CPLM-000475

Genbank Nucleotide ID

3-phosphoinositide-dependent protein kinase 1

Protein Synonyms/Alias

Homo sapiens (Human)

Position	Peptide	Type	References
235	KVLSPESKQARANSF	ubiquitination	[1]
257	SPELLTEKSACKSSD	ubiquitination	[1]
304	LEYDFPEKFFPKARD	acetylation	[2, 3]
304	LEYDFPEKFFPKARD	ubiquitination	[4, 5]
323	LLVLDATKRLGCEEM	ubiquitination	[1]
441	EKRLLLEKQAGGNPW	ubiquitination	[1]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[3] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF- kappa-B activation in macrophages. Isoform 3 is catalytically inactive.

DOMAIN 82 342 Protein kinase.
DOMAIN 459 550 PH.
NP_BIND 88 96 ATP (By similarity).
ACT_SITE 205 205 Proton acceptor (By similarity).
BINDING 111 111 ATP (By similarity).
MOD_RES 9 9 Phosphotyrosine; by SRC and INSR.
MOD_RES 25 25 Phosphoserine.
MOD_RES 241 241 Phosphoserine; by autocatalysis.
MOD_RES 354 354 Phosphothreonine; by MELK.
MOD_RES 373 373 Phosphotyrosine; by SRC and INSR.
MOD_RES 376 376 Phosphotyrosine; by SRC and INSR.
MOD_RES 393 393 Phosphoserine.
MOD_RES 394 394 Phosphoserine; by MAP3K5.
MOD_RES 396 396 Phosphoserine.
MOD_RES 398 398 Phosphoserine; by MAP3K5.
MOD_RES 410 410 Phosphoserine.
MOD_RES 501 501 Phosphoserine; by PKC/PRKCQ (By
MOD_RES 513 513 Phosphothreonine; by autocatalysis.
MOD_RES 529 529 Phosphoserine; by PKC/PRKCQ (By

3D-structure; Activator; Alternative splicing; ATP-binding; Cell junction; Cell membrane; Complete proteome; Cytoplasm; Direct protein sequencing; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0016023; C:cytoplasmic membrane-bounded vesicle; IEA:Compara.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:BHF-UCL.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB.
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
GO:0048041; P:focal adhesion assembly; IEA:Compara.
GO:0006972; P:hyperosmotic response; IEA:Compara.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Compara.
GO:0006469; P:negative regulation of protein kinase activity; IDA:BHF-UCL.
GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Compara.
GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO:0030168; P:platelet activation; TAS:Reactome.
GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IMP:BHF-UCL.
GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
GO:0010594; P:regulation of endothelial cell migration; IEA:Compara.
GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
GO:0043304; P:regulation of mast cell degranulation; IEA:Compara.
GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0007268; P:synaptic transmission; TAS:Reactome.
GO:0031295; P:T cell costimulation; TAS:Reactome.
GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0003323; P:type B pancreatic cell development; IEA:Compara.

IPR011009; Kinase-like_dom.
IPR011993; PH_like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR002290; Ser/Thr_dual-sp_kinase_dom.
IPR008271; Ser/Thr_kinase_AS.

PS50003; PH_DOMAIN
PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST