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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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Lanzillotta C, Prestia F, Greco V, Iavarone F, Cordella F, Sette C, Forte E, Tramutola A, Lanzillotta S, Cassano T, Di Angelantonio S, Urbani A, Barone E, Perluigi M, Di Domenico F. Enhancing protein O-GlcNAcylation in down syndrome mice mitigates memory dysfunctions through the rescue of mitochondrial bioenergetics, stress responses and pathological markers. Redox biology 2025 85 40684658
Abstract:
Disturbances of the single sugar modification of proteins, O-GlcNAc, have been identified as a potential connection between disrupted brain metabolism and intellectual decay. In Alzheimer disease (AD), the reduced uptake of glucose in the brain results in aberrant O-GlcNAc cycling contributing to redox imbalance and neurodegeneration. Notably, alterations of O-GlcNAc homeostasis, associated with impaired O-GlcNAc transferase (OGT)/O-GlcNAcase (OGA) regulation, foster neuropathological mechanisms characterized by the presence of AD hallmarks in Down syndrome (DS) models. In the present study we examined the ability of Thiamet G (TMG), a well-known OGA inhibitor, in improving bio-energetic processes, inducing stress responses, reducing AD-related signatures and ameliorating cognition in a murine model of DS. Our data demonstrate that short-term intranasal administration of TMG restored OGA activity and normalized the global O-GlcNAc profile in mouse cortices. By a proteomic approach we identified protein components whose increased O-GlcNAc levels rescue, resulted to brain molecular and cognitive improvements. Remarkably, these included elements involved in energy production, neuronal architecture, antioxidant and stress response mechanisms. The ability of TMG in rescuing O-GlcNAc cycle and metabolic changes, associated with improved mitochondrial activity in cortical tissue, was further accompanied by changes in the O-GlcNAc/phospho ratio of APP and Tau. Functional improvements translated in enhanced recognition memory in Ts2Cje mice. Our study highlights the pivotal role of altered protein O-GlcNAcylation in DS neuropathology and establishes the molecular basis to envision the O-GlcNAc process as a promising therapeutic target to mitigate genetic- and metabolism-driven brain alterations linked to redox imbalance, mitochondrial failure and the development of AD features.
O-GlcNAc proteins:
APBA1, GDS1, DPYL2, STXB1, DLDH, DPYL4, REPS1, CTBP1, COR1A, GFAP, ALDOC, ALDOA, AATC, AATM, ENPL, NFL, NFM, PDIA1, TAU, KCC2A, NCAM1, ENOA, ENOG, HXK1, NFH, BIP, MAP4, KCRU, CTND1, DYN1, CAP1, TCPQ, NSF, PRS7, ALDH2, LMNA, SAHH, GDIA, KPYM, UBP5, ATPB, EF2, HNRPK, ABI2, LIS1, CH60, TBA4A, TBB4B, DLG3, TIAR, NHRF1, DPYL1, RGS14, TBB5, HNRL2, PLAK, ATPA, ANXA7, PPR21, FUBP2, CMPK2, GRIN1, C1TM, SRC8, TS101, PGCB, TCPW, DSG1A, FSCN1, PACN1, DLG4, SYN2, UBXN7, AT1A3, AT1A2, NEB2, 2AAA, TBB2A, PHF24, EFTU, PSD11, SAM50, MAON, CPNE3, SSDH, SEP11, MIC60, OGT1, PYGB, DNM1L, THIL, HNRPL, SHLB2, SNP47, FIBG, AT1A1, IRGQ, CSDE1, SYYC, PCY2, GMPPA, ARP3, RANB3, QCR1, SCOT1, TBB4A, EF1G, DPYL5, TBB3, LGI1, HABP4, AL9A1, GUAD, PDC6I, PYGM, E41L3, PACN2, P5CS, RASL1, PDPK1
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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Soria LR, Makris G, D'Alessio AM, De Angelis A, Boffa I, Pravata VM, Rüfenacht V, Attanasio S, Nusco E, Arena P, Ferenbach AT, Paris D, Cuomo P, Motta A, Nitzahn M, Lipshutz GS, Martínez-Pizarro A, Richard E, Desviat LR, Häberle J, van Aalten DMF, Brunetti-Pierri N. O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis. Nature communications 2022 13(1) 36064721
Abstract:
Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases.
