Ser45

Site Information
FPTSTsLsPFYLrPP SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448748

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 19 ) , immunoprecipitation ( 6 ) , mass spectrometry ( 15 , 19 , 20 ) , mass spectrometry (in vitro) ( 13 ) , mutation of modification site ( 1 , 3 , 4 , 5 , 6 , 7 , 11 , 12 , 14 , 16 ) , phospho-antibody ( 1 , 4 , 5 , 7 , 8 , 12 , 16 , 17 , 19 ) , western blotting ( 1 , 3 , 5 , 6 , 7 , 8 , 12 , 14 )
Disease tissue studied:	Alexander's disease ( 17 ) , brain cancer ( 4 , 16 , 19 ) , astrocytoma ( 16 , 19 ) , glioblastoma ( 4 ) , glioblastoma multiforme ( 4 ) , glioma ( 4 ) , neuroblastoma ( 1 ) , Down syndrome ( 8 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 8 ) , ARPE19 (retinal) ( 7 ) , COS7 (fibroblast) ( 3 ) , HeLa (cervical) ( 5 , 6 , 11 , 12 , 14 ) , lens ( 15 , 20 ) , SH-SY5Y (neural crest) ( 1 ) , U-118MG (glial) ( 4 ) , U373 MG (glial) ( 4 , 16 , 19 )

Upstream Regulation
Putative in vivo kinases:	ERK1 (human) ( 1 )
Treatments:	anisomycin ( 19 ) , arsenite ( 19 ) , H2O2 ( 19 ) , heat_shock ( 19 ) , menadione ( 5 ) , methylglyoxal ( 7 ) , mutation ( 5 ) , nocodazole ( 18 ) , okadaic_acid ( 16 ) , PD98059 ( 18 ) , phorbol_ester ( 16 , 18 , 19 ) , siRNA ( 1 ) , U0126 ( 1 ) , virus infection ( 1 )

Downstream Regulation
Effects of modification on CRYAB:	activity, induced ( 9 , 10 ) , activity, inhibited ( 3 ) , intracellular localization ( 6 , 11 , 12 ) , molecular association, regulation ( 6 , 7 , 12 , 13 , 14 , 16 ) , protein conformation ( 9 , 13 ) , protein degradation ( 1 , 14 )
Effects of modification on biological processes:	apoptosis, inhibited ( 7 ) , exocytosis, inhibited ( 4 ) , transcription, inhibited ( 1 )
Induce interaction with:	CASP3 (human) ( 7 ) , CASP7 (human) ( 7 ) , FBXO4 (human) ( 12 , 14 ) , GEMIN3 (human) ( 6 )
Inhibit interaction with:	CASP2 (human) ( 7 ) , CRYAB (human) ( 16 )

Disease / Diagnostics Relevance
Relevant diseases:	Down syndrome ( 8 )

References
1	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
2	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
3	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
4	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
5	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
6	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
7	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
8	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
9	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
10	Ecroyd H, et al. (2007) Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochem J 401, 129-41 16928191 Curated Info
11	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
12	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
13	Aquilina JA, et al. (2004) Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure. J Biol Chem 279, 28675-80 15117944 Curated Info
14	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
15	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
16	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
17	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
18	Kato K, et al. (1998) Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation. J Biol Chem 273, 28346-54 9774459 Curated Info
19	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
20	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