dbPTM

PK3CD_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PK3CD_HUMAN
UniProt AC	O00329
Protein Name	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Gene Name	PIK3CD
Organism	Homo sapiens (Human).
Sequence Length	1044
Subcellular Localization	Cytoplasm .
Protein Description	Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Have a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Have important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity..
Protein Sequence	MPPGVDCPMEFWTKEENQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFHMLSGPEAYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQISLLIGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYSFPLQLEPSAQTWGPGTLRLPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKATVFRQPLVEQPEDYTLQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPRAKPPPIPAKKPSSVSLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVSVCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEKAKKARSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLICLPEVAPHPVYYPALEKILELGRHSECVHVTEEEQLQLREILERRGSGELYEHEKDLVWKLRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPDCHVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSVALRFGLILEAYCRGSTHHMKVLMKQGEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMRQEAYLEALSHLQSPLDPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEAGSGGSVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDTIANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDNRQ

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
46	Ubiquitination	NANLSTIKQLLWHRA CCCHHHHHHHHHHHH	34.67	21890473
118	Phosphorylation	KLINSQISLLIGKGL HHHHHHHHHHHCCCH	14.97	24247654
142	Ubiquitination	EVNDFRAKMCQFCEE CCCHHHHHHHHHHHH	35.63	-
226	Phosphorylation	CALRKKATVFRQPLV HHHHHCCEEEECCCC	29.11	20860994
312	Phosphorylation	PIPAKKPSSVSLWSL CCCCCCCCCCCCEEC	52.86	28348404
313	Phosphorylation	IPAKKPSSVSLWSLE CCCCCCCCCCCEECC	25.01	28348404
315	Phosphorylation	AKKPSSVSLWSLEQP CCCCCCCCCEECCCC	26.52	-
357	Phosphorylation	GNEMLCKTVSSSEVS CCCEEEEECCCCCEE	25.32	25332170
372	Ubiquitination	VCSEPVWKQRLEFDI ECCCCHHHHHEEEEE	26.27	-
406	Phosphorylation	EKAKKARSTKKKSKK HHHHHHHCCCCCCCC	49.81	-
411	Phosphorylation	ARSTKKKSKKADCPI HHCCCCCCCCCCCCH	48.55	-
440	Phosphorylation	KTGERCLYMWPSVPD CCCCCEEEECCCCCC	10.76	16497976
449	Ubiquitination	WPSVPDEKGELLNPT CCCCCCCCCCCCCCC	66.13	-
449	Acetylation	WPSVPDEKGELLNPT CCCCCCCCCCCCCCC	66.13	25953088
484	Phosphorylation	EVAPHPVYYPALEKI HHCCCCCHHHHHHHH	14.26	18083107
485	Phosphorylation	VAPHPVYYPALEKIL HCCCCCHHHHHHHHH	5.14	20090780
520	Phosphorylation	EILERRGSGELYEHE HHHHHCCCCCCCHHH	27.55	28355574
524	Phosphorylation	RRGSGELYEHEKDLV HCCCCCCCHHHHHHH	15.78	21082442
528	Ubiquitination	GELYEHEKDLVWKLR CCCCHHHHHHHHHHH	59.26	-
533	Ubiquitination	HEKDLVWKLRHEVQE HHHHHHHHHHHHHHH	28.32	21890473
557	Ubiquitination	LLVTKWNKHEDVAQM HHHHCCCCCHHHHHH	47.45	-
684	Ubiquitination	HHMKVLMKQGEALSK HHHHHHHHHHHHHHH	51.49	-
690	Phosphorylation	MKQGEALSKLKALND HHHHHHHHHHHHHHH	42.88	24719451
691	Ubiquitination	KQGEALSKLKALNDF HHHHHHHHHHHHHHH	55.65	-
693	Ubiquitination	GEALSKLKALNDFVK HHHHHHHHHHHHHHH	55.34	-
712	Ubiquitination	KTPKPQTKELMHLCM CCCCCCHHHHHHHHH	43.53	-
841	Ubiquitination	IANIQLNKSNMAATA EEEEEECCCCHHHHH	52.37	21890473
842	Phosphorylation	ANIQLNKSNMAATAA EEEEECCCCHHHHHH	30.66	26425664
847	Phosphorylation	NKSNMAATAAFNKDA CCCCHHHHHHCCHHH	14.69	26425664
852	Ubiquitination	AATAAFNKDALLNWL HHHHHCCHHHHHHHH	37.61	-
862	Ubiquitination	LLNWLKSKNPGEALD HHHHHHCCCHHHHHH	66.62	-
935	Phosphorylation	ERVPFILTYDFVHVI CCCCEEEEEEHHHHH	19.07	26356563
936	Phosphorylation	RVPFILTYDFVHVIQ CCCEEEEEEHHHHHH	12.16	20090780
950	O-linked_Glycosylation	QQGKTNNSEKFERFR HCCCCCCHHHHHHHH	44.21	29351928
964	Phosphorylation	RGYCERAYTILRRHG HHHHHHHHHHHHHCC	10.67	28634120
999	Ubiquitination	SKDIQYLKDSLALGK CCCHHHHHHHHHCCC	40.10	21890473
1006	Ubiquitination	KDSLALGKTEEEALK HHHHHCCCCHHHHHH	54.32	-
1013	Ubiquitination	KTEEEALKHFRVKFN CCHHHHHHHHHHHHH	47.98	-
1018	Acetylation	ALKHFRVKFNEALRE HHHHHHHHHHHHHHH	37.91	25953088
1030	Ubiquitination	LRESWKTKVNWLAHN HHHHHHHHHHHHHHH	29.82	-
1039	Phosphorylation	NWLAHNVSKDNRQ-- HHHHHHCCCCCCC--	39.34	22115753

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
1039	S	Phosphorylation	Kinase	PK3CD	O00329	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
1039	S	Phosphorylation		10064595
Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity.

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 PK3CD_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P85B_HUMAN	PIK3R2	physical	9113989
P85A_HUMAN	PIK3R1	physical	9113989
PK3CG_HUMAN	PIK3CG	physical	9113989

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
615513	Activated PI3K-delta syndrome (APDS)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00201	Caffeine

Regulatory Network of PK3CD_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-484; SER-520; TYR-524AND SER-1039, AND MASS SPECTROMETRY.	19369195 [Abstract]
"Autophosphorylation of p110 delta phosphoinositide 3-kinase: a newparadigm for the regulation of lipid kinases in vitro and in vivo."; Vanhaesebroeck B., Higashi K., Raven C., Welham M., Anderson S.,Brennan P., Ward S.G., Waterfield M.D.; EMBO J. 18:1292-1302(1999). Cited for: PROTEIN SEQUENCE OF 1031-1040, PHOSPHORYLATION AT SER-1039, ANDMUTAGENESIS OF ARG-894 AND SER-1039.	10064595 [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-524, AND MASSSPECTROMETRY.	18083107 [Abstract]

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