dbPTM

PLCG2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PLCG2_HUMAN
UniProt AC	P16885
Protein Name	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
Gene Name	PLCG2
Organism	Homo sapiens (Human).
Sequence Length	1265
Subcellular Localization
Protein Description	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling..
Protein Sequence	MSTTVNVDSLAEYEKSQIKRALELGTVMTVFSFRKSTPERRTVQVIMETRQVAWSKTADKIEGFLDIMEIKEIRPGKNSKDFERAKAVRQKEDCCFTILYGTQFVLSTLSLAADSKEDAVNWLSGLKILHQEAMNASTPTIIESWLRKQIYSVDQTRRNSISLRELKTILPLINFKVSSAKFLKDKFVEIGAHKDELSFEQFHLFYKKLMFEQQKSILDEFKKDSSVFILGNTDRPDASAVYLHDFQRFLIHEQQEHWAQDLNKVRERMTKFIDDTMRETAEPFLFVDEFLTYLFSRENSIWDEKYDAVDMQDMNNPLSHYWISSSHNTYLTGDQLRSESSPEAYIRCLRMGCRCIELDCWDGPDGKPVIYHGWTRTTKIKFDDVVQAIKDHAFVTSSFPVILSIEEHCSVEQQRHMAKAFKEVFGDLLLTKPTEASADQLPSPSQLREKIIIKHKKLGPRGDVDVNMEDKKDEHKQQGELYMWDSIDQKWTRHYCAIADAKLSFSDDIEQTMEEEVPQDIPPTELHFGEKWFHKKVEKRTSAEKLLQEYCMETGGKDGTFLVRESETFPNDYTLSFWRSGRVQHCRIRSTMEGGTLKYYLTDNLTFSSIYALIQHYRETHLRCAEFELRLTDPVPNPNPHESKPWYYDSLSRGEAEDMLMRIPRDGAFLIRKREGSDSYAITFRARGKVKHCRINRDGRHFVLGTSAYFESLVELVSYYEKHSLYRKMRLRYPVTPELLERYNMERDINSLYDVSRMYVDPSEINPSMPQRTVKALYDYKAKRSDELSFCRGALIHNVSKEPGGWWKGDYGTRIQQYFPSNYVEDISTADFEELEKQIIEDNPLGSLCRGILDLNTYNVVKAPQGKNQKSFVFILEPKQQGDPPVEFATDRVEELFEWFQSIREITWKIDTKENNMKYWEKNQSIAIELSDLVVYCKPTSKTKDNLENPDFREIRSFVETKADSIIRQKPVDLLKYNQKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQMNHALFSLNGRTGYVLQPESMRTEKYDPMPPESQRKILMTLTVKVLGARHLPKLGRSIACPFVEVEICGAEYDNNKFKTTVVNDNGLSPIWAPTQEKVTFEIYDPNLAFLRFVVYEEDMFSDPNFLAHATYPIKAVKSGFRSVPLKNGYSEDIELASLLVFCEMRPVLESEEELYSSCRQLRRRQEELNNQLFLYDTHQNLRNANRDALVKEFSVNENQLQLYQEKCNKRLREKRVSNSKFYS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSTTVNVDS ------CCCEECHHH	44.05	30108239
3	Phosphorylation	-----MSTTVNVDSL -----CCCEECHHHH	46.77	30108239
4	Phosphorylation	----MSTTVNVDSLA ----CCCEECHHHHH	21.26	30108239
13	Phosphorylation	NVDSLAEYEKSQIKR CHHHHHHHHHHHHHH	24.05	27642862
29	Phosphorylation	LELGTVMTVFSFRKS HHHHCEEEEEECCCC	17.67	28064214
32	Phosphorylation	GTVMTVFSFRKSTPE HCEEEEEECCCCCCC	21.58	24719451
42	Phosphorylation	KSTPERRTVQVIMET CCCCCHHHHEEEEEE	22.85	24505115
49	Phosphorylation	TVQVIMETRQVAWSK HHEEEEEECHHHHHH	14.71	24505115
148	Ubiquitination	IIESWLRKQIYSVDQ HHHHHHHHHCCCCCH	38.59	24816145
160	Phosphorylation	VDQTRRNSISLRELK CCHHHCCCCCHHHHH	16.25	29496963
162	Phosphorylation	QTRRNSISLRELKTI HHHCCCCCHHHHHHH	22.61	29496963
167	Ubiquitination	SISLRELKTILPLIN CCCHHHHHHHHHHHC	28.85	21890473
181	Acetylation	NFKVSSAKFLKDKFV CCCCCCCHHHHHHEE	53.85	25953088
