Ser403

Site Information
ESLSQMLsMGFsDEG SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 22264800

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 7 , 8 ) , immunoprecipitation ( 13 , 16 , 19 ) , mass spectrometry ( 14 , 17 , 20 , 22 , 23 ) , mass spectrometry (in vitro) ( 9 ) , mutation of modification site ( 3 , 5 , 6 , 7 , 15 , 18 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 15 , 16 , 18 , 21 , 23 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 15 , 16 , 18 , 19 , 21 , 23 )
Disease tissue studied:	Alzheimer's disease ( 21 ) , brain cancer ( 12 ) , glioblastoma ( 12 ) , glioblastoma multiforme ( 12 ) , glioma ( 12 ) , breast cancer ( 13 , 22 ) , luminal A breast cancer ( 17 ) , luminal B breast cancer ( 17 ) , breast cancer, triple negative ( 17 ) , colorectal cancer ( 4 ) , colorectal carcinoma ( 4 ) , leukemia ( 6 ) , acute myelogenous leukemia ( 6 ) , chronic myelogenous leukemia ( 1 ) , liver cancer ( 5 ) , hepatocellular carcinoma ( 5 ) , neuroblastoma ( 21 ) , prostate cancer ( 6 ) , melanoma skin cancer ( 3 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 21 ) , 'brain, hippocampus' ( 15 ) , 'brain, hippocampus, dentate gyrus' ( 7 ) , 293 (epithelial) ( 11 , 23 ) , A172 (glial) ( 12 ) , A375 (melanocyte) ( 3 ) , AD293 (epithelial) ( 3 ) , breast ( 17 ) , BT-549 (breast cell) ( 22 ) , DK-MG (glial) ( 12 ) , E.coli (bacterial) ( 14 ) , GAMG (glial) ( 12 ) , H4 (glial) ( 12 ) , HAP1 ( 1 ) , HCT116 (intestinal) ( 4 ) , HEK293T (epithelial) ( 13 , 18 , 19 ) , HeLa (cervical) ( 3 , 6 , 7 , 11 , 16 , 18 , 21 ) , HMVEC (endothelial) ( 19 ) , Huh1 (hepatic) ( 5 ) , HUVEC (endothelial) ( 19 ) , liver ( 20 ) , LN18 (glial) ( 12 ) , LNCaP (prostate cell) ( 6 ) , MCF-10A (breast cell) ( 13 ) , MCF-7 (breast cell) ( 13 ) , MDA-MB-231 (breast cell) ( 13 , 22 ) , MEF (fibroblast) [TBK1 (mouse), homozygous knockout] ( 23 ) , MEF (fibroblast) ( 6 , 8 ) , MM1.S (lymphoblast) ( 10 ) , SH-SY5Y (neural crest) ( 21 ) , T98G (glial) ( 12 ) , THP1 (myeloid) ( 6 ) , U-251 MG (glial) ( 12 ) , U87MG (glial) ( 12 )

Upstream Regulation
Regulatory protein:	ATG13 (human) ( 8 ) , CENPU (human) ( 19 ) , NRF1 (human) ( 4 ) , RB1CC1 (human) ( 7 , 8 ) , TAX1BP1 (human) ( 8 ) , TENT5C (human) ( 10 )
Putative in vivo kinases:	CK2A1 (human) ( 3 ) , TBK1 (human) ( 3 , 6 , 7 , 8 , 11 , 23 )
Kinases, in vitro:	TBK1 (human) ( 2 , 6 , 23 ) , ULK1 (human) ( 5 )
Treatments:	amlexanox ( 6 , 7 ) , bafilomycin_A ( 3 , 8 , 21 ) , BIRB-0796 ( 3 ) , bortezomib ( 10 ) , BX795 ( 3 , 6 ) , cycloheximide ( 1 ) , epoxomicin ( 21 ) , KRIBB11 ( 16 ) , LPS ( 8 ) , MG132 ( 3 , 16 ) , MRT67307 ( 6 ) , MRT68921 ( 5 ) , poly(I-C) ( 8 ) , SBI-0206965 ( 3 ) , silmitasertib ( 3 ) , siRNA ( 7 ) , starvation ( 8 ) , ULK-101 ( 5 ) , wortmannin ( 1 )

