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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, HSPA9, 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, SYMPK, SIG10, DDX42, ANFY1, EFTU, TNPO1, ROA3, PLD4, SYAC, S2512, NU107, PTBP3, NRDC, ERC6L, GANAB, SP130, NUP93, SUN2, RCC2, IPO5, 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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Jaiswal R, Liu Y, Petriello M, Zhang X, Yi Z, Fehl C. A reference dataset of O-GlcNAc proteins in quadriceps skeletal muscle from mice. Glycobiology 2025 35(3) 39927985
Abstract:
A key nutrient sensing process in all animal tissues is the dynamic attachment of O-linked N-acetylglucosamine (O-GlcNAc). Determining the targets and roles of O-GlcNAc glycoproteins has the potential to reveal insights into healthy and diseased metabolic states. In cell studies, thousands of proteins are known to be O-GlcNAcylated, but reference datasets for most tissue types in animals are lacking. Here, we apply a chemoenzymatic labeling study to compile a high coverage dataset of quadriceps skeletal muscle O-GlcNAc glycoproteins from mice. Our dataset contains over 550 proteins, and > 80% of the dataset matched known O-GlcNAc proteins. This dataset was further annotated via bioinformatics, revealing the distribution, protein interactions, and gene ontology (GO) functions of these skeletal muscle proteins. We compared these quadriceps glycoproteins with a high-coverage O-GlcNAc enrichment profile from mouse hearts and describe the key overlap and differences between these tissue types. Quadriceps muscles can be used for biopsies, so we envision this dataset to have potential biomedical relevance in detecting aberrant glycoproteins in metabolic diseases and physiological studies. This new knowledge adds to the growing collection of tissues with high-coverage O-GlcNAc profiles, which we anticipate will further the systems biology of O-GlcNAc mechanisms, functions, and roles in disease.
O-GlcNAc proteins:
A0A087WS16, A0A0N4SUN5, A0A286YCS6, A0A5F8MPM4, A0A5F8MPQ4, A0A668KL51, A0A7N9VR94, A2A6J0, A2A6Q8, OBSCN, A2AEX6, A2AI87, A2AKD7, TITIN, KLH41, ARMT1, OSBL8, SHAN1, D3Z0V7, D3Z2B4, CD054, E0CZE0, E9PYG6, E9PYI8, E9PZD8, RYR1, E9Q1W3, NU153, E9Q3P4, RN213, E9Q616, TRDN, E9QL12, E9QN70, E9QND8, F6QYF8, F6VY18, F6YT88, F8VPN4, F8WGD9, MYH2, G3UYC5, RGS22, G3X972, AT2B1, G5E895, G5E8L1, G5E8R7, H7BWZ9, J3QN31, M0QW57, HXK2, CA2D1, PRDX6, DLDH, HCD2, MK12, SYPL1, CASQ1, PHB2, CAN1, CALU, CAVN1, IMPA1, NIPS2, AT2A2, PDLI3, PGAM2, PDLI1, RTN2, NTR1, WDR1, PLIN4, ZFR, SEM3F, ACTN3, SYPL2, CAH2, CO3, LAMC1, NU5M, ATP8, FABP4, MYG, ALDOA, KAPCA, AATC, AATM, TBA3, LDHA, MAOX, KCRM, ANXA2, A1AT1, SPA3K, HS90A, PHKG1, SODC, MDHM, ITB1, PDIA1, PGK1, MYL3, SODM, UBB, CALM3, ANXA1, EF1A1, CATB, TAU, GSTM1, H2B1F, H10, FINC, FABPH, DMD, COX5A, TNNI2, MYH3, MYH8, CAH1, GPDA, RL7, MDHC, HSPB1, ANXA6, GLNA, B4GT1, H12, CAH3, LEG1, LDHB, HS71L, G3P, ENOA, PPIA, TPIS, CATD, COF1, FAS, GSTP1, SERPH, COX5B, COX41, BIP, VIME, TNNC2, PLMN, ENOB, VTDB, CLK1, EST1C, RS2, TLN1, RADI, DHE3, FKB1A, MAP4, PLAP, PDIA3, ADHX, KCC2B, PGS2, MUG1, PABP1, DESM, AIMP1, PRVA, UBP4, ODPA, FAAA, PRDX1, RL12, HSPA9, CAP1, ACSL1, ECI1, STA5B, H14, H11, H15, H13, ALDR, COF2, ACADM, MYO1B, ALDH2, CAZA2, PFKAM, CACP, RL5, CBR1, ADT1, SAHH, CSRP3, ACADV, FMOD, ACADL, CAV3, ADT2, EAA3, AAAT, KPYM, CPT2, ODB2, MOT1, IDHP, STMN1, RD23B, PUR8, ADK, ACYP2, CX6B1, UBP5, ATPB, UCP3, EF2, TPM1, IRPL1, ACTB, CDC42, RAB5B, RAB10, UB2D1, 1433G, RS7, PP1B, 1433E, RS11, EF1A2, H4, RAB1A, RAN, RL23, CYC, RS3, YBOX1, RAC1, LIS1, HSP7C, CH60, 1433Z, HMGB1, IF5A1, ACTS, TBA4A, TBB4B, MP2K6, PEBP1, STIM1, HINT1, MYBPH, NACAM, TCPH, TCPB, TCPD, TCPE, TCPZ, SGCB, WNK1, ARF5, ISC2A, CSRP1, RS3A, SPSY, MYL11, FUMH, LYPA1, ARVC, PRDX5, XDH, NDKB, TERA, UBA1, CAC1S, ATPA, CO6A1, PGBM, PYC, ACADS, KCMA1, PADI2, CD36, Q14BI5, FAT4, CNNM3, Q3TCF3, PDLI7, PRC2C, SCRN3, DDB1, K0930, Q3UER8, LIMC1, PRRC1, EID3, AMPD1, Q561M1, MYPN, Q5F247, MLIP, Q5MJ56, CLU, MYH4, MYH1, UBR3, MYPC2, ODO1, LAMA2, COCA1, STIP1, REEP5, VDAC2, VDAC3, VDAC1, COQ8A, PRDX2, HCFC1, LAMB2, HSP74, HCDH, FBN1, GDIB, PZP, NNTM, DDX3X, MYOM1, SPEG, NDUA4, NUP62, AT2A3, GPDM, VINC, PUR2, CLH1, MYOF, HECD1, F120A, HELZ, Q6NVF7, IF4G1, Q6P1B9, Q6P6L5, KCRS, LPPRC, KMT2D, AT1A2, Q6S9I0, CAND1, CAND2, CMYA5, VWA2, TLN2, 2AAA, MIC27, Q7TPG0, MBB1A, SRCA, ATX2L, Q7TQS8, KPBB, Q80T54, NU214, PANK4, Q810Q0, EFTU, H2A3, LPP, PSD11, S2512, ECHM, EIF2A, ODPX, MAON, ODP2, ECHA, Q8BPI2, Q8BUY2, DHPR, SYP2L, THIM, STAC3, ASGL1, TLK1, PRR33, STBD1, MIC60, SYNPO, CPLN1, SYEP, UN45B, PGP, DRS7C, EI2BE, PDLI5, AGO3, EFGM, FIBB, COQ9, SDHA, VRK3, NNRE, HIBCH, THIL, AIMP2, BLMH, CMBL, UBQL1, TSN8, SLF1, CACB1, AT2A1, CLYBL, PRAF3, LSM1, MAVS, MYLK2, EST1D, MYH9, PSMD2, HNRL1, LMCD1, HNRPU, S25A3, FLNC, NDUS1, RINI, ATPG, DDX1, UBAP2, NDUS2, CISD1, SH319, HEMO, SYNP2, NDUV1, MYH7, PCCA, UGPA, ETFD, MACD1, C1TC, CLIP1, MPI, CPT1B, TALDO, THTM, GORS2, ECHB, ACON, NAMPT, 3HIDH, DHRS4, NDUAA, ETFA, PARK7, ASPN, MCCA, PPR3A, GDIR1, LGUL, NDUC2, DECR, NDUA2, SDHB, TMED6, GLRX3, AT5F1, ACO13, RL14, NDUB7, M2OM, UCRI, CHSP1, SFT2C, PUR9, SGT1, CENPV, SERB1, SPCS2, QCR1, NSF1C, CISY, ODPB, PGM1, SCOT1, GAL3A, RAB1B, ODO2, NDUV2, FUND2, IDH3A, RL4, EF1G, CA074, ATPO, PXL2B, QCR2, ACDSB, MYPT1, Q9DBT6, DCAF6, OCTC, NDUA9, NDUA8, PUR6, NDUBA, NDUS3, ETFB, ATP5H, MIC26, MMSA, RB27A, JPH2, JPH1, IVD, DYHC1, NIT2, ACTN2, MYOTI, PROF2, MYOZ1, PRELP, YBOX3, MBNL1, LDB3, HIG1A, TRXR1, B4GT5, PPCE, PLEC, S2513, NDRG2, DNJA2, UBQL2, FHL3, GLYG, ESTD, KAD1, PDC6I, PYGM, SUCA, ECI2, SH3BG, ARC1B, ABEC2, VAPA, AIFM1, GYS1, STRAP, LETM1, SUCB1, S4R1W1
Species: Mus musculus
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Hao Y, Li Z, Du X, Xie Q, Li D, Lei S, Guo Y. Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model. Molecular medicine (Cambridge, Mass.) 2025 31(1) 40021952
Abstract:
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been found to affect the processing of several important proteins implicated in ALS. However, the overall level and cellular localization of O-GlcNAc during ALS progression are incompletely understood, and large-scale profiling of O-GlcNAcylation sites in this context remains unexplored.
