Ser282

Site Information
tAPLsPMsPPGykLV SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448854

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 7 , 8 , 13 , 15 ) , mass spectrometry ( 14 , 16 ) , mutation of modification site ( 2 , 5 , 6 , 7 , 10 , 15 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 17 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 )
Relevant cell line - cell type - tissue:	'heart, ventricle' ( 2 ) , brain ( 6 , 7 ) , epidermal ( 8 ) , fibroblast-heart ( 7 ) , H9c2 (myoblast) ( 1 ) , heart ( 4 , 7 , 8 , 13 ) , HeLa (cervical) ( 10 ) , Leydig TM3 (Leydig) ( 3 ) , liver ( 7 ) , macrophage-bone marrow ( 7 ) , MEF (fibroblast) ( 13 , 14 ) , MLO-Y4 (osteoblast) ( 11 ) , myocyte-heart ( 5 , 7 , 8 ) , oocyte ( 12 , 15 ) , ovary ( 15 , 17 ) , PYS-2 (epithelial) ( 16 ) , TM4 (sertoli) ( 9 )

In vivo Characterization

Methods used to characterize site in vivo:

immunoassay ( 7 , 8 , 13 , 15 ) , mass spectrometry ( 14 , 16 ) , mutation of modification site ( 2 , 5 , 6 , 7 , 10 , 15 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 17 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 )

Relevant cell line - cell type - tissue:

'heart, ventricle' ( 2 ) , brain ( 6 , 7 ) , epidermal ( 8 ) , fibroblast-heart ( 7 ) , H9c2 (myoblast) ( 1 ) , heart ( 4 , 7 , 8 , 13 ) , HeLa (cervical) ( 10 ) , Leydig TM3 (Leydig) ( 3 ) , liver ( 7 ) , macrophage-bone marrow ( 7 ) , MEF (fibroblast) ( 13 , 14 ) , MLO-Y4 (osteoblast) ( 11 ) , myocyte-heart ( 5 , 7 , 8 ) , oocyte ( 12 , 15 ) , ovary ( 15 , 17 ) , PYS-2 (epithelial) ( 16 ) , TM4 (sertoli) ( 9 )

Upstream Regulation
Regulatory protein:	Desmoplakin (mouse) ( 8 ) , FGF21 (human) ( 1 ) , lamin A/C (mouse) ( 13 ) , NEDD4 (human) ( 1 ) , RIPK3 (mouse) ( 14 )
Putative in vivo kinases:	CDK5 (mouse) ( 10 ) , ERK1 (mouse) ( 8 , 13 ) , ERK2 (mouse) ( 8 , 13 )
Kinases, in vitro:	CDK5 (human) ( 10 )
Treatments:	adriamycin ( 1 , 5 ) , ATP ( 5 ) , benzo(a)pyrene ( 9 ) , fluid_shear_stress ( 11 ) , hypoxia ( 6 ) , LH ( 12 , 17 ) , normoxia ( 6 ) , PGE2 ( 11 ) , U0124 ( 17 ) , U0126 ( 8 , 17 )

Downstream Regulation
Effects of modification on GJA1:	activity, induced ( 6 ) , intracellular localization ( 8 , 10 , 15 ) , protein degradation ( 8 , 10 ) , receptor internalization, induced ( 8 ) , ubiquitination ( 8 )
Effects of modification on biological processes:	apoptosis, induced ( 2 ) , apoptosis, inhibited ( 1 , 7 ) , cell growth, induced ( 15 )

References
1	Huang Y, et al. (2023) FGF21 protects against doxorubicin-induced cardiotoxicity by inhibiting connexin 43 ubiquitination. Free Radic Biol Med 208, 748-758 37774805 Curated Info
2	Wu L, et al. (2023) Connexin 43 dephosphorylation at serine 282 induces spontaneous arrhythmia and increases susceptibility to ischemia/reperfusion injury. Heliyon 9, e15879 37215881 Curated Info
3	Yawer A, et al. (2020) Endocrine-disrupting chemicals rapidly affect intercellular signaling in Leydig cells. Toxicol Appl Pharmacol 404, 115177 32739526 Curated Info
4	Solan JL, Marquez-Rosado L, Lampe PD (2019) Cx43 phosphorylation mediated effects on ERK and Akt protect against ischemia reperfusion injury and alter stability of stress-inducible protein NDRG1. J Biol Chem 31189653 Curated Info
5	Sun Z, et al. (2019) Connexin 43-serine 282 modulates serine 279 phosphorylation in cardiomyocytes. Biochem Biophys Res Commun 513, 567-572 30981509 Curated Info
6	Freitas-Andrade M, et al. (2019) Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke. J Exp Med 216, 916-935 30872361 Curated Info
7	Yang Y, et al. (2019) Connexin43 dephosphorylation at serine 282 is associated with connexin43-mediated cardiomyocyte apoptosis. Cell Death Differ 30770876 Curated Info
8	Kam CY, et al. (2018) Desmoplakin maintains gap junctions by inhibiting Ras/MAPK and lysosomal degradation of connexin-43. J Cell Biol 29959233 Curated Info
9	Ji X, et al. (2018) Benzo[a]pyrene-decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells. J Appl Toxicol 29578247 Curated Info
10	Qi GJ, et al. (2016) Phosphorylation of Connexin 43 by Cdk5 Modulates Neuronal Migration During Embryonic Brain Development. Mol Neurobiol 53, 2969-82 25952543 Curated Info
11	Riquelme MA, et al. (2015) Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2 Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to Continuous Flow Shear Stress. J Biol Chem 290, 28321-8 26442583 Curated Info
12	Shuhaibar LC, et al. (2015) Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles. Proc Natl Acad Sci U S A 112, 5527-32 25775542 Curated Info
13	Chen SC, Kennedy BK, Lampe PD (2013) Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects. Exp Cell Res 319, 888-96 23261543 Curated Info
14	Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51 22942356 Curated Info
15	Dyce PW, Norris RP, Lampe PD, Kidder GM (2012) Phosphorylation of Serine Residues in the C-terminal Cytoplasmic Tail of Connexin43 Regulates Proliferation of Ovarian Granulosa Cells. J Membr Biol 245, 291-301 22729691 Curated Info
16	Zhou J (2010) CST Curation Set: 9108; Year: 2010; Biosample/Treatment: cell line, PY2/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-102) Cat#: 9416 Curated Info
17	Norris RP, et al. (2008) Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption. Development 135, 3229-38 18776144 Curated Info