Thr592
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Home > Phosphorylation Site Page: > Thr592  -  SAMHD1 (human)

Site Information
DVIAPLItPQkkEWN   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 468674
Associated spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 18 , 24 ) , labeling using "Shokat-modified" upstream kinase ( 46 ) , mass spectrometry ( 4 , 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 21 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 47 , 48 , 49 , 51 ) , mass spectrometry (in vitro) ( 1 , 46 , 50 ) , mutation of modification site ( 1 , 2 , 3 , 7 , 18 , 23 , 24 ) , phospho-antibody ( 1 , 3 , 7 , 15 , 23 ) , western blotting ( 1 , 3 , 7 , 15 , 18 , 23 , 24 )
Disease tissue studied:
breast cancer ( 12 , 13 , 28 , 29 ) , breast ductal carcinoma ( 12 ) , HER2 positive breast cancer ( 5 ) , luminal A breast cancer ( 5 ) , luminal B breast cancer ( 5 ) , breast cancer, surrounding tissue ( 5 ) , breast cancer, triple negative ( 5 , 12 ) , cervical cancer ( 40 ) , cervical adenocarcinoma ( 40 ) , gastric cancer ( 49 ) , leukemia ( 3 , 23 , 30 , 33 ) , acute myelogenous leukemia ( 3 , 23 , 30 , 33 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 27 , 30 ) , acute megakaryoblastic leukemia (M7) ( 27 ) , acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) ( 27 ) , acute myeloblastic leukemia, with granulocytic maturation (M2) ( 27 ) , acute myeloblastic leukemia, without maturation (M1) ( 27 ) , lung cancer ( 19 , 29 , 37 ) , non-small cell lung cancer ( 29 ) , non-small cell lung adenocarcinoma ( 19 ) , lymphoma ( 1 , 14 , 18 , 23 , 24 ) , B cell lymphoma ( 27 ) , Burkitt's lymphoma ( 14 ) , non-Hodgkin's lymphoma ( 27 ) , follicular lymphoma ( 14 ) , mantle cell lymphoma ( 14 ) , neuroblastoma ( 26 ) , ovarian cancer ( 12 ) , multiple myeloma ( 27 ) , melanoma skin cancer ( 10 ) , HIV/AIDS ( 7 , 23 )
Relevant cell line - cell type - tissue:
'stem, embryonic' ( 42 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 39 ) , 293 (epithelial) [AT1 (human), transfection] ( 38 ) , 293 (epithelial) ( 44 ) , 786-O (renal) [VHL (human), transfection] ( 8 ) , 786-O (renal) ( 8 ) , A549 (pulmonary) ( 21 ) , AML-193 (monocyte) ( 27 , 30 ) , BJAB (B lymphocyte) ( 14 ) , breast ( 5 , 12 ) , BT-20 (breast cell) ( 29 ) , BT-549 (breast cell) ( 29 ) , Calu 6 (pulmonary) ( 29 ) , CD4+ (T lymphocyte) ( 23 ) , CL1-0 (pulmonary) ( 37 ) , CL1-1 (pulmonary) ( 37 ) , CL1-2 (pulmonary) ( 37 ) , CL1-5 (pulmonary) ( 37 ) , CMK (megakaryoblast) ( 27 ) , CTS (myeloid) ( 27 ) , dendritic cell ( 15 ) , DOHH2 ('B lymphocyte, precursor') ( 27 ) , E.coli (bacterial) ( 2 ) , FL-18 (B lymphocyte) ( 14 ) , FL-318 (B lymphocyte) ( 14 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 31 ) , Flp-In T-Rex-293 (epithelial) ( 31 ) , H2009 (pulmonary) ( 29 ) , H2077 (pulmonary) ( 29 ) , H2887 (pulmonary) ( 29 ) , H322M (pulmonary) ( 29 ) , HCC1937 (breast cell) ( 29 ) , HCC366 (pulmonary) ( 29 ) , HCC78 (pulmonary) ( 29 ) , HCC827 (pulmonary) ( 29 ) , HCT116 (intestinal) ( 43 ) , HEK293T (epithelial) ( 9 , 24 ) , HEL (erythroid) ( 27 , 30 ) , HeLa (cervical) ( 4 , 11 , 18 , 25 , 34 , 36 , 41 , 45 , 48 ) , HeLa S3 (cervical) ( 40 , 47 ) , HFF1 (fibroblast) ( 1 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 13 ) , HMLER ('stem, breast cancer') ( 13 ) , HOP62 (pulmonary) ( 29 ) , HUES-9 ('stem, embryonic') ( 35 ) , JEKO-1 (B lymphocyte) ( 14 ) , K562 (erythroid) ( 25 , 41 ) , Kasumi-1 (myeloid) ( 27 ) , KG-1 (myeloid) ( 27 , 33 ) , LCLC-103H (pulmonary) ( 29 ) , liver ( 17 ) , LOU-NH91 (squamous) ( 29 ) , lung ( 19 ) , MCF-7 (breast cell) ( 29 ) , MDA-MB-231 (breast cell) ( 29 ) , MDA-MB-468 (breast cell) ( 29 ) , mononuclear-blood ( 23 ) , MV4-11 (macrophage) ( 27 ) , NB10 (neural crest) ( 26 ) , NCEB-1 (B lymphocyte) ( 14 ) , NCI-H1395 (pulmonary) ( 29 ) , NCI-H157 (pulmonary) ( 29 ) , NCI-H1648 (pulmonary) ( 29 ) , NCI-H1666 (pulmonary) ( 29 ) , NCI-H2030 (pulmonary) ( 29 ) , NCI-H322 (pulmonary) ( 29 ) , NCI-H460 (pulmonary) ( 29 ) , NCI-H520 (squamous) ( 29 ) , NPC (neural crest) ( 26 ) , OCI-ly1 (B lymphocyte) ( 14 ) , OCUM-1 (gastric) ( 49 ) , OPM-2 (plasma cell) ( 27 ) , ovary ( 12 ) , P31/FUJ (erythroid) ( 27 ) , PC9 (pulmonary) ( 29 ) , Raji (B lymphocyte) ( 14 ) , RAMOS (B lymphocyte) ( 14 ) , RL ('B lymphocyte, precursor') ( 27 ) , RPMI-8266 (plasma cell) ( 27 ) , SEM (B lymphocyte) ( 51 ) , SH-SY5Y (neural crest) [LRRK2 (human), transfection, over-expression of LRRK2(G2019S)] ( 16 ) , SKBr3 (breast cell) ( 28 ) , SU-DHL-4 (B lymphocyte) ( 14 ) , SU-DHL-6 (B lymphocyte) ( 27 ) , T lymphocyte ( 15 ) , T lymphocyte-blood ( 7 ) , THP1 (myeloid) ( 3 , 23 ) , U-937 (myeloid) ( 1 , 18 , 23 , 24 ) , U266 (plasma cell) ( 27 ) , UPN-1 (B lymphocyte) ( 14 ) , WM239A (melanocyte) ( 10 )