208	Ubiquitination	QFHLFYKKLMFEQQK HHHHHHHHHHHHHHH	33.53	-
222	Ubiquitination	KSILDEFKKDSSVFI HHHHHHHCCCCCEEE	54.33	29967540
242	Phosphorylation	RPDASAVYLHDFQRF CCCCCEEEEHHHHHH	9.68	-
276	Phosphorylation	MTKFIDDTMRETAEP HHHHHHHHHHHHCCC	17.87	19664994
371	Phosphorylation	PDGKPVIYHGWTRTT CCCCEEEEECCCCCE	8.43	22817900
431	Phosphorylation	VFGDLLLTKPTEASA HHHHHHCCCCCCCCC	34.64	30108239
432	Ubiquitination	FGDLLLTKPTEASAD HHHHHCCCCCCCCCC	50.33	21906983
434	Phosphorylation	DLLLTKPTEASADQL HHHCCCCCCCCCCCC	45.82	30108239
437	Phosphorylation	LTKPTEASADQLPSP CCCCCCCCCCCCCCH	26.58	30108239
443	Phosphorylation	ASADQLPSPSQLREK CCCCCCCCHHHHHHH	45.86	30108239
445	Phosphorylation	ADQLPSPSQLREKII CCCCCCHHHHHHHHH	46.30	30108239
482	Phosphorylation	HKQQGELYMWDSIDQ HHHCCCEEEEECCCC	7.58	25147952
495	Phosphorylation	DQKWTRHYCAIADAK CCCCHHHEEHHHCCC	4.74	28796482
554	Phosphorylation	LQEYCMETGGKDGTF HHHHHHHHCCCCCEE	25.09	25690035
557	Ubiquitination	YCMETGGKDGTFLVR HHHHHCCCCCEEEEE	55.09	-
590	Phosphorylation	VQHCRIRSTMEGGTL CEEEEEEEECCCCEE	29.72	23898821
647	Phosphorylation	PHESKPWYYDSLSRG CCCCCCCCCCCCCCC	13.11	-
677	Phosphorylation	LIRKREGSDSYAITF EEEEECCCCEEEEEE	20.73	28152594
679	Phosphorylation	RKREGSDSYAITFRA EEECCCCEEEEEEEE	20.40	28152594
680	Phosphorylation	KREGSDSYAITFRAR EECCCCEEEEEEEEC	13.65	28152594
683	Phosphorylation	GSDSYAITFRARGKV CCCEEEEEEEECCCE	10.01	28152594
720	Phosphorylation	LVELVSYYEKHSLYR HHHHHHHHHHCCHHH	15.82	-
733	Phosphorylation	YRKMRLRYPVTPELL HHHHCHHCCCCHHHH	13.47	20090780
743	Phosphorylation	TPELLERYNMERDIN CHHHHHHHCCCCCHH	14.97	12181444
751	Phosphorylation	NMERDINSLYDVSRM CCCCCHHHHHHHHHE	28.74	21945579
753	Phosphorylation	ERDINSLYDVSRMYV CCCHHHHHHHHHEEC	17.70	21945579
756	Phosphorylation	INSLYDVSRMYVDPS HHHHHHHHHEECCHH	14.39	21945579
759	Phosphorylation	LYDVSRMYVDPSEIN HHHHHHEECCHHHCC	10.69	21945579
763	Phosphorylation	SRMYVDPSEINPSMP HHEECCHHHCCCCCC	46.79	-
775	Ubiquitination	SMPQRTVKALYDYKA CCCHHHHHHHHHHCC	31.87	-
778	Phosphorylation	QRTVKALYDYKAKRS HHHHHHHHHHCCCCC	23.30	-
780	Phosphorylation	TVKALYDYKAKRSDE HHHHHHHHCCCCCCC	10.17	21253578
789	Phosphorylation	AKRSDELSFCRGALI CCCCCCCCCCCCEEC	21.91	-
811	Phosphorylation	GGWWKGDYGTRIQQY CCCCCCCCHHHHHHH	29.12	22817900
818	Phosphorylation	YGTRIQQYFPSNYVE CHHHHHHHCCCCCCC	10.90	22817900
847	Phosphorylation	IEDNPLGSLCRGILD HHCCCCHHHHHHCCC	31.79	28674151
857	Phosphorylation	RGILDLNTYNVVKAP HHCCCCCCCEEEECC	24.62	28796482
858	Phosphorylation	GILDLNTYNVVKAPQ HCCCCCCCEEEECCC	12.60	28796482
862	Ubiquitination	LNTYNVVKAPQGKNQ CCCCEEEECCCCCCC	50.49	29967540
