Thr76

Site Information
tkkVAVAtPAkkAAV SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 483581

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 1 , 2 ) , immunoprecipitation ( 2 , 3 ) , labeling using "Shokat-modified" upstream kinase ( 45 ) , mass spectrometry ( 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 46 , 47 , 48 , 49 , 50 , 51 ) , mass spectrometry (in vitro) ( 45 ) , mutation of modification site ( 2 ) , phospho-antibody ( 1 , 3 ) , western blotting ( 1 , 2 , 3 )
Disease tissue studied:	bladder cancer ( 3 ) , breast cancer ( 9 , 10 ) , breast ductal carcinoma ( 9 ) , 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 , 9 ) , cervical cancer ( 42 ) , cervical adenocarcinoma ( 42 ) , leukemia ( 1 , 20 ) , acute myelogenous leukemia ( 1 , 20 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 1 , 16 ) , acute megakaryoblastic leukemia (M7) ( 16 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 1 , 16 ) , acute myeloblastic leukemia, with granulocytic maturation (M2) ( 16 ) , acute myeloblastic leukemia, without maturation (M1) ( 16 ) , lung cancer ( 2 , 11 , 17 ) , non-small cell lung cancer ( 2 , 17 ) , non-small cell lung adenocarcinoma ( 2 , 11 ) , B cell lymphoma ( 16 ) , non-Hodgkin's lymphoma ( 16 ) , multiple myeloma ( 16 )
Relevant cell line - cell type - tissue:	A549 (pulmonary) ( 2 , 12 ) , AML-193 (monocyte) ( 16 ) , BEAS-2B (epithelial) ( 2 ) , breast ( 6 , 9 ) , Calu 6 (pulmonary) ( 17 ) , CMK (megakaryoblast) ( 16 ) , CTS (myeloid) ( 16 ) , DOHH2 ('B lymphocyte, precursor') ( 16 ) , fibroblast-skin ( 51 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 18 ) , Flp-In T-Rex-293 (epithelial) ( 18 ) , H2009 (pulmonary) ( 17 ) , H2077 (pulmonary) ( 17 ) , H2887 (pulmonary) ( 17 ) , H322M (pulmonary) ( 17 ) , HCC2279 (pulmonary) ( 17 ) , HCC366 (pulmonary) ( 17 ) , HCC78 (pulmonary) ( 17 ) , HEL (erythroid) ( 16 ) , HeLa (cervical) ( 5 , 8 , 15 , 24 , 29 , 33 , 34 , 35 , 36 , 37 , 43 , 44 , 47 , 48 , 49 , 50 ) , HeLa S3 (cervical) [PLK1 (human), knockdown, Tet-inducible PLK1 siRNA] ( 31 ) , HeLa S3 (cervical) ( 31 , 42 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 10 ) , HMLER ('stem, breast cancer') ( 10 ) , HOP62 (pulmonary) ( 17 ) , HUES-9 ('stem, embryonic') ( 32 ) , Jurkat (T lymphocyte) ( 13 , 21 , 22 , 25 , 26 , 27 , 28 , 30 , 38 , 39 , 40 , 41 , 46 ) , Kasumi-1 (myeloid) ( 16 ) , KG-1 (myeloid) ( 1 , 16 , 20 ) , lung ( 2 , 11 ) , MOLM 13 (myeloid) ( 1 ) , mononuclear ( 1 ) , MV4-11 (macrophage) ( 1 , 16 ) , NCI-H1395 (pulmonary) ( 17 ) , NCI-H1568 (pulmonary) ( 17 ) , NCI-H157 (pulmonary) ( 17 ) , NCI-H1648 (pulmonary) ( 17 ) , NCI-H1666 (pulmonary) ( 17 ) , NCI-H1975 (pulmonary) ( 2 ) , NCI-H2030 (pulmonary) ( 17 ) , NCI-H2172 (pulmonary) ( 17 ) , NCI-H322 (pulmonary) ( 17 ) , NCI-H520 (squamous) ( 17 ) , NCI-H647 (pulmonary) ( 17 ) , OCI/AML2 (myeloid) ( 1 ) , OCI/AML3 (myeloid) ( 1 ) , OPM-2 (plasma cell) ( 16 ) , P31/FUJ (erythroid) ( 16 ) , PC9 (pulmonary) ( 17 ) , RL ('B lymphocyte, precursor') ( 16 ) , RPMI-8266 (plasma cell) ( 16 ) , SPCA-1 (pulmonary) ( 2 ) , SU-DHL-6 (B lymphocyte) ( 16 ) , U266 (plasma cell) ( 16 ) , UMUC3 (bladder cell) ( 3 )