O-GlcNAc proteins:
A0A075B5P3, A0A075B5P5, A0A075B5R4, A0A075B5V1, A0A077S9N1, A0A097PUH2, A0A0M4KM70, A0A0R4J135, A0A0R4J293, A0A1B0GT41, A0AUN0, A0JLV3, A2AA71, A5JUZ1, B1AXW5, B2RTM0, D3Z041, D3Z6F5, E9Q175, E9Q1S3, E9Q3W4, DESP, E9QNH6, E9QPE7, G5E8R3, H7BXC3, H9KV01, K3W4R2, BHMT1, IGKC, K2C1, K2C8, SPTN1, CPSM, HSPA9, KPYM, ATPB, CH60, TBA4A, WNK1, PKP1, PLAK, GSDA2, Q3TD51, Q3TH57, Q3TLH6, Q3TN99, Q3TZR8, Q3UF58, Q3UGJ7, Q3UHW2, Q3UKH3, PRRC1, SC31A, Q3UTZ4, K22O, Q3V222, Q4KL81, Q504P4, Q52L87, Q542G9, Q544B1, Q546G4, Q58E56, Q58E64, Q5FW97, Q5M9N9, Q5QNU0, MYH4, MYH1, HCFC1, DSG1A, MYH10, SPTB2, EST3A, Q68FG2, Q6ZQC2, Q71LX8, NU214, Q80WR0, Q80ZX0, ECHA, NUP54, Q8C140, Q8C153, CPSM, Q8C7S2, Q8CF71, OGT1, Q8CIF2, Q8N7N8, HUTU, MYH9, Q91V38, Q9CV13, Q9D828, ECHP, Q9DC41, MVP, Q9JJ20, Q9QZF3, MYO1C, CARM1, S4R192, S4R1W1, S4R2A9, S4R2L9
Species: Mus musculus, Homo sapiens
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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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Burt RA, Dejanovic B, Peckham HJ, Lee KA, Li X, Ounadjela JR, Rao A, Malaker SA, Carr SA, Myers SA. Novel Antibodies for the Simple and Efficient Enrichment of Native O-GlcNAc Modified Peptides. Molecular & cellular proteomics : MCP 2021 20 34678516
Abstract:
Antibodies against posttranslational modifications (PTMs) such as lysine acetylation, ubiquitin remnants, or phosphotyrosine have resulted in significant advances in our understanding of the fundamental roles of these PTMs in biology. However, the roles of a number of PTMs remain largely unexplored due to the lack of robust enrichment reagents. The addition of N-acetylglucosamine to serine and threonine residues (O-GlcNAc) by the O-GlcNAc transferase (OGT) is a PTM implicated in numerous biological processes and disease states but with limited techniques for its study. Here, we evaluate a new mixture of anti-O-GlcNAc monoclonal antibodies for the immunoprecipitation of native O-GlcNAcylated peptides from cells and tissues. The anti-O-GlcNAc antibodies display good sensitivity and high specificity toward O-GlcNAc-modified peptides and do not recognize O-GalNAc or GlcNAc in extended glycans. Applying this antibody-based enrichment strategy to synaptosomes from mouse brain tissue samples, we identified over 1300 unique O-GlcNAc-modified peptides and over 1000 sites using just a fraction of sample preparation and instrument time required in other landmark investigations of O-GlcNAcylation. Our rapid and robust method greatly simplifies the analysis of O-GlcNAc signaling and will help to elucidate the role of this challenging PTM in health and disease.
O-GlcNAc proteins:
IQIP1, A0A0A6YWG7, A0A0G2JF55, A0A0N4SW93, A0A0R4J060, A0A0U1RPL0, A0A140LIW3, A0A140T8K9, A0A1B0GS41, A0A1B0GS91, A0A1D5RMI8, A0A1L1M1J8, A0A1L1SR84, A0A1N9NPH8, A0A1Y7VNZ6, A0A286YDB3, A0JNY3, A2A482, A2A654, TANC2, LZTS3, AJM1, BCORL, A2AUD5, A2AWN8, B1ASA5, B1ATC3, B1AUX2, B2RQL0, CSPP1, B2RY58, B7ZNA5, CTTB2, D3YU22, D3YUV1, D3YWX2, D3YZ21, SHAN1, D3Z5K8, E0CXZ9, E9PUL3, PRRT2, E9PUR0, E9PV26, E9PVY8, SET1A, E9Q0N0, E9Q3E2, NU153, E9Q4K0, ARI1B, SETD2, E9Q6H8, E9Q6L9, E9Q828, E9Q9C0, E9Q9Y4, E9QAQ7, E9QAU4, E9QAU9, E9QKI2, E9QLZ9, E9QM77, F2Z3U3, F6RQA2, SYGP1, F7C376, BICRA, F8VQL9, F8WIS9, G3UZM1, G3X8R8, G3X928, RFIP2, H3BKF3, H3BKP8, H9KV00, J3QNT7, DPYL2, PRDX6, MNT, NUMBL, PEX5, BMPR2, CTND2, PITM1, ACK1, CAC1B, SYUA, DSG2, SPT5H, E41L2, SP3, KDM6A, CPNS1, ZFR, HCN1, CTBP1, BSN, STAM2, SYN1, MBP, EGR1, NFL, NFM, ITB1, RC3H2, ATX1L, RL7A, MAP1B, VIME, EIF3A, RGRF1, PABP1, FOXK1, EAA2, CBP, RFX1, SOX2, KPYM, CTBP2, GCP3, TB182, GMEB2, PI5PA, DOCK4, PCBP1, LIPA3, RS3, PAX6, KCNJ3, PP2BA, TBA4A, STAM1, NCOA1, CXB6, WNK1, PSME2, WBP2, SHPS1, NRSN1, CTNB1, PLAK, S30BP, ZEP1, YES, CAPR2, MITF, GRD2I, Q0VF59, HDX, MA6D1, F171B, ZFHX2, MLXIP, PDLI7, PRC2C, CIART, YETS2, SRBP2, Q3U2K8, GSE1, RREB1, WNK2, DAB2P, ZEP2, AAK1, TNR6A, GRIN1, SRBS2, GRM5, Q3UZG4, RBM44, Q3ZB57, PHAR4, RESF1, Q5EBP8, UNKL, VP13A, COBL, KDM6B, PRSR1, Q5RIM6, SMG7, RBM27, TM1L2, Q5SVJ0, Q5SXC4, SIN3A, GAS7, CAPR1, KLF3, SIX4, AP180, GRID2, PACN1, LASP1, RAI1, NOTC3, SALL3, SPTB2, ARI3A, NUP62, PHC1, TFE3, PAN3, TIF1A, SF01, SYN2, SBNO1, CRTC1, RIPR1, GIT1, PKP4, ABLM3, ARMX2, CE170, Q6AXD2, NIPBL, FBX41, RPRD2, WWC2, Q6P1J1, Q6P5E3, UGGG1, SPRE3, Q6P9N8, AHDC1, PTN23, TRAK1, DLGP3, NYAP1, DHX29, NFRKB, MAGI1, Q6XZL8, CNOT1, SYNE2, IF2A, PLPR4, PLPR3, CCNT2, PRC2A, MAP6, MCAF1, RERE, NU214, SESD1, C2C2L, CNKR2, SLIK5, RHG32, LPP, NELFA, C42S2, TB10B, TGO1, RFOX3, SP130, ANS1B, ZC3HE, ZC21A, BAIP2, KAT6B, RELL2, LIPA2, CNOT4, TOX4, GASP2, CREST, KDM4A, GRIN3, KAT6A, ZN609, PAK5, A16L1, SI1L1, SH3R3, SKA3, RBM14, Q8C5J0, CNOT2, WDR26, UBA6, ANK2, DIDO1, SYNPO, VCIP1, FHI2A, NUP88, NED4L, SET1B, TENS2, OGT1, NAV1, STAU2, AFG32, S4A8, ZBT20, HS12A, GLT18, UNC5A, AGFG1, FRRS1, KCNQ3, PO121, T2FB, MTSS1, Q8R2E1, NUP35, MAVS, SGIP1, HNRL1, PP16B, CCG8, SFPQ, UBAP2, NCOA5, AJUBA, DCP1A, TWF1, ALS2, ETFD, GRIP1, GORS2, NONO, ZN281, CT2NL, RN111, ANR17, PPP6, RBM7, CYGB, SARNP, DLGP1, SUN1, TM263, GON4L, PLIN3, MYPT1, NBEA, ZN704, RBP2, ARHG7, RTN3, NUDT3, TULP4, Q9JIZ5, PAR6G, SCAM5, PRG4, ZN207, SRCN1, ASAP1, DREB, ULK2, ADDA, PCLO, UBQL2, FBX6, PCM1, SYT7, CRY2, FOXO1, MAST1, LYPA2, TEN3, GANP, DEMA, E41L3, ZO2, BAG6, E41L1, RM40, GRIA3, S4R294, V9GWU7, V9GX40
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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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, NU153, 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, 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, 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, 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, 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
Species: Mus musculus, Rattus norvegicus
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Ji S, Kang JG, Park SY, Lee J, Oh YJ, Cho JW. O-GlcNAcylation of tubulin inhibits its polymerization. Amino acids 2011 40(3) 20665223
Abstract:
The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins is an abundant and reversible modification that involves many cellular processes including transcription, translation, cell proliferation, apoptosis, and signal transduction. Here, we found that the O-GlcNAc modification pattern was altered during all-trans retinoic acid (tRA)-induced neurite outgrowth in the MN9D neuronal cell line. We identified several O-GlcNAcylated proteins using mass spectrometric analysis, including α- and β-tubulin. Further analysis of α- and β-tubulin revealed that O-GlcNAcylated peptides mapped between residues 173 and 185 of α-tubulin and between residues 216 and 238 of β-tubulin, respectively. We found that an increase in α-tubulin O-GlcNAcylation reduced heterodimerization and that O-GlcNAcylated tubulin did not polymerize into microtubules. Consequently, when O-GlcNAcase inhibitors were co-incubated with tRA, the extent of neurite outgrowth was decreased by 20% compared to control. Thus, our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation.
O-GlcNAc proteins:
TBA1B, CTND1, YBOX1, TBA4A, TBA1A, TBB4B, TBA1C, FOXC1, NUP62, DDHD2, PSD11, NUP54, TBB6, TBB2B, TBB3, UBQL2
Species: Mus musculus
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