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Jeon BC, Kim YJ, Park AK, Song MR, Na KM, Lee J, An D, Park Y, Hwang H, Kim TD, Lim J, Park SK. Dynamic O-GlcNAcylation governs long-range chromatin interactions in V(D)J recombination during early B-cell development. Cellular & molecular immunology 2025 22(1) 39627609
Abstract:
V(D)J recombination secures the production of functional immunoglobulin (Ig) genes and antibody diversity during the early stages of B-cell development through long-distance interactions mediated by cis-regulatory elements and trans-acting factors. O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins that regulates various protein functions, including DNA-binding affinity and protein-protein interactions. However, the effects of O-GlcNAcylation on proteins involved in V(D)J recombination remain largely unknown. To elucidate this relationship, we downregulated O-GlcNAcylation in a mouse model by administering an O-GlcNAc inhibitor or restricting the consumption of a regular diet. Interestingly, the inhibition of O-GlcNAcylation in mice severely impaired Ig heavy-chain (IgH) gene rearrangement. We identified several factors crucial for V(D)J recombination, including YY1, CTCF, SMC1, and SMC3, as direct targets of O-GlcNAc modification. Importantly, O-GlcNAcylation regulates the physical interaction between SMC1 and SMC3 and the DNA-binding patterns of YY1 at the IgH gene locus. Moreover, O-GlcNAc inhibition downregulated DDX5 protein expression, affecting the functional association of CTCF with its DNA-binding sites at the IgH locus. Our results showed that locus contraction and long-range interactions throughout the IgH locus are disrupted in a manner dependent on the cellular O-GlcNAc level. In this study, we established that V(D)J recombination relies on the O-GlcNAc status of stage-specific proteins during early B-cell development and identified O-GlcNAc-dependent mechanisms as new regulatory components for the development of a diverse antibody repertoire.
O-GlcNAc proteins:
MPEG1, CUL4B, DHX8, RHG27, VIR, PNISR, FRPD1, RENT2, LAS1L, ITIH4, THOC2, MMRN1, PYR1, YTDC2, PTPRB, ANR44, RBM25, OSBL8, DAAF5, SAFB1, KI67, DESP, YTDC1, UBE4A, NUMA1, MORC3, HXK2, LEG9, KNG1, UBE3A, DCTN1, DIAP1, U5S1, RL21, PHB2, CPSF2, DHX15, EXOC4, STAG2, AP1B1, PININ, HNRH1, SP100, GP1BA, ITB3, RL35A, SPT5H, DHX9, E41L2, BAZ1A, ZFR, ROA2, PRS6A, FA5, AFAM, COR1A, SP1, C1QR1, COX2, AMY1, CO3, CO4B, B2MG, HBA, HBB1, K1C10, K2C1, CFAB, ALDOA, TBA1B, TBA3, ITAM, K1C18, LDHA, LCK, APOA4, PTPRC, CFAH, TTHY, ANXA2, ALBU, A1AT1, SPA3K, HS90A, TRFL, ENPL, APOE, MDHM, GNAI2, RPB1, ITB1, PDIA1, NUCL, APOA2, PTPRQ, CALM2, EF1A1, 4F2, PARP1, PERM, FINC, HS90B, K2C8, ITA5, ITB2, TCPA, RL7A, GELS, ICAM1, DNMT1, S10A6, RL27A, RS16, RL7, RSSA, LMNB1, ANXA6, RLA0, CD44, LEUK, H12, CN37, AMPE, HS71L, G3P, LAMP2, HSP72, ENOA, PTBP1, PPIA, TPIS, LYZ1, PCNA, PTPRA, BASI, KS6A1, KS6A3, COF1, FAS, THRB, RL13A, BIP, VIME, PLMN, VTDB, A1AT2, CBL, AP1G1, EIF3A, EST1C, ITAL, CD11B, MCM3, RS2, CD19, UBF1, TLN1, EZRI, MOES, KLKB1, H2AX, VAV, NCKP1, MUG1, KIF2A, DPP4, PTN6, FETUA, C5AR1, CEAM1, CD68, ANT3, SYWC, KIF4, DPOLA, RAB5C, RAB18, CD22, TSP1, CALX, RFC1, PRDX1, RL12, RL18, DNLI1, GRP75, DYN2, RL28, MMP9, STAT1, STA5B, EPS15, TCPQ, MSH2, H14, H15, RAGP1, SIPA1, NSF, PRS7, BRCC3, NEDD4, CAPZB, RL6, RL5, RL13, RL36, KSYK, PERE, ROA1, MCM4, MCM5, SAHH, K2C6A, VATA, PA2G4, RAB7A, RL9, ADT2, IMA1, PON1, DPOD1, UBP10, KPYM, STAT6, RL10A, CEBPZ, PIPNB, MSH6, UBP5, ATPB, UBP25, NICA, ACTN4, EF2, OPA1, FOXP1, TPM2, WDHD1, ARPC4, RUVB1, PCBP1, ACTB, IF4A1, RS20, UB2D3, ARF3, RL26, RL27, RL37A, ARF4, HNRPK, RS7, PRS4, RS8, RS15A, RS14, RS23, RS18, RS11, RS13, SMD2, ARF6, PRS10, RS4X, RL18A, RL23A, RS6, H4, VATB2, RAB1A, RAN, RL23, RS24, RS25, RS26, RL30, RL31, RS3, RL8, PROF1, RL40, HSP7C, PHB1, RL22, RACK1, ACTS, TBA4A, TBB4B, 