O-GlcNAc proteins:
TANC2, ZEP3, MA7D2, AMRA1, AJM1, CNTRL, SKT, TITIN, ARI1A, S14L1, KI16B, TM245, RHG42, CTTB2, SAFB1, CCDC6, SHAN1, CE350, SYGP1, TPR, DPYL2, EMD, SYPL1, M3K5, PPE2, VIAAT, CTND2, LIMK2, ACK1, SYUA, ATX2, PDLI1, ZN106, DC1I1, PLIN4, ZFR, HCN2, BSN, SYN1, CO4B, MBP, ARAF, ALDOA, GCR, CATL1, NFL, NFM, RC3H2, NCAM1, HSPB1, MAP1B, G3P, NFH, VIME, MTAP2, MOV10, CRYAB, KCC2B, PABP1, AIMP1, KIF4, FOXK1, STAT3, EAA2, AINX, SOX2, LMNA, INPP, RORG, APC1, ATX1, PCBP3, KCNN2, GCP3, TB182, KCNH8, NPHP4, YTHD1, PI5PA, MRTFB, DOCK4, RUVB1, ABI2, RS3, KCNA2, ZHX1, TRAF5, SURF6, NCOA1, RGRF2, LYAG, IRS2, GBX1, TNIK, WNK1, CSRP1, G3BP2, RLA2, CTNB1, PLAK, S30BP, ENAH, EMAL1, CNN2, CDK12, MA6D1, M3K13, PSD3, PLBL2, PRC2C, MILK2, YETS2, PBIP1, TPPC9, FUBP2, WNK2, LIMC1, TNR6C, ZEP2, AAK1, TNR6A, CAMKV, MINY4, GRM5, ARMX5, N42L1, PACS2, ABL2, OXR1, UN13A, HERC2, PHAR4, SRRM1, TR150, LIN54, TAB3, ZBTB4, UNKL, RBM27, TM1L2, MYO1G, ANR40, SYNRG, NACAD, A1CF, LAMA2, PMEL, NCOR1, LAMA5, BCAR1, HCFC1, MRE11, PACN1, MAFK, MCM7, PTN14, SPTB2, TAF6, SRBS1, DBNL, SH3G1, TLE4, IF4G2, MINT, ZYX, OMGP, HECAM, NR2E1, SF01, SYN2, GPDM, PLK4, SBNO1, SLAI1, PKP4, SYMC, SAM9L, SH3R1, HECD1, ABLM3, ARMX2, CE170, CDC5L, LAR4B, RHG20, F135A, SPKAP, SR140, KIF24, RPRD2, WWC2, REXO4, PTN23, IQCE, TRAK1, RN220, ERC2, NFRKB, MAGI1, TEX2, PF21A, CNOT1, NU188, TRPV1, SC6A5, SMAP2, CPEB3, PLPR3, MYCB2, PRC2B, TPPP, ATX2L, CCNT2, MAP6, SI1L2, ERBIN, R3HD2, AUXI, RERE, SNPH, RIMB2, NU214, INT2, SDA1, EPN1, AGFG2, C2C2L, NRAP, DDHD1, BCAS1, ZN598, CTIP, SHAN2, MACA1, ANR26, MAST4, RHG32, LPP, MYPT2, IF4B, ZN750, WDR48, TB10B, CSTP1, SP130, ZC21A, ZNT6, SUN2, RCC2, ABLM2, HSP13, CLAP2, CNOT4, SRRM2, IKZF5, TOX4, GEPH, DIP2A, LARP4, IFFO1, OSBL6, YTHD3, POGZ, ZHX2, TT21A, SI1L1, RBM14, UBP44, CNOT2, HYCC2, ANK2, DIDO1, PARP9, SYNPO, VCIP1, MB214, TAB1, RPB2, ASPP2, F193A, NAV1, SYNJ1, RPGF2, EP400, PHC3, VP37A, EPN2, PDLI5, CSR2B, FBP1L, SCAM1, ZBT20, HS12A, AGFG1, MATR3, FANCI, PO121, MRTFA, MTSS1, SPART, PPR42, NUP58, RFIP5, BRD8, PP6R2, CS047, LUZP1, RBM12, SC6A8, MAVS, MICA1, SIR2, AMOT, AGAP3, P66B, CCG8, TAF9, WDR13, UBAP2, NCOA5, PEX16, DCP1A, YTHD2, BMP2K, DYST, LRP1, SYUB, ALS2, BICD2, CLIP1, S12A6, NRBP, RP25L, TAB2, DDAH2, HGS, TM2D1, SNCAP, ASH1L, ANR17, RTN4, RRBP1, NUDC2, TPPP3, FLIP1, DDAH1, DLGP1, FIP1, TM263, CNN3, AL7A1, PLIN3, MYPT1, NDUBA, CRIP2, TSC1, NBEA, INP4A, RIMS2, SO1C1, RBP2, MKRN2, RTN3, NUDT3, LGI1, TULP4, ADRM1, FMN2, GIT2, BAG3, ZN207, ASAP1, SON, TBL1X, PLEC, MACF1, NPHP1, VAPB, ADDA, GOGA5, MAP1A, QKI, PCLO, GAB1, FBX6, FOXO1, ADA23, AKA12, NCOR2, C8AP2, TNIP1, DEMA, E41L3, SYUG, ITSN2, ZO2, ADNP, NEK4, APCL, MTMR1, MECP2, E41L1
Species: Mus musculus
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Hou C, Zhang H, Deng J, Wang X, Byers S, Levi M, Pak DTS, Moremen KW, Pei H, Hart GW, Ma J. Comprehensive Evaluation of Cleavable Bioorthogonal Probes for Site-Specific O-GlcNAc Proteomics. Molecular & cellular proteomics : MCP 2025 24(10) 40885482
Abstract:
O-linked β-N-acetylglucosamine (O-GlcNAc) modification (i.e., O-GlcNAcylation) on proteins is an essential modification in physiology and pathology. Although O-GlcNAcylation is functionally critical, its analysis has been challenging. Despite the existence of a number of methods developed in the past years, which one(s) might have the best performance is largely unclear. To that end, we conducted a rigorous comparison of several cleavable bioorthogonal biotin-alkyne probes which showed promise for sensitive O-GlcNAc proteomics. In brief, we developed chemoenzymatic labeling/click chemistry-based analytical workflows for O-GlcNAc proteomics by utilizing four cleavable bioorthogonal probes, including photocleavabe-biotin-alkyne (PC-biotin-alkyne), dialkoxydiphenylsilane-biotin-alkyne (DADPS-biotin-alkyne); 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl-biotin-alkyne (Dde-biotin-alkyne), and diazobenzene-biotin-alkyne (Diazo-biotin-alkyne). The analytical performance of these probes was evaluated with synthetic O-GlcNAc peptides and then benchmarked by using mouse brain lysates for O-GlcNAc proteomics. Besides providing valuable technical insights into O-GlcNAc proteomics methods, our work yielded an unprecedented O-GlcNAc proteome depth in the mouse brain. In total, 2906 O-GlcNAc sites were unambiguously assigned on 878 proteins. Among them, 1611 sites were newly identified, including 138 O-GlcNAcylated tyrosine residues. Our work will help guide the selection/development of O-GlcNAc proteomics methods for future studies, provide an invaluable resource for functional elucidation of protein O-GlcNAcylation in brain biology, and yield critical insights into tyrosine O-GlcNAcylation.
O-GlcNAc proteins:
QSER1, TANC2, ZEP3, MA7D2, CKAP5, AMRA1, CAMP1, LZTS3, AJM1, MA7D1, FRPD1, RPGP1, UBR4, SKT, BCORL, AGRIN, TITIN, SVEP1, ARI1A, SPAS1, KANL3, PHRF1, PTPRS, SCN2A, DLGP4, EP300, RBM25, ILDR2, CTTB2, PTPRZ, NLRC5, CCDC6, SHAN1, SET1A, PARP4, PRR12, TENS1, I2BP2, AKP13, C2CD2, ARI1B, ZC3HD, ARID2, NUMA1, PDZD7, SC16A, SYGP1, TPR, BICRA, SI1L3, PLGT3, DPYL2, EMD, STXB1, AKAP1, CLOCK, DCTN1, NUMBL, DBIL5, SYPL1, M3K5, SCRB2, ATN1, NOTC2, VIAAT, HAP1, CTND2, PITM1, OX2G, REPS1, AKAP2, ACK1, CNTP1, CAC1B, SYUA, PI51C, ATX2, E41L2, PDLI1, ULK1, UBR1, HCN4, KDM6A, ZN106, PDE8A, PPT1, ZFR, HCN2, HCN1, CTBP1, BSN, TOM1, AKA10, HIPK1, SYN1, LGMN, TPP1, THY1, LAMC1, MBP, ALDOA, GCR, CATL1, EGR1, HCK, ENPL, KCC4, NFL, NFM, ITB1, RC3H2, MAMD1, ATX1L, CATB, TAU, LAMP1, DMD, KCC2A, ITPR1, CNTN1, NCAM1, AT1B2, HSPB1, MAP1B, G3P, ATF2, PPIA, CATD, BASI, COF1, NFH, BIP, HEXB, MTAP2, MAG, CYTC, EMB, GRIA1, GRIA2, RS2, RGRF1, KCC2B, PABP1, C5AR1, AIMP1, DPOA2, RAB23, NMDE1, NMDZ1, FMR1, FOXK1, STAT3, EAA2, EGR3, RAD52, ITAV, CBP, AINX, NEDD4, STT3A, RP3A, EPB41, RFX1, SOX2, LMNA, MPIP1, INPP, DHI1, ARSB, VATA, DVL1, ADCY7, DBX1, E41LA, ARNT, SOX1, ATX1, RD23B, 3BP1, AMRP, CX6B1, CTBP2, MAZ, WFS1, PCBP3, PTPA, KCNN2, FOXP1, TB10A, TB182, GMEB2, KCNH8, CAPAM, RHG39, YTHD1, RPC2, PI5PA, MRTFB, DOCK4, IRPL1, MYPR, ABI2, GBB1, RAB3A, VAMP2, KCNA2, KCNJ3, ZHX1, DCC, NFIX, NCOA1, RGRF2, USP9X, TP53B, NACAM, LYAG, IRS2, TNIK, WNK1, G3BP2, ARG28, MPRIP, CAC1A, NPAS2, GRM1, XRN1, SHPS1, NEO1, G3BP1, NFIB, RLA2, GABPA, CBPE, NMDE2, NMDE3, NOTC1, CTNB1, PLAK, S30BP, NFIA, ZEP1, ENAH, KCNB1, RCN1, PGBM, EMAL1, LG3BP, TLE3, MITF, SSRP1, CHD8, TRIO, TANC1, RELCH, CDK12, MA6D1, F171B, SHRM4, PHAR1, GSK3A, PSD3, MLXIP, NELL1, ESP1, PLBL2, PDLI7, PRC2C, MILK2, YETS2, SRSF6, FUBP2, SRBP2, GSE1, F117B, WDR62, FOXK2, CARL3, DIP2B, WNK2, LIMC1, TNR6C, DAB2P, AGAP2, ZEP2, ZSWM8, AAK1, TEN4, TNR6A, CAMKV, MTCL1, PKHA7, COBL1, GRIN1, PRRC1, MINY4, FCHO2, SNX21, LIGO2, MRCKA, KSR2, GRM5, ARMX5, ELAP2, GARL3, 