Upstream Regulation
Kinases, in vitro:	CDC7 (human) ( 4 ) , CDK2 (human) ( 45 )
Treatments:	adriamycin ( 2 ) , CXCL12 ( 10 ) , ischemia ( 9 ) , nocodazole ( 42 ) , RITA ( 1 ) , ZK-Thiazolidinone ( 31 )

Downstream Regulation
Effects of modification on NCL:	molecular association, regulation ( 3 )
Effects of modification on biological processes:	cell cycle regulation ( 1 ) , cell growth, induced ( 2 , 3 ) , cell motility, induced ( 2 )
Induce interaction with:	DDX31 (human) ( 3 )

Disease / Diagnostics Relevance
Relevant diseases:	non-small cell lung cancer ( 2 )

References
1	Wolfová K, Otevřelová P, Holoubek A, Brodská B (2023) Nucleolar phosphoprotein modifications as a marker of apoptosis induced by RITA treatment. Biochim Biophys Acta Mol Cell Res 1870, 119501 37276927 Curated Info
2	Huang F, et al. (2018) Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells. Oncol Rep 30320343 Curated Info
3	Daizumoto K, et al. (2018) A DDX31/mutant-p53/EGFR axis promotes multistep progression of muscle invasive bladder cancer. Cancer Res 29440146 Curated Info
4	Wu KZ, et al. (2016) DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach. Nucleic Acids Res 44, 8786-8798 27407105 Curated Info
5	Huang H, et al. (2016) Simultaneous Enrichment of Cysteine-containing Peptides and Phosphopeptides Using a Cysteine-specific Phosphonate Adaptable Tag (CysPAT) in Combination with titanium dioxide (TiO2) Chromatography. Mol Cell Proteomics 15, 3282-3296 27281782 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	Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610 27184836 Curated Info
8	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
9	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
10	Yi T, et al. (2014) Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 111, E2182-90 24782546 Curated Info
11	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
12	Kim JY, et al. (2013) Dissection of TBK1 signaling via phosphoproteomics in lung cancer cells. Proc Natl Acad Sci U S A 110, 12414-9 23836654 Curated Info
13	Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7 23749302 Curated Info
14	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
15	Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71 23186163 Curated Info
16	Casado P, et al. (2013) Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors. Genome Biol 14, R37 23628362 Curated Info
17	Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68 22617229 Curated Info
18	Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70 22496350 Curated Info
19	Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25 22424773 Curated Info
20	Weber C, Schreiber TB, Daub H (2012) Dual phosphoproteomics and chemical proteomics analysis of erlotinib and gefitinib interference in acute myeloid leukemia cells. J Proteomics 75, 1343-56 22115753 Curated Info
21	Mulhern D (2012) CST Curation Set: 13341; Year: 2012; 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 Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996 Curated Info
22	Mulhern D (2012) CST Curation Set: 13342; Year: 2012; 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 Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996 Curated Info
23	Rikova K (2011) CST Curation Set: 13117; Year: 2011; Biosample/Treatment: cell line, MGH-5/unknown; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]) Curated Info
24	Grosstessner-Hain K, et al. (2011) Quantitative phospho-proteomics to investigate the polo-like kinase 1-dependent phospho-proteome. Mol Cell Proteomics 10, M111.008540 21857030 Curated Info
25	Guo A (2011) CST Curation Set: 12435; 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: p[ST]P Curated Info
26	Guo A (2011) CST Curation Set: 12436; 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: p[ST]P Curated Info
27	Guo A (2011) CST Curation Set: 12437; 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: p[ST]P Curated Info