1433F, IMB1, M4K1, PKN1, STIM1, PYRG2, ROCK1, RAD50, PYRG1, TCPH, TCPB, TCPD, TCPE, TCPZ, TCPG, WNK1, RHOG, RL19, H33, BACH2, MCM2, MCM6, RS3A, ANX11, SMRC1, FUMH, ARVC, TBB5, APOA1, A1AT4, TYY1, HNRL2, LYAM3, TOP2A, APOH, TERA, UBA1, PLAK, ATPA, IKZF1, SPA3M, SMRCD, TOP1, RAC2, PYC, IF2P, CBG, ACADS, AMBP, PECA1, SSRP1, ZCH18, K2C80, PSA, PTCD3, NSUN2, EDEM3, MCM9, TMC5, HMHA1, HP1B3, GUAA, H2AV, SMCA4, PRC2C, MIDN, K1C26, K22E, PSMD1, BRE1B, ESYT1, AAK1, RHG17, EDC4, UBP19, GPD1L, ELNE, SC31A, IQGA2, K22O, ITB2L, C1TM, UN13A, PLCH1, PDS5B, CENPJ, DDX46, TR150, A16A1, EHMT1, MCTP2, RBM27, CYFP2, PSME4, MYO1G, LC7L3, PUR4, MYH1, LEO1, SIN3A, XRCC1, ODO1, HNRPD, SAMH1, HELLS, ARHG2, I17RA, PML, 2A5G, PPM1G, CFAI, CERU, CTCF, PRDX2, EZH2, HCFC1, PA1B3, ARHG1, PLSL, A2AP, HSP74, DSG1A, GSLG1, EWS, RAD21, FSCN1, GDIB, DDX5, HS105, ITIH2, ITA6, EI2BD, SERA, KINH, PDCD4, PZP, PRG2, MYH10, MCM7, NPM, PCBP2, CTR9, DDX3X, CD180, SPTB2, SPR1A, TIF1B, TFR1, RU17, SPT6H, NDUA4, IF4G2, MINT, RHG30, H2B1B, TOP2B, TPP2, AT2A3, H2A2C, VINC, PUR2, CLH1, SYMC, GNPTA, PDS5A, CDC5L, CE290, F120A, UBP7, JADE3, K1C42, K2C72, SR140, K2C73, S23IP, IF4G1, RBM26, P4R3A, U520, ABCF1, SMHD1, UGGG1, XPO1, ANO6, KIF15, KIF11, FHOD1, FKB15, PTN23, LPPRC, SMRC2, ECM29, CHD4, PK3C3, NUP98, GMIP, NFRKB, TEX2, UBE2O, KDM3B, CE162, CNOT1, CAND1, LARP1, VIP2, RS9, RL35, RS27L, 2AAA, SND1, ASAP2, IPO8, HUWE1, LC7L2, MBB1A, INT7, CTDP1, PP6R1, ELP1, DCAF1, CLAP1, SCRIB, PUM1, NU214, NAA15, FACD2, FBLL1, UBP2L, SYMPK, SIG10, DDX42, ANFY1, EFTU, TNPO1, ROA3, PLD4, SYAC, S2512, NU107, PTBP3, NRDC, ERC6L, GANAB, SP130, NUP93, SUN2, RCC2, IPO5, EMSY, ODP2, RBGPR, SYLC, SYQ, ECHA, RL24, CLAP2, CNDH2, PB1, FLNA, SYIC, IFIX, CIP2A, GEMI5, UBP47, CTL2, TBCD, POGZ, ANC2, KS6A5, EFL1, LCAP, DOCK8, CND2, IWS1, RBM14, DOCK2, UBA6, MIC60, UFL1, VCIP1, NUP88, NED4L, RPB2, AQR, SMC4, SMC2, SYEP, TCRG1, LONM, OGT1, CHERP, CCAR1, INT5, PYGB, COPA, PLCG2, INT4, EIF3B, BCLF1, K319L, URP2, DNM1L, NEK9, FCHO1, PAF1, IPO11, CND1, MATR3, PLCL2, DP13A, PO121, SF3A1, HNRPL, NU133, EIF3C, BST2, CD177, ADIPL, CDC16, STPAP, LRC8C, ACSF2, EVI2B, MYH9, UHRF1, VIGLN, ADPGK, PSMD2, HNRL1, AT1A1, MICA1, CCAR2, DX39A, SRSF4, K2C79, RFA1, HNRPU, S25A3, RBM39, SEC63, IPO4, SFPQ, ACLY, IF4A3, NDUS1, ATPG, DDX1, UBAP2, HEMO, IPO9, RBM5, PRP6, SMCA5, SP16H, TADBP, SF3B3, SYDC, PP6R3, C1TC, NOP2, PDE2A, KIF2C, K2C5, SIR1, XPO5, SMRD2, ECHB, ARP3, EMIL1, UN45A, ACON, DPP3, HSP7E, GTPB4, ARBK1, SRRT, SF3B1, NU155, RRBP1, DHX30, RL17, NUDC2, 6PGL, COTL1, RM18, TRAP1, AT5F1, RL14, XPOT, PRPS2, RRP44, SMC1A, SMUF1, SMC3, PUR9, SNX2, ROA0, RL11, GARS, RL15, MTREX, MMS19, HNRPM, SYRC, NH2L1, RL34, GRIFN, UB2V2, S10AE, CORO7, STAG1, CUL5, SC23B, CALL3, NOP56, RL4, EF1G, PRP4, QCR2, PELP1, AP2B1, XRN2, NVL, EIF3K, 6PGD, SYF1, EIF3F, XPO7, IPO7, RENT1, BCAP, PESC, ERAP1, VPS35, EHD4, TFP11, XPO2, PKHA2, RBP2, UBE4B, SHIP1, HRG, XPO4, AN32B, GTF2I, DYHC1, STK4, COPB, DDX21, ACINU, FLII, IQGA1, HYOU1, HIP1R, FMNL1, SACS, SART3, GIT2, MY18A, ITA2B, FAK2, CAF1A, K1C17, FETUB, PLEC, PO210, ADDA, PCLO, COPG1, UBQL2, H2AY, ZEB2, GALK1, SC11A, MTA2, PR40A, TIM, MYO1C, INSRR, MD1L1, PDC6I, PFKAP, CXA10, GANP, IF2G, ADNP, P5CS, SAE2, ARI1, DX39B, CLIC1, SYVC, AP3B1, ILF3, USO1, HNRPC, BAZ1B, K1C16, SNUT1
Species: Mus musculus
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Hao Y, Li X, Qin K, Shi Y, He Y, Zhang C, Cheng B, Zhang X, Hu G, Liang S, Tang Q, Chen X. Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network. Angewandte Chemie (International ed. in English) 2023 62(17) 36852467
Abstract:
Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. Herein, we report the identification of 979 O-GlcNAcylated proteins and 1340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. Transcriptomic profiling reveals 2456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to mESC fate determination.