5NTC, PACS2, STOX2, UBN1, ABL2, OXR1, DSCL1, CDV3, PHAR4, ANR28, LRC47, SRRM1, EME2, LIN54, TAB3, STB5L, NEXMI, JCAD, NYNRI, NUFP2, UNKL, PRSR1, OSBP2, SMG7, LRRK2, RBM27, PHF12, CYFP2, TM1L2, ANR40, CCD42, SYNRG, RPGP2, NACAD, LHPL4, EPAB2, LMTK3, SIN3A, SRC8, ICAM5, LAMA2, ITF2, CAPR1, NCOR1, FOXG1, LAMA5, NCOA2, LAMC2, IL18R, NAB1, ASTN1, SPIN1, PAPOA, HCFC1, SAP, NELL2, APC, PGCB, ZN638, AP180, FXR1, GRID2, GRID1, PACN1, HIRA, RAI1, MAFK, NPM, NOTC3, CSPG2, M3K7, DAG1, RO52, SN, SPTB2, TAF6, SPEG, ASPP1, SRBS1, DBNL, SH3G1, TLE4, SP4, IF4G2, MINT, ZYX, OMGP, MEF2D, TFE3, PAN3, HECAM, SF01, SYN2, TBR1, DHSO, CGT, CH058, SBNO1, CRTC1, BEGIN, K1549, GIT1, SLAI1, PKP4, SYMC, CDK13, GBA2, SH3R1, PREX1, JHD2C, HECD1, MOR2A, ABLM3, TBC12, ARMX2, CE170, LAR4B, RHG21, HELZ, MEG10, SCAF8, LIGO3, ZZZ3, F135A, FBX41, SPKAP, RPRD2, WWC2, ZN532, DPP10, TAF9B, S23IP, IF4G1, RBM26, NSD3, SNX19, FHOD1, FKB15, MTSS2, BCR, AHDC1, AAKB2, PTN23, LPPRC, PAPD7, MFF, PIGS, TRAK1, PHLB1, KMT2D, RN220, DLGP3, RA54B, GMIP, WASC2, ERC2, KCC2D, NFRKB, ALEX, MAGI1, CENPE, DNMBP, GGYF2, TEX2, PF21A, KDM3B, FNBP4, CNOT1, LARP1, NU188, SYNE1, IF2A, UB2R2, CMYA5, SEM6D, SOX11, PICAL, ASAP2, HUWE1, SMAP2, PLPR3, PRC2B, C2CD5, TPPP, MACOI, AMPH, ATX2L, PRC2A, TMM94, PP6R1, MAP6, MCAF1, DAAF9, SI1L2, LRRC7, ERBIN, PHF24, R3HD2, NAV3, AGRL1, DEND, AUXI, RERE, SNPH, MADD, RIMB2, PUM1, NU214, SEPT9, SESD1, CBPM, SRA1, EPN1, AKNA, HYDIN, UBN2, AGFG2, CHST2, UBP2L, T106B, C2C2L, REPS2, WNK3, DDHD1, CNKR2, BCAS1, ZN598, SHAN2, PKHL1, S2611, ZFYV1, NRCAM, DLG1, MAST4, RHG32, GPHB5, RN214, LPP, MYPT2, TB10B, CSTP1, SP130, ZC3HE, DLGP2, ZC21A, ZNT6, SUN2, EME1, TNR6B, BAIP2, ABLM2, NCEH1, LRFN3, EMSY, SHC2, SEN34, FAT3, DMXL2, GORAB, CLAP2, K1671, FAKD3, LIPA2, CNOT4, RALYL, SRRM2, TOX4, PAMR1, F163B, GEPH, CREST, KCC1D, GRIN3, LARP4, Z385B, IFFO1, OSBL6, CC169, TENR, YTHD3, STON2, TM266, POGZ, DOC10, ZHX2, EPC2, SWAHC, ZHX3, SI1L1, SH3R3, FRS2, RBM14, CNOT2, MOR2B, HYCC2, ANK2, ELFN1, TM163, DIDO1, SMAG1, SYNPO, BCAS3, VCIP1, BAKOR, TAB1, SCYL2, NED4L, MEF2C, ASPP2, TENS2, F193A, OGT1, CHERP, NAV1, SYNJ1, RPGF2, EP400, PHC3, DPYD, VP37A, EPN2, P66A, PDLI5, ANM5, DOCK3, PLXB1, DNER, SPAT2, SCAM1, SAM14, ZBT20, PHYIP, RTN1, HS12A, C2D1A, UNC5A, PACS1, TRI68, BRD3, LS14A, AGFG1, MATR3, DEN1A, I2BPL, PO121, ABLM1, MRTFA, RPTOR, PLCE1, SPNS1, CACL1, KCNC4, DC1L1, MTSS1, SPART, LRC42, ZN445, RFIP5, IGSF8, BRD8, WIPI1, CDK8, PP6R2, SHLB2, CS047, NTNG2, PP14C, STAB2, LUZP1, RBM12, STAB1, OTU7A, SC6A8, ULA1, CLPT1, MAVS, GRAP1, SGIP1, PI3R4, PHIP, SIR2, GOLI, AMOT, AGAP3, WASF3, P66B, CCG8, TAF9, ZCH14, MCR, SFPQ, WDR13, UBAP2, SMAP1, NCOA5, CXXC5, FRS3, SPS2L, FUBP1, SH319, ZFN2B, VPS36, DLG2, DYH8, DCP1A, YTHD2, PTBP2, SRGP2, SRGP1, BMP2K, DYST, LRP1, SYUB, ALS2, TRFE, GPS2, CLIP1, CIC, WAC, SPRE1, MED1, NRBP, NPTXR, GGT7, GORS2, NONO, TAB2, DPP3, EPN4, RNF34, GAK, DDAH2, ZN281, HGS, RB6I2, RIMS1, ANR17, RTN4, RRBP1, ZN318, TRI33, MZT2, PCYOX, NECP1, FLIP1, NRX1A, SNX2, DDAH1, YIF1B, NOPC1, CYGB, GFOD2, TPD54, CEP97, CD37L, SSBP3, SARNP, SP2, UB2V2, DLGP1, NDUV2, SH24A, FIP1, ST1C2, F135B, TM263, CNPY3, RM12, BTBDH, AL7A1, PLIN3, MYPT1, LNEBL, DCAF6, KC1D, CRIP2, TSC1, NBEA, TCF20, CPSF1, DPYL5, RIMS2, ZN704, RBP2, RTN3, SPN90, SP6, GILT, CLD12, ELF2, TSSC4, LRP1B, NUDT3, CATR, PPR3F, NUP50, TULP4, ORC3, ATR, HYOU1, ADRM1, FMN2, NCOA6, BAG3, MINK1, ZN207, PHC2, SRCN1, ASAP1, SON, SALL2, LIMD1, TBL1X, APBB1, PLEC, MACF1, ULK2, ADDB, ADDA, PCX1, GOGA5, NDRG2, MAGD1, MAP1A, QKI, PCLO, GAB1, MAGL2, FBX6, NPAS3, HIPK2, SH2D3, CATJ, YLPM1, CELR2, RHG07, GUAD, FOXO1, TAGL3, ADA22, AKA12, TEN1, TEN3, NCOR2, ATRN, COR1B, SR5A3, GANP, NFAT5, ASAH1, GSK3B, DEMA, E41L3, CARM1, JIP1, KCNH3, MAGI2, FXR2, SYUG, CLIP2, PALM, ITSN1, ITSN2, ZO2, DYR1B, APCL, BAG6, DPP6, MTMR1, MECP2, SE1L1, E41L1, GRIA3, HOME1
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, 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, 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, WNK3, ZN598, CTIP, SHAN2, NANOG, DDX42, RHG32, VGLU3, LPP, TET3, MYPT2, IF4B, CNO10, MISSL, TB10B, CARF, TGO1, ZN879, SP130, ZC3HE, ZNT6, SUN2, TNR6B, ARI5B, BNC2, KAT6B, KMT2C, CLAP2, CNOT4, SRRM2, TOX4, GEPH, SYP2L, LARP4, KANK2, SALL4, YTHD3, TOIP2, KAT6A, ASXL2, POGZ, 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, WAC, TRPS1, MED1, ACATN, NRBP, RP25L, NONO, TAB2, 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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Gonzalez-Rellan MJ, Parracho T, Heras V, Rodriguez A, Fondevila MF, Novoa E, Lima N, Varela-Rey M, Senra A, Chantada-Vazquez MDP, Ameneiro C, Bernardo G, Fernandez-Ramos D, Lopitz-Otsoa F, Bilbao J, Guallar D, Fidalgo M, Bravo S, Dieguez C, Martinez-Chantar ML, Millet O, Mato JM, Schwaninger M, Prevot V, Crespo J, Frühbeck G, Iruzubieta P, Nogueiras R. Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function. Molecular metabolism 2023 75 37453647
Abstract:
O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. The addition and removal of O-GlcNAc of target proteins are mediated by two highly conserved enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), respectively. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, and cardiovascular diseases. The contribution of deregulated O-GlcNAcylation to the progression and pathogenesis of NAFLD remains intriguing, and a better understanding of its roles in this pathophysiological context is required to uncover novel avenues for therapeutic intervention. By using a translational approach, our aim is to describe the role of OGT and O-GlcNAcylation in the pathogenesis of NAFLD.
O-GlcNAc proteins:
