Ser775
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Home > Phosphorylation Site Page: > Ser775  -  ataxin-1 (human)

Site Information
AtRKRRWsAPESRKL   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449110
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 25 ) , immunoassay ( 22 ) , immunoprecipitation ( 22 , 24 ) , mass spectrometry ( 3 , 6 , 7 , 10 , 11 , 14 , 16 , 17 , 21 , 25 ) , mass spectrometry (in vitro) ( 2 ) , mutation of modification site ( 5 , 12 , 15 , 18 , 19 , 20 , 22 , 23 , 24 , 25 ) , phospho-antibody ( 2 , 4 , 8 , 12 , 15 , 18 , 20 , 23 , 25 ) , western blotting ( 2 , 4 , 5 , 8 , 12 , 18 , 22 , 24 , 25 )
Disease tissue studied:
brain cancer ( 2 , 4 ) , medulloblastoma ( 2 , 4 ) , breast cancer ( 10 ) , breast ductal carcinoma ( 10 ) , HER2 positive breast cancer ( 6 ) , luminal A breast cancer ( 6 ) , luminal B breast cancer ( 6 ) , breast cancer, surrounding tissue ( 6 ) , breast cancer, triple negative ( 6 , 10 ) , cervical cancer ( 5 ) , cervical squamous cell carcinoma ( 5 ) , leukemia ( 16 ) , T cell leukemia ( 16 ) , lung cancer ( 14 ) , non-small cell lung cancer ( 14 ) , neuroblastoma ( 12 ) , pancreatic ductal adenocarcinoma ( 11 ) , melanoma skin cancer ( 7 )
Relevant cell line - cell type - tissue:
'brain, brainstem' ( 2 ) , 'brain, cerebellum' ( 12 , 19 ) , 'neuron, cerebellar granule'-brain ( 4 ) , 'neuron, Purkinje'-'brain, cerebellum' ( 2 , 25 ) , 'pancreatic, ductal'-pancreas ( 11 ) , 'stem, induced pluripotent' ( 2 ) , 293 (epithelial) ( 8 , 18 ) , breast ( 6 , 10 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 25 ) , CHO (fibroblast) ( 23 ) , COS (fibroblast) ( 15 , 22 , 24 , 25 ) , Daoy ( 2 , 4 ) , H2077 (pulmonary) ( 14 ) , H322M (pulmonary) ( 14 ) , HCC1359 (pulmonary) ( 14 ) , HCC366 (pulmonary) ( 14 ) , HCC4006 (pulmonary) ( 14 ) , HCC78 (pulmonary) ( 14 ) , HCC827 (pulmonary) ( 14 ) , HeLa (cervical) ( 17 , 19 , 20 , 24 ) , HOP62 (pulmonary) ( 14 ) , Kit225 (T lymphocyte) ( 16 ) , LCLC-103H (pulmonary) ( 14 ) , NCI-H322 (pulmonary) ( 14 ) , NCI-H3255 (pulmonary) ( 21 ) , Neuro-2a (neuron) ( 12 ) , SiHa (squamous) ( 5 ) , Vero E6-S ('epithelial, kidney') ( 3 ) , WM239A (melanocyte) ( 7 )

Upstream Regulation
Regulatory protein:
FNTA (human) ( 12 ) , HRas (human) ( 12 ) , MEK1 (human) ( 12 )
Putative in vivo kinases:
Akt1 (human) ( 20 , 24 ) , MSK1 (human) ( 2 , 12 ) , PKACA (human) ( 4 , 8 , 18 ) , RSK3 (human) ( 2 )
Kinases, in vitro:
Akt1 (human) ( 24 ) , MSK1 (human) ( 4 , 12 ) , MSK2 (human) ( 4 ) , PKACA (human) ( 1 , 4 ) , RSK3 (human) ( 2 )
Treatments:
5-iodotubercidin ( 23 ) , AG17 ( 23 ) , AG490 ( 23 ) , BI-D1870 ( 2 ) , bromocriptine ( 18 ) , cantharidin ( 23 ) , colforsin ( 18 ) , GSK690693 ( 4 ) , H-89 ( 4 , 8 , 12 , 18 , 23 ) , indirubin ( 23 ) , KN-93 ( 23 ) , ML-9 ( 23 ) , NKH_477 ( 8 ) , piceatannol ( 23 ) , PKI ( 8 ) , PP1 ( 23 ) , quercetin ( 23 ) , Ro31-8220 ( 12 , 23 ) , rottlerin ( 23 ) , SB-747651A ( 2 , 4 ) , siRNA ( 2 , 12 ) , staurosporine ( 4 ) , Synb1-ELP-PKI ( 8 ) , tyrphostin_25A ( 23 ) , wortmannin ( 23 )

