REFERENCES


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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, GRP75, 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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Narayanan B, Zahra F, Reeves RA, Aggarwal A, O'Meally RN, Henry RK, Craven M, Jacobson A, Cole RN, Kohr MJ, Umapathi P, Zachara NE. Differential Detection of O-GlcNAcylated proteins in the heart using antibodies. Analytical biochemistry 2023 678 37507081
Abstract:
Thousands of mammalian intracellular proteins are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc). Global changes in O-GlcNAcylation have been associated with the development of cardiomyopathy, heart failure, hypertension, and neurodegenerative disease. Levels of O-GlcNAc in cells and tissues can be detected using numerous approaches; however, immunoblotting using GlcNAc-specific antibodies and lectins is commonplace. The goal of this study was to optimize the detection of O-GlcNAc in heart lysates by immunoblotting. Using a combination of tissue fractionation, immunoblotting, and galactosyltransferase labeling, as well as hearts from wild-type and O-GlcNAc transferase transgenic mice, we demonstrate that contractile proteins in the heart are differentially detected by two commercially available antibodies (CTD110.6 and RL2). As CTD110.6 displays poor reactivity toward contractile proteins, and as these proteins represent a major fraction of the heart proteome, a better assessment of cardiac O-GlcNAcylation is obtained in total tissue lysates with RL2. The data presented highlight tissue lysis approaches that should aid the assessment of the cardiac O-GlcNAcylation by immunoblotting.
O-GlcNAc proteins:
A0A023T778, A0A075B5P3, A0A075B5P4, A0A075B5P6, A0A075B5T2, A0A075B5T7, A0A087WP81, A0A087WPL5, A0A087WR50, A0A087WS16, A0A087WS46, A0A087WSC6, A0A0A0MQ79, A0A0A0MQA5, A0A0A0MQD2, A0A0A0MQF6, A0A0A0MQJ4, A0A0A0MQM0, A0A0A6YVU8, A0A0A6YW67, A0A0A6YW80, A0A0A6YWP6, A0A0A6YX26, A0A0A6YXF6, A0A0A6YXH3, A0A0A6YXV1, A0A0B4J1E7, A0A0B4J1H7, A0A0F6AIX5, A0A0G2JDI9, A0A0G2JDL9, A0A0G2JDR9, GBP6, A0A0G2JDW2, A0A0G2JE25, A0A0G2JEP0, A0A0G2JEX1, A0A0G2JEY6, A0A0G2JF52, A0A0G2JF85, A0A0G2JG74, A0A0G2JGJ1, A0A0G2JGS0, A0A0J9YU07, A0A0J9YU24, A0A0J9YUZ4, A0A0M3HEQ0, A0A0N4SV40, A0A0N4SV66, A0A0N4SVB1, A0A0N4SVB8, A0A0N4SVK8, A0A0N4SVL9, A0A0N4SW07, A0A0R4J023, A0A0R4J038, A0A0R4J050, A0A0R4J052, A0A0R4J093, A0A0R4J0H8, A0A0R4J0I1, A0A0R4J0K2, A0A0R4J0L5, A0A0R4J0L6, A0A0R4J0S3, A0A0R4J0T5, A0A0R4J0X5, A0A0R4J0Z1, A0A0R4J138, A0A0R4J196, A0A0R4J1E2, A0A0R4J1J3, A0A0R4J1Q6, A0A0R4J1R7, A0A0R4J1W0, A0A0R4J1W7, A0A0R4J260, A0A0R4J275, A0A0U1RPW2, A0A0U1RPY8, A0A140LHG8, A0A140LIU4, A0A140LIZ5, A0A140LJ98, A0A140LJB7, A0A171EBL2, A0A1B0GQU8, A0A1B0GR11, A0A1B0GRP7, A0A1B0GRV0, A0A1B0GRV3, A0A1B0GRW3, A0A1B0GS58, A0A1B0GS68, A0A1B0GS70, A0A1B0GS91, A0A1B0GSG5, A0A1B0GSK8, A0A1B0GSR9, A0A1B0GX27, A0A1C7CYV0, A0A1C7ZN10, A0A1D5RM79, A0A1L1SQ51, A0A1L1SQA8, A0A1L1SS27, A0A1L1SST0, A0A1L1STE6, A0A1L1SV25, A0A1L1SV73, A0A1W2P6E6, A0A1W2P6P1, A0A1W2P768, A0A1W2P7A1, A0A1W2P812, A0A1Y7VJY8, A0A1Y7VKT9, A0A1Y7VKY1, A0A1Y7VLP0, A0A286YCI8, A0A286YCS6, A0A286YD12, A0A286YDA2, A0A2I3BPW0, A0A2I3BQE3, A0A2I3BQF4, A0A2I3BRL8, A0A2K6EDJ7, A0A2R8VHF9, A0A2R8VHX0, A0A338P6D9, A0A338P6G0, A0A338P6N4, A0A338P703, A0A338P731, A0A338P786, A0A338P7D7, A0A338P7F1, A0A338P7G4, A0A3B2W824, A0A3B2WB97, A0A3B2WBC6, A0A3B2WCN9, A0A3Q4EBV4, A0A3Q4EG54, A0A3Q4EH93, A0A3Q4EI56, A0A494B908, A0A494B923, A0A494B955, A0A494B985, A0A494B9D8, A0A494B9P3, A0A494B9W3, A0A494B9X1, A0A494B9Y4, A0A494BA51, A0A494BAJ6, A0A494BB38, A0A494BBC1, A0A494BBG8, A0A571BEC9, A0A571BEG4, A0A571BG59, A0A571BGD8, A0A5F8MPB9, A0A5F8MPD6, A0A5F8MPK9, A0A5F8MPM4, A0A5F8MPN8, A0A5F8MPW1, A0A5F8MPY2, A0A5K1VVQ9, A0A668KL51, A0A668KLD3, A0A6I8MWZ8, A0A6I8MX27, A1BN54, A2A513, A2A5F5, A2A6F8, A2A6Q8, A2A7A7, A2A813, A2A848, TM201, A2A997, A2A9Q2, OBSCN, A2AAW9, A2AE89, A2AEX6, A2AFQ0, A2AFQ2, A2AGJ9, A2AI69, A2AI87, NDUF6, A2AIM4, A2AIW9, A2AK42, A2AKD7, A2AKU9, A2AKV9, A2AL12, A2ALV7, CAVN4, A2AMW0, UBR4, A2AN84, A2APD7, A2AQN4, MYH7B, A2AQR0, A2AQY8, A2AS98, TITIN, A2AT02, A2AU61, A2AUD5, RBGP1, A2BDW0, A2BH06, A2BI12, A2CEK3, A2CES4, A2CG35, A3KFU5, A3KGU5, ARMT1, A6X925, A8DUK4, A8JYK8, CISD3, B1AR28, B1AR93, B1ARA3, B1ASE2, B1ASZ3, B1AT10, B1AU25, B1AUX2, B1AV14, B1AXW5, B1AZ14, B1B0C7, B2C3G8, GNAI1, B2RXT3, B2RY24, B7FAU9, B7ZCI2, B8JJI4, B8JJM5, B8JK32, B9EIZ7, D3YTL5, D3YU39, D3YUG3, D3YUK5, D3YUM1, D3YUP1, D3YVF4, D3YVI6, D3YVV9, D3YW19, D3YWA4, D3YX99, D3YXT0, D3YY36, D3YYE1, D3YYG9, D3YYS6, D3YZ06, D3YZ71, D3Z041, D3Z067, D3Z0G0, D3Z0X5, D3Z0Y2, D3Z1B5, D3Z1V4, D3Z263, D3Z2B3, D3Z2Y8, D3Z4A4, D3Z5K6, D3Z5W3, D3Z627, D3Z636, D3Z6F5, D3Z780, D3Z7A7, D3Z7D5, D3Z7K3, D3Z7U0, D3Z7V3, D5MCW4, D6REH1, D6RFU2, D6RFU9, D6RGM3, D6RH37, E0CXB1, E0CXH2, E0CXN7, E0CXS3, E0CY23, E0CZ90, E0CZE0, E9PUD2, E9PUE8, E9PUM3, E9PUU2, E9PUY9, E9PV12, FIBA, E9PV63, E9PV66, E9PVP0, E9PVU0, E9PWE8, E9PX89, E9PYF1, E9PYI8, E9PZ00, E9PZ88, E9PZC4, E9PZD8, E9PZF0, E9PZI9, E9PZP8, E9Q133, E9Q1J7, E9Q1T9, E9Q1V0, E9Q264, RYR2, E9Q4T8, ACACB, DESP, E9Q5B5, E9Q5I9, E9Q616, E9Q6A9, E9Q6C2, E9Q6W2, E9Q7A5, E9Q800, E9Q933, E9Q9C0, E9Q9T8, E9QJV4, E9QKY4, E9QL13, E9QN70, E9QPD7, E9QPX3, F6QPR1, F6QYE1, F6QYF8, F6RR81, F6VVE6, F6VVY4, F6VY18, F6XI62, F6YCA7, F6ZV59, F7A3N3, F7DBQ0, SKI3, F8VPN4, F8VQJ3, F8WGL3, F8WHU8, F8WIB1, F8WIE5, F8WIT2, F8WIV2, F8WIV5, F8WJ05, G3UVU2, G3UVV4, G3UW30, G3UW85, G3UWN9, G3UX26, G3UXI6, G3UXX3, G3UYR8, G3UZ33, G3UZ48, G3X8R0, G3X8R1, G3X8T3, G3X8T9, QNG1, G3X956, G3X975, G3X977, G3X983, G3X9Q1, G3X9U9, G3XA48, G5DDB7, G5E823, G5E839, G5E883, G5E8R7, H3BIY9, H3BJI5, H3BJP9, H3BJQ7, H3BKH4, H3BKH6, H3BL49, H3BLH2, H7BWZ3, H7BX01, H7BX88, H7BX99, I7HLV2, J3QMG3, J3QPW1, J3QPZ9, J3QQ13, K3W4R2, K3W4S6, K4DI63, L7N451, M0QWU8, CAN2, DPYL2, DLDH, GSTO1, RL21, AMACR, SCRB2, PSMD4, ECH1, ANXA3, C1QBP, TIM44, AL1A7, CAVN1, SYUA, IMPCT, DSG2, NIPS2, AT2A2, PGAM2, PDLI1, AOC3, FHL2, PSA3, DHB12, WDR1, MTX2, ROA2, COMT, BIRC6, IDHC, GNPI1, KBL, AFAM, C1QR1, LANC1, ADH1, COX1, CAH2, CO3, CO4B, HBE, NU1M, NU4M, NU5M, FABP4, MYG, ALDOA, KAPCA, AATC, AATM, TBA1B, CO5, G6PI, MAOX, TTHY, KCRM, ANXA2, ALBU, K2C4, HS90A, CBR2, ENPL, MDHM, PDIA1, NUCL, PGK1, FRIH, SODM, H2AZ, IFI5B, ANXA1, EF1A1, NID1, CATB, THIO, RRAS, H2B1M, H10, LIPL, FABPH, HS90B, DMD, K2C8, ITPR1, TCPA, UCP1, PFKAL, RL7A, GELS, CAH1, GPDA, AT1B1, RS16, RSSA, CALR, HA2B, PSMD3, LMNB1, GLNA, PMGE, CAH3, LEG1, LEG3, CN37, DDX3L, AMPE, ENOA, SBP1, TPIS, CATD, FAS, SERPH, COX41, BIP, PRDX3, VIME, PLMN, ENOB, VTDB, TGM2, AP1G1, EIF3A, CXA1, CRYAB, EST1C, CATA, PPIB, GSTA4, LKHA4, AL1A1, RS2, LYN, TLN1, EZRI, MOES, CTNA1, PTMA, DHE3, PSMD7, FKB1A, PDIA3, ACOHC, ADHX, PGS1, PGS2, NP1L1, ATX10, MUG1, OAT, FKBP4, HMGB2, DESM, MP2K1, SCP2, LA, ANT3, SYWC, MIF, RAB21, HSPB7, TSP1, ODPA, CALX, RL12, PPM1B, TAGL, HMGCL, GRP75, CAP1, TKT, VP26A, INMT, ECI1, H14, ALDR, ALD2, COF2, ACADM, NSF, VPS4B, PRS7, RB11B, NEDD4, PA24A, ALDH2, GSHR, MK14, PFKAM, RL6, ANXA5, ABCD1, LMNA, CBR1, COX8B, TNNI3, ADT1, HEP2, ROA1, INPP, MCM4, CAV1, SAHH, FMO1, GDIA, CSRP3, VATA, ACADL, DHB4, MLRV, HDGF, ADT2, THTR, PON1, KPYM, NDUS6, CPT2, ODB2, IDHP, RD23A, PUR8, DDX6, ADK, ACYP2, AP4A, CX6B1, UBP5, ATPB, CD38, ERP29, EF2, TPM1, B2L13, RUVB1, EIF3E, PCBP1, NPL4, ACTB, CDC42, IF4A1, UBC12, UBE2N, ARP2, ARF3, RL27, 