Ser345
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Home > Phosphorylation Site Page: > Ser345  -  p47phox (human)

Site Information
QARPGPQsPGsPLEE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 451727

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 20 , 21 ) , immunoprecipitation ( 7 , 12 ) , mass spectrometry ( 5 , 8 , 10 , 14 , 15 , 16 , 17 ) , mutation of modification site ( 6 , 7 , 12 , 13 , 17 , 19 , 20 ) , peptide sequencing ( 21 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 9 , 11 , 12 , 13 , 17 ) , phosphoamino acid analysis ( 21 ) , phosphopeptide mapping ( 20 , 21 ) , western blotting ( 1 , 2 , 3 , 4 , 9 , 11 , 12 , 13 )
Disease tissue studied:
HER2 positive breast cancer ( 5 ) , luminal A breast cancer ( 5 ) , luminal B breast cancer ( 5 ) , breast cancer, surrounding tissue ( 5 ) , breast cancer, triple negative ( 5 ) , leukemia ( 19 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 10 ) , acute megakaryoblastic leukemia (M7) ( 10 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 10 ) , acute myeloblastic leukemia, with granulocytic maturation (M2) ( 10 ) , acute myeloblastic leukemia, without maturation (M1) ( 10 ) , chronic myelogenous leukemia ( 19 ) , lung cancer ( 2 ) , non-small cell lung cancer ( 2 ) , non-small cell lung adenocarcinoma ( 2 ) , B cell lymphoma ( 10 ) , non-Hodgkin's lymphoma ( 10 ) , ovarian cancer ( 8 ) , multiple myeloma ( 10 ) , rheumatoid arthritis ( 17 )
Relevant cell line - cell type - tissue:
A549 (pulmonary) ( 2 ) , AML-193 (monocyte) ( 10 ) , B lymphocyte-blood ( 13 ) , B lymphocyte-spleen ( 20 ) , breast ( 5 ) , CMK (megakaryoblast) ( 10 ) , COS7 (fibroblast) ( 12 ) , CTS (myeloid) ( 10 ) , DOHH2 ('B lymphocyte, precursor') ( 10 ) , GM00130 (B lymphocyte) ( 14 ) , HEK293T (epithelial) ( 1 ) , HEL (erythroid) ( 10 ) , HL60 (myeloid) ( 17 ) , K562 (erythroid) ( 19 ) , Kasumi-1 (myeloid) ( 10 ) , KG-1 (myeloid) ( 10 ) , leukocyte-blood ( 15 ) , microvessel endothelial ( 6 ) , MV4-11 (macrophage) ( 10 ) , neutrophil ( 3 , 16 , 17 , 20 , 21 ) , neutrophil-blood ( 4 , 9 , 11 ) , OPM-2 (plasma cell) ( 10 ) , ovary ( 8 ) , P31/FUJ (erythroid) ( 10 ) , Rat2 (fibroblast) ( 7 ) , RL ('B lymphocyte, precursor') ( 10 ) , RPMI-8266 (plasma cell) ( 10 ) , SU-DHL-6 (B lymphocyte) ( 10 ) , SVEC (endothelial) ( 12 ) , U266 (plasma cell) ( 10 )

Upstream Regulation
Regulatory protein:
RHOA (human) ( 2 )
Putative in vivo kinases:
ERK1 (human) ( 17 ) , ERK2 (human) ( 17 ) , IRAK4 (human) ( 16 ) , P38A (human) ( 17 ) , ROCK2 (human) ( 1 , 2 )
Kinases, in vitro:
ERK1 (human) ( 20 ) , IRAK4 (human) ( 16 ) , P38A (human) ( 18 ) , ROCK2 (human) ( 1 )
Treatments:
apocynin ( 2 ) , CL097 ( 11 ) , DPI ( 2 ) , fMLP ( 3 , 11 , 17 , 21 ) , genistein ( 17 ) , GM-CSF ( 17 ) , juglone ( 11 ) , LPS ( 4 , 16 ) , NAC ( 2 ) , pansorbin ( 13 ) , PD98059 ( 17 ) , peptide inhibitor ( 17 ) , phorbol_ester ( 2 , 3 , 11 , 13 , 17 , 21 ) , PP2 ( 2 ) , SB203580 ( 17 ) , Tat ( 2 ) , TNF ( 11 , 17 ) , U0126 ( 17 ) , Wnt3a ( 1 ) , Y27632 ( 1 , 2 ) , zymosan ( 9 )