871	Phosphorylation	PQGKNQKSFVFILEP CCCCCCCEEEEEECC	19.51	28348404
902	Phosphorylation	ELFEWFQSIREITWK HHHHHHHHHHHCCCE	17.71	24719451
925	Phosphorylation	KYWEKNQSIAIELSD HHHHHCCEEEEEHHH	24.31	22210691
931	Phosphorylation	QSIAIELSDLVVYCK CEEEEEHHHEEEEEC	18.99	22210691
936	Phosphorylation	ELSDLVVYCKPTSKT EHHHEEEEECCCCCC	6.30	22210691
941	Phosphorylation	VVYCKPTSKTKDNLE EEEECCCCCCCCCCC	47.02	-
957	Phosphorylation	PDFREIRSFVETKAD CCHHHHHHHHHHHHH	39.03	27251275
962	Ubiquitination	IRSFVETKADSIIRQ HHHHHHHHHHHHHHH	36.37	21906983
965	Phosphorylation	FVETKADSIIRQKPV HHHHHHHHHHHHCCC	25.44	27251275
980	Ubiquitination	DLLKYNQKGLTRVYP CHHHCCCCCCEEEEC	52.85	29967540
994	Phosphorylation	PKGQRVDSSNYDPFR CCCCCCCCCCCCCCE	20.02	-
1007	Phosphorylation	FRLWLCGSQMVALNF CEEEECCCCEEEECC	17.69	-
1016	Phosphorylation	MVALNFQTADKYMQM EEEECCCCHHHHHHH	32.46	-
1020	Phosphorylation	NFQTADKYMQMNHAL CCCCHHHHHHHCCHH	7.98	-
1029	Phosphorylation	QMNHALFSLNGRTGY HHCCHHHCCCCCCCE	23.06	-
1034	Phosphorylation	LFSLNGRTGYVLQPE HHCCCCCCCEEECCH	33.97	-
1036	Phosphorylation	SLNGRTGYVLQPESM CCCCCCCEEECCHHH	9.43	-
1042	Phosphorylation	GYVLQPESMRTEKYD CEEECCHHHCCCCCC	21.90	28985074
1045	Phosphorylation	LQPESMRTEKYDPMP ECCHHHCCCCCCCCC	28.34	-
1047	Ubiquitination	PESMRTEKYDPMPPE CHHHCCCCCCCCCHH	55.10	21890473
1048	Phosphorylation	ESMRTEKYDPMPPES HHHCCCCCCCCCHHH	21.03	20393185
1062	Phosphorylation	SQRKILMTLTVKVLG HHHHHHHHHHHHHHC	18.81	-
1064	Phosphorylation	RKILMTLTVKVLGAR HHHHHHHHHHHHCCC	14.76	-
1137	Phosphorylation	AFLRFVVYEEDMFSD EEEEEEEECHHHCCC	14.32	22817900
1164	Phosphorylation	AVKSGFRSVPLKNGY HHHCCCCCCCCCCCC	26.31	-
1197	Phosphorylation	LESEEELYSSCRQLR CCCHHHHHHHHHHHH	11.21	15509800
1198	Phosphorylation	ESEEELYSSCRQLRR CCHHHHHHHHHHHHH	35.27	29978859
1199	Phosphorylation	SEEELYSSCRQLRRR CHHHHHHHHHHHHHH	10.36	29978859
1217	Phosphorylation	LNNQLFLYDTHQNLR HHHHHEEHHHHHHHH	16.09	21945579
1219	Phosphorylation	NQLFLYDTHQNLRNA HHHEEHHHHHHHHHC	16.29	21945579
1233	Ubiquitination	ANRDALVKEFSVNEN CCHHHHHHEECCCHH	54.62	22817900
1236	Phosphorylation	DALVKEFSVNENQLQ HHHHHEECCCHHHHH	25.73	21945579
1245	Phosphorylation	NENQLQLYQEKCNKR CHHHHHHHHHHHHHH	11.15	21945579
1248	Ubiquitination	QLQLYQEKCNKRLRE HHHHHHHHHHHHHHH	27.81	29967540
1259	Phosphorylation	RLREKRVSNSKFYS- HHHHHHCCCCCCCC-	39.14	28796482
1261	Phosphorylation	REKRVSNSKFYS--- HHHHCCCCCCCC---	19.35	28796482
1262	Ubiquitination	EKRVSNSKFYS---- HHHCCCCCCCC----	53.20	-
1264	Phosphorylation	RVSNSKFYS------ HCCCCCCCC------	19.73	28796482
1265	Phosphorylation	VSNSKFYS------- CCCCCCCC-------	36.56	28796482

