Ser19

Site Information
RPFFPFHsPsrLFDQ SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447728

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 23 ) , immunoprecipitation ( 9 ) , mass spectrometry ( 4 , 10 , 11 , 13 , 19 , 23 , 24 ) , mass spectrometry (in vitro) ( 17 ) , mutation of modification site ( 2 , 3 , 5 , 8 , 9 , 12 , 16 , 18 , 20 ) , phospho-antibody ( 1 , 2 , 5 , 8 , 12 , 20 , 21 , 22 , 23 ) , western blotting ( 1 , 2 , 3 , 8 , 9 , 12 , 18 , 22 )
Disease tissue studied:	Alexander's disease ( 21 ) , brain cancer ( 5 , 20 , 22 , 23 ) , astrocytoma ( 20 , 23 ) , glioblastoma ( 5 , 22 ) , glioblastoma multiforme ( 5 , 22 ) , glioma ( 5 , 22 ) , HER2 positive breast cancer ( 4 ) , luminal A breast cancer ( 4 ) , luminal B breast cancer ( 4 ) , breast cancer, surrounding tissue ( 4 ) , breast cancer, triple negative ( 4 ) , neuroblastoma ( 1 ) , major depressive disorder ( 10 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 10 , 13 ) , 'muscle, skeletal' ( 11 ) , ARPE19 (retinal) ( 12 ) , breast ( 4 ) , COS7 (fibroblast) ( 3 ) , HEK293T (epithelial) ( 2 ) , HeLa (cervical) ( 8 , 9 , 16 , 18 , 22 ) , L6 (myoblast) ( 2 ) , lens ( 19 , 24 ) , SH-SY5Y (neural crest) ( 1 ) , U-118MG (glial) ( 5 ) , U373 MG (glial) ( 5 , 20 , 22 , 23 )

Upstream Regulation
Putative in vivo kinases:	PLK2 (human) ( 2 )
Treatments:	arsenite ( 22 ) , BI2536 ( 2 ) , menadione ( 8 ) , methylglyoxal ( 12 ) , MG132 ( 2 ) , mutation ( 8 ) , nocodazole ( 22 ) , okadaic_acid ( 20 ) , PD98059 ( 22 ) , phorbol_ester ( 20 , 22 ) , SB202190 ( 22 ) , siRNA ( 2 )

Downstream Regulation
Effects of modification on CRYAB:	activity, induced ( 14 , 15 ) , activity, inhibited ( 3 ) , intracellular localization ( 5 , 12 , 16 ) , molecular association, regulation ( 9 , 12 , 16 , 18 , 20 ) , protein conformation ( 14 ) , protein degradation ( 18 )
Effects of modification on biological processes:	apoptosis, inhibited ( 2 , 12 ) , exocytosis, inhibited ( 5 )
Induce interaction with:	CASP3 (human) ( 12 ) , CASP7 (human) ( 12 ) , FBXO4 (human) ( 16 , 18 ) , GEMIN3 (human) ( 9 )
Inhibit interaction with:	CASP2 (human) ( 12 ) , CRYAB (human) ( 20 )

Disease / Diagnostics Relevance
Relevant diseases:	major depressive disorder ( 10 )

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	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
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	Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62 27251275 Curated Info
5	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
6	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
7	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
8	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
9	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
10	Martins-de-Souza D, et al. (2012) Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function. Eur Arch Psychiatry Clin Neurosci 262, 657-66 22350622 Curated Info
11	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
12	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
13	Herskowitz JH, et al. (2010) Phosphoproteomic Analysis Reveals Site-Specific Changes in GFAP and NDRG2 Phosphorylation in Frontotemporal Lobar Degeneration. J Proteome Res 9, 6368-79 20886841 Curated Info
14	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
15	Ecroyd H, et al. (2007) Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochem J 401, 129-41 16928191 Curated Info
16	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
17	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
18	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
19	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
20	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
21	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
22	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
23	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
24	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