O-GlcNAc proteins:
AMRA1, SETX, SKT, BCORL, AGRIN, MGAP, ARI1A, KANL3, CHD6, PHRF1, ZCH24, EP300, KIF7, KI67, CE350, ANR11, NUMA1, TPR, MORC3, TAF4B, KMT2B, EMD, AKAP1, TCOF, DCTN1, MNT, NCOA3, ATN1, ECP3, DPOD2, CTND2, PIAS3, AF10, ACK1, GET3, DSG2, ESS2, ATX2, PDLI1, ULK1, BARD1, KDM6A, ZN106, NSD1, ZFR, HIPK1, SETB1, LAMC1, MYCN, GCR, EGR1, RC3H2, ATX1L, DERPC, K2C8, HSPB1, JUND, FGFR1, G3P, ATF2, COF1, HEXB, VIME, PO5F1, CBL, CCNB1, PO2F1, RS2, NFKB1, MAX, PABP1, NEDD1, PTN12, FMR1, ELK1, FOXK1, STAT3, SOX15, PLIN2, CBP, NEDD4, YAP1, RFX1, SOX2, LMNA, ROA1, S1PR2, ARNT, RD23A, PLTP, KMT2A, KLF16, FOXP1, TB182, GMEB2, SENP1, YTHD1, MRTFB, DOCK4, STIM1, TBX3, NCOA1, ERF, SIAE, NACAM, ATF1, WNK1, G3BP2, DNLI3, G3BP1, RLA2, GABPA, S30BP, ZEP1, ENAH, SOX13, CAPR2, APLP2, CLUS, TLE3, GATA4, MITF, CHD8, ZCH18, TANC1, CDK12, SAP25, LIN41, MLXIP, HROB, VRTN, CO039, PDLI7, SMCA4, PRC2C, MILK2, MIDN, YETS2, PBIP1, FUBP2, TFPT, SRBP2, GSE1, F117B, ZN865, WDR62, QRIC1, FOXK2, RREB1, TNR6C, DAB2P, TNR6A, RHG17, PKHA7, COBL1, FCHO2, TET1, ARMX5, GARL3, TET2, CDV3, PHAR4, C2CD3, LIN54, NPA1P, TAB3, TASO2, RESF1, NUFP2, UNKL, COBL, KDM6B, PRSR1, SMG7, RBM27, PHF12, ZDBF2, PUR4, SYNRG, UIMC1, SIN3A, NFAC2, SRC8, SKIL, ELF1, KLF4, NCOR1, KLF3, NCOA2, FOXD3, PAPOA, HCFC1, P3C2A, SIX4, ZFHX3, TOB1, AP180, GLI3, ATRX, MAFK, NPM, M3K7, DAG1, SPTB2, TAF6, TIF1B, SPT6H, SH3G1, ARI3A, TLE1, TLE4, IF4G2, MINT, ZIC3, ZYX, NUP62, PHC1, TFE3, TIF1A, SF01, DAZL, RBL1, KNL1, BCL9L, SBNO1, SLAI1, PKP4, CDK13, SH3R1, JHD2C, HECD1, ARMX2, LAR4B, RHG21, HELZ, SCAF8, UTF1, PKHG2, NIPBL, CCD66, F135A, RPRD2, WWC2, ZN532, KRBA1, TAF9B, RBM26, INT1, BCR, AHDC1, PTN23, PAPD7, KDM3A, KMT2D, CHD4, RN220, NUP98, NFRKB, GGYF2, LCOR, TEX2, PF21A, KDM3B, FNBP4, CNOT1, LARP1, RHG26, NU188, CNDD3, PICAL, SPAG5, HUWE1, SMAP2, CPEB3, MYCB2, PRC2B, PRR14, MACOI, ATX2L, CKP2L, PRC2A, MCAF1, SI1L2, KANL1, ERBIN, R3HD2, RERE, PUM2, PUM1, NU214, WNK4, TCAM1, SAS6, CAMP3, UBN2, TNC18, AGFG2, UBP2L, WNK3, ZN598, CTIP, SHAN2, NANOG, DDX42, RHG32, VGLU3, LPP, TET3, MYPT2, IF4B, CNO10, MISSL, TB10B, CARF, TGO1, ZN879, SP130, ZC3HE, ZNT6, SUN2, TNR6B, ARI5B, EMSY, BNC2, KAT6B, KMT2C, CLAP2, CNOT4, SRRM2, TOX4, GEPH, SYP2L, LARP4, KANK2, SALL4, YTHD3, TOIP2, KAT6A, ASXL2, POGZ, SREK1, TAF5, ZHX2, EPC2, SI1L1, CND2, RBM14, SUCO, CNOT2, DIDO1, SMAG1, LENG8, CDAN1, DPPA4, LRIF1, VCIP1, MB214, TAB1, SCYL2, ASPP2, LS14B, SYEP, F193A, BCOR, OGT1, SUGP1, NAV1, SYNJ1, ADNP2, RPGF2, BICRL, EP400, PHC3, VP37A, EPN2, P66A, PDLI5, ELYS, ZBT20, ANLN, AGFG1, MATR3, CASC3, I2BPL, PO121, ALMS1, SF3A1, GRHL2, ATF7, CACL1, DC1L1, MTSS1, SPART, TDIF2, HBP1, NUP58, RFIP5, BRD8, WIPI1, CDK8, CS047, ATX7, NUP35, LUZP1, RPAP2, NDC1, MAVS, AMOT, CSKI2, P66B, TAF9, IPO4, ZCH14, UBAP2, NCOA5, FUBP1, RBM47, AJUBA, VPS36, DCP1A, EGLN2, YTHD2, SRGP2, GRHL1, BCL7B, P4R3B, PLRG1, CIC, WAC, TRPS1, MED1, ACATN, NRBP, RP25L, NONO, TAB2, RBM10, EPN4, DDAH2, NOG2, ZN281, HGS, NASP, ARIP4, ANR17, ZN318, TRI33, MZT2, ZWINT, ECD, YIF1B, ROA0, DHRS7, TPD54, SSBP3, PSRC1, SARNP, BCL9, SP2, NOP56, SH24A, FIP1, PLIN3, MYPT1, KC1D, TCF20, TOR3A, SALL1, ZN704, RBP2, UBE4B, TBX20, AFF4, RBCC1, 4ET, PALLD, ELF2, TSSC4, NUDT3, HAKAI, ADRM1, NCOA6, FANCA, GIT2, BAG3, TOB2, ZN207, SON, TBL1X, PLEC, MACF1, GOGA5, QKI, GAB1, DMRT1, YLPM1, PCM1, RHG07, TAF7, FOXO1, ADA23, AKA12, UXT, MAN1, NCOR2, AKT3, COR1B, TNIP1, GANP, DEMA, CARM1, RGAP1, ITSN2, ZO2, KLF5, ADNP, ARI3B, BCL3, SE1L1, E41L1, ZN292
Species: Mus musculus
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Chuh KN, Batt AR, Zaro BW, Darabedian N, Marotta NP, Brennan CK, Amirhekmat A, Pratt MR. The New Chemical Reporter 6-Alkynyl-6-deoxy-GlcNAc Reveals O-GlcNAc Modification of the Apoptotic Caspases That Can Block the Cleavage/Activation of Caspase-8. Journal of the American Chemical Society 2017 139(23) 28528544
Abstract:
O-GlcNAc modification (O-GlcNAcylation) is required for survival in mammalian cells. Genetic and biochemical experiments have found that increased modification inhibits apoptosis in tissues and cell culture and that lowering O-GlcNAcylation induces cell death. However, the molecular mechanisms by which O-GlcNAcylation might inhibit apoptosis are still being elucidated. Here, we first synthesize a new metabolic chemical reporter, 6-Alkynyl-6-deoxy-GlcNAc (6AlkGlcNAc), for the identification of O-GlcNAc-modified proteins. Subsequent characterization of 6AlkGlcNAc shows that this probe is selectively incorporated into O-GlcNAcylated proteins over cell-surface glycoproteins. Using this probe, we discover that the apoptotic caspases are O-GlcNAcylated, which we confirmed using other techniques, raising the possibility that the modification affects their biochemistry. We then demonstrate that changes in the global levels of O-GlcNAcylation result in a converse change in the kinetics of caspase-8 activation during apoptosis. Finally, we show that caspase-8 is modified at residues that can block its cleavage/activation. Our results provide the first evidence that the caspases may be directly affected by O-GlcNAcylation as a potential antiapoptotic mechanism.