Upstream Regulation
Putative in vivo kinases:
CDK1 (human) ( 23 , 24 ) , UL97 (herpesvirus) ( 1 )
Kinases, in vitro:
CDK1 (human) ( 23 , 24 , 50 ) , CDK2 (human) ( 46 ) , UL97 (herpesvirus) ( 1 )
Treatments:
anti-CD3/CD28 ( 15 ) , dasatinib ( 7 ) , IFN-alpha ( 15 , 23 ) , IFN-beta ( 15 ) , IL-2 ( 7 , 15 ) , IL-7 ( 7 ) , JAK_inhibitor_I ( 30 ) , phorbol_ester ( 3 , 23 ) , phytohemagglutinin ( 15 ) , rapamycin ( 45 ) , virus infection ( 1 )

Downstream Regulation
Effects of modification on SAMHD1:
protein conformation ( 2 )

References 

1

Kim ET, et al. (2019) SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-κB Activation. Cell Rep 28, 434-448.e6
31291579   Curated Info

2

Patra KK, Bhattacharya A, Bhattacharya S (2017) Allosteric Signal Transduction in HIV-1 Restriction Factor SAMHD1 Proceeds via Reciprocal Handshake across Monomers. J Chem Inf Model 57, 2523-2538
28956603   Curated Info

3

Badia R, et al. (2017) SAMHD1 is active in cycling cells permissive to HIV-1 infection. Antiviral Res 142, 123-135
28359840   Curated Info