Downstream Regulation
Effects of modification on p47phox:
activity, induced ( 17 ) , enzymatic activity, induced ( 3 ) , intracellular localization ( 3 ) , molecular association, regulation ( 1 ) , phosphorylation ( 12 )
Effects of modification on biological processes:
cell growth, induced ( 1 ) , signaling pathway regulation ( 3 , 4 , 12 )
Induce interaction with:
ROCK2 (human) ( 1 )

Disease / Diagnostics Relevance
Relevant diseases:
rheumatoid arthritis ( 17 )

References 

1

Kim JG, et al. (2020) RhoA GTPase phosphorylated at tyrosine 42 by src kinase binds to β-catenin and contributes transcriptional regulation of vimentin upon Wnt3A. Redox Biol 40, 101842
33388549   Curated Info

2

Cap KC, Kim JG, Hamza A, Park JB (2020) P-Tyr42 RhoA GTPase amplifies superoxide formation through p47phox, phosphorylated by ROCK. Biochem Biophys Res Commun
31973815   Curated Info

3

Chniguir A, et al. (2019) Eugenol prevents fMLF-induced superoxide anion production in human neutrophils by inhibiting ERK1/2 signaling pathway and p47phox phosphorylation. Sci Rep 9, 18540
31811262   Curated Info

4

Liu M, et al. (2019) The Prolyl Isomerase Pin1 Controls Lipopolysaccharide-Induced Priming of NADPH Oxidase in Human Neutrophils. Front Immunol 10, 2567
31736979   Curated Info

5

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

6

Meijles DN, Fan LM, Howlin BJ, Li JM (2014) Molecular Insights of p47phox Phosphorylation Dynamics in the Regulation of NADPH Oxidase Activation and Superoxide Production. J Biol Chem 289, 22759-70
24970888   Curated Info

7

Park MT, et al. (2014) Novel signaling axis for ROS generation during K-Ras-induced cellular transformation. Cell Death Differ 21, 1185-97
24632950   Curated Info

8

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

9

Makni-Maalej K, et al. (2013) Zymosan induces NADPH oxidase activation in human neutrophils by inducing the phosphorylation of p47phox and the activation of Rac2: involvement of protein tyrosine kinases, PI3Kinase, PKC, ERK1/2 and p38MAPkinase. Biochem Pharmacol 85, 92-100
23085266   Curated Info

10

Casado P, et al. (2013) Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors. Genome Biol 14, R37
23628362   Curated Info

11

Makni-Maalej K, et al. (2012) The TLR7/8 Agonist CL097 Primes N-Formyl-Methionyl-Leucyl-Phenylalanine-Stimulated NADPH Oxidase Activation in Human Neutrophils: Critical Role of p47phox Phosphorylation and the Proline Isomerase Pin1. J Immunol 189, 4657-65
23002436   Curated Info

12

Teng L, Fan LM, Meijles D, Li JM (2012) Divergent Effects of p47phox Phosphorylation at S303-4 or S379 on Tumor Necrosis Factor-α Signaling via TRAF4 and MAPK in Endothelial Cells. Arterioscler Thromb Vasc Biol 32, 1488-96
22460559   Curated Info

13

Belambri SA, et al. (2012) Phosphorylation of p47phox is required for receptor-mediated NADPH oxidase/NOX2 activation in Epstein-Barr virus-transformed human B lymphocytes. Am J Blood Res 2, 187-93
23119229   Curated Info

14

Bennetzen MV, et al. (2010) Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol Cell Proteomics 9, 1314-23
20164059   Curated Info

15

Raijmakers R, et al. (2010) Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase-TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to a quadrupole time-of-flight mass spectrometer. Anal Chem 82, 824-32
20058876   Curated Info

16

Pacquelet S, et al. (2007) Cross-talk between IRAK-4 and the NADPH oxidase. Biochem J 403, 451-61
17217339   Curated Info

17

Dang PM, et al. (2006) A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. J Clin Invest 116, 2033-43
16778989   Curated Info

18

Manke IA, et al. (2005) MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation. Mol Cell 17, 37-48
15629715   Curated Info

19

Ago T, Nunoi H, Ito T, Sumimoto H (1999) Mechanism for phosphorylation-induced activation of the phagocyte NADPH oxidase protein p47(phox). Triple replacement of serines 303, 304, and 328 with aspartates disrupts the SH3 domain-mediated intramolecular interaction in p47(phox), thereby activating the oxidase. J Biol Chem 274, 33644-53
10559253   Curated Info

20

El Benna J, Faust RP, Johnson JL, Babior BM (1996) Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J Biol Chem 271, 6374-8
8626435   Curated Info

21

el Benna J, Faust LP, Babior BM (1994) The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases. J Biol Chem 269, 23431-6
8089108   Curated Info