Ser349

Site Information
sskEVDPstGELQsL SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 14580829

In vivo Characterization
Methods used to characterize site in vivo:	immunoprecipitation ( 9 , 22 , 23 , 24 , 25 , 26 ) , mass spectrometry ( 28 ) , mutation of modification site ( 5 , 10 , 17 , 20 , 23 ) , phospho-antibody ( 1 , 4 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 24 , 25 , 27 ) , western blotting ( 1 , 4 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 )
Disease tissue studied:	Alzheimer's disease ( 27 ) , brain cancer ( 17 , 18 ) , glioblastoma ( 18 ) , glioblastoma multiforme ( 18 ) , glioma ( 17 , 18 ) , breast cancer ( 19 , 22 ) , esophageal cancer ( 7 ) , esophageal carcinoma ( 7 ) , leukemia ( 12 ) , chronic myelogenous leukemia ( 4 , 12 ) , liver cancer ( 5 , 10 , 11 ) , hepatocellular carcinoma ( 5 , 10 ) , lung cancer ( 19 ) , non-small cell lung cancer ( 19 ) , neuroblastoma ( 9 , 27 ) , rheumatoid arthritis ( 21 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 27 ) , 'muscle, skeletal' ( 15 ) , 293 (epithelial) ( 16 , 17 , 20 , 23 , 25 ) , A172 (glial) ( 18 ) , BEAS-2B (epithelial) ( 19 ) , DK-MG (glial) ( 18 ) , epidermal ( 6 ) , fibroblast ( 13 ) , GAMG (glial) ( 18 ) , H4 (glial) ( 17 , 18 ) , HAP1 ( 4 ) , HEK293T (epithelial) ( 10 , 22 , 26 ) , HeLa (cervical) ( 1 , 16 , 24 , 27 ) , hepatocyte ( 10 ) , HepG2 (hepatic) ( 11 ) , HK2 (epithelial) ( 19 ) , HMVEC (endothelial) ( 26 ) , Huh1 (hepatic) ( 5 , 10 ) , HUVEC (endothelial) ( 8 , 26 ) , Jurkat (T lymphocyte) ( 28 ) , K562 (erythroid) ( 12 ) , keratinocyte ( 6 ) , Kyse150 (esophageal) ( 7 ) , Kyse30 (esophageal) ( 7 ) , LN18 (glial) ( 18 ) , MCF-10A (breast cell) ( 22 ) , MCF-7 (breast cell) ( 22 ) , MDA-MB-231 (breast cell) ( 19 , 22 ) , MEF (fibroblast) ( 25 ) , MM1.S (lymphoblast) ( 14 ) , NCI-H1299 (pulmonary) ( 19 ) , RASFs (fibroblast) ( 21 ) , SH-SY5Y (neural crest) ( 9 , 27 ) , synovium ( 13 ) , T98G (glial) ( 18 ) , U-251 MG (glial) ( 18 ) , U87MG (glial) ( 18 )

Upstream Regulation
Regulatory protein:	ATG2B (human) ( 12 ) , CASP8 (human) ( 7 ) , CENPU (human) ( 26 ) , GSKIP (human) ( 12 ) , NGLY1 (human) ( 20 ) , PIK3C3 (human) ( 22 ) , TAK1 (human) ( 1 ) , TBK1 (human) ( 16 ) , TENT5C (human) ( 14 ) , TFEB (human) ( 17 ) , USP10 (human) ( 9 ) , USP8 (human) ( 1 )
Putative in vivo kinases:	CK1A (human) ( 24 ) , PKCD (human) ( 22 ) , ULK1 (human) ( 5 )
Kinases, in vitro:	CK1A (human) ( 24 ) , PKCD (human) ( 22 ) , ULK1 (human) ( 5 )
Treatments:	autophinib ( 13 ) , BafA1 ( 9 ) , bafilomycin_A ( 12 , 27 ) , bortezomib ( 14 ) , cycloheximide ( 4 ) , cysteine hydrochloride ( 11 ) , DEM ( 27 ) , dopamine ( 9 ) , epoxomicin ( 27 ) , exercise ( 15 ) , fingolimod ( 13 ) , Fugene ( 27 ) , GDS-23 ( 6 ) , hypoxia ( 15 ) , ischemia ( 15 ) , KRIBB11 ( 24 ) , licochalcone_A ( 21 ) , Lipofectamine ( 27 ) , MG132 ( 13 , 20 , 24 ) , MHY1485 ( 20 ) , monoammonium glycyrrhizinate ( 11 ) , MRT68921 ( 5 ) , serum ( 20 ) , serum_starvation ( 20 ) , TTM ( 8 ) , ULK-101 ( 5 ) , wortmannin ( 4 )