O-GlcNAc proteins:
A2A4A6, A2A5R8, GPTC8, SPD2B, A2ACG7, A2AFQ9, A2AFW6, A2AG46, CKAP5, A2AH75, A2AJ72, MA7D1, A2AL12, A2AMW0, A2AMY5, TPX2, PPIG, LAS1L, A5A4Y9, A6PWC3, A6PWK7, UBP36, B1AT03, B1AT82, B1AU75, B2RQG2, OTUD4, B7ZCP4, B7ZP47, D3YUW8, D3YWF6, D3YWK1, D3YX62, SAFB1, D3YXM7, D3YZ06, D3YZP6, D3Z069, D3Z158, D3Z3F8, D3Z6W2, E0CYM1, E9PUH7, E9PVM7, E9PWG6, E9PWV3, E9PWW9, E9PY48, E9PYT3, E9PZM7, E9Q066, E9Q2X6, E9Q3G8, E9Q450, E9Q4K7, E9Q4Q2, KIF23, BD1L1, NUMA1, E9Q7M2, E9Q986, E9Q9E1, E9Q9H2, E9QKG3, E9QKG6, E9QKZ2, E9QLA5, E9QP49, E9QP59, E9QPI5, F2Z3X7, F6S5I0, F7AA26, F7BQE4, FARP1, F8VQ93, F8VQC7, F8VQE9, F8VQK5, F8WI30, G3UZ44, G3UZX6, G3X8R0, G3X8Y3, G3X928, G3X963, G3X972, G3X9V0, G5E896, G5E8E1, H3BJU7, H3BK31, H3BKK2, H7BX26, I1E4X0, I7HIK9, J3QNW0, DPYL2, GTPB1, AKAP1, TCOF, AIP, HDAC1, RL21, GSH0, KIF1C, DHX15, SC6A6, IF6, ILK, ATX2, NMT1, E41L2, DHB12, SRPK1, ZN326, ZFR, PARG, SPD2A, SP1, CASP8, HPRT, LDHA, G6PI, TYSY, RIR1, GNAI2, ITB1, 4F2, H2B1F, MAP1B, HMOX1, LEG1, G3P, KS6A3, COF1, GNAO, IFRD1, VIME, UBL4A, CBX3, CXA1, CATA, IMDH2, IL1RA, MCM3, CDK4, NKTR, FKBP4, CBX2, HMGB2, AIMP1, KAP3, MP2K1, SYWC, KIF4, NEDD1, DPOLA, RANG, UBP4, PTN11, RAB18, PTN1, PTN12, LDLR, DNLI1, CAP1, STAT3, STA5B, PURA, ALD2, RAGP1, NEDD4, STT3A, ALDH2, GSHR, GFPT1, PCY1A, MCM4, ICAL, PLCB3, CDN2A, HDGF, UBP10, KPYM, CCHL, IDHP, DDX6, GOGA3, COX17, ACTN4, GCP3, TB182, EIF3E, ABCE1, PFD3, 1433E, RAP1A, RS25, TCTP, DNJA1, HMGB1, IF5A1, RS17, RS12, UB2L3, HXD13, HDAC2, ELAV1, TP53B, CASP3, PYRG1, TCPB, STIM2, SRSF3, CSRP2, SPTC2, BOP1, SMAD4, M4K4, HNRL2, MARK3, LARP7, CNN2, PP4R2, PEPD, CDCA2, Q3TFP0, GUAA, PDE12, Q3TL72, PRC2C, NOL9, FUBP2, TRADD, CTU2, ZN865, Q3U4W8, Q3UG37, NAT9, NOL8, Q3UJQ9, SC31A, NCBP1, LRRF1, DDX17, LRC47, JIP4, EHMT1, CA050, AAPK1, NSRP1, Q5RL57, Q5SQB0, TENS3, PUR4, Q5UE59, SRC8, SAMH1, KHDR1, GRB10, HELLS, SPB6, RIPK1, CAPR1, ASNS, LAP2A, CDC37, TS101, SNTB2, FNTA, BAP31, PLPP1, FSCN1, FXR1, DDX5, ATRX, DDX3Y, DDX3X, TGFI1, DBNL, SH3G1, CYTB, SMAD2, NDRG1, ZYX, SQSTM, TPP2, ZN512, LAR4B, F120A, CNDG2, NOP58, LTV1, Q6NV52, Q6NXL1, Q6NZD2, ANKL2, Q6P5B5, XPO1, KIF15, FHOD1, TXLNA, PTN23, JUPI2, NUDC1, TACC1, UBE2O, LARP1, ACAP2, 2AAA, MTCH2, ZN503, CYFP1, HNRPQ, SPAG7, DEK, ACTN1, ATX2L, CKP2L, ZN516, ERBIN, SEPT9, PGRC2, Q80VB6, UBP2L, PI42B, ZN598, SAFB2, Q80ZX0, DLG1, LPP, PEF1, IF4B, FTO, TIPRL, Q8BH80, MISSL, ERC6L, CARF, PRUN1, NUP93, FBX30, HBAP1, AHSA1, RCC2, IPO5, SYLC, CKAP4, MAP11, PALM2, CPNE3, SENP7, CSN7B, NSD2, DPP9, Q8BWW3, KANK2, PXK, PIGT, ITPK1, NHLC2, MAP1S, GWL, PKHH2, CND2, THOP1, SEP11, SKA3, CA198, SEP10, AROS, UBA6, LIPB1, SMAG1, Q8CCM0, ZN276, NAA30, SNX8, SYEP, OGT1, GNL3, PDLI5, FERM2, AGO2, HMCS1, AMERL, SCNM1, DNM1L, NEK9, ANLN, EDC3, MATR3, CHAP1, MEPCE, ERF3A, CC137, TDIF2, VPS18, RFC3, MCMBP, HEXI1, LUZP1, SNP47, TMX1, MAVS, UBXN4, Q8VCQ8, ACSF2, PARN, VIGLN, PSMD2, NAA40, F1142, ZNG1, PAXI, SFPQ, CPIN1, RAB14, IPYR2, PUS7, CSDE1, PIP30, RABE2, CISD1, Q91X76, DUS3L, KCC1A, TTC1, SRGP2, SNX18, RISC, HNRLL, Q921K2, PP6R3, LRC59, UBXN1, DBR1, KCC2G, Q924B0, WAC, SMC6, PAWR, SIAS, STML2, PSIP1, NXF1, PDXD1, NONO, PLST, RRAGC, VMA5A, MAOM, DCTN2, ZN281, CT2NL, GRPE1, ABD12, NU155, OGFR, NPM3, NOP16, GLOD4, DUT, MTAP, IFM3, CYB5B, PAF15, PSMD9, WIPI3, SKA2, VATG1, CHSP1, LRC40, RANB3, SMC1A, MFR1L, ARHGP, DDX47, TBC15, PPIL4, MPPB, CYBP, TECR, SERB1, ZCHC8, SPCS2, Q9CZP3, CD37L, SSBP3, MMS19, MGRN1, ARPIN, HNRPM, SYRC, MCES, Q9D4G5, ATAD1, F162A, TRIR, IPYR, PHF10, ARFG3, ORN, BOLA1, CNN3, KAP0, PLIN3, AKAP8, XRN2, GNAI3, PUR6, RAI14, SENP3, ARFG1, SIL1, VPS35, DGCR8, SYCC, ELP4, LIMA1, XPO2, RBP2, RTN3, PALLD, TMOD3, STK3, COPB, NUP50, DDX21, SH3L1, DDX20, MBNL1, BAG3, GKAP1, ZN207, TRXR1, PPCE, CAF1A, LIMD1, NDRG3, DNJC7, NFU1, COPG1, NUBP1, SMAP, DEST, ACOT9, PR40A, FOXO1, FIZ1, NFKB2, KAD2, AKA12, PRKRA, PDC6I, CHIP, COR1C, VAPA, NDKM, E41L3, TAGL2, CARM1, MTNB, BCL10, IF2G, P5CS, COG1, MD2L1, EIF3G, SAE2, ILF3, TRIP6, USO1, BAZ1B, HNRPF, KEAP1
Species: Mus musculus
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Trinidad JC, Barkan DT, Gulledge BF, Thalhammer A, Sali A, Schoepfer R, Burlingame AL. Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Molecular & cellular proteomics : MCP 2012 11(8) 22645316
Abstract:
O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic, reversible monosaccharide modifier of serine and threonine residues on intracellular protein domains. Crosstalk between O-GlcNAcylation and phosphorylation has been hypothesized. Here, we identified over 1750 and 16,500 sites of O-GlcNAcylation and phosphorylation from murine synaptosomes, respectively. In total, 135 (7%) of all O-GlcNAcylation sites were also found to be sites of phosphorylation. Although many proteins were extensively phosphorylated and minimally O-GlcNAcylated, proteins found to be extensively O-GlcNAcylated were almost always phosphorylated to a similar or greater extent, indicating the O-GlcNAcylation system is specifically targeting a subset of the proteome that is also phosphorylated. Both PTMs usually occur on disordered regions of protein structure, within which, the location of O-GlcNAcylation and phosphorylation is virtually random with respect to each other, suggesting that negative crosstalk at the structural level is not a common phenomenon. As a class, protein kinases are found to be more extensively O-GlcNAcylated than proteins in general, indicating the potential for crosstalk of phosphorylation with O-GlcNAcylation via regulation of enzymatic activity.
O-GlcNAc proteins:
A0JNY3, A2A653, A2A654, TANC2, ZEP3, MA7D2, CKAP5, CAMP1, LZTS3, A2AJ19, AJM1, MA7D1, A2ALK6, RPGP1, UBR4, A2AP92, SKT, ANR63, A2ATK9, A2AUD5, A2BI30, A6H6J9, A6MDD2, A8DUV1, B1AQX6, B1AR09, GRIK3, B1ATI9, B1AWT3, NHSL2, FRS1L, UBP24, DLGP4, B2RQ57, B2RQ80, PYR1, B2RQL0, B2RQQ5, GNAI1, B2RUE8, OTU7B, B2RWX1, B6ZHC4, B6ZHC5, B7ZCA7, B7ZMP8, B7ZNA4, B7ZNF6, B7ZWM6, B9EHE8, CTTB2, B9EKL9, PTPRZ, D1FNM8, D3YU59, D3YWX2, DGKH, D3YXR8, PGBD5, SHAN1, D3Z0V7, D3Z2J5, D9HP81, E0CYT1, E9PUA3, E9PUC4, DGKD, E9PUR0, E9PV14, E9PV26, KI67, E9PWL1, E9PWM3, E9PY55, E9PZP8, E9Q1M1, E9Q2B2, E9Q3D6, E9Q3G8, E9Q3M9