Thr412
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Site Information
NQVFLGFtYVAPSVL   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448607

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 117 ) , flow cytometry ( 60 ) , immunoprecipitation ( 47 , 66 , 69 , 116 ) , mass spectrometry ( 6 , 11 , 117 ) , mutation of modification site ( 47 , 88 , 106 ) , peptide sequencing ( 6 , 108 , 117 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 26 , 30 , 31 , 33 , 35 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 74 , 75 , 76 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 109 , 110 , 111 , 113 , 114 , 115 , 116 ) , phosphoamino acid analysis ( 117 ) , phosphopeptide mapping ( 117 ) , western blotting ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 30 , 31 , 33 , 35 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 74 , 75 , 76 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 101 , 102 , 103 , 106 , 107 , 108 , 109 , 110 , 111 , 114 , 115 , 116 )
Disease tissue studied:
Alzheimer's disease ( 4 ) , bone cancer ( 106 ) , osteosarcoma ( 106 ) , brain cancer ( 82 ) , astrocytoma ( 82 ) , breast cancer ( 68 ) , cervical cancer ( 111 ) , cervical adenocarcinoma ( 111 ) , colorectal cancer ( 88 ) , colorectal carcinoma ( 88 ) , kidney cancer ( 45 , 79 ) , liver cancer ( 67 , 79 , 102 ) , lung cancer ( 83 ) , non-small cell lung cancer ( 83 ) , lymphoma ( 46 ) , T cell lymphoma ( 46 ) , neuroblastoma ( 24 ) , diabetes mellitus ( 70 ) , type 2 diabetes ( 70 ) , tuberous sclerosis ( 79 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 14 ) , 'brain, hippocampus' [FKBP12 (mouse), homozygous knockout] ( 69 ) , 'brain, hippocampus, dentate gyrus' [FKBP12 (mouse), homozygous knockout] ( 69 ) , 'kidney, tubule' [TSC2 (mouse), homozygous knockout] ( 45 ) , 'muscle, skeletal' ( 6 , 62 , 76 , 78 , 84 ) , 'muscle, skeletal' [RICTOR (mouse), homozygous knockout] ( 81 ) , 'neuron, cortical' ( 3 , 31 ) , 'neuron, hippocampal' ( 31 ) , 'stem, embryonic' ( 55 , 76 ) , 293 (epithelial) ( 23 , 26 , 27 , 58 , 67 , 68 , 74 , 92 , 97 , 101 ) , 293E (epithelial) ( 88 ) , 32D (myeloid) [BCR-ABL1 (human), transfection] ( 53 ) , 32D (myeloid) ( 115 ) , 3T3 (fibroblast) [INSR (mouse), transfection] ( 66 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 105 ) , 3T3 (fibroblast) ( 26 , 44 , 51 , 66 , 67 , 83 , 90 , 92 , 111 , 114 ) , 3T3-L1 (fibroblast) ( 57 , 59 , 67 , 75 , 84 , 102 ) , 786-O (renal) ( 45 ) , A549 (pulmonary) ( 83 ) , adipocyte ( 91 ) , adipocyte-adipose tissue ( 23 ) , adipose tissue ( 76 ) , adipose tissue [p70S6K (mouse), homozygous knockout] ( 108 ) , astrocyte ( 82 ) , BaF3 ('B lymphocyte, precursor') ( 66 ) , BALB/MK (keratinocyte) ( 116 ) , beta-pancreas [INSR (mouse), transgenic] ( 49 ) , BMMC (mast) ( 43 ) , brain ( 9 , 82 ) , C2C12 (myoblast) ( 35 , 80 , 86 , 87 , 89 , 97 , 113 ) , Calu-1 (squamous) ( 83 ) , CHO (fibroblast) [Tau iso8 (human)] ( 98 ) , CHO (fibroblast) ( 75 , 84 ) , COS (fibroblast) ( 66 ) , CT-2A (astrocyte) ( 82 ) , embryonic ( 50 ) , ES (stem) ( 99 ) , Fao (hepatic) ( 84 ) , fibroblast-embryo ( 27 ) , glial ( 79 ) , H4IIe (hepatic) ( 67 ) , heart ( 2 , 76 ) , heart [AMPKA2 (mouse), homozygous knockout] ( 71 ) , HEK293T (epithelial) ( 88 , 92 ) , HeLa (cervical) ( 19 , 42 , 68 , 84 , 88 , 92 , 108 ) , HeLa S3 (cervical) ( 111 ) , hepatocyte ( 27 , 99 ) , hepatocyte-liver ( 109 ) , hepatocyte-liver [TSC1 (mouse), homozygous knockout] ( 40 ) , HepG2 (hepatic) ( 102 ) , HK2 (epithelial) ( 45 ) , HT-29 (intestinal) ( 88 ) , HUVEC (endothelial) ( 91 ) , JB6 CI41 (epidermal) ( 110 ) , keratinocyte-skin ( 100 ) , keratinocyte-skin [IGF1 (mouse)] ( 101 ) , kidney ( 9 , 79 ) , L6 (myoblast) ( 51 , 84 , 102 ) , liver ( 5 , 9 , 20 , 76 , 79 ) , liver [LKB1 (mouse), homozygous knockout] ( 103 ) , liver [p70S6K (mouse), homozygous knockout] ( 108 ) , lymphocyte ( 11 ) , M059J (glial) ( 85 ) , macrophage-bone marrow ( 4 ) , MC3T3-E1 (preosteoblast) ( 97 ) , MCF-7 (breast cell) ( 68 ) , MCT cells (epithelial) ( 70 ) , MEF (fibroblast) ( 19 , 30 , 33 , 41 , 42 , 47 , 56 , 57 , 58 , 65 , 79 , 83 , 85 , 88 , 92 , 93 , 94 , 95 , 96 , 97 , 109 ) , MEF (fibroblast) [DEDD (mouse), homozygous knockout] ( 63 ) , MEF (fibroblast) [IGF1R (mouse)] ( 104 ) , MEF (fibroblast) [mTOR (mouse), heterozygous knockout] ( 107 ) , MEF (fibroblast) [mTOR (mouse), homozygous knockout] ( 68 ) , MEF (fibroblast) [p70S6K (mouse), homozygous knockout] ( 55 ) , MEF (fibroblast) [Sin1 (mouse), homozygous knockout] ( 52 , 64 ) , MEF (fibroblast) [TSC2 (mouse), heterozygous knockout] ( 45 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 54 ) , MN9D ('neuron, mesencephalic') ( 15 ) , muscle ( 9 ) , muscle [LKB1 (mouse), homozygous knockout] ( 103 ) , muscle [p70S6K (mouse), homozygous knockout] ( 108 ) , myoblast [AMPKA1 (mouse), homozygous knockout] ( 48 ) , myoblast [AMPKA2 (mouse), homozygous knockout] ( 48 ) , myocyte-heart ( 18 , 22 ) , NCI-H157 (pulmonary) ( 83 ) , Neuro-2a (neuron) ( 24 ) , neuron-'brain, cerebral cortex' ( 24 ) , oocyte ( 10 , 21 ) , osteoblast-calvarium ( 13 ) , ovary ( 21 ) , pancreas ( 63 ) , placenta ( 12 ) , preadipocyte ( 91 ) , Rat1 (fibroblast) ( 85 , 97 ) , RIE (epithelial) ( 97 ) , sertoli-testis ( 8 ) , ST2 (stromal) ( 97 ) , stem ( 7 ) , Swiss 3T3 (fibroblast) ( 117 ) , T lymphocyte-lymph node ( 60 ) , WEHI-7 (T lymphocyte) ( 46 )