28	Guo A (2011) CST Curation Set: 12017; 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: p[ST]P Curated Info
29	Guo A (2011) CST Curation Set: 11453; Year: 2011; Biosample/Treatment: cell line, HeLa/nocodazole &'\|\|' pervanadate; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-PLK Binding Motif (STP) (D73F6) Rabbit mAb Cat#: 5243, PTMScan(R) Phospho-PLK Binding Motif (STP) Immunoaffinity Beads Cat#: 5756 Curated Info
30	Guo A (2011) CST Curation Set: 11289; 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: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996 Curated Info
31	Santamaria A, et al. (2011) The Plk1-dependent phosphoproteome of the early mitotic spindle. Mol Cell Proteomics 10, M110.004457 20860994 Curated Info
32	Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3 21406692 Curated Info
33	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
34	Zhou J (2010) CST Curation Set: 10712; Year: 2010; Biosample/Treatment: cell line, HeLa/untreated; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-PLK Binding Motif (STP) (D73F6) Rabbit mAb Cat#: 5243, PTMScan(R) Phospho-PLK Binding Motif (STP) Immunoaffinity Beads Cat#: 5756 Curated Info
35	Zhou J (2010) CST Curation Set: 10713; Year: 2010; Biosample/Treatment: cell line, HeLa/nocodazole; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-PLK Binding Motif (STP) (D73F6) Rabbit mAb Cat#: 5243, PTMScan(R) Phospho-PLK Binding Motif (STP) Immunoaffinity Beads Cat#: 5756 Curated Info
36	Zhou J (2010) CST Curation Set: 10709; Year: 2010; Biosample/Treatment: cell line, HeLa/nocodazole; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXSP, SPXK/R) Immunoaffinity Beads Cat#: 1982 Curated Info
37	Zhou J (2010) CST Curation Set: 10685; Year: 2010; Biosample/Treatment: cell line, HeLa/nocodazole; Disease: cervical adenocarcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: PXpSP, pSPX(K/R) Antibodies Used to Purify Peptides prior to LCMS: Phospho-MAPK/CDK Substrates (PXSP or SPXR/K) (34B2) Rabbit mAb Cat#: 2325, PTMScan(R) Phospho-MAPK/CDK Substrate Motif (PXSP, SPXK/R) Immunoaffinity Beads Cat#: 1982 Curated Info
38	Possemato A (2010) CST Curation Set: 9438; 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: p[ST]P Curated Info
39	Possemato A (2010) CST Curation Set: 9435; 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: p[ST]P Curated Info
40	Possemato A (2010) CST Curation Set: 9352; 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: p[ST]XX(K/R) Curated Info
41	Possemato A (2010) CST Curation Set: 8993; 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: p[ST]P Antibodies Used to Purify Peptides prior to LCMS: Phospho-Thr-Pro Motif Antibody (polyAB) Cat#: 3003, PTMScan(R) Phospho-Thr-Pro Motif (T*P) Immunoaffinity Beads Cat#: 1996 Curated Info
42	Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3 20068231 Curated Info
43	Chen Y, et al. (2009) Combined integrin phosphoproteomic analyses and small interfering RNA--based functional screening identify key regulators for cancer cell adhesion and migration. Cancer Res 69, 3713-20 19351860 Curated Info
44	Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8 19276368 Curated Info
45	Chi Y, et al. (2008) Identification of CDK2 substrates in human cell lysates. Genome Biol 9, R149 18847512 Curated Info
46	Possemato A (2008) CST Curation Set: 5276; Year: 2008; 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
47	Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7 18669648 Curated Info
48	McNulty DE, Annan RS (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971-80 18212344 Curated Info
49	Yu LR, et al. (2007) Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res 6, 4150-62 17924679 Curated Info
50	Beausoleil SA, et al. (2006) A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol 24, 1285-92 16964243 Curated Info
51	Yang F, et al. (2006) Phosphoproteome profiling of human skin fibroblast cells in response to low- and high-dose irradiation. J Proteome Res 5, 1252-60 16674116 Curated Info