4

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

5

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

6

Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610
27184836   Curated Info

7

Coiras M, et al. (2016) IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle. Cell Rep 14, 2100-7
26923586   Curated Info

8

Malec V, Coulson JM, Urbé S, Clague MJ (2015) Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells. J Proteome Res 14, 5263-72
26506913   Curated Info

9

Franchin C, et al. (2015) Quantitative analysis of a phosphoproteome readily altered by the protein kinase CK2 inhibitor quinalizarin in HEK-293T cells. Biochim Biophys Acta 1854, 609-23
25278378   Curated Info

10

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

11

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

12

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

13

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

14

Rolland D, et al. (2014) Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas. Am J Pathol 184, 1331-42
24667141   Curated Info

15

Bloch N, et al. (2014) HIV Type 1 Infection of Plasmacytoid and Myeloid Dendritic Cells Is Restricted by High Levels of SAMHD1 and Cannot be Counteracted by Vpx. AIDS Res Hum Retroviruses 30, 195-203
23924154   Curated Info

16

Luerman GC, et al. (2014) Phosphoproteomic evaluation of pharmacological inhibition of leucine-rich repeat kinase 2 reveals significant off-target effects of LRRK-2-IN-1. J Neurochem 128, 561-76
24117733   Curated Info

17

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

18

Welbourn S, Dutta SM, Semmes OJ, Strebel K (2013) Restriction of virus infection but not catalytic dNTPase activity is regulated by phosphorylation of SAMHD1. J Virol 87, 11516-24
23966382   Curated Info

19

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

20

Amie SM, Bambara RA, Kim B (2013) GTP is the primary activator of the anti-HIV restriction factor SAMHD1. J Biol Chem 288, 25001-6
23880768   Curated Info

21

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

22

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

23

Cribier A, et al. (2013) Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1. Cell Rep 3, 1036-43
23602554   Curated Info

24

White TE, et al. (2013) The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation. Cell Host Microbe 13, 441-51
23601106   Curated Info

25

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
23186163   Curated Info

26

DeNardo BD, et al. (2013) Quantitative phosphoproteomic analysis identifies activation of the RET and IGF-1R/IR signaling pathways in neuroblastoma. PLoS One 8, e82513
24349301   Curated Info

27

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

28

Imami K, et al. (2012) Temporal profiling of lapatinib-suppressed phosphorylation signals in EGFR/HER2 pathways. Mol Cell Proteomics 11, 1741-57
22964224   Curated Info

29

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

30

Alcolea MP, et al. (2012) Phosphoproteomic analysis of leukemia cells under basal and drug-treated conditions identifies markers of kinase pathway activation and mechanisms of resistance. Mol Cell Proteomics 11, 453-66
22547687   Curated Info

31

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

32

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

33

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

34

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

35

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

36

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

37

Wang YT, et al. (2010) An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res 9, 5582-97
20815410   Curated Info

38

Xiao K, et al. (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci U S A 107, 15299-304
20686112   Curated Info

39

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
20363803   Curated Info

40

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
20068231   Curated Info

41

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

42

Brill LM, et al. (2009) Phosphoproteomic analysis of human embryonic stem cells. Cell Stem Cell 5, 204-13
19664994   Curated Info

43

Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64
19369195   Curated Info

44

Gauci S, et al. (2009) Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem 81, 4493-501
19413330   Curated Info

45

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

46

Chi Y, et al. (2008) Identification of CDK2 substrates in human cell lysates. Genome Biol 9, R149
18847512   Curated Info

47

Daub H, et al. (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31, 438-48
18691976   Curated Info

48

Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7
18669648   Curated Info

49

Ren H (2008) CST Curation Set: 3920; Year: 2008; Biosample/Treatment: cell line, OCUM-1/serum starved; Disease: gastric cancer; 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-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

50

Blethrow JD, Glavy JS, Morgan DO, Shokat KM (2008) Covalent capture of kinase-specific phosphopeptides reveals Cdk1-cyclin B substrates. Proc Natl Acad Sci U S A 105, 1442-7
18234856   Curated Info

51

Moritz A (2006) CST Curation Set: 1819; Year: 2006; Biosample/Treatment: cell line, SEM/Flt3 inhibitor; Disease: acute lymphocytic leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info