Downstream Regulation
Effects of modification on SQSTM1:	activity, induced ( 19 ) , intracellular localization ( 3 , 19 ) , molecular association, regulation ( 12 , 14 , 19 ) , phosphorylation ( 5 , 11 ) , protein degradation ( 11 ) , ubiquitination ( 7 )
Effects of modification on biological processes:	autophagy, induced ( 6 , 8 , 11 , 12 , 14 , 16 , 23 ) , autophagy, inhibited ( 7 , 19 ) , cell differentiation, induced ( 7 ) , cell growth, induced ( 7 ) , signaling pathway regulation ( 11 ) , transcription, induced ( 19 )
Induce interaction with:	KEAP1 (human) ( 12 , 19 ) , ubiquitin (human) ( 14 )

References
1	Danieli A, Vucak G, Baccarini M, Martens S (2023) Sequestration of translation initiation factors in p62 condensates. Cell Rep 42, 113583 38096057 Curated Info
2	Thinwa JW, et al. (2023) CDKL5 regulates p62-mediated selective autophagy and confers protection against neurotropic viruses. J Clin Invest 37917202 Curated Info
3	Zhang C, Duan Y, Huang C, Li L (2023) Inhibition of SQSTM1 S403 phosphorylation facilitates the aggresome formation of ubiquitinated proteins during proteasome dysfunction. Cell Mol Biol Lett 28, 85 37872526 Curated Info
4	Hatanaka A, et al. (2023) The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. Sci Rep 13, 14405 37658135 Curated Info
5	Ikeda R, et al. (2023) Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response. EMBO J, e113349 37306101 Curated Info
6	Tsuchiya M, et al. (2022) TBK1 inhibitors enhance transfection efficiency by suppressing p62/SQSTM1 phosphorylation. Genes Cells 36284367 Curated Info
7	Liu H, et al. (2021) Non-canonical function of FIP200 is required for neural stem cell maintenance and differentiation by limiting TBK1 activation and p62 aggregate formation. Sci Rep 11, 23907 34903812 Curated Info
8	Schlütermann D, et al. (2021) FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates. Sci Rep 11, 13863 34226595 Curated Info
9	Xu L, Zhang Y, Li YM, Lu XF (2020) Total chemical synthesis of the phosphorylated p62 UBA domain reveals that SerPi but not SerPi enhances ubiquitin binding. Org Biomol Chem 18, 8709-8715 33084718 Curated Info
10	Fucci C, et al. (2020) The Interaction of the Tumor Suppressor FAM46C with p62 and FNDC3 Proteins Integrates Protein and Secretory Homeostasis. Cell Rep 32, 108162 32966780 Curated Info
11	Foster AD, et al. (2020) ALS-associated TBK1 variant p.G175S is defective in phosphorylation of p62 and impacts TBK1-mediated signalling and TDP-43 autophagic degradation. Mol Cell Neurosci 108, 103539 32835772 Curated Info
12	Pölönen P, et al. (2019) Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma. Oncogene 31444413 Curated Info
13	Jiang X, et al. (2017) VPS34 stimulation of p62 phosphorylation for cancer progression. Oncogene 36, 6850-6862 28846113 Curated Info
14	Tan XL, et al. (2017) Sortase-mediated chemical protein synthesis reveals the bidentate binding of bisphosphorylated p62 with K63 diubiquitin. Chem Sci 8, 6881-6887 29147513 Curated Info
15	Ha S, et al. (2017) Phosphorylation of p62 by AMP-activated protein kinase mediates autophagic cell death in adult hippocampal neural stem cells. J Biol Chem 292, 13795-13808 28655770 Curated Info
16	Watanabe Y, Tsujimura A, Taguchi K, Tanaka M (2017) HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis. Autophagy 13, 133-148 27846364 Curated Info
17	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
18	Richter B, et al. (2016) Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A 113, 4039-44 27035970 Curated Info
19	Gjyshi O, et al. (2015) Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 Activation in Latently Infected Endothelial Cells through SQSTM1 Phosphorylation and Interaction with Polyubiquitinated Keap1. J Virol 89, 2268-86 25505069 Curated Info
20	Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62 24275569 Curated Info
21	Tanji K, et al. (2014) Phosphorylation of serine 349 of p62 in Alzheimer's disease brain. Acta Neuropathol Commun 2, 50 24886973 Curated Info
22	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
23	Pilli M, et al. (2012) TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation. Immunity 37, 223-34 22921120 Curated Info