Ser77
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Home > Phosphorylation Site Page: > Ser77  -  RARA (human)

Site Information
EIVPsPPsPPPLPRI   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 455459

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 8 , 11 ) , immunoassay ( 1 ) , immunoprecipitation ( 3 , 7 ) , mass spectrometry ( 4 ) , mutation of modification site ( 2 , 6 , 7 , 8 , 9 , 10 , 11 ) , phospho-antibody ( 1 , 3 , 7 , 8 ) , western blotting ( 1 , 3 , 7 , 8 )
Disease tissue studied:
breast cancer ( 1 , 3 , 7 , 8 ) , breast cancer, triple negative ( 1 ) , leukemia ( 6 ) , lymphoma ( 3 ) , anaplastic large cell lymphoma ( 3 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
CCNH (human) ( 8 ) , MSK1 (human) ( 7 ) , P38A (human) ( 7 )
Putative in vivo kinases:
CDK7 (human) ( 1 , 7 , 8 , 10 , 11 )
Kinases, in vitro:
CDK7 (human) ( 5 , 7 , 8 , 11 )
Treatments:
AM580 ( 1 ) , NKH_477 ( 8 ) , retinoic_acid ( 1 , 7 ) , tamibarotene ( 1 ) , THZ1 ( 1 )

Downstream Regulation
Effects of modification on RARA:
activity, induced ( 11 ) , activity, inhibited ( 1 ) , molecular association, regulation ( 3 , 5 , 6 , 7 , 8 , 9 , 10 ) , protein conformation ( 5 ) , protein degradation ( 9 )
Effects of modification on biological processes:
apoptosis, inhibited ( 1 ) , autophagy, inhibited ( 1 ) , carcinogenesis, induced ( 1 ) , cell cycle regulation ( 1 ) , RNA stability, induced ( 1 ) , signaling pathway regulation ( 7 , 8 ) , transcription, altered ( 9 , 10 ) , transcription, induced ( 7 , 8 ) , transcription, inhibited ( 1 , 6 )
Induce interaction with:
CCNH (human) ( 5 ) , DNA ( 6 , 7 , 8 , 10 ) , N-CoR1 (human) ( 6 ) , PIN1 (human) ( 3 , 9 ) , RXRA (human) ( 8 )
Inhibit interaction with:
SRC-3 (human) ( 6 )

Disease / Diagnostics Relevance
Relevant diseases:
breast cancer, triple negative ( 1 ) , Xeroderma pigmentosum ( 11 )

References 

1

Lou S, et al. (2021) Inhibition of retinoic acid receptor α phosphorylation represses the progression of triple-negative breast cancer via transactivating miR-3074-5p to target DHRS3. J Exp Clin Cancer Res 40, 141
33902658   Curated Info

2

Gianni M, et al. (2018) S100A3 a partner protein regulating the stability/activity of RARα and PML-RARα in cellular models of breast/lung cancer and acute myeloid leukemia. Oncogene
30532072   Curated Info

3

Wei S, et al. (2015) Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer. Nat Med 21, 457-66
25849135   Curated Info

4

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

5

Samarut E, et al. (2011) Evolution of Nuclear Retinoic Acid Receptor Alpha (RAR{alpha}) Phosphorylation Sites. Serine Gain Provides Fine-Tuned Regulation. Mol Biol Evol 28, 2125-37
21297158   Curated Info

6

Wang A, et al. (2010) Loss of CAK phosphorylation of RAR{alpha} mediates transcriptional control of retinoid-induced cancer cell differentiation. FASEB J 24, 833-43
19917671   Curated Info

7

Bruck N, et al. (2009) A coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs RARalpha to target promoters. EMBO J 28, 34-47
19078967   Curated Info

8

Gaillard E, et al. (2006) Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7. Proc Natl Acad Sci U S A 103, 9548-53
16769902   Curated Info

9

Brondani V, Schefer Q, Hamy F, Klimkait T (2005) The peptidyl-prolyl isomerase Pin1 regulates phospho-Ser77 retinoic acid receptor alpha stability. Biochem Biophys Res Commun 328, 6-13
15670742   Curated Info

10

Brondani V, Klimkait T, Egly JM, Hamy F (2002) Promoter of FGF8 reveals a unique regulation by unliganded RARalpha. J Mol Biol 319, 715-28
12054865   Curated Info

11

Keriel A, et al. (2002) XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Cell 109, 125-35
11955452   Curated Info