dbPTM

PI51C_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PI51C_MOUSE
UniProt AC	O70161
Protein Name	Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma
Gene Name	Pip5k1c
Organism	Mus musculus (Mouse).
Sequence Length	661
Subcellular Localization	Cell membrane Peripheral membrane protein Cytoplasmic side. Endomembrane system. Cytoplasm. Cell junction, focal adhesion. Cell junction, adherens junction. Cell projection, ruffle membrane. Cell projection, phagocytic cup. Cell projection, uropodium. N
Protein Description	Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth..
Protein Sequence	MELEVPDEAESAEAGAVTAEAAWSAESGAAAGMTQKKAGLAEAPLVTGQPGPGHGKKLGHRGVDASGETTYKKTTSSTLKGAIQLGIGYTVGNLSSKPERDVLMQDFYVVESIFFPSEGSNLTPAHHFQDFRFKTYAPVAFRYFRELFGIRPDDYLYSLCNEPLIELSNPGASGSVFYVTSDDEFIIKTVMHKEAEFLQKLLPGYYMNLNQNPRTLLPKFYGLYCVQSGGKNIRVVVMNNVLPRVVKMHLKFDLKGSTYKRRASKKEKEKSLPTYKDLDFMQDMPEGLLLDSDTFGALVKTLQRDCLVLESFKIMDYSLLLGVHNIDQQERERQAEGAQSKADEKRPVAQKALYSTAMESIQGGAARGEAIETDDTMGGIPAVNGRGERLLLHIGIIDILQSYRFIKKLEHTWKALVHDGDTVSVHRPSFYAERFFKFMSSTVFRKSSSLKSSPSKKGRGALLAVKPLGPTAAFSASQIPSEREDVQYDLRGARSYPTLEDEGRPDLLPCTPPSFEEATTASIATTLSSTSLSIPERSPSDTSEQPRYRRRTQSSGQDGRPQEEPHAEDLQKITVQVEPVCGVGVVPKEEGAGVEVPPCGASAAASVEIDAASQASEPASQASDEEDAPSTDIYFPTDERSWVYSPLHYSARPASDGESDT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
11	O-linked_Glycosylation	EVPDEAESAEAGAVT CCCCHHHHHHHCCEE	38.16	113301535
71	Phosphorylation	DASGETTYKKTTSST CCCCCCCCCCCCCHH	20.22	29514104
97	Ubiquitination	TVGNLSSKPERDVLM EECCCCCCCCHHCHH	47.74	-
200	Ubiquitination	KEAEFLQKLLPGYYM HHHHHHHHHCCCHHC	54.89	-
265	Acetylation	TYKRRASKKEKEKSL HHHCCCCHHHHHHCC	65.06	20668706
268	Acetylation	RRASKKEKEKSLPTY CCCCHHHHHHCCCCH	78.35	20668706
431	Phosphorylation	SVHRPSFYAERFFKF EEECCHHHHHHHHHH	16.34	29899451
447	Phosphorylation	SSTVFRKSSSLKSSP HHHHHHCCCCCCCCC	22.39	22817900
448	Phosphorylation	STVFRKSSSLKSSPS HHHHHCCCCCCCCCC	42.60	21183079
449	Phosphorylation	TVFRKSSSLKSSPSK HHHHCCCCCCCCCCC	47.08	22817900
452	Phosphorylation	RKSSSLKSSPSKKGR HCCCCCCCCCCCCCC	53.42	21183079
453	Phosphorylation	KSSSLKSSPSKKGRG CCCCCCCCCCCCCCC	31.44	22817900
455	Phosphorylation	SSLKSSPSKKGRGAL CCCCCCCCCCCCCEE	49.28	23335269
457	Acetylation	LKSSPSKKGRGALLA CCCCCCCCCCCEEEE	59.17	7718855
459	Methylation	SSPSKKGRGALLAVK CCCCCCCCCEEEEEE	35.77	24129315
459	Asymmetric dimethylarginine	SSPSKKGRGALLAVK CCCCCCCCCEEEEEE	35.77	-
471	Phosphorylation	AVKPLGPTAAFSASQ EEEECCCCCCCCHHH	28.90	29899451
475	Phosphorylation	LGPTAAFSASQIPSE CCCCCCCCHHHCCCC	23.45	26824392
477	Phosphorylation	PTAAFSASQIPSERE CCCCCCHHHCCCCCC	27.69	28066266
494 (in isoform 2)	Phosphorylation	-	39.28	19144319
538	Phosphorylation	SLSIPERSPSDTSEQ CCCCCCCCCCCCCCC	27.39	-
540	Phosphorylation	SIPERSPSDTSEQPR CCCCCCCCCCCCCCC	55.56	25521595
543	Phosphorylation	ERSPSDTSEQPRYRR CCCCCCCCCCCCCCH	38.94	22817900
548	Phosphorylation	DTSEQPRYRRRTQSS CCCCCCCCCHHCCCC	18.36	29899451
552	Phosphorylation	QPRYRRRTQSSGQDG CCCCCHHCCCCCCCC	30.87	25521595
554	Phosphorylation	RYRRRTQSSGQDGRP CCCHHCCCCCCCCCC	35.50	25521595
555	Phosphorylation	YRRRTQSSGQDGRPQ CCHHCCCCCCCCCCC	30.56	25521595
581	S-nitrosylation	TVQVEPVCGVGVVPK EEEEEECCEEEEECC	5.52	24895380
585 (in isoform 2)	Phosphorylation	-	6.56	30372032
595 (in isoform 2)	Phosphorylation	-	48.68	29899451
601 (in isoform 2)	Phosphorylation	-	11.60	29899451
634	Phosphorylation	DAPSTDIYFPTDERS CCCCCCCCCCCCCCC	13.30	17635937
641	Phosphorylation	YFPTDERSWVYSPLH CCCCCCCCEEECCCE	20.88	25177544
644	Phosphorylation	TDERSWVYSPLHYSA CCCCCEEECCCEECC	9.79	14691141
645	Phosphorylation	DERSWVYSPLHYSAR CCCCEEECCCEECCC	16.03	24925903
649	Phosphorylation	WVYSPLHYSARPASD EEECCCEECCCCCCC	16.23	24925903
650	Phosphorylation	VYSPLHYSARPASDG EECCCEECCCCCCCC	13.67	22324799
655	Phosphorylation	HYSARPASDGESDT- EECCCCCCCCCCCC-	49.16	24925903
659	Phosphorylation	RPASDGESDT----- CCCCCCCCCC-----	52.67	24925903
661	Phosphorylation	ASDGESDT------- CCCCCCCC-------	50.19	22324799