1433G, RRAS2, RS7, PP1B, RS8, RS15A, 1433E, RS23, SMD3, EF1A2, RS4X, AP2S1, RS6, H4, RAN, RS24, RS26, CYC, RL32, FBX40, PROF1, LIS1, HSP7C, TCTP, CH60, IF4E, 1433Z, RS17, PHB1, ACTC, RACK1, 1433T, TBB4B, 1433F, USP9X, IDHG1, NACAM, F16P2, DCUP, PYRG1, TCPB, TCPE, TCPZ, ARF5, AP2M1, RL19, ISC2A, CSRP1, NRP1, RS3A, CPT1A, WBP2, FUMH, LAMA4, TBB5, G6PD1, APOA1, A1AT5, APOH, TERA, UBA1, PLAK, MYH6, KCRB, CO6A1, FABP5, ATP5I, CBG, MPRI, ACADS, AMBP, CD36, Q14BI5, ACSS3, A1BG, TRI72, Q20BD0, NLR1A, HSDL2, OSBP1, CUL4A, Q3TG45, Q3TGM7, GUAA, TM38A, Q3TXN1, PSMD1, SC31B, SYRM, DDB1, Q3U2G2, Q3U422, Q3U816, Q3U8Y1, Q3UER8, Q3UF75, TM10C, Q3UGX2, HAP28, MYLK3, Q3UJQ9, GPD1L, PP1R7, HDGR2, SC31A, THEM4, Q3UZJ4, ST1D1, Q3V117, HSPB6, D39U1, Q5SQ27, Q5SQB0, Q5SUS9, Q5SWN2, ACACA, MYH4, MYH1, COPD, A1AG1, ODO1, LAMA2, STIP1, VDAC1, COQ8A, ADIPO, 2A5G, LAMA5, HARS1, HCDH, GDIB, HS105, SERA, PZP, MIME, POSTN, PON3, DAG1, MYOM1, SPTB2, TX261, TIF1B, TSN, TFR1, NDUA4, CYTB, CAVN2, BTF3, CH10, ADH7, CP4B1, TOP2B, TPP2, H2A2B, H2A2C, NQO1, VINC, PUR2, CTNA3, CLH1, RFTN1, NOMO1, K2C73, 2ABA, U520, XPO1, KCRS, Q6P8N8, OXSR1, LPPRC, UBR2, CAND1, CAND2, MLEC, RS9, IF2A, KAT3, 2AAA, ATPMK, Q7TNL5, SRCA, ELP1, SESD1, FLNB, PANK4, IREB2, EFTU, MIRO1, SAM50, S2540, SYAC, SYNM, F210A, S2512, F13A, EHD2, ECHM, SYIM, AHSA1, RCC2, IPO5, ODPX, MAON, ODP2, ECHA, PPA6, Q8BRB6, AAPK2, Q8BTS3, CSN7B, PPME1, NUDT9, AOFB, SSDH, THIM, KANK2, VP13C, COMD2, PGM5, NHLC2, GPCP1, ASGL1, LCAP, EXOG, THOP1, Q8C483, EMC1, Q8C845, Q8C8G3, ANK2, VWA8, ARK72, SYEP, LONM, UN45B, BICRL, PGP, FBX4, AL4A1, PDLI5, DI3L2, PYGB, FERM2, COPA, PAK2, HMCS1, ACAD9, MIRO2, AFG32, EIF3B, ACSL5, FIBB, TACO1, PDXK, COQ9, SDHA, FMO2, LZIC, HIBCH, THIL, ERF3A, SUOX, FAHD1, S2542, EIF3C, CMBL, COQ6, Q8R2P8, FABD, GBRL1, CLYBL, TMC2, UBP15, RMC1, MAVS, EST1D, ACSF2, CK068, SYLM, MYH9, PPCS, HNRL1, AT1A1, LMCD1, HNRPU, S25A3, RBM39, FLNC, ETFR1, Q91VB8, NDUS1, HNMT, DDX1, CBR4, EIF3H, CISD1, HEMO, VPS36, RHG35, FAKD4, L2HDH, RPN1, TWF1, MYH7, PCCA, UGPA, SMCA5, HNRLL, ETFD, TRFE, RHEB, MACD1, SYDC, MPI, RT02, CPT1B, DCMC, SMRD2, EIF3M, ECHB, Q99JZ4, RRAGC, VMA5A, ACON, DCTN2, NAMPT, PPIF, DHRS1, 3HIDH, DHRS4, MAT2B, NDUAA, ETFA, DDAH2, RTCB, GRPE1, NDUS5, DNJA3, ASPN, MCCA, PPR3A, RM09, ACS2L, NUDT7, RTN4, GDIR1, PRP8, NDUA5, COX6C, ATP5L, LGUL, AMPL, MYL9, NDUC2, DECR, MTAP, PKP2, NDUA2, SDHB, NDUB4, TM223, COTL1, NDUB9, TXD17, TRAP1, AT5F1, ACO13, 1433B, DPH2, M2OM, CHSP1, NAR4, TPPP3, MIC19, SMC1A, NUD17, PUR9, SNX2, CYGB, ROA0, COQ5, MITOS, MPPB, CYBP, BIEA, QCR1, HS12B, RL15, GLYM, EFTS, AL1B1, CISY, 5NT3A, ODPB, SYRC, EXOS7, CY1, SYTC, HINT2, ILEUA, GAL3A, HHATL, RM53, ODO2, OXSM, CUL2, EFHD1, PLCC, NDUV2, FUND2, F162A, ECHD3, IPYR, QCR7, ITPA, RL4, EF1G, T126A, PHP14, MTU1, ATPO, QCR2, PLIN3, LMAN2, PGAM1, ACDSB, OCTC, RT15, 6PGD, NDUA8, PUR6, GSTK1, MECR, NDUBA, NDUS3, CRIP2, RMD1, ETFB, LACTB, DHB11, MMSA, ERAP1, VPS35, RM46, EHD4, PARVB, M3K20, PSMG2, PYGL, IVD, DYHC1, NQO2, ACTN2, COPB, AK1A1, DDX21, RL38, SH3L1, PROF2, TBA8, PRELP, IQGA1, HYOU1, LDB3, GLTP, PALS2, PPCE, MLRA, DRG2, PLEC, S2513, TOM40, CLIC4, DNJA2, ACOT2, AAKB1, DEST, ACOT9, KAD1, PSA4, PSB3, PSB2, SAE1, BMP10, MYO1C, KAD2, KAD3, CUL1, PDC6I, COR1C, SUCA, KAD4, CATZ, ABEC2, CBPQ, EHD1, S12A7, GRK1, MTNB, GBP2, SYUG, TWF2, NFS1, NDUA7, CLIC1, STK39, MTMR9, SUCB2, SUCB1, PCKGC, PSD10, MCAT, S4R1F2, S4R1N1, S4R242
