Ser59

Site Information
PsFLRAPsWFDTGLS SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448783

In vivo Characterization
Methods used to characterize site in vivo:	2D analysis ( 22 ) , [32P] bio-synthetic labeling ( 30 ) , immunoassay ( 1 , 4 ) , immunoprecipitation ( 13 ) , mass spectrometry ( 5 , 7 , 9 , 10 , 15 , 17 , 26 , 29 , 30 , 31 ) , mutation of modification site ( 3 , 6 , 8 , 12 , 13 , 16 , 23 , 24 , 25 , 27 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 8 , 12 , 16 , 18 , 19 , 22 , 27 , 28 , 30 ) , western blotting ( 1 , 2 , 3 , 4 , 6 , 12 , 13 , 16 , 18 , 19 , 25 )
Disease tissue studied:	Alexander's disease ( 28 ) , brain cancer ( 8 , 27 , 30 ) , astrocytoma ( 27 , 30 ) , glioblastoma ( 8 ) , glioblastoma multiforme ( 8 ) , glioma ( 8 ) , breast cancer ( 9 ) , HER2 positive breast cancer ( 7 ) , luminal A breast cancer ( 7 ) , luminal B breast cancer ( 7 ) , breast cancer, triple negative ( 7 , 9 ) , hepatocellular carcinoma, surrounding tissue ( 17 ) , neuroblastoma ( 2 ) , Down syndrome ( 19 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 19 ) , 'muscle, skeletal' ( 4 , 15 ) , ARPE19 (retinal) ( 16 ) , brain ( 5 ) , breast ( 7 , 9 ) , C2C12 (myoblast) ( 18 ) , COS7 (fibroblast) ( 6 ) , glial ( 1 ) , heart ( 22 ) , HEK293T (epithelial) ( 3 ) , HeLa (cervical) ( 12 , 13 , 23 , 24 , 25 ) , hepatocyte-liver ( 17 ) , L6 (myoblast) ( 3 ) , lens ( 26 , 29 , 31 ) , liver ( 10 ) , MIO-M1 ( 1 ) , retinal-retina ( 1 ) , SH-SY5Y (neural crest) ( 2 ) , U-118MG (glial) ( 8 ) , U373 MG (glial) ( 8 , 27 , 30 )

Upstream Regulation
Regulatory protein:	PLK2 (human) ( 3 )
Putative in vivo kinases:	P38A (human) ( 1 , 18 )
Phosphatases, in vitro:	PPP1CA (human) ( 29 )
Treatments:	anisomycin ( 30 ) , antibody ( 1 ) , arsenite ( 30 ) , exercise ( 4 ) , exercise training ( 4 ) , H2O2 ( 30 ) , heart failure ( 22 ) , heat_shock ( 30 ) , IL-1b ( 1 ) , IL-6 ( 1 ) , ischemia ( 9 ) , menadione ( 12 ) , methylglyoxal ( 16 ) , MG132 ( 3 ) , mutation ( 12 ) , okadaic_acid ( 27 ) , phorbol_ester ( 27 ) , SB203580 ( 1 ) , serum ( 18 ) , TNF ( 1 )

Downstream Regulation
Effects of modification on CRYAB:	activity, induced ( 6 , 20 , 21 ) , intracellular localization ( 13 , 16 , 23 , 24 ) , molecular association, regulation ( 13 , 16 , 27 ) , protein conformation ( 20 )
Effects of modification on biological processes:	apoptosis, inhibited ( 3 , 16 ) , cytoskeletal reorganization ( 4 ) , exocytosis, inhibited ( 8 )
Induce interaction with:	CASP3 (human) ( 16 ) , CASP7 (human) ( 16 ) , GEMIN3 (human) ( 13 )
Inhibit interaction with:	CASP2 (human) ( 16 ) , CRYAB (human) ( 27 )

Disease / Diagnostics Relevance
Relevant diseases:	Down syndrome ( 19 ) , multiple sclerosis ( 5 )