DJC25, TITIN, FIBA, AOXC, LEG9, CLCA, MTP, MYH11, NTCP, PRDX6, DLDH, HCD2, GLU2B, PRDX4, RL21, GSH0, HGD, AMACR, PHB2, DOPD, PSMD4, SRSF5, PAHX, AGT1, S27A2, BHMT1, ANXA3, AP1B1, CP4AE, TIM44, CALU, AL1A7, OST48, PGRC1, COPB2, NIPS1, RL35A, AT2A2, PSB5, DPM1, EIF3D, EF1B, NMT1, UGDH, DHB12, WDR1, RDH7, ROA2, COMT, JAM1, IDHC, CP8B1, COPE, RBM3, CP1A1, ADH1, COX1, COX2, CO3, HVM14, IGKC, IGHG1, B2MG, HA1B, HBA, HBB1, K1C10, NU3M, ATP8, K2C1, ALDOA, AATC, AATM, K1C18, LDHA, G6PI, MAOX, ANXA2, ALBU, SPA3K, HS90A, PDIA4, ENPL, APOE, SODC, MDHM, PDIA1, NUCL, PGK1, FRIH, SODM, EF1A1, CATB, THIO, GSTM1, RRAS, H10, GPX1, HS90B, MUP2, K2C8, CP2D9, OTC, TCPA, FABPL, PDCD6, RL7A, MYH8, GPDA, RL27A, RS16, RL7, MDHC, RSSA, CALR, GTR2, HSPB1, PSMD3, ANXA6, RLA0, GLNA, NDKA, CAH3, LEG3, SRP14, PH4H, MUTA, ASSY, G3P, ENOA, PTBP1, AP2A2, SBP1, COX7C, UDB17, PPIA, TPIS, PTPRA, CATD, COF1, FAS, GSTP1, RL13A, COX5B, COX41, BIP, PRDX3, VIME, CP2A5, TPM3, VTDB, TGM2, EIF3A, MOV10, CATA, PPIB, CP2DA, LKHA4, AL1A1, CO8A2, RS2, URIC, TLN1, MOES, RADI, 3BHS3, CTNA1, U2AF2, DHE3, SYSC, MA2A1, RL3, PDIA3, PSB8, ACOHC, APEX1, ADHX, MUG1, GRN, DPP4, PABP1, FRIL1, OAT, VTNC, GSTA3, CTND1, ACBP, SCP2, LA, DRG1, CP2F2, HYES, RAB18, FAAA, FBRL, CALX, PRDX1, RL12, RL18, HEM6, NCPR, HMGCL, HSPA9, CAP1, TKT, INMT, RL28, ACSL1, ECI1, SEPT2, STAT1, PURA, PXMP2, TCPQ, H14, PLIN2, ACADM, MYO1B, STT3A, QOR, ALDH2, AL3A2, CAZA2, GSHR, RL6, RL29, RLA1, RL5, RL13, RL36, ANXA5, LMNA, CBR1, T23O, ROA1, HPPD, ODBA, DHB8, DHI1, SAHH, GLYC, K2C6A, VATA, ACADV, PA2G4, RAB7A, ACADL, RL9, DHB2, DHB4, GSHB, ADT2, THTR, PON1, KPYM, RIDA, CPT2, ST1A1, ST2A1, RL10A, ODB2, KPYR, MOT1, CNBP, IDHP, HMCS2, ABCD3, RAB8A, ADK, ATPK, CX6B1, CYB5, ATPB, CP2AC, FUS, EF1D, ACTN4, TM9S2, EF2, GGLO, IF5, ARPC4, EIF3E, PCBP1, ACTB, CDC42, IF4A1, RS20, UBE2N, ARP2, ARF3, ABCE1, RL26, RL27, RL37A, S61A1, ARF4, GABT, HNRPK, 1433G, RRAS2, RS7, PP1B, PRS8, RS8, RS15A, 1433E, RS14, RS23, RS18, RS29, RS11, RS13, RS4X, RL18A, RL23A, RS6, H4, RAB1A, RAN, RL23, RS15, RS24, RS25, RS26, RS28, RS30, GBB2, RL30, CYC, RL31, RS3, RL32, RL8, YBOX1, PROF1, RS27A, RAC1, HSP7C, TCTP, DNJA1, CH60, 1433Z, IF5A1, RS17, RS10, PHB1, RL22, RACK1, ACTS, 1433T, TBA4A, TBB4B, TBA1C, 1433F, IMB1, EBP, NFIX, PEBP1, HNRH2, ELAV1, NHRF1, NACAM, DHB5, TCPB, TCPD, TCPE, TCPZ, TCPG, RL36A, AP2M1, RL19, ISC2A, KHK, RS3A, PSME2, ANXA4, MYL11, RS5, GSH1, FMO3, CPT1A, FUMH, CATC, LYPA1, G3BP1, FMO5, TBB5, RLA2, PRDX5, RET4, A1AT4, HNRL2, SC23A, NDKB, TERA, UBA1, PLAK, ATPA, PPA5, CP2E1, PYC, ATP5I, CLUS, ANXA7, ACADS, LG3BP, HSDL2, ML12B, METK2, K22E, AGT2, RMD3, MCCB, SC31A, IQGA2, S27A5, DDX17, OPA3, GLSL, ACBD5, COPD, A1CF, ODO1, MYL6, HNRPD, PSB6, GCDH, IRGM1, SPB6, STIP1, CAPR1, VDAC2, VDAC3, VDAC1, COQ8A, PRDX2, ARGI1, PLSL, ABCD2, HCDH, GPAT1, GDIB, HPT, DDX5, HS105, LASP1, NPM, NNTM, PCBP2, DDX3X, SSRD, SPR1A, NDUA4, CYTB, VAT1, SBP2, EST3A, UD11, SPRE, BTF3, RGN, CH10, UD16, DHSO, CP2CT, GSTT1, GPDM, CLH1, F120A, IF4G1, ODBB, ABCF1, LPPRC, SRSF1, RS9, RS27, RL10, RL35, IF2A, RS27L, H2B1C, KAT3, 2AAA, ATPMK, MIC27, 3HAO, S22AI, SND1, OSTC, MTCH2, NDUAC, HNRPQ, TBB2A, LDHD, ACTN1, GVIN1, MOGS, FA98B, COEA1, FLNB, ACD11, BDH, EFTU, LPP, ROA3, ALAT2, AL8A1, S2512, ECHM, CHDH, IPO5, TM214, SRP68, ECHA, SYNC, RL24, ASPH, FLNA, DHPR, AOFB, SSDH, ACOT4, UD2A3, THIM, ERF1, CPSM, NAKD2, MIC60, PARP9, THIC, S2545, G6PE, SYEP, LONM, NT8F2, DPYD, AL4A1, PDLI5, COPA, CP2DQ, EIF3B, ACSL5, TXTP, UD3A2, GALM, COQ9, SDHA, HACD3, MATR3, NDUS8, ALAT1, THIL, EIF3L, HNRPL, EPIPL, SGPL1, AL1L1, BPHL, EIF3C, CMBL, QCR9, H2AJ, SDHL, HUTU, AK1CD, TKFC, GYS2, THIKB, CGL, DHB13, ABHEB, EST1D, EST3B, ACSF2, MYH9, VIGLN, PSMD2, AT1A1, HNRPU, S25A3, SEC63, OASL1, SFPQ, TRAM1, CK054, ACLY, ACSM1, NDUS1, RINI, RMXL1, ATPG, DDX1, MGST1, CBR4, GCSP, NDUS2, EIF3H, KMO, SYYC, EST1F, BAAT, GCKR, DCXR, METK1, NADC, FTCD, GLYAT, TM205, ALDOB, ATLA3, ARLY, RPN1, NDUV1, GRHPR, PCCA, UGPA, FPPS, FADS1, TADBP, ETFD, THIKA, TRFE, PDIA5, SYDC, C1TC, MARC2, LRC59, PDIA6, ATAD3, SFXN2, ROAA, S14L2, THTM, STML2, SFXN1, GORS2, ECHB, ARP3, NONO, PLST, AASS, GLO2, ACON, DPP3, DHRS1, 3HIDH, IF2B, DHRS4, SARDH, NDUAA, ETFA, RTCB, PARK7, NDUS5, DNJA3, PCCB, MCCA, PECR, NUDT7, RTN4, AAAD, RRBP1, GDIR1, NDUA5, ATP5L, RL17, AMPL, DECR, MTAP, QCR8, NDUA2, SDHB, NDUB4, SAR1B, PCYOX, NDUB5, NDUB9, TXD17, TRAP1, AT5F1, ACO13, PPP6, SC61B, MTNA, RER1, 1433B, CYB5B, MAGT1, NDUA6, RL14, M2OM, TMM33, UCRI, VKOR1, OCAD1, ARPC2, MARC1, PUR9, DDAH1, ROA0, KYNU, CENPV, RL11, TECR, SERB1, QCR1, C560, RL15, GLYM, AL1B1, CISY, RS19, ODPB, HNRPM, LMAN1, PGM1, SYRC, CY1, SYTC, GAL3A, CNDP2, TMEDA, FKB11, ERP44, HYEP, HACD2, ATPD, PLCC, NDUV2, GHC1, IDH3A, MSRA, GLGB, ACAD8, PRPS1, SAPC2, IPYR, RL37, SOX, U2AF1, RL4, EF1G, ATPO, IAH1, QCR2, HUTI, CSAD, AL7A1, CP27A, AP2B1, RPN2, PGAM1, COASY, ECHP, KCY, M2GD, NDUA9, NDUS7, RT11, 6PGD, SSRG, EIF3F, NDUA8, PUR6, GSTK1, NB5R3, ASPDH, MTL26, NDUBA, NDUS3, HOGA1, RMD1, ETFB, ATP5H, KEG1, TMT1B, LACTB, RENT1, DHB11, MMSA, DPYS, ERAP1, VPS35, MVP, SET, RT29, PYGL, IVD, TMOD3, NIT2, COPB, AK1A1, CMLO1, PLS1, RL38, PXMP4, GNA1, AL9A1, CD2AP, STA10, TRXR1, RHOA, PSA6, K1C17, F16P1, HACL1, GNMT, S2513, CLIC4, VKGC, DIC, EIF3I, COPG1, TBL2, ACOX1, ESTD, DEST, TEBP, MPU1, SQOR, PSA1, TPSN, RUVB2, KAD3, HAOX1, PDC6I, PROD, SYFB, SUCA, PREB, ECI2, ENTP5, DECR2, TAGL2, ORNT1, PACN2, EHD1, MAAI, IF2G, BPNT1, AIFM1, DX39B, SYVC, ILF3, STRAP, HNRPC, PX11A, LETM1, SUCB2, SUCB1, PSA7, HNRPF, MCAT
Species: Mus musculus, Mus spicilegus
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Zhu WZ, Palazzo T, Zhou M, Ledee D, Olson HM, Paša-Tolić L, Olson AK. First comprehensive identification of cardiac proteins with putative increased O-GlcNAc levels during pressure overload hypertrophy. PloS one 2022 17(10) 36288343
Abstract:
Protein posttranslational modifications (PTMs) by O-GlcNAc globally rise during pressure-overload hypertrophy (POH). However, a major knowledge gap exists on the specific proteins undergoing changes in O-GlcNAc levels during POH primarily because this PTM is low abundance and easily lost during standard mass spectrometry (MS) conditions used for protein identification. Methodologies have emerged to enrich samples for O-GlcNAcylated proteins prior to MS analysis. Accordingly, our goal was to identify the specific proteins undergoing changes in O-GlcNAc levels during POH. We used C57/Bl6 mice subjected to Sham or transverse aortic constriction (TAC) to create POH. From the hearts, we labelled the O-GlcNAc moiety with tetramethylrhodamine azide (TAMRA) before sample enrichment by TAMRA immunoprecipitation (IP). We used LC-MS/MS to identify and quantify the captured putative O-GlcNAcylated proteins. We identified a total of 700 putative O-GlcNAcylated proteins in Sham and POH. Two hundred thirty-three of these proteins had significantly increased enrichment in POH over Sham suggesting higher O-GlcNAc levels whereas no proteins were significantly decreased by POH. We examined two MS identified metabolic enzymes, CPT1B and the PDH complex, to validate by immunoprecipitation. We corroborated increased O-GlcNAc levels during POH for CPT1B and the PDH complex. Enzyme activity assays suggests higher O-GlcNAcylation increases CPT1 activity and decreases PDH activity during POH. In summary, we generated the first comprehensive list of proteins with putative changes in O-GlcNAc levels during POH. Our results demonstrate the large number of potential proteins and cellular processes affected by O-GlcNAc and serve as a guide for testing specific O-GlcNAc-regulated mechanisms during POH.
