Ser74
Javascript is not enabled on this browser. This site will not work properly without Javascript.
PhosphoSitePlus Homepage PhosphoSitePlus® v6.7.1.1
Powered by Cell Signaling Technology
Home > Phosphorylation Site Page: > Ser74  -  CDC6 (human)

Site Information
tPHLPPCsPPKQGKK   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 450915

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 14 ) , [32P] bio-synthetic labeling ( 15 ) , immunoassay ( 5 ) , immunoprecipitation ( 13 , 15 ) , mass spectrometry ( 2 , 3 , 4 , 6 , 10 , 11 , 12 ) , mutation of modification site ( 5 , 8 , 9 , 13 , 15 ) , phospho-antibody ( 1 , 5 , 8 ) , phosphoamino acid analysis ( 14 ) , phosphopeptide mapping ( 14 ) , western blotting ( 1 , 5 , 8 , 13 , 15 )
Disease tissue studied:
bladder cancer ( 1 ) , bone cancer ( 13 , 15 ) , brain cancer ( 13 ) , glioblastoma ( 13 ) , glioblastoma multiforme ( 13 ) , glioma ( 13 ) , HER2 positive breast cancer ( 2 ) , luminal A breast cancer ( 2 ) , luminal B breast cancer ( 2 ) , melanoma skin cancer ( 3 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 14 ) , breast ( 2 ) , COS (fibroblast) ( 15 ) , CV1 (fibroblast) ( 15 ) , HEK293T (epithelial) ( 9 ) , HeLa (cervical) ( 4 , 5 , 8 , 10 , 12 , 14 ) , HSF8 (fibroblast) ( 14 ) , Jurkat (T lymphocyte) ( 6 , 11 ) , T98G (glial) ( 13 ) , U2OS (bone cell) [GR (human)] ( 14 ) , U2OS (bone cell) ( 13 , 15 ) , UMUC3 (bladder cell) ( 1 ) , UMUC3R (bladder cell) ( 1 ) , WM239A (melanocyte) ( 3 )

Upstream Regulation
Putative in vivo kinases:
CDK2 (human) ( 5 , 8 , 15 )
Kinases, in vitro:
CDK2 (human) ( 14 , 15 )
Treatments:
cisplatin ( 1 ) , hydroxyurea ( 5 )

Downstream Regulation
Effects of modification on CDC6:
intracellular localization ( 1 , 5 , 8 , 14 , 15 ) , molecular association, regulation ( 13 ) , protein stabilization ( 9 , 13 )
Effects of modification on biological processes:
cell cycle regulation ( 13 , 15 )
Inhibit interaction with:
CDH1 (human) ( 13 )

References 

1

Chen S, et al. (2016) Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells. Oncotarget 7, 40362-40376
27246979   Curated Info

2

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

3

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

4

Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94
25159151   Curated Info

5

Hwang IS, et al. (2014) Two nuclear export signals of Cdc6 are differentially associated with CDK-mediated phosphorylation residues for cytoplasmic translocation. Biochim Biophys Acta 1843, 223-33
24216307   Curated Info

6

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   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

Yim H, et al. (2013) Phosphorylation of Cdc6 at serine 74, but not at serine 106, drives translocation of Cdc6 to the cytoplasm. J Cell Physiol 228, 1221-8
23129444   Curated Info

9

Martin L, Rainey M, Santocanale C, Gardner LB (2012) Hypoxic activation of ATR and the suppression of the initiation of DNA replication through cdc6 degradation. Oncogene 31, 4076-84
22179839   Curated Info

10

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

11

Possemato A (2009) CST Curation Set: 6850; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

12

Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8
19276368   Curated Info

13

Mailand N, Diffley JF (2005) CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell 122, 915-26
16153703   Curated Info

14

Jiang W, Wells NJ, Hunter T (1999) Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6. Proc Natl Acad Sci U S A 96, 6193-8
10339564   Curated Info

15

Petersen BO, et al. (1999) Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization. EMBO J 18, 396-410
9889196   Curated Info

Developed with grants from  NIH Logo and literature mining with Linguamatics  I2E Logo Creative Commons License PhosphoSite, created by Cell Signaling Technology is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

©2003-2019 Cell Signaling Technology, Inc.