, E9Q4N6, E9Q616, E9Q6T8, E9Q6Y8, NUMA1, E9Q828, E9Q9I2, E9Q9J6, E9QA16, E9QAP7, E9QAR5, SC16A, E9QJU8, E9QMJ1, SYGP1, RFIP2, HXK2, CAN2, SC22B, DPYL2, STXB1, TCOF, DCTN1, GLU2B, EF2K, PRDX4, AIP, NUMBL, GSTO1, GSH0, M3K5, PSMD4, DHX15, NPC1, BMPR2, VIAAT, BCAT2, CTND2, PITM1, CSK22, REPS1, ACK1, SLK, CAC1B, PGRC1, IMPA1, SYUA, AKA7A, STRN, RL35A, AT2A2, PGAM2, ATX2, NMT1, E41L2, GPX4, EMC8, DHB12, HCN4, KDM6A, ZN326, SORL, GRPE2, KLC1, ZFR, O88568, HCN2, HCN1, BSN, TOM1, RPP30, DNJB5, COX1, HA1D, HBA, K2C1, MBP, ALDOA, PGFRB, LDHA, G6PI, ENPP1, NEUM, ANXA2, RIR1, HS90A, EGR1, MDHM, KCC4, NFL, NFM, GNAI2, PDIA1, NUCL, CADH1, RC3H2, LRC4B, IGS11, DERPC, UBB, IFI5B, IFI4, ANXA1, EF1A1, H2B1F, PARP1, HS90B, DMD, KCC2A, TCPA, A4, COX5A, GELS, UMPS, NCAM1, GPDA, MDHC, SRP54, RLA0, GLNA, H12, LEG1, DDX3L, SPTN1, AP2A2, TPIS, KS6A3, COF1, GNAO, NFH, SERPH, VIME, MTAP2, EIF3A, CBX3, IMDH2, MCM3, CTNA1, MAP4, GNA12, GNA13, PDIA3, PSB8, NCKP1, PABP1, FKBP4, HMGB2, AIMP1, LA, ACM4, SYWC, RANG, RAB5C, RAB18, CALX, PRDX1, RL12, PPM1B, DNLI1, CAP1, STAT3, PURA, OPRM, TCPQ, CX6A1, MSH2, H14, H11, ALDR, ALD2, CBP, AINX, NEDD4, RP3A, CAPZB, SRPRB, RL36, SOX2, HS74L, ADT1, ROA1, INPP, PCY1A, MCM4, CSRP3, RAB7A, CDN2A, HDGF, ADT2, IMA1, UBP10, KPYM, RIDA, HMGA2, RL10A, CCHL, SOX1, RAB2A, ATX1, CACB3, HMCS2, GOGA3, ATPK, ATPB, ACTN4, IDI1, ACOT8, PTPA, KCNN2, KCNN3, TB10A, TB182, SF3B6, MRTFB, DOCK4, MYPR, EIF3E, PCBP1, LIPA3, ACTB, IF4A1, SNP25, RAB10, CSN2, RRAS2, PRS8, RS15A, 1433E, RS18, RS11, SMD1, ABI2, EF1A2, ACTA, VATB2, RL23, RS24, GBB1, HSP7C, TCTP, GNAS2, 1433Z, HMGB1, IF5A1, ACTG, RS17, RS12, UB2L3, RACK1, ACTS, TBA4A, TBA1A, TBB4B, PLXA2, DCC, EBP, NFIX, EM55, HNRH2, NCOA1, ELAV1, RGRF2, USP9X, TCPB, TCPE, TCPZ, NUCB2, IRS2, WNK1, RL36A, CSRP1, SEPR, RS3A, DPYL1, MPRIP, CAC1A, ATP5J, BOP1, RS5, WBP2, CXAR, PLPL9, G3BP1, RBBP6, CDS1, TBB5, IL6RB, NMDE2, NMDE3, TOP2A, NOTC1, NDKB, AQP1, UBA1, CTNB1, S30BP, NFIA, NUCB1, MARK3, APLP1, ENAH, ATPA, TF65, YES, MARK2, PGBM, PYC, CAPR2, EMAL1, LARP7, BAX, CNN2, LYAR, CHD8, CNNM1, INF2, TT21B, Q0IJ77, TRIO, VGF, TANC1, CDK12, Q14B66, MA6D1, NSUN2, MCM9, PHAR1, PSD3, Q2Q7P0, FILA2, Q3TAD4, NB5R4, GUAA, METK2, PRC2C, Q3TRG3, PLPL6, K22E, YETS2, Q3TY93, FUBP2, F117B, Q3U882, LBR, TM109, FOXK2, Q3UFK1, Q3UGZ4, TNR6C, DAB2P, ZEP2, AAK1, Q3UHT7, DTX3L, EDC4, PARP3, WASC4, GRIN1, Q3UQ23, SRBS2, THSD4, MRCKA, SPRY3, KSR2, GRM5, TBCD9, LRRF1, ARMX5, STOX2, SHAN3, UBN1, OXR1, DDX17, PHAR4, ANR28, ZN608, Q571B7, PRAG1, TAB3, Q58DZ3, IQEC2, Q5DU62, AAPK1, NUFP2, UNKL, SMG7, RBM27, CYFP2, TM1L2, PSME4, ANR40, Q5SUH6, GGNB2, SYNRG, Q5SVJ0, RPGP2, TBC9B, ACACA, Q5SXC4, Q5XJV5, LMTK3, RN123, ZDHC8, SRC8, MYL6, SKI, SAMH1, IRGM1, CLD11, NPT2A, SPB6, VDAC2, VDAC3, VDAC1, STYX, RBBP4, ASNS, NCOA2, LAP2A, PPM1G, ASTN1, PRDX2, HCFC1, APC, KCNA4, AP180, FXR1, GDIB, GRID2, GRID1, CBX5, SERA, LASP1, NPM, PCBP2, M3K7, SRBS1, DBNL, SH3G1, CYTB, IF4G2, MINT, ZYX, RALY, TFE3, Q640L6, AR13B, HECAM, NPDC1, SYN2, TBR1, ISG15, ABCG1, ATP4A, MRC2, G3PT, PTN13, TPP2, CTNA3, SBNO1, BEGIN, K1549, GIT1, SLAI1, PKP4, PEAK1, CDK13, SH3R1, MYOF, ABLM3, ARMX2, CE170, LAR4B, NOP58, Q6GR78, TPM4, NIPBL, RRP5, FBX41, Q6NVA3, RPRD2, WWC2, ZN532, Q6NXW0, S23IP, SMHD1, NEST, CSKI1, Q6P9N8, MTSS2, AHDC1, PTN23, TRAK1, SRSF1, CHD4, DLGP3, NUP98, NYAP1, KCC2D, AT1A3, AT1A2, NFRKB, RIGI, MAGI1, WDFY3, TACC1, GGYF2, PF21A, KDM3B, CNOT1, LARP1, Q6ZQB7, NU188, Q6ZQJ9, Q6ZQK4, RS9, RL10, IF2A, SC6A5, SEM6D, 