O-GlcNAc proteins:
MA7D1, CAVN4, OTUD4, FIBA, TRDN, DPYL2, CLCA, MYH11, KNG1, PRDX6, AKAP1, DLDH, NDUBB, GSTO1, CASQ2, RL21, PHB2, ECH1, NDUA1, TIM44, CAVN1, AKAP2, SLK, NIPS2, AT2A2, PGAM2, EF1B, ATX2, NMT1, XIRP1, PDLI1, MYPC3, SNX3, DC1I2, PLIN4, ROA2, RAD, CLPP, TOM1, COX1, COX2, CAH2, CO3, IGJ, KV2A7, IGKC, GCAB, IGHG1, IGH1M, B2MG, HBA, HBB1, LAMC1, FABP4, CFAB, MYG, ALDOA, ANF, AATC, AATM, TBA1B, LDHA, G6PI, TRY2, TTHY, KCRM, ANXA2, ALBU, SPA3K, ENPL, APOE, MDHM, ITB1, PDIA1, NUCL, PGK1, FRIH, MYL3, SODM, NDUB1, ANXA1, EF1A1, CATB, TAU, THIO, GSTM1, H2B1F, H10, CO1A1, FABPH, HS90B, DMD, PFKAL, COX5A, RL7A, GELS, MYH3, AT1B1, GLUT4, RL7, MDHC, RSSA, CALR, HSPB1, ANXA6, GLNA, B4GT1, GSTM2, H12, LDHB, SPTN1, G3P, ENOA, HXK1, PPIA, TPIS, BASI, COF1, RL13A, SERPH, COX5B, COX41, BIP, PRDX3, VIME, CYTC, ENOB, TGM2, EIF3A, CBX3, CXA1, PIMT, CRYAB, CATA, CAPG, GSTA4, RS2, TLN1, MOES, RADI, CTNA1, DHE3, FKB1A, MAP4, RL3, H2AX, PDIA3, PABP1, FRIL1, FETUA, DESM, AIMP1, LA, ANT3, RANG, MIF, PTN11, HSPB7, ODPA, CALX, PRDX1, RL12, RL18, FBLN2, HMGCL, HSPA9, CAP1, TKT, RL28, ACSL1, ECI1, H14, H11, H15, H13, ALDR, COF2, ACADM, PRS7, ADX, ALDH2, CAPZB, RL6, RL29, CACP, RL13, ANXA5, TBCA, LMNA, CX7A2, TNNI3, ADT1, ROA1, PCY1A, CAV1, ODBA, CSRP3, ACADV, PA2G4, TNNT2, ICAL, ACADL, CAV3, MLRV, ADT2, LUM, KPYM, NDUS6, CPT2, RL10A, ODB2, CCHL, MOT1, IDHP, STOM, ADK, ATPK, ACYP2, ATP68, ATP5E, AT5G2, CX6B1, CX7A1, COX7B, CYB5, UBP5, ATPB, WFS1, ACTN4, EF2, OPA1, TPM1, B2L13, PCBP1, ACTB, RS20, PPLA, UB2D3, UBC12, UBE2N, RL26, RL27, SUMO2, 1433G, RS7, RS8, 1433E, RS14, RS18, RS11, RS13, DLRB1, EF1A2, RS4X, RL23A, RS6, H4, RAN, RS15, RS25, RS30, RL30, CYC, RL31, RS3, RL32, RL8, FBX40, YBOX1, RS27A, HSP7C, MPC1, CH60, GNAS2, 1433Z, HMGB1, IF5A1, ACTG, ACTH, RS12, RS10, RL22, ACTC, UB2L3, TBA4A, TBB4B, H31, IMB1, PEBP1, HINT1, IDHG1, NACAM, TCPD, SGCD, SGCA, WNK1, RL19, SRSF3, H32, RS3A, G3BP2, ANXA4, COQ7, G3BP1, LAMA4, QCR6, PRDX5, APOA1, CO1A2, NDKB, TERA, UBA1, MYH6, ATPA, KCRB, CO6A1, PGBM, EMAL1, ATP5I, CLUS, ANXA7, ACADS, CD36, NEBL, PERM1, TRI72, HSDL2, HP1B3, PRC2C, TM38A, Q3TV00, SRSF6, FUBP2, SDHF1, EI3JA, LIMC1, AAK1, NDUB6, MCCB, COBL1, SLMAP, SRBS2, K22O, CPZIP, NDUF2, MYPN, HSPB6, MLIP, IASPP, TM1L2, ODO1, LAMA2, STIP1, REEP5, VDAC2, VDAC1, COQ8A, LAP2B, PRDX2, HCFC1, LAMB2, HSP74, HCDH, FBN1, FXR1, KTN1, GDIB, DDX5, KINH, LASP1, PZP, NPM, NNTM, SNRPA, SPTB2, SPEG, SRBS1, DBNL, NDUA4, FKBP3, IF4G2, ZYX, CAVN2, SPRE, SF01, CD34, CH10, H2A2B, H2A2C, NQO1, VINC, EI3JB, CLH1, H2A2A, GPSM1, IF4G1, KCRS, LPPRC, AT1A2, CAND2, RS9, CMYA5, FHOD3, ATPMK, MIC27, MSRB2, NP1L4, MTCH1, MTCH2, NDUAC, HNRPQ, HUWE1, LC7L2, MIC10, NEXN, SRCA, LNP, CLAP1, SRA1, NRAP, BDH, GLRX5, ATPF1, EFTU, H2A3, LPP, MYPT2, IF4B, ECHM, RCN3, SYIM, EIF2A, ODPX, EEA1, ODP2, ECHA, COQ3, RL24, FLNA, TIDC1, PLIN5, SYP2L, SSDH, THIM, MIC60, PABP2, BOLA3, SYEP, LONM, H2A1F, H2A1H, H2A1K, SEPT8, PGP, AL4A1, SLAI2, PDLI5, PYGB, PAK2, AFG32, EIF3B, FIBB, COXM2, COQ9, SDHA, SIR5, ACD10, NDUS8, NNRE, HIBCH, THIL, MARE2, QCR9, H2AJ, DC1L1, SPART, NAR3, MIC13, CLYBL, PP14C, TXLNB, MAVS, MYH9, VIGLN, PSMD2, AT1A1, LMCD1, HNRPU, S25A3, FLNC, SFPQ, NDUS1, MIC25, ATPG, SH3L3, UBAP2, NDUS2, EIF3H, CISD1, HEMO, EGLN1, L2HDH, RPN1, NDUV1, GRHPR, MYH7, PCCA, UGPA, ETFD, THIKA, TRFE, TOIP1, MACD1, CLIP1, K2C5, UBXN1, ALPK3, RT02, CPT1B, TALDO, ROAA, THTM, STML2, PACN3, ECHB, PLST, ACON, DCTN2, NAMPT, PPIF, NDUAA, ETFA, GRPE1, PARK7, NDUS5, DNJA3, PCCB, MCCA, PPR3A, EH1L1, ACS2L, RRBP1, GDIR1, NDUA5, COX6C, TOM22, ATP5L, NDUB2, COXM1, RM24, NDUC2, DECR, QCR8, NDUA2, FIS1, SDHB, NDUB4, NDUB5, NDUB9, AT5F1, RS21, ACO13, 1433B, CYB5B, KGD4, NDUA6, NDUB3, PSMD9, RL14, NDUB7, M2OM, UCRI, MIC19, OCAD1, PIN4, NDUS4, RT28, SERB1, SPCS2, SSBP, QCR1, NSF1C, C560, CISY, TOM70, RS19, ODPB, HNRPM, PGM1, SCOT1, CY1, HINT2, GAL3A, MCEE, CHCH2, ERP44, NOL3, MMAB, ODO2, COA3, RT33, ATPD, NDUB8, NDUV2, IDH3A, F162A, ARMC1, RL37, QCR7, RL4, EF1G, EFHD2, PRS37, ATPO, QCR2, PGAM1, MYPT1, LNEBL, TELO2, NDUA9, NDUS7, NDUA8, NDUBA, NDUS3, CRIP2, ETFB, ATP5H, MIC26, MMSA, EHD4, NDUAD, POPD1, HRG, PALLD, JPH2, IVD, NHRF2, PALMD, ACTN2, AK1A1, DBLOH, MYOZ2, PDK2, HSPB8, HIG1A, BAG3, AUHM, MACF1, VAPB, NDRG2, ACOT2, QKI, PRS30, UBQL2, H2AY, GLYG, ACOX1, DEST, KAD1, PSA1, KAD2, KAD3, CAD13, PYGM, IF4H, COR1B, SUCA, ECI2, SH3BG, TAGL2, PACN2, EHD1, AIFM1, NDUA7, BAG6, USO1, PLM, LETM1, SUCB2, SUCB1, K2C6B
Species: Mus musculus
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Huynh VN, Wang S, Ouyang X, Wani WY, Johnson MS, Chacko BK, Jegga AG, Qian WJ, Chatham JC, Darley-Usmar VM, Zhang J. Defining the Dynamic Regulation of O-GlcNAc Proteome in the Mouse Cortex---the O-GlcNAcylation of Synaptic and Trafficking Proteins Related to Neurodegenerative Diseases. Frontiers in aging 2021 2 35822049
Abstract:
O-linked conjugation of ß-N-acetyl-glucosamine (O-GlcNAc) to serine and threonine residues is a post-translational modification process that senses nutrient availability and cellular stress and regulates diverse biological processes that are involved in neurodegenerative diseases and provide potential targets for therapeutics development. However, very little is known of the networks involved in the brain that are responsive to changes in the O-GlcNAc proteome. Pharmacological increase of protein O-GlcNAcylation by Thiamet G (TG) has been shown to decrease tau phosphorylation and neurotoxicity, and proposed as a therapy in Alzheimer's disease (AD). However, acute TG exposure impairs learning and memory, and protein O-GlcNAcylation is increased in the aging rat brain and in Parkinson's disease (PD) brains. To define the cortical O-GlcNAc proteome that responds to TG, we injected young adult mice with either saline or TG and performed mass spectrometry analysis for detection of O-GlcNAcylated peptides. This approach identified 506 unique peptides corresponding to 278 proteins that are O-GlcNAcylated. Of the 506 unique peptides, 85 peptides are elevated by > 1.5 fold in O-GlcNAcylation levels in response to TG. Using pathway analyses, we found TG-dependent enrichment of O-GlcNAcylated synaptic proteins, trafficking, Notch/Wnt signaling, HDAC signaling, and circadian clock proteins. Significant changes in the O-GlcNAcylation of DNAJC6/AUXI, and PICALM, proteins that are risk factors for PD and/or AD respectively, were detected. We compared our study with two key prior O-GlcNAc proteome studies using mouse cerebral tissue and human AD brains. Among those identified to be increased by TG, 15 are also identified to be increased in human AD brains compared to control, including those involved in cytoskeleton, autophagy, chromatin organization and mitochondrial dysfunction. These studies provide insights regarding neurodegenerative diseases therapeutic targets.
O-GlcNAc proteins:
TANC2, AMRA1, CAMP1, SKT, AGRIN, TTLL3, NHSL2, CTTB2, CCDC6, SHAN1, SYGP1, DPYL2, STXB1, CLOCK, NOTC2, VIAAT, CTND2, TPD53, REPS1, NLK, ACK1, SYUA, ATX2, PDLI1, ZFR, HCN1, BSN, TOM1, SYN1, GCR, EGR1, NFL, NFM, ATX1L, DERPC, KCC2A, CNTN1, HSPB1, MAP1B, G3P, ATF2, MTAP2, RS2, FOXK1, STAT3, AINX, EPB41, RFX1, LMNA, INPP, VATA, DVL1, CNBP, ATX1, NCAN, GOGA3, PTPA, GCP3, TB182, GMEB2, YTHD1, PI5PA, MRTFB, LIPA3, NACAM, TNIK, WNK1, NPTN, NEO1, S30BP, ZEP1, APOC2, EMAL1, RELCH, PRC2C, YETS2, FUBP2, QRIC1, LIMC1, DAB2P, ZEP2, AAK1, TNR6A, FCHO2, DRC1, SRBS2, GRM5, PACS2, OXR1, PHAR4, LIN54, MLIP, UNKL, SMG7, RBM27, CYFP2, SYNRG, SRC8, SKIL, NCOR1, LAMA5, HCFC1, P3C2A, SAP, APC, TOB1, AP180, FXR1, HS71A, LASP1, MAFK, M3K7, TAF6, ASPP1, SRBS1, DBNL, SH3G1, TLE4, IF4G2, MINT, ZYX, NUP62, OMGP, TFE3, SYN2, TBR1, RBL2, SBNO1, SLAI1, PKP4, SH3R1, JHD2C, ABLM3, ARMX2, LAR4B, HELZ, S23IP, RBM26, BCR, AHDC1, PAPD7, MFF, KMT2D, ERC2, NFRKB, WDFY3, GGYF2, TEX2, CNOT1, IF2A, PLPR3, PRC2B, C2CD5, TPPP, ATX2L, MAP6, NAV3, AUXI, RIMB2, AVL9, NU214, AP4E1, C2C2L, IF4G3, ZN598, SHAN2, LPP, MYPT2, PHIPL, TB10B, CCD40, ZC3HE, DLGP2, ZC21A, BAIP2, CLAP2, LIPA2, SRRM2, PAMR1, GEPH, YTHD3, POGZ, EPC2, SI1L1, RBM14, HYCC2, ANK2, CDAN1, SYNPO, VCIP1, TAB1, MEF2C, F193A, OGT1, EP400, EPN2, P66A, PDLI5, GTPBA, ZBT20, RTN1, BRD3, AGFG1, ABLM1, MRTFA, DC1L1, SPART, RFIP5, NUP35, WASF1, SC6A8, SGIP1, AGAP3, P66B, TAF9, WDR13, LRP5, UBAP2, BASP1, DCP1A, SYUB, TRFE, TRIM7, S12A6, GORS2, TAB2, EPN4, RNF34, ANR17, NECP1, FLIP1, ROA0, RBM33, TPD54, ODO2, DLGP1, FIP1, TM263, PLIN3, LNEBL, KC1D, NBEA, INP4A, RIMS2, RBP2, RTN3, NUDT3, ATR, ADRM1, FMN2, NCOA6, SON, ULK2, ADDA, MAGD1, MAP1A, GRM3, PCLO, GAB1, FBX6, NPAS3, GUAD, NCOR2, ATRN, NFAT5, DEMA, E41L3, SLIT3, CARM1, DYR1B, MECP2, E41L1, HDAC6
Species: Mus musculus
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Lee BE, Kim HY, Kim HJ, Jeong H, Kim BG, Lee HE, Lee J, Kim HB, Lee SE, Yang YR, Yi EC, Hanover JA, Myung K, Suh PG, Kwon T, Kim JI. O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease. Brain : a journal of neurology 2020 143(12) 33300544
Abstract:
The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson's disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson's disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson's disease pathology.