Downstream Regulation
Effects of modification on SQSTM1:	activity, induced ( 6 , 17 , 26 ) , intracellular localization ( 1 , 10 , 26 , 27 ) , molecular association, regulation ( 1 , 5 , 9 , 10 , 18 , 22 , 25 , 26 ) , protein conformation ( 10 ) , protein stabilization ( 17 , 20 )
Effects of modification on biological processes:	apoptosis, inhibited ( 8 , 9 ) , autophagy, induced ( 7 , 8 , 11 , 13 , 18 , 24 ) , autophagy, inhibited ( 20 , 26 ) , cell growth, induced ( 7 , 22 ) , signaling pathway regulation ( 5 , 7 , 8 , 11 ) , transcription, induced ( 5 , 6 , 9 , 10 , 26 ) , transcription, inhibited ( 16 )
Induce interaction with:	KEAP1 (human) ( 1 , 5 , 9 , 10 , 18 , 22 , 25 , 26 )

Disease / Diagnostics Relevance
Relevant diseases:	Alzheimer's disease ( 27 )

References
1	Endo A, et al. (2024) USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes. J Cell Biol 223 38180476 Curated Info
2	McCarty N, Wang Y, Lyu L, Vu T (2024) TRIM44 promotes autophagy through SQSTM1 oligomerization in the response to oxidative stress induced by Arsenic Trioxide in cancer cells. Res Sq 38464079 Curated Info
3	Luo J, et al. (2024) SLC15A3 plays a crucial role in pulmonary fibrosis by regulating macrophage oxidative stress. Cell Death Differ 38374230 Curated Info
4	Danieli A, Vucak G, Baccarini M, Martens S (2023) Sequestration of translation initiation factors in p62 condensates. Cell Rep 42, 113583 38096057 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	Miyoshi T, Keller BC, Ashino T, Numazawa S (2023) Noncanonical mechanism of Nrf2 activation by diacylglycerol polyethylene glycol adducts in normal human epidermal keratinocytes. PLoS One 18, e0291905 37819868 Curated Info
7	Li L, et al. (2022) Caspase-8 mutants activate Nrf2 via phosphorylating SQSTM1 to protect against oxidative stress in esophageal squamous cell carcinoma. Free Radic Biol Med 192, 51-62 36165926 Curated Info
8	Zhang M, et al. (2022) Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells. Cell Death Dis 13, 733 36008391 Curated Info
9	Sango J, et al. (2021) USP10 inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity. J Biol Chem, 101448 34838592 Curated Info
10	Faruk MO, et al. (2021) Phase-separated protein droplets of amyotrophic lateral sclerosis-associated p62/SQSTM1 mutants show reduced inner fluidity. J Biol Chem, 101405 34774801 Curated Info
11	Chu S, et al. (2021) Up-regulation of Nrf2/P62/Keap1 involves in the anti-fibrotic effect of combination of monoammonium glycyrrhizinate and cysteine hydrochloride induced by CCl. Eur J Pharmacol 913, 174628 34774851 Curated Info
12	Sakai SS, et al. (2021) Loss of and impairs the maintenance of the hematopoietic stem cell pool size. Mol Cell Biol, MCB0002421 34748402 Curated Info
13	Relic B, et al. (2021) TFEB phosphorylation on Serine 211 is induced by autophagy in human synovial fibroblasts and by p62/SQSTM1 overexpression in HEK293 cells. Biochem J 478, 3145-3155 34405859 Curated Info
14	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
15	Gallego-Selles A, et al. (2020) Regulation of Nrf2/Keap1 signalling in human skeletal muscle during exercise to exhaustion in normoxia, severe acute hypoxia and post-exercise ischaemia: Influence of metabolite accumulation and oxygenation. Redox Biol 36, 101627 32863217 Curated Info
16	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
17	Park JY, et al. (2019) TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62. Sci Rep 9, 14354 31586112 Curated Info
18	Pölönen P, et al. (2019) Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma. Oncogene 31444413 Curated Info
19	Kerins MJ, et al. (2019) Genome wide CRISPR screen reveals autophagy disruption as the convergence mechanism that regulates the NRF2 transcription factor. Mol Cell Biol 31010806 Curated Info
20	Relic B, et al. (2018) Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death. Oncotarget 9, 35830-35843 30533198 Curated Info
21	Su X, et al. (2018) Licochalcone A activates Keap1-Nrf2 signaling to suppress arthritis via phosphorylation of p62 at serine 349. Free Radic Biol Med 115, 471-483 29233793 Curated Info
22	Jiang X, et al. (2017) VPS34 stimulation of p62 phosphorylation for cancer progression. Oncogene 36, 6850-6862 28846113 Curated Info
23	Jeong K, et al. (2017) CNOT2 promotes degradation of p62/SQSTM1 as a negative regulator in ATG5 dependent autophagy. Oncotarget 8, 46034-46046 28537904 Curated Info
24	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
25	Hashimoto K, et al. (2016) TAK1 Regulates the Nrf2 Antioxidant System Through Modulating p62/SQSTM1. Antioxid Redox Signal 25, 953-964 27245349 Curated Info
26	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
27	Tanji K, et al. (2014) Phosphorylation of serine 349 of p62 in Alzheimer's disease brain. Acta Neuropathol Commun 2, 50 24886973 Curated Info
28	Mulhern D (2011) CST Curation Set: 12679; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M) Curated Info