Species: Mus musculus
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Shu XE, Mao Y, Jia L, Qian SB. Dynamic eIF3a O-GlcNAcylation controls translation reinitiation during nutrient stress. Nature chemical biology 2022 18(2) 34887587
Abstract:
In eukaryotic cells, many messenger RNAs (mRNAs) possess upstream open reading frames (uORFs) in addition to the main coding region. After uORF translation, the ribosome could either recycle at the stop codon or resume scanning for downstream start codons in a process known as reinitiation. Accumulating evidence suggests that some initiation factors, including eukaryotic initiation factor 3 (eIF3), linger on the early elongating ribosome, forming an eIF3-80S complex. Very little is known about how eIF3 is carried along with the 80S during elongation and whether the eIF3-80S association is subject to regulation. Here, we report that eIF3a undergoes dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification in response to nutrient starvation. Stress-induced de-O-GlcNAcylation promotes eIF3 retention on the elongating ribosome and facilitates activating transcription factor 4 (ATF4) reinitiation. Eliminating the modification site from eIF3a via CRISPR genome editing induces ATF4 reinitiation even under the nutrient-rich condition. Our findings illustrate a mechanism in balancing ribosome recycling and reinitiation, thereby linking the nutrient stress response and translational reprogramming.
O-GlcNAc proteins:
A0A075B5P4, A0A087WNV1, A0A087WPT1, A0A087WQF8, A0A087WS88, A0A0A0MQM6, A0A0A6YVP0, A0A0A6YY72, A0A0B4J1E2, A0A0G2JFJ6, A0A0G2JFN8, A0A0G2JFY0, A0A0G2JG10, A0A0G2JG59, A0A0G2JG60, A0A0G2JG65, A0A0G2JGL8, A0A0H2UH17, A0A0J9YTU3, A0A0J9YUT8, A0A0J9YUY8, A0A0N4SV00, A0A0N4SV32, A0A0N4SW94, A0A0N5E9G7, A0A0R4J060, A0A0R4J169, A0A0R4J1E3, A0A0R4J1Y4, A0A0R4J260, A1BN54, A1L341, A1L3S7, A2A485, A2A513, A2A5N3, A2A8V8, A2AGK3, LZTS3, A2AM70, A2AMY5, A2APQ6, A2AS44, A2AVJ7, A2AWT6, A2BGG7, KANL3, K1C28, A6X8Z3, A8Y5K6, B0V2N8, B1AU25, TBD2A, THOC2, TPC11, PLXB2, RBM25, B7FAU9, B7ZWM8, B8JK33, B9EHJ3, D3YTT9, D3YUW7, D3YV30, D3YV43, D3YVH4, D3YX49, D3YX64, D3YX85, SAFB1, D3YYT0, D3YZ62, D3YZL1, D3YZT4, D3Z1X3, D3Z2H7, D3Z3E8, D3Z4B0, CCD78, D3Z6N3, CILP2, D6RCG1, E0CY31, E0CYH0, E9PUA5, E9PUJ2, E9PUX0, GCN1, E9PVC6, E9PVG8, KI67, E9PW24, E9PYF4, SET1A, E9PYI8, E9PZW0, E9Q066, E9Q0F0, E9Q0M9, E9Q0U7, E9Q0Y4, E9Q133, E9Q166, E9Q175, E9Q1Z0, E9Q2X6, E9Q3G8, NOLC1, E9Q5F6, E9Q616, MYO1E, E9Q6A9, E9Q6M7, E9Q6T8, E9Q8F0, E9Q9C7, E9Q9H2, E9QA74, E9QAT0, E9QKG6, E9QLM4, E9QN31, E9QNH6, E9QNN1, E9QPE7, E9QPI5, F2Z480, F6S6G6, F6T0G2, F6TFN2, F6TW20, F6WTC8, F6XWD4, F6YRW4, F6YUI5, F7B296, F7C312, FARP1, F8VPX1, F8VQ29, F8WHR6, G3UWP5, G3UWZ0, G3UX48, G3UYD0, G3UYG6, G3UYW3, G3UYZ0, G3X8P9, G3X8Q0, G3X956, SI1L3, G5E839, G5E846, G5E866, G5E879, G5E8C3, G5E8J8, G5E8N3, G5E8T6, H3BJU7, H3BKF6, H3BKM0, H3BKN0, H3BKT5, H3BL49, J3QMC5, J3QNW0, CAN2, ATN1, SRSF5, IMA3, PININ, EIF3D, ATX2, E41L2, UGDH, SP3, IF2B1, ZFR, HIPK1, IGKC, IGHG1, HBA, K2C1, TBA1B, ALBU, HS90A, NUCL, ATX1L, EF1A1, H2B1F, CO1A1, HS90B, TCPA, GELS, HS71L, AP2A2, K1C19, BIP, VIME, MFGM, EIF3A, MCM3, MOES, CTNA1, U2AF2, PDIA3, GRN, PABP1, FKBP4, KIF4, TSP1, GRP75, TKT, BCL6, FOXK1, H14, NEDD4, LMNA, MCM5, K2C6A, IMA1, KPYM, DDX6, ACTN4, EF2, ASXL1, ACTB, ABCE1, RRAS2, H4, HSP7C, CH60, TBA1A, TBB4B, H31, IMB1, TCPB, TCPE, TCPZ, WNK1, H32, MPRIP, G3BP1, TBB5, HNRL2, TOP2A, UBA1, PLAK, IF2P, EPS8, LRIQ1, ZCH18, LMTD2, FA83H, CDCA2, CYTSA, SPP2B, Q3TJ56, K22E, FUBP2, Q3U6F1, Q3U8S1, FOXK2, PUF60, Q3UID0, Q3UJB0, Q3UNN4, SFSWA, K22O, CFA74, Q3UYN2, LRRF1, ESF1, KIF22, Q3V3Y9, Q45VK5, Q4FJZ2, Q4KL80, Q4TU83, PDS5B, DDX17, LRC47, Q52KR6, TR150, NEXMI, JCAD, NUFP2, PRSR1, RBM27, PHF12, UTP18, LC7L3, Q5SUT0, TSR1, MYO1D, Q5U4C5, SIN3A, SRC8, MYL6, STIP1, CAPR1, IMA5, LAP2A, HCFC1, K1C15, SMRD1, FXR1, DDX5, HS71A, SERA, KINH, MYH10, SIN3B, DDX3X, TIF1B, NUP62, K1C12, SQSTM, TOP2B, Q68EM3, CLH1, CDC5L, F120A, CNDG2, NOP58, SCAF8, K1C42, K2C1B, SR140, ZC11A, ABCF1, RRP12, Q6P5B5, UGGG1, XPO1, KIF11, FHOD1, LPPRC, NUP98, Q6PGF5, NEB2, DAPLE, UBE2O, LARP1, NU188, WDR43, 2AAA, Q792Z1, PICAL, UHRF2, MBB1A, Q7TQE2, NU214, WNK4, KIRR1, UBP2L, FLNB, WNK3, Q80ZX0, LPP, ACTBL, P4HTM, MYPT2, HTSF1, IF4B, NU107, WDR3, NOC4L, CE128, NUP93, SUN2, RCC2, EMSY, SYLC, CKAP4, SRRM2, NUP54, PWP2, SYIC, RL1D1, MAP1S, TTC34, SI1L1, RBM14, Q8C872, DIDO1, ATAD2, NUP88, Q8CFQ9, SMC2, UACA, SYEP, TCRG1, OGT1, CCAR1, SLTM, BICRL, P66A, COPA, HMCS1, Q8JZN2, EIF3B, BCLF1, PHLB2, NAT10, ANLN, SDHA, LS14A, MATR3, DDX18, PO121, EIF3L, HNRPL, NU133, EIF3C, ZC3HA, TDIF2, NUP58, CD109, LUZP1, UTP6, MYH9, UHRF1, VIGLN, CCAR2, CUL7, K2C79, Q8VGW3, DHX36, SFPQ, ACLY, DDX1, U3IP2, SYYC, RPN1, YTHD2, BMP2K, SNX18, SMCA5, Q921K2, SF3B3, DDX27, Q921S6, SMTN, PP6R3, K2C5, DEN2B, NXF1, NONO, ACON, NMD3, RTCB, CT2NL, HSP7E, NU155, IF2B3, Q9CPN9, SMC1A, SMC3, CXXC1, GARS, CEP72, SC23B, Q9D6D0, NOP56, FIP1, SPB1, MYPT1, NVL, EIF3F, RAI14, CPSF1, PESC, VPS35, LIMA1, DKC1, PALLD, NUP50, DDX21, FLII, YBOX3, IQGA1, Q9QUK9, CAF1A, K1C17, MAGD1, MTA2, PR40A, MYO1C, COR1C, E41L3, EHD1, WDR46, ZO2, NU160, ADNP, SYVC, Q9Z1R9, BAZ1B, K1C16, SNUT1, S4R2A9, S4R2J9, V9GX87
Species: Mus musculus
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Massman LJ, Pereckas M, Zwagerman NT, Olivier-Van Stichelen S. O-GlcNAcylation Is Essential for Rapid Pomc Expression and Cell Proliferation in Corticotropic Tumor Cells. Endocrinology 2021 162(12) 34418053
Abstract:
Pituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients because of profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlate with their onset or severity. Herein, we investigate the impact of the O-GlcNAc posttranslational modification in their etiology. Found in more than 7000 human proteins to date, O-GlcNAcylation dynamically regulates proteins in critical signaling pathways, and its deregulation is involved in cancer progression and endocrine diseases such as diabetes. In this study, we demonstrated that O-GlcNAc enzymes were upregulated, particularly in aggressive adrenocorticotropin (ACTH)-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we showed that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hypersecretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushing disease, materialized by severe endocrine disruption and increased mortality. We demonstrated that Pomc messenger RNA is stabilized in an O-GlcNAc-dependent manner in response to corticotrophin-releasing hormone (CRH). By affecting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas' pathophysiology, including cellular proliferation and hypersecretion.