O-GlcNAc proteins:
BIG2, F1712, VIR, AJM1, RPGP1, UBR4, SCN1A, AGRIN, KALRN, STPG3, FXL16, TT23L, PTPRS, GRIK3, SCN2A, DLGP4, OSBL8, PTPRZ, PGBD5, GLSK, GCN1, CE350, PI4KA, RYR2, AGRF2, UBE4A, NRX2A, FRY, SYGP1, OTOGL, AT2B1, ANK3, CA2D1, DPYL2, STXB1, DCTN1, U5S1, GFRA2, GALT1, SEM4D, KIF3C, PLCA, PHB2, NCAM2, GRAK, PURB, IMA3, IMA7, PLD3, FOLH1, FKBP8, STX1A, PSDE, VIAAT, AP1B1, C1QBP, SYT3, HNRH1, SATT, CTND2, SDC4, AP3D1, RGS9, RGS7, CSK22, OX2G, AAKG1, CRYM, PROM1, CNTP1, ENTP2, BCKD, SNG1, NIPS1, NIPS2, SEPT7, AT2A2, PI51C, PI42A, ITB5, GPX4, NPTX2, GNAZ, WDR1, S4A4, MTX2, CNTFR, ZFR, CSN3, HCN2, HCN1, CTBP1, BSN, MPP3, NOE1, CBPD, LGMN, COR1A, CYB, COX1, COX2, COX3, HPRT, ATP6, THY1, H3C, LAMC1, NU1M, NU2M, NU4M, NU5M, ATP8, GFAP, MBP, PRIO, ALDOA, KAPCA, AATM, TBA1B, TBA3, KIT, LDHA, G6PI, MDR1B, ENPP1, HS90A, ENPL, KCC4, NFL, NFM, RASN, PGK2, ITB1, PPBT, NUCL, PGK1, ACE, LRC4B, UBB, UBC, EF1A1, IF4A2, GSTM1, 4F2, H10, LAMP1, HS90B, L1CAM, ITA5, KCC2A, ITB2, ITPR1, TCPA, PFKAL, CNTN1, NCAM1, AT1B1, C1QB, RS16, RL7, AT1B2, PSMD3, MAP1B, GLNA, CADH2, INSR, NTRK2, KCNC1, SPTB1, H12, KPCE, LDHB, CN37, DDX3L, KCNA1, KCNA3, AMPE, ASSY, SPTN1, G3P, LAMP2, ENOA, AP2A1, AP2A2, HXK1, GTR1, PTPRA, COF1, GNAO, FAS, LAMA1, NFH, COX41, BIP, HEXB, VIME, MTAP2, MAG, GNA11, GNAQ, MDR1A, ACES, GBRG2, AP1G1, GBRD, EIF3A, CXA1, GRIA1, GRIA2, TY3H, RS2, GBRA2, RL3, BRAF, KCC2B, NP1L1, NCKP1, SNAB, KIF3A, PABP1, GBB4, KCRU, GNA14, KAP3, SC6A1, S6A11, MP2K1, GTR3, LA, RASK, SYWC, KIF1A, HYES, RAB3D, RAB5C, RAB6A, RAB21, NMDZ1, ODPA, RET, FBRL, KCNJ2, CD81, GPM6A, GPM6B, GNL1, DYN1, DYN2, GRIK2, CAP1, ABCA2, PURA, HD, EAA2, H14, H15, H13, ITAV, SYT1, NSF, RB11B, AINX, MYO1B, NEDD4, ALDH2, GRM8, CAZA2, CAPZB, MP2K4, PFKAM, RL6, RL29, RL5, GLRB, DCE1, DCE2, CBR1, GSTM5, ADT1, INPP, CDK5, SAHH, GDIA, VATA, VATE1, GBRB1, RAB7A, ACADL, VA0D1, ADT2, EAA3, KCNJ4, KPYM, RAB2A, PRS6B, PTN5, NCAN, ABCD3, RAB8A, ATPK, ATP5E, UBP5, ATPB, CTBP2, EAA1, WFS1, FUS, NICA, ACTN4, ASM3B, EF2, OPA1, DOCK4, IRPL1, ARPC4, MYPR, PLPP, ACTB, MDGA2, NEUG, RAC3, IF4A1, MEGF8, RAB5B, RAB10, RAB8B, ARP2, ACTZ, CSN2, ARF3, ARL1, CAH10, RAP2B, STX1B, RAB6B, RL27, ARF4, GABT, 1433G, RS7, PP1A, RS8, SMD1, KCAB2, ABI2, RB11A, EF1A2, RS4X, PP2AB, RL18A, ACTA, AP2S1, RL23A, VISL1, H4, GBRA1, VATB2, RAB1A, RAB3C, RAN, RAP1A, RS24, GBB1, GBB2, RS3, RL8, RS27A, RL40, RAC1, RAB3A, HSP7C, CH60, VAMP2, NOE3, GBRB3, VATL, PP1G, 1433Z, GBRB2, KCNA2, KCAB1, CRNL1, DYL1, ACTG, ACTH, KPCG, PP2BA, PP2AA, PHB1, CSK2B, ACTC, RACK1, ACTS, KAPCB, TBA4A, TBA1A, TBB4B, KPCB, H31, IMB1, PLXA1, PLXA2, PLXA3, DCC, ITPR3, NCHL1, HNRH2, ELAV1, USP9X, IDHG1, LYAG, AT8A1, TCPH, TCPB, TCPD, TCPE, TCPZ, TCPG, TNIK, WNK1, RL36A, ARF1, ARF5, AP2M1, H32, H33, ADCY5, NPTN, RS3A, AT1B3, DPYL1, ZNT3, GRM1, SHPS1, NEO1, M4K4, C1QA, TBB5, PDE4D, PDE1B, NMDE2, SC23A, TERA, C1QC, CTNB1, PLAK, EPHA4, MARK3, ATPA, CHLE, KCND1, KCRB, NF1, CDK18, RAC2, MARK2, PGBM, PTPRG, PYC, KCMA1, PADI2, INF2, TRIO, MDGA1, CTP5A, ITB8, PSA, GRM2, PTCD3, PHAR1, LRFN1, SPP2B, HP1B3, NLRX1, PRC2C, TM38A, VGLU1, BIG3, PLXD1, AGAP2, AAK1, TEN4, CAMKV, DOP2, RMD3, SMU1, MCCB, GPD1L, LIGO2, SRBS2, CDKL5, K22O, VPS51, GRM5, CBAR2, SHAN3, UN13A, SE6L2, KCTD8, KCD16, LRC8B, VP13A, C2C4C, S2551, MRS2, DIRA2, CYFP2, TM1L2, RHG44, MYO1D, RABL6, DJC11, UIMC1, ICAM5, FLOT2, HNRPD, PTPRN, CSK21, KHDR1, IGF1R, CLD11, SPB6, ARHG2, VDAC2, VDAC3, VDAC1, ABCB7, ASTN1, P3C2A, CAC1E, LAMB2, CTNA2, SC6A3, CNTN2, PGCB, NEP, KCNA4, CD166, 5NTD, GSLG1, EWS, AP180, FSCN1, GDIB, GRIK5, GRID1, DDX5, ITIH3, IL1AP, CD47, KINH, KIF3B, LASP1, MYH10, MOG, NPM, PCBP2, CSPG2, DDX3Y, DLG4, RHOC, DAG1, DDX3X, SYPH, TICN1, NDUA4, NPTX1, NUP62, OMGP, HECAM, AOFA, ARP3B, SURF4, SYN2, CP3AD, H2B1H, GLPK, SDC3, GPDM, H2A2C, H2B2B, GRM7, GRM4, CLH1, K1549, GIT1, PKP4, PPR29, CNTN4, NLGN2, SV2C, THS7A, CE170, UBP7, BRNP2, SCMC3, LIGO3, DGKB, RPRD2, DPP10, S23IP, PPRC1, 2ABA, TNPO3, SIK3, U520, S39AA, TTYH3, XPO1, SPCS, KCRS, CSKI1, NRX3A, BCR, SARM1, PRRT3, TEFF1, RAB35, CA2D2, KCC2D, AT1A3, AT1A2, GNAS1, SDK2, WDFY3, NTRK3, RAD9B, DGLA, KCD12, MTMR5, UBE2O, CAND1, UBP34, RS9, 2ABB, H2B1C, TLN2, CSPG5, 2AAA, NP1L4, MTCH2, OPALI, CYFP1, TBB2A, HUWE1, IGS21, ROBO2, ACTN1, IGSF1, TR143, TPPP, OTUB1, KPBB, PP6R1, MAP6, ELP1, RRAGD, MRCKB, GABR2, CSMD3, EPT1, VAT1L, LRRC7, CAPS1, CYLD, AGRL1, AGRL3, CLAP1, AUXI, DAAM2, MADD, MFN2, NU214, UBE3C, PLXA4, FBX2, KCMF1, CBPM, GSTM7, AGFG2, LRC8A, HPLN4, VAC14, C2C2L, LRRT4, BDH, MK15, CNKR2, TENA, ASTN2, NEGR1, RAP2A, THEM6, SLIK5, SLIK4, SLIK3, SLIK2, NFASC, NRCAM, RHG32, SRGP3, EFTU, VGLU3, ERLN2, SV2B, MIRO1, EFR3A, LRRT2, U2AF4, ENPP6, SYAC, FLRT3, CBLN2, LRTM2, HPCL4, COR2B, S2512, ATLA1, NU107, RB39B, RB39A, ZN526, ANS1B, DLGP2, AHSA1, IPO5, NCEH1, LSAMP, CADM2, NOE2, ODP2, RBGPR, ECHA, SPA2L, SYNC, RL24, DAAM1, DMXL2, RLGPB, CLAP2, VMAT2, ARF2, NDRG4, ENPP4, HSDL1, RAP2C, GEPH, VATH, PMGT2, TTC12, AOFB, LRFN5, PIGT, CTL2, TENR, NLGN3, LRRT3, DYN3, LRC4C, ARHGA, SYFA, SI1L1, LCAP, EXOG, CERS6, SEP11, IKZF4, GP158, CWC22, VPS52, SCAI, ANK2, PDE10, PGM2L, SHFL, MIC60, WDR37, ABI1, SYNPO, T132C, GLT13, NED4L, RPB2, TCRG1, GNAL, H2B1K, H2B1P, H2A1F, H2A1H, H2A1K, OGT1, SYNJ1, SEPT8, MBOA7, PGP, NGEF, PYGB, COPA, MARK4, DOCK3, PLXB1, TXTP, AGRL2, TRHDE, R4RL1, RTN1, HS12A, K319L, DNM1L, AGRG1, PACS1, ABCF3, SDHA, HACD3, AGFG1, PAF1, IPO11, CCM2, MATR3, ATAT, LRRT1, LGI3, RPTOR, COL12, NAC2, THIL, EIF3L, MARE2, HNRPL, K0513, IQEC1, CACB4, SCPDL, BPHL, SNG3, EIF3C, H2AJ, DC1L1, S35A3, AP3M2, MUC18, UBQL1, PSPC1, NUP58, IGSF8, EXOC1, CACB1, CADM4, NUP85, SNP47, ACTY, WASF1, AMPB, MICU1, PSMD2, AT1A1, CDIPT, GD1L1, CC50A, HNRPU, REM2, S25A3, MARK1, CSPG4, SORC3, IPO4, SFPQ, BACH, S12A5, RAB14, SFXN3, ACLY, NDUS1, ITM2C, RMXL1, MIC25, ATPG, DDX1, MLP3A, UBAP2, ACSL6, NDUS2, ERLN1, DLG2, PI42C, IPO9, NDUV1, GRHPR, SRGP2, SRGP1, RAB4B, LRP1, WDR7, BRNP1, SYDC, TBB6, PDK3, TSN2, PDE2A, RPAB3, CSMD1, KCC2G, 2ABD, ATAD3, SFXN5, MYO5A, G37L1, RAP1B, SFXN1, NLGN1, NONO, RRAGC, TIP, MLF2, GAK, CDS2, NDUAA, ETFA, TNPO2, PTPRT, DNJA3, T121B, SF3B1, RIMS1, CNTP4, NTRI, PRP8, COX6C, MGST3, CNTP2, 6PGL, QCR8, NDUB4, RAB5A, GLRX3, AT5F1, S2546, MLP3B, 1433B, RL14, M2OM, UCRI, MIC19, PRPS2, NRX1A, MICU3, ARPC2, TBB2B, ROA0, CENPV, RL11, ILF2, TECR, RN181, BIEA, QCR1, OLA1, RL15, AL1B1, TOM70, MPC2, ODPB, MMS19, MGRN1, HNRPM, SCOT1, DYL2, RM28, RAB1B, LIGO1, RUFY3, MEII1, ATAD1, CUL5, GBRA4, TBB4A, GHC1, IDH3A, PRPS1, U2AF1, RL4, PSD12, SNAA, ATPO, BTBDH, QCR2, ALG2, AP2B1, RPN2, SUSD2, NDUA9, NDUS7, 6PGD, EIF3F, NDUS3, RAB13, XPO7, IPO7, NBEA, SORC2, VPS35, RPGF4, TBB3, XPO2, RTN3, LRBA, SPN90, TRIM2, DYHC1, LRP1B, LGI1, PRAF2, SV2A, SCAM5, NECT1, HYOU1, EXTL1, SORC1, DCLK1, MTOR, MINK1, ZN207, AP3B2, RHOA, HPLN1, FAK2, NAGAB, COPG2, KI21A, SHRM3, PLEC, DREB, S2513, EHD3, PLXB3, ADDA, DNJA2, GRM3, PCLO, SIA7A, ARP10, DCTN5, PLXC1, COPG1, GPC1, UBQL2, FBX6, SRR, AT2B2, CELR2, DEST, ARC1A, KAD1, GBRG1, GUAD, CBLN1, DGKE, VAS1, ADA22, ADA23, PEPL, CAD13, TEN1, TEN2, CUL1, ATRN, GLPK2, PDC6I, PFKAP, PYGM, SUCA, RBMX, GABR1, GSK3B, FPRP, E41L3, BUB3, CARM1, PSD13, CP46A, APC7, NCDN, ITB6, KCND2, NU160, HNRDL, SAE2, VATC1, VPP1, ARI1, CA2D3, SEPT3, AP3B1, STK39, DPP6, E41L1, SUCB1, SEPT5, GRIA4, GRIA3, HOME1
Species: Mus musculus
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Tramutola A, Sharma N, Barone E, Lanzillotta C, Castellani A, Iavarone F, Vincenzoni F, Castagnola M, Butterfield DA, Gaetani S, Cassano T, Perluigi M, Di Domenico F. Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer's disease. Biochimica et biophysica acta. Molecular basis of disease 2018 1864(10) 30031227
Abstract:
PET scan analysis demonstrated the early reduction of cerebral glucose metabolism in Alzheimer disease (AD) patients that can make neurons vulnerable to damage via the alteration of the hexosamine biosynthetic pathway (HBP). Defective HBP leads to flawed protein O-GlcNAcylation coupled, by a mutual inverse relationship, with increased protein phosphorylation on Ser/Thr residues. Altered O-GlcNAcylation of Tau and APP have been reported in AD and is closely related with pathology onset and progression. In addition, type 2 diabetes patients show an altered O-GlcNAcylation/phosphorylation that might represent a link between metabolic defects and AD progression. Our study aimed to decipher the specific protein targets of altered O-GlcNAcylation in brain of 12-month-old 3×Tg-AD mice compared with age-matched non-Tg mice. Hence, we analysed the global O-GlcNAc levels, the levels and activity of OGT and OGA, the enzymes controlling its cycling and protein specific O-GlcNAc levels using a bi-dimensional electrophoresis (2DE) approach. Our data demonstrate the alteration of OGT and OGA activation coupled with the decrease of total O-GlcNAcylation levels. Data from proteomics analysis led to the identification of several proteins with reduced O-GlcNAcylation levels, which belong to key pathways involved in the progression of AD such as neuronal structure, protein degradation and glucose metabolism. In parallel, we analysed the O-GlcNAcylation/phosphorylation ratio of IRS1 and AKT, whose alterations may contribute to insulin resistance and reduced glucose uptake. Our findings may contribute to better understand the role of altered protein O-GlcNAcylation profile in AD, by possibly identifying novel mechanisms of disease progression related to glucose hypometabolism.
O-GlcNAc proteins:
DPYL2, ULK1, MDHM, NFL, G3P, ENOA, AKT1, IRS1, 1433E, RAN, TBA1C, ELOC, MPRIP, TDRD9, CCD63, CNTP2
Species: Mus musculus
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Zaro BW, Batt AR, Chuh KN, Navarro MX, Pratt MR. The Small Molecule 2-Azido-2-deoxy-glucose Is a Metabolic Chemical Reporter of O-GlcNAc Modifications in Mammalian Cells, Revealing an Unexpected Promiscuity of O-GlcNAc Transferase. ACS chemical biology 2017 12(3) 28135057
Abstract:
Glycans can be directly labeled using unnatural monosaccharide analogs, termed metabolic chemical reporters (MCRs). These compounds enable the secondary visualization and identification of glycoproteins by taking advantage of bioorthogonal reactions. Most widely used MCRs have azides or alkynes at the 2-N-acetyl position but are not selective for one class of glycoprotein over others. To address this limitation, we are exploring additional MCRs that have bioorthogonal functionality at other positions. Here, we report the characterization of 2-azido-2-deoxy-glucose (2AzGlc). We find that 2AzGlc selectively labels intracellular O-GlcNAc modifications, which further supports a somewhat unexpected, structural flexibility in this pathway. In contrast to the endogenous modification N-acetyl-glucosamine (GlcNAc), we find that 2AzGlc is not dynamically removed from protein substrates and that treatment with higher concentrations of per-acetylated 2AzGlc is toxic to cells. Finally, we demonstrate that this toxicity is an inherent property of the small-molecule, as removal of the 6-acetyl-group renders the corresponding reporter nontoxic but still results in protein labeling.
O-GlcNAc proteins:
A2A5R8, A2A6U3, A2AF81, A2AG39, A2AIW9, A2AJ72, A2AJI1, A2AKV2, A2AL12, A2AMW0, A2AUR3, LAS1L, TRM1L, A5A4Y9, A6PWC3, B0QZF8, B1AU76, UPP, B7ZC19, B7ZP47, B8JJC1, D3YWF6, D3YWK1, D3YWS3, D3YYP4, E9PX53, E9Q066, I2BP2, E9Q4Q2, E9Q5L7, E9Q7W0, E9QP59, F8WGW3, G3UX26, G3UYZ0, G3UZ44, G3X972, H3BKW0, H7BWX9, GTPB1, AIP, ATOX1, HDAC1, GSH0, DHX15, IKBE, AKAP2, SLK, IMPCT, IF6, ACOT1, NMT1, DHB12, SRPK1, ZN326, KLC1, RPP30, IDHC, CASP8, GCR, TYSY, RIR1, S10AA, LEG1, G3P, TPIS, PRDX3, CBX3, TISD, CATA, IMDH2, NFKB1, MAP4, CEBPB, CDK4, FKBP4, HMGB2, KAP3, MP2K1, RANG, PTN11, FBRL, PTN12, FMR1, HMGCL, DYN1, CAP1, STAT1, STAT3, PURA, ALD2, SIPA1, PURA2, GSHR, FOSL2, FOSL1, GSTM5, PCY1A, VATA, HDGF, UBP10, RHOX5, HMGA2, CCHL, NUB1, FAF1, ZNRD2, TB182, PCBP1, ARL1, PFD3, TCTP, HMGB1, DYL1, UB2L3, HDAC2, ELAV1, 4EBP2, PYRG1, TCPB, SPTC2, PSME2, BOP1, WBP2, XDH, HMMR, E2AK2, CO6A1, FABP5, LARP7, CNN2, PP4R2, RM10, Q3TFP0, GUAA, FUBP2, TRADD, CTU2, Q3U4W8, SNX27, BABA1, EDC4, COBL1, SKAP2, ARH40, CSTOS, LRRF1, ZMAT1, Q45VK5, JIP4, MDC1, Q5SUW3, SRC8, SAMH1, KHDR1, SPB6, CAPR1, PAPS1, TS101, PA1B2, FNTA, IGBP1, FSCN1, FXR1, CBX5, RAI1, MELK, FOXC2, DBNL, CYTB, NDRG1, RALY, GPDM, RAB3I, F120A, NOP58, Q6DFZ1, TPM4, Q6NXL1, Q6NZD2, TNPO3, SMHD1, UGGG1, UBXN7, TXLNA, DC1L2, KI18B, JUPI2, LARP1, CAND2, ACAP2, HNRPQ, SPAG7, ATX2L, MAP6, ELP1, PJA2, PGRC2, KCMF1, Q80VB6, FA98B, WDTC1, CPPED, LPP, PEF1, IF4B, ATG4B, FTO, Q8BH80, PRUN1, AHSA1, RCC2, NCEH1, LSS, FBLN3, PPR18, SRRM2, MSRB3, PPME1, RL1D1, TBCD4, NHLC2, MAP1S, TLK1, CND2, RAE1L, SEP10, ZFP57, UBA6, UBA3, STON1, PPM1F, GNL3, PUR1, HMCS1, Q8K0C7, PDXK, ANGE2, LRC41, SDE2, DNM1L, ANLN, MATR3, CBR3, MEPCE, ERF3A, DC1L1, SPART, TDIF2, HEXI1, SNP47, UBP15, MAVS, UBXN4, ACSF2, MICU1, ZNG1, BACH, ISOC1, IPYR2, CSDE1, PIP30, GCSH, Q91X76, DUS3L, BAG2, KCC1A, TTC1, HNRLL, RIN1, PP6R3, MARC2, DBR1, ATAD3, PSIP1, NXF1, NONO, PLST, RRAGC, VMA5A, TARA, DDAH2, TADA1, GRPE1, ABD12, NU155, OGFR, NPM3, GLOD4, COPRS, DPOE4, MIEN1, TRAP1, VATG1, CHSP1, OCAD1, RANB3, MFR1L, NDUF7, TBC15, PPIL4, MPPB, CYBP, ZCHC8, CD37L, MMS19, ARPIN, HNRPM, NXP20, SPF27, TOE1, Q9D4G5, ATAD1, CF226, IPYR, ORN, CNN3, KAP0, PLIN3, AKAP8, EIF3F, IFG15, LIMA1, NEK7, RTN3, STK3, NUP50, SYSM, HSPB8, BAG3, CUL3, RABX5, CAF1A, DREB, TOM40, DNJC7, NFU1, FBX6, NUBP1, DEST, TEBP, ACOT9, NFKB2, KAD2, SKP1, PDC6I, VAPA, CARM1, RAD9A, IF2G, SAE2, TRIP6, MBD2, HNRPF
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, NU153, 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, 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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Chuh KN, Zaro BW, Piller F, Piller V, Pratt MR. Changes in metabolic chemical reporter structure yield a selective probe of O-GlcNAc modification. Journal of the American Chemical Society 2014 136(35) 25153642
Abstract:
Metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain bioorthogonal functionalities and enable the direct visualization and identification of glycoproteins from living cells. Each MCR was initially thought to report on specific types of glycosylation. We and others have demonstrated that several MCRs are metabolically transformed and enter multiple glycosylation pathways. Therefore, the development of selective MCRs remains a key unmet goal. We demonstrate here that 6-azido-6-deoxy-N-acetyl-glucosamine (6AzGlcNAc) is a specific MCR for O-GlcNAcylated proteins. Biochemical analysis and comparative proteomics with 6AzGlcNAc, N-azidoacetyl-glucosamine (GlcNAz), and N-azidoacetyl-galactosamine (GalNAz) revealed that 6AzGlcNAc exclusively labels intracellular proteins, while GlcNAz and GalNAz are incorporated into a combination of intracellular and extracellular/lumenal glycoproteins. Notably, 6AzGlcNAc cannot be biosynthetically transformed into the corresponding UDP sugar-donor by the canonical salvage-pathway that requires phosphorylation at the 6-hydroxyl. In vitro experiments showed that 6AzGlcNAc can bypass this roadblock through direct phosphorylation of its 1-hydroxyl by the enzyme phosphoacetylglucosamine mutase (AGM1). Taken together, 6AzGlcNAc enables the specific analysis of O-GlcNAcylated proteins, and these results suggest that specific MCRs for other types of glycosylation can be developed. Additionally, our data demonstrate that cells are equipped with a somewhat unappreciated metabolic flexibility with important implications for the biosynthesis of natural and unnatural carbohydrates.
