PK3CB_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PK3CB_HUMAN
• UniProt AC: P42338
• Protein Name: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
• Gene Name: PIK3CB
• Organism: Homo sapiens (Human).
• Sequence Length: 1070
• Subcellular Localization: Cytoplasm . Nucleus . Interaction with PIK3R2 is required for nuclear localization and export.
• Protein Description: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(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. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors..
• Protein Sequence: MCFSFIMPPAMADILDIWAVDSQIASDGSIPVDFLLPTGIYIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDPGEKLDSKIGVLIGKGLHEFDSLKDPEVNEFRRKMRKFSEEKILSLVGLSWMDWLKQTYPPEHEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPYDYVLQVSGRVEYVFGDHPLIQFQYIRNCVMNRALPHFILVECCKIKKMYEQEMIAIEAAINRNSSNLPLPLPPKKTRIISHVWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVLDKVKTKKSTKTINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTNPYTENATALHVKFPENKKQPYYYPPFDKIIEKAAEIASSDSANVSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEAYCRGSVGHMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKDYRS

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
113	Phosphorylation	LPVLKLVTRSCDPGE HHHHHHHHCCCCCCC	27.57	-
115	Phosphorylation	VLKLVTRSCDPGEKL HHHHHHCCCCCCCCC	17.32	-
121	Acetylation	RSCDPGEKLDSKIGV CCCCCCCCCHHHHHE	64.61	25953088
125	Ubiquitination	PGEKLDSKIGVLIGK CCCCCHHHHHEEECC	43.05	-
141	Ubiquitination	LHEFDSLKDPEVNEF HHHCCCCCCHHHHHH	75.17	-
159	Acetylation	MRKFSEEKILSLVGL HHHCCHHHHHHHHCH	44.91	11791281
173	Acetylation	LSWMDWLKQTYPPEH HHHHHHHHHHCCCCC	36.02	133451
191	Ubiquitination	IPENLEDKLYGGKLI CCCCHHHHCCCCEEE	33.94	-
230	Ubiquitination	VNELAIQKRLTIHGK HHHHHHEEEEEECCC	43.17	21906983
242	Phosphorylation	HGKEDEVSPYDYVLQ CCCCCCCCCCCEEEE	18.72	28152594
244	Phosphorylation	KEDEVSPYDYVLQVS CCCCCCCCCEEEEEE	16.64	28152594
246	Phosphorylation	DEVSPYDYVLQVSGR CCCCCCCEEEEEECC	9.38	28152594
251	Phosphorylation	YDYVLQVSGRVEYVF CCEEEEEECCEEEEE	14.12	29449344
324	Phosphorylation	PKKTRIISHVWENNN CCCCEEEEEECCCCC	15.04	-
416	Phosphorylation	DKVKTKKSTKTINPS HHHCCCCCCCCCCHH	36.37	26670566
417	Phosphorylation	KVKTKKSTKTINPSK HHCCCCCCCCCCHHH	40.88	26670566
418	Ubiquitination	VKTKKSTKTINPSKY HCCCCCCCCCCHHHH	55.27	-
423	Phosphorylation	STKTINPSKYQTIRK CCCCCCHHHHHHHHH	39.23	-
425	Phosphorylation	KTINPSKYQTIRKAG CCCCHHHHHHHHHCC	18.41	22322096
427	Phosphorylation	INPSKYQTIRKAGKV CCHHHHHHHHHCCCE	21.47	27642862
436	Phosphorylation	RKAGKVHYPVAWVNT HHCCCEECCEEEEEE	11.46	23663014
443	Phosphorylation	YPVAWVNTMVFDFKG CCEEEEEEEEEECCC	12.70	23663014
503	Phosphorylation	PENKKQPYYYPPFDK CCCCCCCCCCCCHHH	17.09	17360941
504	Phosphorylation	ENKKQPYYYPPFDKI CCCCCCCCCCCHHHH	19.04	17360941
505	Phosphorylation	NKKQPYYYPPFDKII CCCCCCCCCCHHHHH	9.89	17360941
514	Ubiquitination	PFDKIIEKAAEIASS CHHHHHHHHHHHHCC	42.35	21906983
520	Phosphorylation	EKAAEIASSDSANVS HHHHHHHCCCCCCCC	40.10	-
579	Phosphorylation	SLPKLLLSIKWNKLE CHHHHHHHCCCCCHH	23.30	24719451
711	Ubiquitination	GHMKVLSKQVEALNK HHHHHHHHHHHHHHH	54.95	-
721	Phosphorylation	EALNKLKTLNSLIKL HHHHHHHHHHHHHHH	41.42	-
724	Phosphorylation	NKLKTLNSLIKLNAV HHHHHHHHHHHHHHH	34.29	24719451
732	Ubiquitination	LIKLNAVKLNRAKGK HHHHHHHHCCHHCCH	37.32	-
747	Methylation	EAMHTCLKQSAYREA HHHHHHHHHHHHHHH	44.33	115975001
772	Phosphorylation	CVILSELYVEKCKYM CHHHHHHHHHHCCCC	11.51	22817900
828	Ubiquitination	RLMDLLWKEAGLDLR HHHHHHHHHHCCCCE	37.34	21906983
886	Ubiquitination	DALLNWLKEYNSGDD HHHHHHHHHHCCCCC	50.17	2190698
947	Phosphorylation	HILGNFKSKFGIKRE HHHCCHHHHHCCCHH	29.13	-
961	Phosphorylation	ERVPFILTYDFIHVI HCCCEEEEEEEEHHH	19.07	26356563
962	Phosphorylation	RVPFILTYDFIHVIQ CCCEEEEEEEEHHHH	12.86	20090780
1025	Ubiquitination	VKDIQYLKDSLALGK HHHHHHHHHHHHCCC	40.10	21906983
1032	Ubiquitination	KDSLALGKSEEEALK HHHHHCCCCHHHHHH	56.39	-
1039	Ubiquitination	KSEEEALKQFKQKFD CCHHHHHHHHHHHHH	61.82	-
1044	Ubiquitination	ALKQFKQKFDEALRE HHHHHHHHHHHHHHH	56.21	-
1070	Phosphorylation	TVRKDYRS------- HHHHHHCC-------	38.04	12661022

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
1070	S	Phosphorylation	Kinase	PK3CB	P42338	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
1070	S	Phosphorylation	Phosphorylation at Ser-1070 down-regulates lipid kinase activity.	12502714

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of PK3CB_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KPCD_HUMAN	PRKCD	physical	11676480
P85A_HUMAN	PIK3R1	physical	8139559
DVL3_HUMAN	DVL3	physical	21900206
HPS6_HUMAN	HPS6	physical	21900206
HEM1_HUMAN	ALAS1	physical	21900206
CBL_HUMAN	CBL	physical	14530346
GAB2_HUMAN	GAB2	physical	14530346
P85A_HUMAN	PIK3R1	physical	26344197
GBB1_HUMAN	GNB1	physical	26895380
WDR26_HUMAN	WDR26	physical	26895380

Drug and Disease Associations

• Kegg Disease
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• DrugBank
• DB00201: Caffeine

Related Literatures of Post-Translational Modification

Phosphorylation

"Identification and characterization of the autophosphorylation sitesof phosphoinositide 3-kinase isoforms beta and gamma.";
Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K.,Krause E., Nurnberg B.;
J. Biol. Chem. 278:11536-11545(2003).
Cited for: AUTOPHOSPHORYLATION AT SER-1070.
PubMed: 12502714