O-GlcNAc proteins:
GPTC8, ITB4, PTPRF, VIR, HMCN2, SETX, RTF1, MYH7B, FSIP2, ARGAL, CO6A5, MMRN2, STOX1, PLXB2, AGRG4, F25A2, LOXH1, HMCN1, TM233, PIEZ1, TOPZ1, CE350, M3K19, RYR2, ACACB, RN213, CF251, ARHG5, BICRA, FOXM1, DLDH, PEX5, WRN, CELR1, PROM1, STK10, MYPC3, DTNB, IKKB, ACTN3, ALDOC, RPB1, LMNB1, MAP1B, HVM57, PAI1, MCM3, MIS, RGRF1, MSRE, CTND1, RB22A, ZO1, QOR, ANXA5, MSH6, EVC, KCNN2, DEPD5, NOE3, TBB4B, ROCK1, GSH1, G3BP1, ATS1, TBB5, NF1, PGBM, IF2P, FA8, GDF3, KCMA1, ZCH18, TANC1, NSUN7, SHRM4, FAT4, IGFN1, HMHA1, FA98A, SCRN3, CH048, K22E, SHLD2, BIG3, SDK1, BAHC1, SLMAP, TBCD9, RIMB3, DYH12, ITAD, CKAP2, IGS10, A3LT2, ITA1, HERC2, XIRP2, TR150, IQEC2, LRC8B, FAT2, S39AC, VP13A, MTUS1, GSTCD, TENS3, ACACA, UTP20, KLRA4, PAPOA, STAR3, EWS, KTN1, GRID1, DDX5, CP131, SEM3B, TLL1, MINT, CCPG1, BTF3, TPP2, RBL1, COBA2, TASOR, PDS5A, CE290, NAL14, A2MG, ZZZ3, FREM2, CPSF6, RPRD2, HEAT6, P4R3A, FIL1L, SNX6, GAPD1, PTN23, TRI37, MON1A, MSL1, SARM1, CENPE, DAPLE, TIAM2, UBE2O, KDM3B, SYNE1, CMYA5, FHOD3, TBB2A, MYCB2, SGO2, MCAF1, STAR9, CAPS1, PHF8, CUL9, CLAP1, ST18, SGSM2, TAF1, M18BP, UBP2L, FLNB, OFD1, PTHB1, PDK1, TMCO3, NRDC, MARF1, TM87B, UNC80, TCAF1, KTU, UBP43, CAPS2, ZN609, DOCK2, RHG24, NAKD2, LENG8, UFL1, CD158, CLASR, SSPO, SLTM, NAV1, FBX4, RFWD3, MICA3, STAU2, NEIL3, CCD14, DDX18, UBP45, AL1L1, CCD80, TF2H3, FYCO1, HNRPU, DYH5, DHX36, AGRV1, FLNC, REST, NDUS1, CREL1, CELR3, DYST, BRWD1, GOGA2, PDIA6, TM1L1, RT4I1, CSTN3, PRP19, TARA, UBP16, NOG2, MYO7B, BCDO2, RRBP1, ZN318, DHX30, MITOS, RBM33, NARF, KLH35, ACSL3, SYRC, C16L2, NBEA, TBB3, XPO4, RBCC1, LRP1B, CAC1F, PRG4, BIR1B, SRCN1, SHRM3, ING1, MACF1, ACL7A, SMK2B, H17B6, RPGR, RHG07, MAST1, ADA11, TIM, PFKAP, IRAG1, DEMA, P2R3D, SETBP, NEK4, PLD1
Species: Mus musculus
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Gurel Z, Zaro BW, Pratt MR, Sheibani N. Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy. PloS one 2014 9(5) 24788674
Abstract:
Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR.
O-GlcNAc proteins:
UBP36, PYR1, RBM25, TRIPC, CAN2, PRDX4, AIP, GSTO1, X3CL1, DHX15, HNRH1, AT2A2, GPX4, TRI18, O88568, HA1W, LDHA, ANXA2, RIR1, HS90A, ANXA1, HS90B, TCPA, UMPS, H12, LEG1, DDX3L, TPIS, HB2I, FAS, IMDH2, MCM3, PSB8, SYWC, PRDX1, DNLI1, CAP1, STAT3, PURA, TCPQ, H14, H11, NEDD4, CAPZB, RL36, HS74L, ADT1, MCM4, RAB7A, ADT2, KPYM, RL10A, ACTN4, EF2, RIPK2, SF3B6, PCBP1, ABCE1, 1433E, RS11, 1433Z, TBA1A, EM55, HNRH2, ELAV1, TP53B, TCPB, ARF1, PSME2, TBB5, UBA1, CNN2, TGM3, INF2, GUAA, FUBP2, LRRF1, DDX17, SRC8, MYL6, SAMH1, KHDR1, IRGM1, SPB6, VDAC3, ASNS, LAP2A, PPM1G, PSN2, ZN638, FXR1, SERA, PZP, NPM, GPDM, NOP58, TPM4, NEST, TNKS1, RS9, MBB1A, ATX2L, FLNB, SYAC, LSS, CKAP4, HEAT3, THOP1, AROS, TXNL1, SYEP, STAU2, AGO4, HMCS1, PNPT1, ANLN, MATR3, WIPI1, MYH9, PARN, AT1A1, FLNC, RAB14, SFXN3, IPYR2, SMC1B, TADBP, LRC59, NONO, GRPE1, NU155, OGFR, MTAP, CYB5B, MPPB, GARS, HNRPM, TRIR, IPYR, EF1G, PUR6, RAI14, LIMA1, PALLD, TMOD3, DDX21, WDR12, CUL3, TRXR1, DREB, ZBP1, TOM40, DNJC7, IIGP1, DEST, ACOT9, KAD2, TEN1, VAPA, GBP2, P5CS, SAE2, SYVC, HNRPF
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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Trinidad JC, Barkan DT, Gulledge BF, Thalhammer A, Sali A, Schoepfer R, Burlingame AL. Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse. Molecular & cellular proteomics : MCP 2012 11(8) 22645316
Abstract:
O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic, reversible monosaccharide modifier of serine and threonine residues on intracellular protein domains. Crosstalk between O-GlcNAcylation and phosphorylation has been hypothesized. Here, we identified over 1750 and 16,500 sites of O-GlcNAcylation and phosphorylation from murine synaptosomes, respectively. In total, 135 (7%) of all O-GlcNAcylation sites were also found to be sites of phosphorylation. Although many proteins were extensively phosphorylated and minimally O-GlcNAcylated, proteins found to be extensively O-GlcNAcylated were almost always phosphorylated to a similar or greater extent, indicating the O-GlcNAcylation system is specifically targeting a subset of the proteome that is also phosphorylated. Both PTMs usually occur on disordered regions of protein structure, within which, the location of O-GlcNAcylation and phosphorylation is virtually random with respect to each other, suggesting that negative crosstalk at the structural level is not a common phenomenon. As a class, protein kinases are found to be more extensively O-GlcNAcylated than proteins in general, indicating the potential for crosstalk of phosphorylation with O-GlcNAcylation via regulation of enzymatic activity.