Upstream Regulation
Regulatory protein:
4E-BP1 (mouse) ( 30 ) , Akt1 (human) ( 74 , 80 ) , Akt1 (mouse) ( 24 , 48 ) , AML3 (mouse) ( 13 ) , AMPKA1 (human) ( 74 ) , AMPKA1 (mouse) ( 36 , 48 , 89 , 101 ) , AMPKA2 (mouse) ( 48 , 71 ) , AMPKB1 (mouse) ( 36 ) , Bcl-xL (human) ( 54 ) , CDK1 (mouse) ( 63 ) , CPT2 (mouse) ( 2 ) , DEDD (mouse) ( 63 ) , DKK1 (human) ( 97 ) , DNAPK (mouse) ( 72 ) , Ezrin (mouse) ( 106 ) , FAK (human) ( 92 ) , FKBP12 (mouse) ( 69 ) , FOXO1A (mouse) ( 86 , 91 ) , Fyn (mouse) ( 46 ) , GLUT1 (mouse) ( 13 ) , GRB10 (human) ( 23 ) , GRN (mouse) ( 3 ) , HRas (human) ( 74 ) , IKKB (human) ( 67 ) , IRS1 (human) ( 22 ) , K17 (mouse) ( 100 ) , KRas (mouse) ( 116 ) , LAMTOR1 (mouse) ( 56 ) , LAMTOR2 (mouse) ( 56 ) , LKB1 (mouse) ( 10 , 78 , 103 ) , LST8 (mouse) ( 93 ) , MAPKAPK5 (mouse) ( 36 ) , MKK6 (human) ( 36 ) , Mnk1 (mouse) ( 83 ) , Mnk2 (mouse) ( 83 ) , mTOR (mouse) ( 8 , 24 , 107 ) , P38A (mouse) ( 47 ) , P38B (human) ( 36 ) , P38B (mouse) ( 36 ) , p53 (mouse) ( 16 ) , p70S6K (human) ( 45 ) , PCTP (human) ( 27 ) , PDK1 (mouse) ( 76 , 99 ) , PIP4K2C (mouse) ( 9 ) , PKCI (mouse) ( 110 ) , PRAS40 iso3 (human) ( 88 ) , PSEN1 (mouse) ( 50 ) , PTEN (mouse) ( 65 ) , PTGER3 (mouse) ( 43 ) , Raptor (human) ( 54 , 88 ) , Raptor (mouse) ( 13 , 35 , 43 , 56 , 96 ) , Rb (mouse) ( 16 ) , RHEB (human) ( 61 , 74 , 102 ) , RHEB (mouse) ( 24 , 35 ) , RICTOR (human) ( 58 ) , RICTOR (mouse) ( 43 , 58 , 65 , 93 ) , ROCK1 (mouse) ( 62 ) , SESN1 (human) ( 74 ) , SESN1 (mouse) ( 74 ) , SESN2 (human) ( 74 ) , SESN2 (mouse) ( 74 ) , SGK1 (human) ( 68 ) , Sin1 (human) ( 64 ) , Sin1 (mouse) ( 52 , 64 , 95 ) , TBC1D1 (mouse) ( 75 ) , THEM2 (human) ( 27 ) , TSC1 (human) ( 23 , 61 ) , TSC1 (mouse) ( 13 , 21 , 24 , 30 , 40 , 57 , 61 , 79 ) , TSC2 (human) ( 49 ) , TSC2 (mouse) ( 24 , 36 , 49 , 74 , 79 , 88 , 91 , 92 , 94 , 96 ) , ULK1 (mouse) ( 15 ) , VEGF (human) ( 25 )
Putative in vivo kinases:
mTOR (human) ( 27 ) , PIK3C2A (human) ( 25 )
Kinases, in vitro:
mTOR (human) ( 68 )
Treatments:
15d-PGJ2 ( 67 ) , 2-deoxyglucose ( 57 , 82 ) , acadesine ( 45 , 87 , 97 ) , actinomycin_D ( 55 ) , adiponectin ( 12 , 89 ) , adriamycin ( 47 ) , AMDE-1 ( 19 ) , amino_acid_starvation ( 47 , 51 , 54 , 57 , 66 , 93 ) , amino_acids ( 36 , 56 , 57 , 61 , 66 , 94 , 101 ) , anisomycin ( 36 ) , anti-CTLA-4 ( 60 ) , arsenite ( 36 ) , AS252424 ( 43 ) , BAPTA-AM ( 114 ) , butaprost ( 43 ) , butyrate ( 79 ) , BX795 ( 64 ) , calorie_restriction ( 7 ) , calyculin_A ( 116 ) , catalase ( 110 ) , cell_detachment ( 92 ) , compound_C ( 74 ) , culturing_of_cells ( 31 ) , cycloheximide ( 54 ) , dexamethasone ( 46 ) , eccentric contractions ( 6 ) , EGF ( 109 , 116 ) , exercise ( 78 ) , fasting ( 20 ) , FGF2 ( 73 ) , formate ( 110 ) , glucose ( 13 , 36 , 45 , 49 , 70 , 102 ) , glucose_starvation ( 97 ) , H2O2 ( 36 , 110 ) , hepatitis C virus expression ( 5 ) , high-fat diet ( 23 , 108 ) , IC87114 ( 43 ) , IGF-1 ( 18 , 52 , 80 , 94 , 101 , 115 , 116 ) , IL-3 ( 66 ) , imatinib ( 53 ) , insulin ( 22 , 23 , 36 , 40 , 44 , 49 , 51 , 57 , 59 , 61 , 62 , 64 , 65 , 66 , 70 , 74 , 75 , 76 , 81 , 88 , 89 , 91 , 93 , 95 , 