O-GlcNAc proteins:
A1BN54, A2A4Z1, A2A6U3, A2AFJ1, A2AG83, A2AL12, A2AMW0, A2AMY5, LAS1L, B1AU75, OTUD4, B7FAU9, B7ZP47, D3YUC9, D3YVJ7, SAFB1, D3Z4W3, E9PVC5, E9PZM7, E9Q066, E9Q2X6, E9Q310, E9Q5L7, E9Q7M2, E9Q986, F6T2Z7, G3UZ44, G3UZI2, G3X8Q0, G3X8Y3, G3X928, G3X972, G3X9V0, G5E8E1, H3BKK2, J3JS94, CAN2, DPYL2, AIP, HDAC1, MP2K3, GSH0, DHX15, ZW10, AKAP2, SLK, NMT1, E41L2, SRPK1, PARG, SPD2A, LDHA, ANXA2, RIR1, ANXA1, LMNB1, LEG1, G3P, TPIS, COF1, FAS, CBX3, BCAT1, MCM3, MAP4, FKBP4, HMGB2, AIMP1, MP2K1, SYWC, RANG, UBP4, PTN11, RAB5C, DNLI1, CAP1, STAT3, EPS15, PURA, MSH2, ALD2, PURA2, NEDD4, GFPT1, PCY1A, ICAL, HDGF, UBP10, ACTN4, EF2, TB182, SF3B6, PCBP1, PSME3, PFD3, MTPN, DNJA1, SUMO1, IF5A1, UB2L3, HDAC2, ELAV1, 4EBP2, PYRG1, TCPB, BOP1, DAB2, XDH, UBA1, LARP7, CNN2, PP4R2, PSA, Q3TFP0, GUAA, METK2, FA98A, Q3TT92, UAP1L, NOL9, FUBP2, Q3U4W8, YRDC, NOL8, COBL1, CSTOS, LRRF1, Q3V3Y9, DDX17, MDC1, TENS3, Q5UE59, SRC8, SAMH1, KHDR1, SPB6, CAPR1, PAPS1, ASNS, LAP2B, LAP2A, PPM1G, CDC37, FXR1, PCBP2, KPCI, DDX3X, TSN, DBNL, CYTB, ZYX, RALY, SQSTM, TPP2, PEAK1, NOP58, TPM4, LTV1, ZC11A, Q6P5B5, SMHD1, GGA2, TXLNA, JUPI2, UBE2O, LARP1, 2AAA, MTCH2, DEK, MBB1A, ATX2L, OTUB1, MAP6, AFTIN, FLNB, PI42B, ZN598, SAFB2, GRWD1, CPPED, LPP, PEF1, IF4B, SYAC, RUFY1, PRUN1, CTF18, AHSA1, RCC2, IPO5, CKAP4, PPR18, HEAT3, SRRM2, HAT1, MAP1S, TLK1, CND2, THOP1, SEP11, TBL3, SEP10, UBA6, SYEP, GNL3, PDLI5, HMCS1, PKHO2, NEK9, ANLN, MATR3, CBR3, MEPCE, ERF3A, SPART, TDIF2, MCMBP, UBP15, MAVS, Q8VCQ8, PSMD2, FLNC, CPIN1, ACLY, MK67I, RINI, PUS7, CSDE1, DUS3L, KCC1A, TTC1, TADBP, RIN1, NONO, RRAGC, SERB, UBQL4, OGFR, NPM3, GLOD4, MTAP, CYB5B, PSMD9, CHSP1, OCAD1, RANB3, MFR1L, TBC15, CYBP, ZCHC8, GARS, CD37L, UB2V1, HNRPM, Q9D4G5, NOP56, IPYR, CNN3, KAP0, PLIN3, AKAP8, XRN2, MYPT1, PUR6, WDR4, SENP3, LIMA1, ANM1, NUP50, DDX20, IQGA1, MBNL1, ELOV1, DCLK1, BAG3, PPCE, CAF1A, LIMD1, DREB, TOM40, DEST, FOXO1, NFKB2, PDC6I, COR1C, TAGL2, CARM1, MTNB, GBP2, P5CS, EIF3G, SAE2, USO1, HNRPF, KEAP1
Species: Mus musculus
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Alfaro JF, Gong CX, Monroe ME, Aldrich JT, Clauss TR, Purvine SO, Wang Z, Camp DG 2nd, Shabanowitz J, Stanley P, Hart GW, Hunt DF, Yang F, Smith RD. Tandem mass spectrometry identifies many mouse brain O-GlcNAcylated proteins including EGF domain-specific O-GlcNAc transferase targets. Proceedings of the National Academy of Sciences of the United States of America 2012 109(19) 22517741
Abstract:
O-linked N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification of Ser and Thr residues on cytosolic and nuclear proteins of higher eukaryotes catalyzed by O-GlcNAc transferase (OGT). O-GlcNAc has recently been found on Notch1 extracellular domain catalyzed by EGF domain-specific OGT. Aberrant O-GlcNAc modification of brain proteins has been linked to Alzheimer's disease (AD). However, understanding specific functions of O-GlcNAcylation in AD has been impeded by the difficulty in characterization of O-GlcNAc sites on proteins. In this study, we modified a chemical/enzymatic photochemical cleavage approach for enriching O-GlcNAcylated peptides in samples containing ∼100 μg of tryptic peptides from mouse cerebrocortical brain tissue. A total of 274 O-GlcNAcylated proteins were identified. Of these, 168 were not previously known to be modified by O-GlcNAc. Overall, 458 O-GlcNAc sites in 195 proteins were identified. Many of the modified residues are either known phosphorylation sites or located proximal to known phosphorylation sites. These findings support the proposed regulatory cross-talk between O-GlcNAcylation and phosphorylation. This study produced the most comprehensive O-GlcNAc proteome of mammalian brain tissue with both protein identification and O-GlcNAc site assignment. Interestingly, we observed O-β-GlcNAc on EGF-like repeats in the extracellular domains of five membrane proteins, expanding the evidence for extracellular O-GlcNAcylation by the EGF domain-specific OGT. We also report a GlcNAc-β-1,3-Fuc-α-1-O-Thr modification on the EGF-like repeat of the versican core protein, a proposed substrate of Fringe β-1,3-N-acetylglucosaminyltransferases.
O-GlcNAc proteins:
ZEP3, CAMP1, FRPD1, SKT, DLGP4, DPYL2, STXB1, MAP2, NUMBL, M3K5, NOTC2, CTND2, CSK22, ACK1, SYUA, ATX2, ZFR, BSN, GCR, EGR1, NFL, NFM, RC3H2, MAMD1, ATX1L, DERPC, NCAM1, MAP1B, G3P, ATF2, MAP4, KCC2B, AIMP1, FOXK1, STAT3, AINX, NEDD4, RP3A, DVL1, GOGA3, FOXP1, TB182, GMEB2, PI5PA, MRTFB, DOCK4, ABI2, KCNJ3, NCOA1, RGRF2, TNIK, WNK1, G3BP2, MPRIP, XRN1, RLA2, S30BP, MARK3, ENAH, PGBM, CDK12, MA6D1, PHAR1, PSD3, NELL1, PRC2C, YETS2, FOXK2, WNK2, LIMC1, TNR6C, AGAP2, ZEP2, AAK1, TNR6A, CAMKV, PKHA7, GRIN1, FCHO2, GARL3, STOX2, UBN1, ABL2, CDV3, PHAR4, TAB3, NUFP2, UNKL, OSBP2, RBM27, CYFP2, TM1L2, ANR40, NACAD, SIN3A, NCOR1, LAMA5, NCOA2, AP180, RAI1, M3K7, TAF6, SRBS1, SH3G1, TLE4, MINT, ZYX, SF01, SYN2, TBR1, SBNO1, CRTC1, GIT1, SLAI1, PKP4, CDK13, RHG23, SH3R1, JHD2C, HECD1, ABLM3, ARMX2, LAR4B, RHG21, FBX41, RPRD2, WWC2, ZN532, BCR, DLGP3, NYAP1, GMIP, NFRKB, MAGI1, CNOT1, NU188, SMAP2, SPAG7, PRC2B, ATX2L, MAP6, MCAF1, PHF24, NAV3, AUXI, RERE, RIMB2, PUM1, NU214, KCMF1, EPN1, AGFG2, C2C2L, CNKR2, ZN598, SHAN2, MAST4, RHG32, MYPT2, TB10B, FRM4A, SP130, DLGP2, ZNT6, ABLM2, CLAP2, CNOT4, PAMR1, CREST, IFFO1, OSBL6, YTHD3, TM266, SI1L1, SH3R3, RBM14, CNOT2, ANK2, DIDO1, SYNPO, VCIP1, TAB1, SCYL2, ASPP2, F193A, OGT1, NAV1, SYNJ1, RPGF2, EP400, P66A, PDLI5, SCAM1, HS12A, AGFG1, I2BPL, PO121, ABLM1, SPART, RFIP5, CS047, SIR2, AMOT, CCG8, ZCH14, WDR13, UBAP2, NCOA5, FRS3, ZFN2B, BASP1, DCP1A, SRGP2, SRGP1, SYUB, CLIP1, UBXN1, GORS2, EPN4, RB6I2, ANR17, TXD12, NECP1, DLGP1, FIP1, F135B, TM263, PLIN3, MYPT1, CRIP2, TSC1, NBEA, RIMS2, ZN704, RBP2, RTN3, 4ET, ELF2, NUDT3, FMN2, NCOA6, SRCN1, ASAP1, RAD1, SON, PLEC, ULK2, ADDA, PCLO, HIPK2, SH2D3, YLPM1, RHG07, TEN1, NCOR2, COR1B, TNIP1, DEMA, E41L3, SYUG, APCL, MECP2, E41L1
Species: Mus musculus
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