O-GlcNAc proteins:
A0JNY3, A2A653, A2A654, TANC2, ZEP3, MA7D2, CKAP5, CAMP1, LZTS3, A2AJ19, AJM1, MA7D1, A2ALK6, RPGP1, UBR4, A2AP92, SKT, ANR63, A2ATK9, A2AUD5, A2BI30, A6H6J9, A6MDD2, A8DUV1, B1AQX6, B1AR09, GRIK3, B1ATI9, B1AWT3, NHSL2, FRS1L, UBP24, DLGP4, B2RQ57, B2RQ80, PYR1, B2RQL0, B2RQQ5, GNAI1, B2RUE8, OTU7B, B2RWX1, B6ZHC4, B6ZHC5, B7ZCA7, B7ZMP8, B7ZNA4, B7ZNF6, B7ZWM6, B9EHE8, CTTB2, B9EKL9, PTPRZ, D1FNM8, D3YU59, D3YWX2, DGKH, D3YXR8, PGBD5, SHAN1, D3Z0V7, D3Z2J5, D9HP81, E0CYT1, E9PUA3, E9PUC4, DGKD, E9PUR0, E9PV14, E9PV26, KI67, E9PWL1, E9PWM3, E9PY55, E9PZP8, E9Q1M1, E9Q2B2, E9Q3D6, E9Q3G8, E9Q3M9, E9Q4N6, E9Q616, E9Q6T8, E9Q6Y8, NUMA1, E9Q828, E9Q9I2, E9Q9J6, E9QA16, E9QAP7, E9QAR5, SC16A, E9QJU8, E9QMJ1, SYGP1, RFIP2, HXK2, CAN2, SC22B, DPYL2, STXB1, TCOF, DCTN1, GLU2B, EF2K, PRDX4, AIP, NUMBL, GSTO1, GSH0, M3K5, PSMD4, DHX15, NPC1, BMPR2, VIAAT, BCAT2, CTND2, PITM1, CSK22, REPS1, ACK1, SLK, CAC1B, PGRC1, IMPA1, SYUA, AKA7A, STRN, RL35A, AT2A2, PGAM2, ATX2, NMT1, E41L2, GPX4, EMC8, DHB12, HCN4, KDM6A, ZN326, SORL, GRPE2, KLC1, ZFR, O88568, HCN2, HCN1, BSN, TOM1, RPP30, DNJB5, COX1, HA1D, HBA, K2C1, MBP, ALDOA, PGFRB, LDHA, G6PI, ENPP1, NEUM, ANXA2, RIR1, HS90A, EGR1, MDHM, KCC4, NFL, NFM, GNAI2, PDIA1, NUCL, CADH1, RC3H2, LRC4B, IGS11, DERPC, UBB, IFI5B, IFI4, ANXA1, EF1A1, H2B1F, PARP1, HS90B, DMD, KCC2A, TCPA, A4, COX5A, GELS, UMPS, NCAM1, GPDA, MDHC, SRP54, RLA0, GLNA, H12, LEG1, DDX3L, SPTN1, AP2A2, TPIS, KS6A3, COF1, GNAO, NFH, SERPH, VIME, MTAP2, EIF3A, CBX3, IMDH2, MCM3, CTNA1, MAP4, GNA12, GNA13, PDIA3, PSB8, NCKP1, PABP1, FKBP4, HMGB2, AIMP1, LA, ACM4, SYWC, RANG, RAB5C, RAB18, CALX, PRDX1, RL12, PPM1B, DNLI1, CAP1, STAT3, PURA, OPRM, TCPQ, CX6A1, MSH2, H14, H11, ALDR, ALD2, CBP, AINX, NEDD4, RP3A, CAPZB, SRPRB, RL36, SOX2, HS74L, ADT1, ROA1, INPP, PCY1A, MCM4, CSRP3, RAB7A, CDN2A, HDGF, ADT2, IMA1, UBP10, KPYM, RIDA, HMGA2, RL10A, CCHL, SOX1, RAB2A, ATX1, CACB3, HMCS2, GOGA3, ATPK, ATPB, ACTN4, IDI1, ACOT8, PTPA, KCNN2, KCNN3, TB10A, TB182, SF3B6, MRTFB, DOCK4, MYPR, EIF3E, PCBP1, LIPA3, ACTB, IF4A1, SNP25, RAB10, CSN2, RRAS2, PRS8, RS15A, 1433E, RS18, RS11, SMD1, ABI2, EF1A2, ACTA, VATB2, RL23, RS24, GBB1, HSP7C, TCTP, GNAS2, 1433Z, HMGB1, IF5A1, ACTG, RS17, RS12, UB2L3, RACK1, ACTS, TBA4A, TBA1A, TBB4B, PLXA2, DCC, EBP, NFIX, EM55, HNRH2, NCOA1, ELAV1, RGRF2, USP9X, TCPB, TCPE, TCPZ, NUCB2, IRS2, WNK1, RL36A, CSRP1, SEPR, RS3A, DPYL1, MPRIP, CAC1A, ATP5J, BOP1, RS5, WBP2, CXAR, PLPL9, G3BP1, RBBP6, CDS1, TBB5, IL6RB, NMDE2, NMDE3, TOP2A, NOTC1, NDKB, AQP1, UBA1, CTNB1, S30BP, NFIA, NUCB1, MARK3, APLP1, ENAH, ATPA, TF65, YES, MARK2, PGBM, PYC, CAPR2, EMAL1, LARP7, BAX, CNN2, LYAR, CHD8, CNNM1, INF2, TT21B, Q0IJ77, TRIO, VGF, TANC1, CDK12, Q14B66, MA6D1, NSUN2, MCM9, PHAR1, PSD3, Q2Q7P0, FILA2, Q3TAD4, NB5R4, GUAA, METK2, PRC2C, Q3TRG3, PLPL6, K22E, YETS2, Q3TY93, FUBP2, F117B, Q3U882, LBR, TM109, FOXK2, Q3UFK1, Q3UGZ4, TNR6C, DAB2P, ZEP2, AAK1, Q3UHT7, DTX3L, EDC4, PARP3, WASC4, GRIN1, Q3UQ23, SRBS2, THSD4, MRCKA, SPRY3, KSR2, GRM5, TBCD9, LRRF1, ARMX5, STOX2, SHAN3, UBN1, OXR1, DDX17, PHAR4, ANR28, ZN608, Q571B7, PRAG1, TAB3, Q58DZ3, IQEC2, Q5DU62, AAPK1, NUFP2, UNKL, SMG7, RBM27, CYFP2, TM1L2, PSME4, ANR40, Q5SUH6, GGNB2, SYNRG, Q5SVJ0, RPGP2, TBC9B, ACACA, Q5SXC4, Q5XJV5, LMTK3, RN123, ZDHC8, SRC8, MYL6, SKI, SAMH1, IRGM1, CLD11, NPT2A, SPB6, VDAC2, VDAC3, VDAC1, STYX, RBBP4, ASNS, NCOA2, LAP2A, PPM1G, ASTN1