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
743	Y	Phosphorylation	Kinase	FYN	P06241	PhosphoELM
743	Y	Phosphorylation	Kinase	LYN	P07948	PhosphoELM
743	Y	Phosphorylation	Kinase	LCK	P06239	PhosphoELM
753	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
753	Y	Phosphorylation	Kinase	FYN	P06241	PSP
753	Y	Phosphorylation	Kinase	SRC	P12931	PSP
753	Y	Phosphorylation	Kinase	LCK	P06239	PSP
753	Y	Phosphorylation	Kinase	BTK	Q06187	Uniprot
759	Y	Phosphorylation	Kinase	LCK	P06239	PSP
759	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
759	Y	Phosphorylation	Kinase	SRC	P12931	PSP
759	Y	Phosphorylation	Kinase	SYK	P43405	PSP
759	Y	Phosphorylation	Kinase	FYN	P06241	PSP
759	Y	Phosphorylation	Kinase	BTK	Q06187	Uniprot
1045	T	Phosphorylation	Kinase	CHAK1	Q96QT4	PSP
1164	S	Phosphorylation	Kinase	CHAK1	Q96QT4	PSP
1197	Y	Phosphorylation	Kinase	LCK	P06239	PSP
1197	Y	Phosphorylation	Kinase	BTK	Q06187	Uniprot
1217	Y	Phosphorylation	Kinase	LCK	P06239	PSP
1217	Y	Phosphorylation	Kinase	BTK	Q06187	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of PLCG2_HUMAN !!

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
242	Phosphorylation	244 (2)	H ⇒ R	rs11548656	Inflammatory bowel disease Ulcerative colitis	28067908

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SHC1_HUMAN	SHC1	physical	10623845
LYN_HUMAN	LYN	physical	8395016
GAB2_HUMAN	GAB2	physical	12135708
PTN11_HUMAN	PTPN11	physical	12135708
KPCD1_HUMAN	PRKD1	physical	8885868
VAV_HUMAN	VAV1	physical	10981967
KSYK_HUMAN	SYK	physical	10981967
BTK_HUMAN	BTK	physical	10981967
LYN_HUMAN	LYN	physical	10981967
KPCA_HUMAN	PRKCA	physical	16923831
PLD1_HUMAN	PLD1	physical	16923831
LHX8_HUMAN	LHX8	physical	25814554
PTTG1_HUMAN	PTTG1	physical	25814554
P53_HUMAN	TP53	physical	25814554
ELK1_HUMAN	ELK1	physical	25814554
EPYC_HUMAN	EPYC	physical	25814554
CH60_HUMAN	HSPD1	physical	25814554
ASB9_HUMAN	ASB9	physical	25814554
BOP_HUMAN	C22orf29	physical	25814554
SETD9_HUMAN	SETD9	physical	25814554
GABP2_HUMAN	GABPB2	physical	25814554
KCD17_HUMAN	KCTD17	physical	25814554
PSMD3_HUMAN	PSMD3	physical	25814554
FSBP_HUMAN	RAD54B	physical	25814554
RA54B_HUMAN	RAD54B	physical	25814554
RBP1_HUMAN	RALBP1	physical	25814554
TWST2_HUMAN	TWIST2	physical	25814554
ZKSC7_HUMAN	ZKSCAN7	physical	25814554
ESTD_HUMAN	ESD	physical	25814554
ISL1_HUMAN	ISL1	physical	25814554
PLCG1_HUMAN	PLCG1	physical	25241761
ERBB2_HUMAN	ERBB2	physical	25241761

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
614468	Familial cold autoinflammatory syndrome 3 (FCAS3)
614878	Autoinflammation, antibody deficiency, and immune dysregulation PLCG2-associated (APLAID)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of PLCG2_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-753; TYR-759 ANDTYR-1217, AND MASS SPECTROMETRY.	19690332 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-733, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Robust phosphoproteomic profiling of tyrosine phosphorylation sitesfrom human T cells using immobilized metal affinity chromatography andtandem mass spectrometry."; Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,Peters E.C.; Anal. Chem. 76:2763-2772(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1245, AND MASSSPECTROMETRY.	15144186 [Abstract]
"Activation of phospholipase Cgamma2 by tyrosine phosphorylation."; Ozdener F., Dangelmaier C., Ashby B., Kunapuli S.P., Daniel J.L.; Mol. Pharmacol. 62:672-679(2002). Cited for: PHOSPHORYLATION AT TYR-753 AND TYR-759.	12181444 [Abstract]
"Tyrosine residues in phospholipase Cgamma 2 essential for the enzymefunction in B-cell signaling."; Rodriguez R., Matsuda M., Perisic O., Bravo J., Paul A., Jones N.P.,Light Y., Swann K., Williams R.L., Katan M.; J. Biol. Chem. 276:47982-47992(2001). Cited for: PHOSPHORYLATION AT TYR-753 AND TYR-759.	11606584 [Abstract]