Ser325

Site Information
tsVsRGssLkILskG SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 3849622

In vivo Characterization
Methods used to characterize site in vivo:	flow cytometry ( 4 ) , immunoassay ( 2 ) , immunoprecipitation ( 2 , 21 ) , mass spectrometry ( 6 , 10 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 ) , mutation of modification site ( 2 , 21 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 8 , 15 , 18 , 21 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 15 , 18 , 21 )
Disease tissue studied:	breast cancer ( 15 ) , cervical cancer ( 19 ) , cervical adenocarcinoma ( 19 ) , leukemia ( 3 ) , chronic lymphocytic leukemia ( 4 ) , T cell leukemia ( 3 ) , lung cancer ( 5 ) , non-small cell lung cancer ( 5 ) , non-small cell lung adenocarcinoma ( 5 ) , non-small cell large cell lung carcinoma ( 5 )
Relevant cell line - cell type - tissue:	293 (epithelial) ( 1 , 2 , 8 , 18 , 21 ) , A498 (renal) ( 16 ) , A549 (pulmonary) ( 5 ) , astrocyte ( 18 ) , B lymphocyte-blood ( 4 ) , HCC827 (pulmonary) ( 5 ) , HeLa (cervical) ( 2 , 6 , 12 , 14 , 20 , 22 ) , HeLa S3 (cervical) ( 19 ) , Jurkat (T lymphocyte) ( 3 , 10 , 13 , 17 , 23 , 24 , 25 , 26 ) , NCI-H1299 (pulmonary) ( 5 ) , NCI-H460 (pulmonary) ( 5 ) , T47D (breast cell) ( 15 )

Upstream Regulation
Regulatory protein:	CXCL12 (human) ( 3 ) , PKCA (human) ( 2 )
Putative in vivo kinases:	GRK6 (human) ( 2 , 18 ) , PKCD (human) ( 18 )
Treatments:	AG1478 ( 15 ) , antibody ( 4 ) , ATI-2341 ( 1 , 8 ) , Bis_V ( 18 ) , bisindolylmaleimide ( 18 ) , CID755673 ( 4 ) , CXCL12 ( 1 , 2 , 8 , 15 , 18 , 21 ) , GF109203X ( 2 , 8 ) , Go_6976 ( 18 ) , heregulin ( 15 ) , IL-24 ( 5 ) , nocodazole ( 19 ) , peptide_antagonist ( 18 ) , phorbol_ester ( 2 ) , plerixafor ( 3 , 15 ) , rottlerin ( 18 ) , siRNA ( 2 ) , X4-2-6 ( 3 )

Downstream Regulation
Effects of modification on CXCR4:	activity, induced ( 21 ) , enzymatic activity, induced ( 2 ) , intracellular localization ( 21 ) , molecular association, regulation ( 21 ) , protein degradation ( 2 , 21 ) , receptor desensitization, induced ( 2 ) , receptor internalization, induced ( 2 , 3 ) , ubiquitination ( 2 , 21 )
Effects of modification on biological processes:	endocytosis, induced ( 1 )
Induce interaction with:	ITCH (human) ( 21 )

References
1	Luo J, et al. (2021) Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4. J Biol Chem 298, 101551 34973340 Curated Info
2	Caballero A, et al. (2019) Heterologous regulation of CXCR4 lysosomal trafficking. J Biol Chem 294, 8023-8036 30936203 Curated Info
3	Hitchinson B, et al. (2018) Biased antagonism of CXCR4 avoids antagonist tolerance. Sci Signal 11 30327409 Curated Info
4	Saint-Georges S, et al. (2016) Protein kinase D-dependent CXCR4 down-regulation upon BCR triggering is linked to lymphadenopathy in chronic lymphocytic leukaemia. Oncotarget 7, 41031-41046 27127886 Curated Info
5	Panneerselvam J, et al. (2015) IL-24 Inhibits Lung Cancer Cell Migration and Invasion by Disrupting The SDF-1/CXCR4 Signaling Axis. PLoS One 10, e0122439 25775124 Curated Info
6	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
7	Chandrasekaran P, et al. (2014) HIV-1 Nef down-modulates C-C and C-X-C chemokine receptors via ubiquitin and ubiquitin-independent mechanism. PLoS One 9, e86998 24489825 Curated Info
8	Quoyer J, et al. (2013) Pepducin targeting the C-X-C chemokine receptor type 4 acts as a biased agonist favoring activation of the inhibitory G protein. Proc Natl Acad Sci U S A 110, E5088-97 24309376 Curated Info
9	Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96 23911959 Curated Info
10	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
11	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
12	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
13	Mulhern D (2011) CST Curation Set: 12682; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M) Curated Info
14	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
15	Sosa MS, et al. (2010) Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Mol Cell 40, 877-92 21172654 Curated Info
16	Schreiber TB, et al. (2010) An integrated phosphoproteomics work flow reveals extensive network regulation in early lysophosphatidic acid signaling. Mol Cell Proteomics 9, 1047-62 20071362 Curated Info
17	Possemato A (2010) CST Curation Set: 9348; Year: 2010; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)Xp[ST](I/L/V) Curated Info
18	Busillo JM, et al. (2010) Site-specific Phosphorylation of CXCR4 Is Dynamically Regulated by Multiple Kinases and Results in Differential Modulation of CXCR4 Signaling. J Biol Chem 285, 7805-17 20048153 Curated Info
19	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
20	Pan C, Olsen JV, Daub H, Mann M (2009) Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics 8, 2796-808 19651622 Curated Info
21	Bhandari D, Robia SL, Marchese A (2009) The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. Mol Biol Cell 20, 1324-39 19116316 Curated Info
22	Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8 19276368 Curated Info
23	Farnsworth C (2009) CST Curation Set: 6186; 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: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
24	Farnsworth C (2009) CST Curation Set: 6185; 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: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
25	Zhou J (2009) CST Curation Set: 5902; Year: 2009; Biosample/Treatment: cell line, Jurkat/untreated; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info
26	Zhou J (2009) CST Curation Set: 5903; Year: 2009; Biosample/Treatment: cell line, Jurkat/untreated; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (K/R)XpSX(K/R)Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) PKC Substrate Antibody Cat#: 2261, PTMScan(R) Phospho-PKC Substrate Motif (K/RXpSXK/R) Immunoaffinity Beads Cat#: 1985 Curated Info