Phosphorylation sites in human translation factors and associated proteins, regulatory kinases, and functional consequences of the phosphorylationa

ProteinPhosphorylation site(s)b (reference) [main kinase(s)]Biological function(s) (reference[s])
4E-BP1Thr37 (317), Thr46 (317) [mTORC1 (117), GSK3β (126)]Priming sites (118, 119, 116)
Ser65 (317) [mTORC1 (117)], Thr70 (317) [mTORC1?/CDK1?]Dissociation from eIF4E (118, 119, 116)
Ser83 (129) [CDK1?], Ser85 (318) [?], Ser94 (319) [ATM?], Ser101 (320) [?], Ser112 (321) [CK2A1 (320)]Unknown
4E-BP2Thr37 (322), Thr46 (322) [mTORC1]Priming sites (by analogy with 4E-BP1)
Ser65 [mTORC1], Thr70 [mTORC1?/CDK1?]Dissociation from eIF4E (by analogy with 4E-BP1)
eIF4ESer209 (243) [MNK1/2 (245)]Unknown (244, 245), increases oncogenic activity and promotes translation of a subset of mRNAs (e.g., Mcl-1, MMPs, CCLs) (252)
eIF4GISer1185 [PKCα (323), TBK1? (324)]Modulates MNK binding (323)
Ser1106, Ser1147, Ser1194 [mTORC1] (184)Stimulation of translation of mRNAs containing uORFs (227) (?)
Ser896 [Pak2] (310)Inhibition of cap-dependent translation (310)
Ser1231 (325) [CDK1?]Inhibition of eIF4A/mRNA binding? (325)
eIF2αSer52 (326) [HRI, PKR, GCN2, PERK (reviewed in reference 4)]Stabilizes the eIF2/GDP/eIF2B complex, thus preventing recycling of eIF2 (reviewed in reference 4)
eIF2βS2, S67 [CK2 (327), mTORC1? (232)]Stimulates translation and proliferation (327); stimulates eIF2α dephosphorylation (232)
rpS6Ser235 (328) and Ser236 [S6K1/2, RSK (147)], Ser240, Ser244, and Ser247 [S6K1/2]Unknown (329, 330, 122, 147), global translation rates increased in MEFs expressing a nonphosphorylatable form of rpS6 (148)
PDCD4Ser67 [S6K1/2, AKT (163, 165)], Ser71 [?], Ser76 [RSK (331, 164)], Ser94 [?], Ser457 [S6K1/2, AKT (163, 165), RSK (164), PLK1? (332)]Degradation by the ubiquitin-proteasome system and subsequent activation of eIF4A (163, 164, 165)
eIF4BSer406 (172) [?], Ser422 [S6K1/2 (170), AKT (172), RSK (171)], Ser422 [MELK? (333)]Increases binding to eIF3 (173, 171), affects translation and proliferation (170)
eIF4HTyr12 (334), Tyr45 (334), Tyr101 (334), Ser193 (334) [?]Unknown
eIF2BεSer540 [GSK3] (335)Inhibits recycling of eIF2 (335)
Ser544 [DYRK] (336)Priming site for GSK3 (336)
Ser717/718 [CK2] (337)Facilitates eIF2 binding (337)
eIF3Subunit? [S6K1/2 (175)]Paip1-eIF3 interaction (175)
eIF3b: Ser83 (338), Ser85 (338), Ser125 (338) [?]Unknown
eIF3c: Ser39 (339), Ser166 (338), Thr524 (338), Ser909 (340) [?]Unknown
eIF3f: Ser46, Thr119 [CDK11] (341, 311)Regulation of protein synthesis and apoptosis (341, 311)
eIF3g: Thr41 (175), Ser42 (175) [?]Unknown
eIF3h: Ser183 (342) [?]Increased oncogenic activity (342)
eIF3i: Tyr445 (334) [?]Unknown
eIF1Tyr30 (334) [?]Unknown
Tyr72 (343) [?]Stimulation of mRNA translation (343)
eIF5Ser389, Ser390 [CK2] (344)Promotes cell cycle progression (344)
eIF5BSer107 (338), Ser113 (338), S135 (338), S137 (340), S164 (338), S182 (338), S183 (340), S186 (338), S190 (338), S214 (345), S1168 (338) [?]Unknown
eIF6Ser174/175 [CK1] (346)Nucleocytoplasmic shuttling (346)
Ser235 [PKCβII] (347)Dissociation of eIF6 from the 60S, 80S assembly (347)
eEF1A1Thr432 [PKCδ] (348)Activation (?) (348)
Ser21 (349) [BRAF?]Apoptosis (349)
Ser300 [TβR-I] (350)Inhibition of mRNA translation (350)
eEF1A2Ser205, Ser358 [JNK (351)]Degradation of newly synthesized polypeptides (351)
eEF2Thr56 [eEF2K] (352)Inhibits binding to the ribosome (353)
eEF2KSer78 (157) [mTOR?]Inhibits CaM binding (157)
Ser359 (155) [SAPK/p38δ?]Inhibition (?) (155)
Ser366 [S6K1, RSK] (150)Inhibition (150)
Ser398 [AMPK] (354)Activation (354)
Ser500 [PKA] (355)Induces Ca2+-independent activity (355)
  • a This table includes selected phosphoacceptor sites identified in large-scale mass spectrometry-based experiments which await functional characterization (e.g., eIF5B; unknown kinase/function is indicated by a question mark), as well as phosphorylation sites with established role in translational control (e.g., 4E-BPs and eIF2α). Further information on the as-of-yet functionally noncharacterized phosphorylated residues of the components of the translational apparatus can be found in the PhosphoSitePlus ( or UniProt ( database. In the case of eIF4G1, the phosphorylation sites indicated are corrected from the published article (Ser1108, Ser1148, and Ser1192). Abbreviations: CDK, cyclin-dependent kinase; PKC, protein kinase C; Pak2, p21-activated kinase 2; HRI, heme-regulated eIF2α kinase; PKR, double-stranded-RNA-activated eIF2α kinase; GCN2, general control nonrepressed eIF2α kinase; PERK, double-stranded-RNA-activated protein kinase-like ER kinase; DYRK, dual-specificity tyrosine phosphorylation-regulated kinase; CK2, protein kinase CK2 (formerly known as casein kinase II); TβR-I, transforming growth factor β1 (TGF-β1) receptor; eEF2K, eukaryotic translation elongation factor 2 kinase; PKA, protein kinase A; SAPK, stress-activated protein kinase; TBK1, TANK-binding kinase 1, PLK1, polo-like kinase 1, MELK, maternal embryonic leucine zipper kinase; Paip1, polyadenylate-binding protein-interacting protein 1. Additional abbreviations are provided in the text.

  • b Amino acid numbering is based on human proteins.