Downstream Regulation
Effects of modification on ataxin-1:
intracellular localization ( 15 , 25 ) , molecular association, regulation ( 1 , 9 , 15 , 19 , 24 ) , protein degradation ( 20 ) , protein stabilization ( 2 , 4 , 12 , 24 )
Effects of modification on biological processes:
cell growth, induced ( 5 ) , cytoskeletal reorganization ( 25 ) , transcription, induced ( 5 )
Induce interaction with:
14-3-3 beta (human) ( 24 ) , 14-3-3 epsilon (human) ( 24 ) , 14-3-3 sigma (human) ( 1 ) , 14-3-3 zeta (human) ( 1 , 15 , 19 , 24 ) , RBM17 (human) ( 9 )
Inhibit interaction with:
RBM17 (human) ( 19 ) , U2AF2 (human) ( 19 )

Disease / Diagnostics Relevance
Relevant diseases:
spinocerebellar ataxia type 1 ( 4 , 8 , 23 , 25 )

References 

1

Leysen S, et al. (2021) A Structural Study of the Cytoplasmic Chaperone Effect of 14-3-3 Proteins on Ataxin-1. J Mol Biol 433, 167174
34302818   Curated Info

2

Lee WS, et al. (2021) Dual targeting of brain region-specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1. EMBO J 40, e106106
33709453   Curated Info

3

Bouhaddou M, et al. (2020) The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell
32645325   Curated Info

4

PĂ©rez Ortiz JM, et al. (2018) Reduction of protein kinase A-mediated phosphorylation of ATXN1-S776 in Purkinje cells delays onset of Ataxia in a SCA1 mouse model. Neurobiol Dis 116, 93-105
29758256   Curated Info

5

Kang AR, et al. (2017) Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR-RAS-MAPK signaling pathway. Oncotarget 8, 94606-94618
29212253   Curated Info

6

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

7

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
25850435   Curated Info

8

Hearst SM, et al. (2014) The design and delivery of a PKA inhibitory polypeptide to treat SCA1. J Neurochem 131, 101-14
24903464   Curated Info

9

Kim E, Lee Y, Choi S, Song JJ (2014) Structural basis of the phosphorylation dependent complex formation of neurodegenerative disease protein Ataxin-1 and RBM17. Biochem Biophys Res Commun 449, 399-404
24858692   Curated Info

10

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

11

Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948
24670416   Curated Info

12

Park J, et al. (2013) RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature 498, 325-31
23719381   Curated Info

13

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

14

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

15

Menon RP, et al. (2012) The importance of serine 776 in Ataxin-1 partner selection: a FRET analysis. Sci Rep 2, 919
23213356   Curated Info

16

Osinalde N, et al. (2011) Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics. J Proteomics 75, 177-91
21722762   Curated Info

17

Kettenbach AN, et al. (2011) Quantitative phosphoproteomics identifies substrates and functional modules of aurora and polo-like kinase activities in mitotic cells. Sci Signal 4, rs5
21712546   Curated Info

18

Hearst SM, et al. (2010) Dopamine D2 receptor signaling modulates mutant ataxin-1 S776 phosphorylation and aggregation. J Neurochem 114, 706-16
20477910   Curated Info

19

de Chiara C, et al. (2009) Phosphorylation of S776 and 14-3-3 binding modulate ataxin-1 interaction with splicing factors. PLoS One 4, e8372
20037628   Curated Info

20

Jorgensen ND, et al. (2007) Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1. J Neurochem 102, 2040-8
17540008   Curated Info

21

Moritz A (2007) CST Curation Set: 2946; Year: 2007; Biosample/Treatment: cell line, NCI-H3255/Iressa; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: RXXp[ST] Antibodies Used to Purify Peptides prior to LCMS: Phospho-Akt Substrate (RXRXXT-P) (60D12F4) Rabbit mAb Cat#: 10002
Curated Info

22

Riley BE, Zoghbi HY, Orr HT (2005) SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on a functional nuclear localization signal. J Biol Chem 280, 21942-8
15824120   Curated Info

23

Kaytor MD, et al. (2005) A cell-based screen for modulators of ataxin-1 phosphorylation. Hum Mol Genet 14, 1095-105
15757972   Curated Info

24

Chen HK, et al. (2003) Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell 113, 457-68
12757707   Curated Info

25

Emamian ES, et al. (2003) Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 38, 375-87
12741986   Curated Info