Ser63
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Site Information
kNsDLLtsPDVGLLK   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447686

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 94 , 96 , 100 ) , [32P] bio-synthetic labeling ( 7 , 98 , 101 , 102 ) , electrophoretic mobility shift ( 74 , 101 ) , immunoprecipitation ( 2 , 3 , 7 , 39 , 94 , 96 , 100 , 102 ) , mass spectrometry ( 5 , 6 , 7 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 19 , 20 , 21 , 22 , 23 , 24 , 29 , 33 , 34 , 35 , 36 , 37 , 40 , 42 , 43 , 45 , 46 , 47 , 48 , 50 , 54 , 56 , 58 , 59 ) , mutation of modification site ( 49 , 57 , 73 , 77 , 79 , 88 , 89 , 91 , 94 , 96 , 97 , 98 , 100 , 101 , 102 ) , peptide sequencing ( 72 ) , phospho-antibody ( 1 , 2 , 3 , 7 , 8 , 17 , 27 , 30 , 31 , 32 , 38 , 39 , 41 , 44 , 51 , 52 , 53 , 55 , 57 , 60 , 61 , 64 , 65 , 66 , 67 , 68 , 70 , 71 , 73 , 74 , 76 , 77 , 78 , 79 , 81 , 82 , 83 , 84 , 85 , 88 , 89 , 90 , 92 , 93 , 94 , 95 , 102 ) , phosphoamino acid analysis ( 49 ) , phosphopeptide mapping ( 96 , 98 , 100 , 101 ) , western blotting ( 1 , 2 , 3 , 7 , 8 , 17 , 27 , 30 , 31 , 32 , 38 , 39 , 41 , 44 , 49 , 51 , 52 , 53 , 55 , 57 , 61 , 64 , 65 , 66 , 68 , 72 , 78 , 79 , 83 , 84 , 92 , 93 , 94 , 96 , 100 , 102 )
Disease tissue studied:
adrenal cancer ( 98 ) , pheochromocytoma ( 98 ) , bone cancer ( 45 , 49 , 61 ) , osteosarcoma ( 45 ) , brain cancer ( 64 ) , glioblastoma ( 64 ) , glioma ( 64 ) , breast cancer ( 12 , 21 , 22 , 44 , 83 ) , cervical cancer ( 46 ) , cervical adenocarcinoma ( 46 ) , colorectal cancer ( 3 , 39 , 55 , 83 ) , colorectal carcinoma ( 3 , 39 , 55 , 83 ) , gastric cancer ( 40 ) , gastric carcinoma ( 40 ) , leukemia ( 30 , 43 , 58 ) , chronic myelogenous leukemia ( 43 , 58 ) , T cell leukemia ( 30 ) , liver cancer ( 27 , 102 ) , hepatocellular carcinoma ( 27 ) , lung cancer ( 2 , 15 , 22 , 54 , 55 , 66 , 74 , 83 , 93 ) , non-small cell lung cancer ( 2 , 22 , 54 , 55 , 66 ) , non-small cell lung adenocarcinoma ( 2 , 15 ) , non-small cell squamous cell lung carcinoma ( 55 ) , small-cell lung cancer ( 93 ) , lymphoma ( 31 , 101 , 102 ) , anaplastic large cell lymphoma ( 31 ) , pancreatic cancer ( 38 ) , pancreatic carcinoma ( 38 ) , pancreatic ductal adenocarcinoma ( 13 ) , melanoma skin cancer ( 6 ) , testicular cancer ( 98 , 102 )
Relevant cell line - cell type - tissue:
'brain, hippocampus, dentate gyrus' ( 1 ) , 'neuron, cerebellar granule'-brain ( 85 ) , 'pancreatic, ductal'-pancreas ( 13 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 37 ) , 293 (epithelial) [AT1 (human), transfection] ( 35 ) , 293 (epithelial) ( 2 , 3 , 8 , 10 , 39 , 48 , 49 , 60 , 61 , 66 , 79 , 91 , 92 , 96 ) , 293E (epithelial) ( 29 ) , 293GP (epithelial) [NPM-ALK (human), transfection] ( 36 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 67 , 73 ) , A431 (epithelial) ( 98 ) , A549 (pulmonary) ( 2 , 16 , 55 , 74 , 83 ) , breast cell-breast ( 89 ) , BT-549 (breast cell) ( 22 ) , CEF ( 94 ) , epithelial-corneal ( 53 ) , F9 (testicular) ( 98 , 102 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 24 ) , Flp-In T-Rex-293 (epithelial) ( 24 ) , Fr 3T3 (fibroblast) ( 100 ) , GM00637 (lymphoblast) ( 97 ) , H2009 (pulmonary) ( 22 ) , H2077 (pulmonary) ( 22 ) , H2887 (pulmonary) ( 22 ) , H322M (pulmonary) ( 22 ) , HaCaT (keratinocyte) ( 61 ) , HCC1359 (pulmonary) ( 22 ) , HCC1937 (breast cell) ( 22 , 76 ) , HCC366 (pulmonary) ( 22 ) , HCC4006 (pulmonary) ( 22 ) , HCC78 (pulmonary) ( 22 ) , HCC827 (pulmonary) ( 22 ) , HCT116 (intestinal) ( 39 , 55 , 83 ) , HEK293T (epithelial) ( 5 , 17 , 41 , 65 , 73 , 76 ) , HeLa (cervical) ( 9 , 20 , 32 , 34 , 52 , 56 , 59 , 72 , 89 , 97 , 100 ) , HeLa S3 (cervical) ( 46 ) , HepG2 (hepatic) ( 102 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 12 ) , HMLER ('stem, breast cancer') ( 12 ) , HOP62 (pulmonary) ( 22 ) , HOS (bone cell) ( 81 ) , HT-29 (intestinal) ( 3 ) , HUES-7 ('stem, embryonic') ( 47 ) , HUES-9 ('stem, embryonic') ( 33 ) , Huh7 (hepatic) ( 27 ) , HUVEC (endothelial) ( 51 , 88 ) , JB-6 (lymphocyte) ( 31 ) , JB6 CI41 (epidermal) ( 49 ) , Jurkat (T lymphocyte) ( 19 , 30 , 42 , 50 , 100 ) , K562 (erythroid) ( 20 , 43 , 58 ) , keratinocyte ( 61 ) , LCLC-103H (pulmonary) ( 22 ) , LLC-PK1 (renal) ( 68 ) , lung ( 15 ) , MCF-10A (breast cell) ( 44 ) , MCF-7 (breast cell) ( 22 , 76 , 83 , 89 ) , MDA-MB-231 (breast cell) ( 22 ) , MEF (fibroblast) ( 57 ) , MKN-45 (gastric) ( 40 ) , MM (B lymphocyte) ( 71 ) , monocyte ( 84 ) , MRC5 (fibroblast) ( 57 , 90 ) , NCI-H1299 (pulmonary) ( 54 , 55 ) , NCI-H1395 (pulmonary) ( 22 ) , NCI-H1568 (pulmonary) ( 22 ) , NCI-H157 (pulmonary) ( 22 ) , NCI-H1650 (pulmonary) ( 55 ) , NCI-H1666 (pulmonary) ( 22 ) , NCI-H1703 (squamous) ( 55 ) , NCI-H2030 (pulmonary) ( 22 ) , NCI-H23 (pulmonary) ( 55 ) , NCI-H322 (pulmonary) ( 22 ) , NCI-H460 (pulmonary) ( 55 , 66 ) , NCI-H520 (squamous) ( 22 ) , NCI-H647 (pulmonary) ( 22 ) , NCI-H82 (pulmonary) ( 93 ) , P815 (mast) ( 82 ) , PANC-1 (pancreatic) [PRKD1 (human), transfection] ( 38 ) , PANC-1 (pancreatic) [PRP4 (human), knockdown, Lentiviral introduced doxycycline-inducible PRP4 shRNA] ( 14 ) , PANC-1 (pancreatic) ( 14 ) , PC-12 (chromaffin) ( 98 ) , PC3 (prostate cell) ( 78 ) , PC9 (pulmonary) ( 22 ) , Saos-2 (bone cell) ( 49 ) , SH-SY5Y (neural crest) ( 77 ) , SHEP (neuron) ( 77 ) , SK-N-MC (neural crest) ( 95 ) , SKBr3 (breast cell) ( 21 ) , spinal cord ( 1 ) , T98G (glial) ( 70 ) , U-937 (myeloid) ( 101 , 102 ) , U2OS (bone cell) [GR (human)] ( 76 ) , U2OS (bone cell) ( 45 , 61 ) , U87MG (glial) [p53 (human)] ( 64 ) , WM239A (melanocyte) ( 6 )