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
634	Y	Phosphorylation	Kinase	EGFR	P00533	PSP
634	Y	Phosphorylation	Kinase	EGFR	Q01279	Uniprot
644	Y	Phosphorylation	Kinase	CSK	P41241	Uniprot
644	Y	Phosphorylation	Kinase	SRC	P12931	PSP
644	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
645	S	Phosphorylation	Kinase	CDK1	P11440	Uniprot
645	S	Phosphorylation	Kinase	CDK5	P49615	Uniprot
645	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
265	K	Acetylation	-
Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity.
268	K	Acetylation	-
Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity.
645	S	Phosphorylation	17635937
Phosphorylation on Ser-645 and Tyr-644 are mutually exclusive.
645	S	Phosphorylation	17635937
Phosphorylation on Ser-645 negatively regulates binding to TLN2 and is strongly stimulated in mitosis.
645	S	Phosphorylation	17635937
Some studies suggest that phosphorylation on Tyr-644 enhances binding to tailins (TLN1 and TLN2); others that phosphorylation at Tyr-644 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-645.

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 PI51C_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of PI51C_MOUSE !!

Drug and Disease Associations

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

Regulatory Network of PI51C_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Type I gamma phosphatidylinositol phosphate kinase is required forEGF-stimulated directional cell migration."; Sun Y., Ling K., Wagoner M.P., Anderson R.A.; J. Cell Biol. 178:297-308(2007). Cited for: FUNCTION IN CELL MIGRATION AND ADHESION, INTERACTION WITH PLCG1,PHOSPHORYLATION AT TYR-634, AND MUTAGENESIS OF TYR-634; TYR-644 ANDSER-645.	17635937 [Abstract]
"Tyrosine phosphorylation of type Igamma phosphatidylinositolphosphate kinase by Src regulates an integrin-talin switch."; Ling K., Doughman R.L., Iyer V.V., Firestone A.J., Bairstow S.F.,Mosher D.F., Schaller M.D., Anderson R.A.; J. Cell Biol. 163:1339-1349(2003). Cited for: INTERACTION WITH TLN1, SUBCELLULAR LOCATION, PHOSPHORYLATION ATTYR-644, AND MUTAGENESIS OF TYR-644.	14691141 [Abstract]
"Type I gamma phosphatidylinositol phosphate kinase targets andregulates focal adhesions."; Ling K., Doughman R.L., Firestone A.J., Bunce M.W., Anderson R.A.; Nature 420:89-93(2002). Cited for: FUNCTION IN FOCAL ADHESION DYNAMIC, SUBCELLULAR LOCATION,PHOSPHORYLATION AT TYROSINE RESIDUES, INTERACTION WITH TLN1, ANDMUTAGENESIS OF ASP-253.	12422220 [Abstract]

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