2AAA, EEIG1, MTCH2, PICAL, MRO2B, SCN4B, PLPR4, HNRPQ, TBB2A, SMAP2, Q7TNS5, PLPR3, MBB1A, LNP, TPPP, ATX2L, OTUB1, EXOS3, MAP6, ELP1, SI1L2, LRRC7, ERBIN, PHF24, R3HD2, NAV3, AGRL3, Q80TS6, AUXI, MADD, AVL9, PUM1, UBP8, NU214, SEPT9, NAA15, CAMP3, FA98B, TDRKH, EPN1, TMCC2, AGFG2, UBP2L, Q80X68, C2C2L, FLNB, LRRT4, WNK3, PRIC2, CNKR2, ZN598, SHAN2, AGRB3, Q80ZX0, ZFYV1, MAST4, RHG32, ENTP3, LPP, PEF1, ACTBL, TET3, MYPT2, IF4B, SYAC, F168A, TBL1R, TB10B, CSTP1, CARF, TGO1, FRM4A, SYIM, ANS1B, DLGP2, ZNT6, RCC2, ABLM2, LSS, UNC80, NOE2, CF015, EMSY, ODP2, GGA3, SYLC, DMXL2, IMP2L, CLAP2, LIPA2, ASPH, CNOT4, FLNA, F163B, GEPH, CREST, KCC1D, PGES2, KANK2, GEMI5, IFFO1, OSBL6, YTHD3, TM266, POGZ, LACC1, MAP1S, A16L1, SI1L1, PP4R4, MYO9A, THOP1, RBM14, Q8C2R1, CNOT2, Q8C6E9, CC134, ANK2, ELFN1, DIDO1, NHSL1, WDR37, DCTN4, SYNPO, BCAS3, VCIP1, Q8CE98, TAB1, SCYL2, NED4L, SYEP, F193A, GNAL, OGT1, NAV1, SYNJ1, RPGF2, EP400, PHC3, P66A, TBCE, VWF, STAU2, LIN7A, TBC23, ZBT20, RTN1, HS12A, DNM1L, UNC5B, UNC5A, ANLN, AGFG1, MATR3, Q8K314, AHI1, NDUS8, I2BPL, PREP, ABLM1, EIF3L, ERF3A, HNRPL, IQEC1, DOCK7, DC1L1, SPART, BST2, RFIP5, AT2A1, NUP35, LUZP1, MAVS, MYH9, PARN, AT1A1, SIR2, SNRK, ZDHC5, CC50A, AMOT, AGAP3, MARK1, Q8VHM5, FLNC, SFPQ, CPIN1, WDR13, BACH, S12A5, RAB14, ACLY, MIC25, ATPG, DDX1, SH3L3, UBAP2, NCOA5, CSDE1, FRS3, ZFN2B, DLG2, PTBP2, SRGP1, TMLH, DYST, SYUB, ELOV6, ALS2, TADBP, TBB6, CLIP1, LRC59, K2C5, UBXN1, SIR1, SPRE1, PAWR, MED1, MEP50, STML2, UBP11, NONO, RRAGC, VMA5A, MAOM, DCTN2, NEUA, DDAH2, DNJA3, TRXR3, RB6I2, SRRT, DSRAD, Q99NC2, RIMS1, ANR17, NU155, NTRI, RRBP1, ZN318, TRI33, ATP5L, RL17, GLOD4, DUT, SDHB, GLRX3, IFM3, NECP1, OCAD1, RRP44, TBB2B, DDAH1, YIF1B, ROA0, NIP7, MPPB, CYBP, RL11, TECR, CHTOP, SERB1, QCR1, NNRD, GARS, TOM70, RS19, SYRC, CNDP2, TMEDA, ODO2, DLGP1, TBB4A, IDH3A, IPYR, RL37, FIP1, TIM50, EF1G, RM17, GSDMD, DDA1, F135B, TM263, CNN3, PLIN3, PGAM1, XRN2, MYPT1, DJC10, KC1D, GNAI3, PUR6, S38A3, NDUBA, CRIP2, TSC1, RAI14, NBEA, TCF20, SORC2, DPYL5, TBB3, RBP2, ARHG7, RTN3, SPN90, RBCC1, PSMG2, DDX24, CLD12, PALLD, ELF2, TMOD3, NUDT3, COPB, NUP50, DDX21, TULP4, FLII, RPF2, CCG3, TBA8, IQGA1, NECT1, ADRM1, FMN2, PALS1, DCLK1, BAG3, CUL3, MINK1, REEP6, TRXR1, SYGP1, SON, APBB1, DREB, SPY2, MACF1, ULK2, ZBP1, TOM40, ADDA, GOGA5, DNJB1, MAP1A, PCLO, GAB1, RIPK3, NPAS3, SH2D3, NUBP2, ZEB2, SYT7, DEST, TEBP, SRS10, RPGR, PR40A, KHDR3, TPSN, CDYL, KAD2, TEN1, PDC6I, CHIP, IF4H, COR1B, COR1C, TNIP1, GANP, ARC, MPP2, SHAN1, VAPA, GSK3B, DEMA, E41L3, JIP1, GBP2, CAD20, P5CS, LAT1, DYR1B, MD2L1, SAE2, APCL, SYVC, MTMR1, MECP2, E41L1, SUCB1, HDAC6, GRIA4, HOME1, OSB10
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