CPLM-000873

Genbank Nucleotide ID

3-phosphoinositide-dependent protein kinase 1

Protein Synonyms/Alias

Protein kinase B kinase; PkB kinase

Rattus norvegicus (Rat)

Position	Peptide	Type	References
307	LEYDFPEKFFPKARD	acetylation	[1]

[1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405]

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 (By similarity).

DOMAIN 85 345 Protein kinase.
DOMAIN 462 553 PH.
NP_BIND 91 99 ATP (By similarity).
ACT_SITE 208 208 Proton acceptor (By similarity).
BINDING 114 114 ATP (By similarity).
MOD_RES 9 9 Phosphotyrosine; by SRC and INSR (By
MOD_RES 25 25 Phosphoserine (By similarity).
MOD_RES 244 244 Phosphoserine; by autocatalysis (By
MOD_RES 357 357 Phosphothreonine; by MELK (By
MOD_RES 376 376 Phosphotyrosine; by SRC and INSR (By
MOD_RES 379 379 Phosphotyrosine; by SRC and INSR (By
MOD_RES 396 396 Phosphoserine (By similarity).
MOD_RES 397 397 Phosphoserine; by MAP3K5 (By similarity).
MOD_RES 399 399 Phosphoserine (By similarity).
MOD_RES 401 401 Phosphoserine; by MAP3K5 (By similarity).
MOD_RES 413 413 Phosphoserine (By similarity).
MOD_RES 504 504 Phosphoserine; by PKC/PRKCQ (By
MOD_RES 516 516 Phosphothreonine; by autocatalysis (By
MOD_RES 532 532 Phosphoserine; by PKC/PRKCQ (By

ATP-binding; Cell junction; Cell membrane; Complete proteome; Cytoplasm; 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; IDA:RGD.
GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0005886; C:plasma membrane; IDA:RGD.
GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:RGD.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0005158; F:insulin receptor binding; IDA:RGD.
GO:0019901; F:protein kinase binding; IDA:RGD.
GO:0032148; P:activation of protein kinase B activity; IEA:Compara.
GO:0032869; P:cellular response to insulin stimulus; IEA:Compara.
GO:0048041; P:focal adhesion assembly; IMP:RGD.
GO:0006972; P:hyperosmotic response; IEA:Compara.
GO:0035556; P:intracellular signal transduction; IEA:Compara.
GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Compara.
GO:0006469; P:negative regulation of protein kinase activity; IEA:Compara.
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; IEA:Compara.
GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Compara.
GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IEA:Compara.
GO:0010594; P:regulation of endothelial cell migration; IEA:Compara.
GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
GO:0043304; P:regulation of mast cell degranulation; IEA:Compara.
GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
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