Upstream Regulation
Regulatory protein:
CDCA4 (human) ( 52 ) , CDK3 (human) ( 49 ) , FAT (human) ( 68 ) , FBXW7 (human) ( 26 ) , HER4 (human) ( 65 ) , HRas (human) ( 65 , 93 ) , LKB1 (human) ( 55 ) , MEKK1 (human) ( 79 ) , PPP3CA (human) ( 63 ) , PRKD1 (human) ( 24 , 38 , 92 ) , PRP4 (human) ( 14 ) , PRR7 (human) ( 30 ) , RACK1 (human) ( 26 ) , RALA (human) ( 91 ) , ROCK1 (human) ( 61 ) , TBK1 (human) ( 16 )
Putative in vivo kinases:
CDK3 (human) ( 3 , 49 ) , ERK1 (human) ( 102 ) , ERK2 (human) ( 102 ) , ERK7 (human) ( 39 ) , JNK1 (human) ( 32 , 57 , 69 , 77 , 78 , 97 , 100 ) , JNK2 (human) ( 57 , 77 ) , PBK (human) ( 2 ) , PLK3 (human) ( 53 ) , VRK1 (human) ( 73 )
Kinases, in vitro:
CDK3 (human) ( 3 , 49 ) , ERK1 (human) ( 102 ) , ERK2 (human) ( 102 ) , ERK7 (human) ( 39 ) , JNK1 (human) ( 49 , 62 , 87 , 97 , 99 , 100 ) , JNK2 (human) ( 97 ) , PBK (human) ( 2 ) , PRKD1 (human) ( 86 ) , VRK1 (human) ( 73 )
Putative upstream phosphatases:
PPP5C (human) ( 74 )
Treatments:
15d-PGJ2 ( 51 ) , AG1478 ( 38 ) , angiotensin_2 ( 37 ) , anisomycin ( 26 , 66 , 67 , 75 , 81 ) , anti-CD3 ( 50 ) , anti-TCR ( 30 ) , arsenite ( 81 ) , beta-glycerophosphate ( 102 ) , Boc-D-FMK ( 80 ) , bortezomib ( 71 ) , bryostatin_1 ( 101 ) , Cd(2+) ( 90 ) , CHIR99021 ( 7 ) , cobalt ( 53 ) , cycloheximide ( 26 ) , DCVC ( 68 ) , EGF ( 31 , 32 , 39 , 49 , 65 , 92 ) , EKI-785 ( 49 ) , etoposide ( 60 ) , FGF1 ( 95 ) , hepatitis C virus expression ( 27 ) , hypoxia ( 53 , 74 , 88 ) , hypoxia/reoxygenation ( 53 ) , IL-1a ( 57 , 82 ) , insulin ( 67 ) , ionizing_radiation ( 76 ) , JNK_inhibitor_I ( 65 , 66 ) , JNK_inhibitor_VII ( 17 ) , kainic_acid ( 8 ) , LY294002 ( 65 ) , MMS ( 97 ) , neurotensin ( 38 ) , NGF_withdrawal ( 80 ) , nocodazole ( 46 , 83 ) , okadaic_acid ( 18 , 101 ) , PD98059 ( 49 , 65 , 66 ) , phorbol_ester ( 17 , 52 , 63 , 96 , 100 , 101 , 102 ) , plasmin ( 84 ) , rapamycin ( 29 , 67 ) , SB203580 ( 51 , 65 , 66 , 68 , 75 , 85 , 95 ) , selumetinib ( 6 ) , serum ( 39 ) , serum_withdrawal ( 85 ) , SII_angiotensin_2 ( 35 ) , siRNA ( 49 , 52 , 55 , 74 ) , SNP ( 77 ) , SP600125 ( 7 , 27 , 32 , 41 , 49 , 51 , 57 , 64 , 67 , 68 , 72 , 75 , 81 , 83 ) , staurosporine ( 41 ) , U0126 ( 75 ) , UV ( 52 , 53 , 61 , 64 , 72 , 76 , 77 , 92 , 94 , 100 ) , vemurafenib ( 6 ) , Y27632 ( 61 )