, PRDX2, HCFC1, APC, KCNA4, AP180, FXR1, GDIB, GRID2, GRID1, CBX5, SERA, LASP1, NPM, PCBP2, M3K7, SRBS1, DBNL, SH3G1, CYTB, IF4G2, MINT, ZYX, RALY, TFE3, Q640L6, AR13B, HECAM, NPDC1, SYN2, TBR1, ISG15, ABCG1, ATP4A, MRC2, G3PT, PTN13, TPP2, CTNA3, SBNO1, BEGIN, K1549, GIT1, SLAI1, PKP4, PEAK1, CDK13, SH3R1, MYOF, ABLM3, ARMX2, CE170, LAR4B, NOP58, Q6GR78, TPM4, NIPBL, RRP5, FBX41, Q6NVA3, RPRD2, WWC2, ZN532, Q6NXW0, S23IP, SMHD1, NEST, CSKI1, Q6P9N8, MTSS2, AHDC1, PTN23, TRAK1, SRSF1, CHD4, DLGP3, NUP98, NYAP1, KCC2D, AT1A3, AT1A2, NFRKB, RIGI, MAGI1, WDFY3, TACC1, GGYF2, PF21A, KDM3B, CNOT1, LARP1, Q6ZQB7, NU188, Q6ZQJ9, Q6ZQK4, RS9, RL10, IF2A, SC6A5, SEM6D, 2AAA, EEIG1, MTCH2, PICAL, MRO2B, SCN4B, PLPR4, HNRPQ, TBB2A, SMAP2, Q7TNS5, PLPR3, MBB1A, LNP, TPPP, ATX2L, OTUB1, EXOS3, MAP6, ELP1, SI1L2, LRRC7, ERBIN, PHF24, R3HD2, NAV3, AGRL3, Q80TS6, AUXI, MADD, AVL9, PUM1, UBP8, NU214, SEPT9, NAA15, CAMP3, FA98B, TDRKH, EPN1, TMCC2, AGFG2, UBP2L, Q80X68, C2C2L, FLNB, LRRT4, WNK3, PRIC2, CNKR2, ZN598, SHAN2, AGRB3, Q80ZX0, ZFYV1, MAST4, RHG32, ENTP3, LPP, PEF1, ACTBL, TET3, MYPT2, IF4B, SYAC, F168A, TBL1R, TB10B, CSTP1, CARF, TGO1, FRM4A, SYIM, ANS1B, DLGP2, ZNT6, RCC2, ABLM2, LSS, UNC80, NOE2, CF015, EMSY, ODP2, GGA3, SYLC, DMXL2, IMP2L, CLAP2, LIPA2, ASPH, CNOT4, FLNA, F163B, GEPH, CREST, KCC1D, PGES2, KANK2, GEMI5, IFFO1, OSBL6, YTHD3, TM266, POGZ, LACC1, MAP1S, A16L1, SI1L1, PP4R4, MYO9A, THOP1, RBM14, Q8C2R1, CNOT2, Q8C6E9, CC134, ANK2, ELFN1, DIDO1, NHSL1, WDR37, DCTN4, SYNPO, BCAS3, VCIP1, Q8CE98, TAB1, SCYL2, NED4L, SYEP, F193A, GNAL, OGT1, NAV1, SYNJ1, RPGF2, EP400, PHC3, P66A, TBCE, VWF, STAU2, LIN7A, TBC23, ZBT20, RTN1, HS12A, DNM1L, UNC5B, UNC5A, ANLN, AGFG1, MATR3, Q8K314, AHI1, NDUS8, I2BPL, PREP, ABLM1, EIF3L, ERF3A, HNRPL, IQEC1, DOCK7, DC1L1, SPART, BST2, RFIP5, AT2A1, NUP35, LUZP1, MAVS, MYH9, PARN, AT1A1, SIR2, SNRK, ZDHC5, CC50A, AMOT, AGAP3, MARK1, Q8VHM5, FLNC, SFPQ, CPIN1, WDR13, BACH, S12A5, RAB14, ACLY, MIC25, ATPG, DDX1, SH3L3, UBAP2, NCOA5, CSDE1, FRS3, ZFN2B, DLG2, PTBP2, SRGP1, TMLH, DYST, SYUB, ELOV6, ALS2, TADBP, TBB6, CLIP1, LRC59, K2C5, UBXN1, SIR1, SPRE1, PAWR, MED1, MEP50, STML2, UBP11, NONO, RRAGC, VMA5A, MAOM, DCTN2, NEUA, DDAH2, DNJA3, TRXR3, RB6I2, SRRT, DSRAD, Q99NC2, RIMS1, ANR17, NU155, NTRI, RRBP1, ZN318, TRI33, ATP5L, RL17, GLOD4, DUT, SDHB, GLRX3, IFM3, NECP1, OCAD1, RRP44, TBB2B, DDAH1, YIF1B, ROA0, NIP7, MPPB, CYBP, RL11, TECR, CHTOP, SERB1, QCR1, NNRD, GARS, TOM70, RS19, SYRC, CNDP2, TMEDA, ODO2, DLGP1, TBB4A, IDH3A, IPYR, RL37, FIP1, TIM50, EF1G, RM17, GSDMD, DDA1, F135B, TM263, CNN3, PLIN3, PGAM1, XRN2, MYPT1, DJC10, KC1D, GNAI3, PUR6, S38A3, NDUBA, CRIP2, TSC1, RAI14, NBEA, TCF20, SORC2, DPYL5, TBB3, RBP2, ARHG7, RTN3, SPN90, RBCC1, PSMG2, DDX24, CLD12, PALLD, ELF2, TMOD3, NUDT3, COPB, NUP50, DDX21, TULP4, FLII, RPF2, CCG3, TBA8, IQGA1, NECT1, ADRM1, FMN2, PALS1, DCLK1, BAG3, CUL3, MINK1, REEP6, TRXR1, SYGP1, SON, APBB1, DREB, SPY2, MACF1, ULK2, ZBP1, TOM40, ADDA, GOGA5, DNJB1, MAP1A, PCLO, GAB1, RIPK3, NPAS3, SH2D3, NUBP2, ZEB2, SYT7, DEST, TEBP, SRS10, RPGR, PR40A, KHDR3, TPSN, CDYL, KAD2, TEN1, PDC6I, CHIP, IF4H, COR1B, COR1C, TNIP1, GANP, ARC, MPP2, SHAN1, VAPA, GSK3B, DEMA, E41L3, JIP1, GBP2, CAD20, P5CS, LAT1, DYR1B, MD2L1, SAE2, APCL, SYVC, MTMR1, MECP2, E41L1, SUCB1, HDAC6, GRIA4, HOME1, OSB10
Species: Mus musculus, Rattus norvegicus
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