97 , 102 , 105 , 108 , 109 , 114 ) , ionomycin ( 90 , 116 ) , JAK_inhibitor_I ( 25 ) , KU-0063794 ( 11 ) , L-744,832 ( 116 ) , L-glutamine_withdrawal ( 54 ) , leptin ( 112 ) , leucine ( 23 , 87 , 102 ) , lithium ( 97 ) , LY294002 ( 25 , 60 , 66 , 93 , 106 , 110 , 111 , 116 ) , meal feeding ( 40 , 76 , 103 ) , metformin ( 102 ) , MPP+ ( 15 ) , NAC ( 110 ) , NADPH ( 110 ) , NP68 ( 60 ) , okadaic_acid ( 115 ) , ouabain ( 54 ) , PD184352 ( 109 ) , PD98059 ( 23 , 36 , 110 , 116 ) , PDGF ( 59 , 94 ) , PGE2 ( 43 ) , PGRN ( 3 ) , phorbol_ester ( 104 , 116 ) , PI-103 ( 68 ) , PIF ( 80 ) , PIK90 ( 64 ) , PP242 ( 55 , 64 ) , pressure ( 71 ) , PTX ( 43 ) , RAD001 ( 53 ) , rapamycin ( 2 , 7 , 9 , 16 , 18 , 20 , 23 , 26 , 27 , 30 , 36 , 40 , 43 , 44 , 45 , 47 , 48 , 49 , 51 , 52 , 54 , 55 , 57 , 60 , 61 , 64 , 66 , 67 , 68 , 79 , 81 , 83 , 89 , 91 , 93 , 94 , 97 , 98 , 99 , 101 , 102 , 105 , 106 , 107 , 109 , 110 , 115 , 116 ) , refeeding ( 20 ) , retinoic_acid ( 55 ) , SB202190 ( 116 ) , SB203580 ( 36 , 47 ) , serum ( 24 , 30 , 36 , 50 , 56 , 58 , 88 , 93 , 94 , 95 , 96 , 99 , 107 , 111 , 116 ) , serum_starvation ( 93 , 95 ) , serum_withdrawal ( 50 ) , siRNA ( 63 , 74 , 75 , 88 , 96 , 97 , 102 , 106 ) , SOD ( 110 ) , sulprostone ( 43 ) , tamoxifen ( 86 ) , thapsigargin ( 90 ) , TNF ( 67 , 102 ) , Torin1 ( 43 , 47 ) , troglitazone ( 98 , 101 ) , U0126 ( 49 , 60 , 66 , 97 , 106 ) , UV ( 110 ) , Wnt ( 97 ) , Wnt10b ( 97 ) , Wnt3a ( 97 ) , wortmannin ( 4 , 43 , 49 , 51 , 57 , 61 , 67 , 94 , 97 , 98 , 101 , 105 , 111 , 116 )

Downstream Regulation
Effects of modification on p70S6K:
enzymatic activity, induced ( 63 ) , molecular association, regulation ( 63 ) , ubiquitination ( 47 )
Effects of modification on biological processes:
apoptosis, induced ( 15 ) , cell cycle regulation ( 85 ) , signaling pathway regulation ( 25 )
Induce interaction with:
DEDD (mouse) ( 63 )

Disease / Diagnostics Relevance
Relevant diseases:
type 2 diabetes ( 70 , 84 ) , obesity, hyperphagic ( 67 )

References 

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46

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47

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48

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49

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51

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52

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53

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54

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55

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56

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57

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63

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64

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65

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66

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67

Zhang J, et al. (2008) S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem 283, 35375-82
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68

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