	Phosphorylation	PPRGPSDYGRPLSFP CCCCCCCCCCCCCCC	21.26	22817900
1166	Phosphorylation	SDYGRPLSFPPPRIR CCCCCCCCCCCHHHH	38.09	26824392
1175	Phosphorylation	PPPRIRESIQEDLAE CCHHHHHHHHHHHHH	21.52	25159016
1193	Phosphorylation	CPQGGRASGLGEAGM CCCCCCCCCCCCCHH	32.94	24899341
1252	Phosphorylation	HKRLLLDTLQLSK-- HHHHHHHHHHCCC--	19.17	29514104
1256	Phosphorylation	LLDTLQLSK------ HHHHHHCCC------	24.29	-

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

Oops, there are no upstream regulatory protein records of SHIP2_MOUSE !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SHIP2_MOUSE !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of SHIP2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
2AAA_MOUSE	Ppp2r1a	physical	19825976
SHC1_MOUSE	Shc1	physical	14502564

Drug and Disease Associations

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