References
1	Yamamoto T, et al. (2023) Phosphorylation of αB-Crystallin Involves Interleukin-1β-Mediated Intracellular Retention in Retinal Müller Cells: A New Mechanism Underlying Fibrovascular Membrane Formation. Invest Ophthalmol Vis Sci 64, 20 37459063 Curated Info
2	Chen D, et al. (2023) ERK inhibition aids IFN-β promoter activation during EV71 infection by blocking CRYAB degradation in SH-SY5Y cells. Pathog Dis 81 37259226 Curated Info
3	Ueda S, et al. (2022) Polo-Like Kinase 2 Plays an Essential Role in Cytoprotection against MG132-Induced Proteasome Inhibition via Phosphorylation of Serine 19 in HSPB5. Int J Mol Sci 23 36232565 Curated Info
4	Jacko D, et al. (2020) Coordinated alpha-crystallin B phosphorylation and desmin expression indicate adaptation and deadaptation to resistance exercise-induced loading in human skeletal muscle. Am J Physiol Cell Physiol 32520607 Curated Info
5	Kuipers HF, et al. (2017) Phosphorylation of αB-crystallin supports reactive astrogliosis in demyelination. Proc Natl Acad Sci U S A 114, E1745-E1754 28196893 Curated Info
6	Ciano M, et al. (2016) Differential phosphorylation-based regulation of αB-crystallin chaperone activity for multipass transmembrane proteins. Biochem Biophys Res Commun 479, 325-330 27641668 Curated Info
7	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
8	Kore RA, Abraham EC (2016) Phosphorylation negatively regulates exosome mediated secretion of cryAB in glioma cells. Biochim Biophys Acta 1863, 368-77 26620801 Curated Info
9	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
10	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
11	Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21 23312004 Curated Info
12	Simon S, et al. (2013) Analysis of the Dominant Effects Mediated by Wild Type or R120G Mutant of αB-crystallin (HspB5) towards Hsp27 (HspB1). PLoS One 8, e70545 23950959 Curated Info
13	den Engelsman J, et al. (2013) Pseudophosphorylated αB-Crystallin Is a Nuclear Chaperone Imported into the Nucleus with Help of the SMN Complex. PLoS One 8, e73489 24023879 Curated Info
14	Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25 22424773 Curated Info
15	Lundby A, et al. (2012) Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun 3, 876 22673903 Curated Info
16	Jeong WJ, et al. (2012) Cytoplasmic and Nuclear Anti-Apoptotic Roles of αB-Crystallin in Retinal Pigment Epithelial Cells. PLoS One 7, e45754 23049853 Curated Info
17	Han G, et al. (2010) Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis. Electrophoresis 31, 1080-9 20166139 Curated Info
18	Singh BN, Rao KS, Rao ChM (2010) Ubiquitin-proteasome-mediated degradation and synthesis of MyoD is modulated by alphaB-crystallin, a small heat shock protein, during muscle differentiation. Biochim Biophys Acta 1803, 288-99 20005263 Curated Info
19	Palminiello S, et al. (2009) Upregulation of phosphorylated alphaB-crystallin in the brain of children and young adults with Down syndrome. Brain Res 1268, 162-73 19272359 Curated Info
20	Ahmad MF, Raman B, Ramakrishna T, Rao ChM (2008) Effect of phosphorylation on alpha B-crystallin: differences in stability, subunit exchange and chaperone activity of homo and mixed oligomers of alpha B-crystallin and its phosphorylation-mimicking mutant. J Mol Biol 375, 1040-51 18061612 Curated Info
21	Ecroyd H, et al. (2007) Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochem J 401, 129-41 16928191 Curated Info
22	Dohke T, et al. (2006) Proteomic analysis reveals significant alternations of cardiac small heat shock protein expression in congestive heart failure. J Card Fail 12, 77-84 16500585 Curated Info
23	den Engelsman J, et al. (2005) Nuclear import of {alpha}B-crystallin is phosphorylation-dependent and hampered by hyperphosphorylation of the myopathy-related mutant R120G. J Biol Chem 280, 37139-48 16129694 Curated Info
24	den Engelsman J, et al. (2004) Mimicking phosphorylation of the small heat-shock protein alphaB-crystallin recruits the F-box protein FBX4 to nuclear SC35 speckles. Eur J Biochem 271, 4195-203 15511225 Curated Info
25	den Engelsman J, Keijsers V, de Jong WW, Boelens WC (2003) The small heat-shock protein alpha B-crystallin promotes FBX4-dependent ubiquitination. J Biol Chem 278, 4699-704 12468532 Curated Info
26	MacCoss MJ, et al. (2002) Shotgun identification of protein modifications from protein complexes and lens tissue. Proc Natl Acad Sci U S A 99, 7900-5 12060738 Curated Info
27	Ito H, et al. (2001) Phosphorylation-induced change of the oligomerization state of alpha B-crystallin. J Biol Chem 276, 5346-52 11096101 Curated Info
28	Kato K, et al. (2001) Ser-59 is the major phosphorylation site in alphaB-crystallin accumulated in the brains of patients with Alexander's disease. J Neurochem 76, 730-6 11158243 Curated Info
29	Kamei A, et al. (2000) Post-translational modification of alphaB-crystallin of normal human lens. Biol Pharm Bull 23, 226-30 10706390 Curated Info
30	Ito H, et al. (1997) Phosphorylation of alphaB-crystallin in response to various types of stress. J Biol Chem 272, 29934-41 9368070 Curated Info
31	Miesbauer LR, et al. (1994) Post-translational modifications of water-soluble human lens crystallins from young adults. J Biol Chem 269, 12494-502 8175657 Curated Info