Downstream Regulation
Effects of modification on Jun:
activity, induced ( 49 , 73 , 85 , 89 , 91 , 98 , 100 ) , enzymatic activity, induced ( 102 ) , molecular association, regulation ( 57 , 89 , 96 , 100 ) , protein stabilization ( 27 , 73 )
Effects of modification on biological processes:
apoptosis, altered ( 55 ) , apoptosis, induced ( 77 ) , cell growth, altered ( 49 , 92 ) , cell motility, induced ( 3 ) , transcription, altered ( 39 , 49 , 79 ) , transcription, induced ( 2 , 3 , 57 , 73 , 88 , 91 , 97 , 98 , 101 , 102 )
Induce interaction with:
DNA ( 57 ) , NFkB-p65 (human) ( 57 ) , PIN1 (human) ( 89 )
Inhibit interaction with:
DNA ( 96 ) , HDAC3 (human) ( 57 ) , JNK1 (human) ( 100 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 1 )

References 

1

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2

Li Y, et al. (2016) TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun. Oncotarget 7, 6748-64
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3

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6

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
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7

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11

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12

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16

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17

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20

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21

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22

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24

Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70
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25

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26

Zhang J, et al. (2012) Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. Oncogene 31, 1835-44
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27

Deng L, et al. (2011) Hepatitis C virus infection promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway. J Virol 85, 8556-68
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28

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29

Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22
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30

Hrdinka M, et al. (2011) PRR7 is a transmembrane adaptor protein expressed in activated T cells involved in regulation of T cell receptor signaling and apoptosis. J Biol Chem 286, 19617-29
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31

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32

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33

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34

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35

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36

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37

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38

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39

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40

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41

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42

Moritz A (2010) CST Curation Set: 8838; Year: 2010; Biosample/Treatment: cell line, Jurkat/pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

43

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44

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47

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48

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49

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50

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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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58

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60

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64

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65

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69

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70

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71

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73

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74

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75

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76

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77

Li L, Feng Z, Porter AG (2004) JNK-dependent phosphorylation of c-Jun on serine 63 mediates nitric oxide-induced apoptosis of neuroblastoma cells. J Biol Chem 279, 4058-65
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78

Salas TR, et al. (2003) Alleviating the suppression of glycogen synthase kinase-3beta by Akt leads to the phosphorylation of cAMP-response element-binding protein and its transactivation in intact cell nuclei. J Biol Chem 278, 41338-46
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79

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