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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 spicilegus, 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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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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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: Rattus norvegicus, Mus musculus
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Zaro BW, Yang YY, Hang HC, Pratt MR. Chemical reporters for fluorescent detection and identification of O-GlcNAc-modified proteins reveal glycosylation of the ubiquitin ligase NEDD4-1. Proceedings of the National Academy of Sciences of the United States of America 2011 108(20) 21540332
Abstract:
The dynamic modification of nuclear and cytoplasmic proteins by the monosaccharide N-acetyl-glucosamine (GlcNAc) continues to emerge as an important regulator of many biological processes. Herein we describe the development of an alkynyl-modified GlcNAc analog (GlcNAlk) as a new chemical reporter of O-GlcNAc modification in living cells. This strategy is based on metabolic incorporation of reactive functionality into the GlcNAc biosynthetic pathway. When combined with the Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition, this chemical reporter allowed for the robust in-gel fluorescent visualization of O-GlcNAc and affinity enrichment and identification of O-GlcNAc-modified proteins. Using in-gel fluorescence detection, we characterized the metabolic fates of GlcNAlk and the previously reported azido analog, GlcNAz. We confirmed previous results that GlcNAz can be metabolically interconverted to GalNAz, whereas GlcNAlk does not, thereby yielding a more specific metabolic reporter of O-GlcNAc modification. We also used GlcNAlk, in combination with a biotin affinity tag, to identify 374 proteins, 279 of which were not previously reported, and we subsequently confirmed the enrichment of three previously uncharacterized proteins. Finally we confirmed the O-GlcNAc modification of the ubiquitin ligase NEDD4-1, the first reported glycosylation of this protein.
O-GlcNAc proteins:
E9QA16, EF2K, PRDX4, GSTO1, GSH0, DHX15, NOTC2, BCAT2, IMPA1, FHL2, S10A4, ANXA2, RIR1, HS90A, HME2, NUCL, ANXA1, EF1A1, CADH3, CATB, RLA0, H12, FGFR1, TPIS, COF1, VIME, CBX3, IMDH2, FKBP4, PRDX1, CAP1, ALD2, NEDD4, CAPZB, CRKL, LMNA, ROA1, ADT2, KPYM, HMGA2, RL10A, TB182, 1433E, RS3, RS27A, IF5A1, RS12, ACTS, TCPB, SGCG, CDS1, TBB5, XDH, CAPR2, CNN2, FOXO1, NB5R4, PRC2C, MILK2, FUBP2, PRRC1, SRC8, MYL6, VDAC2, VDAC1, RBBP7, ASNS, LAP2A, HCFC1, SERA, TIF1B, NUP62, ABCG1, G3PT, NOP58, TPM4, Q6NVA3, SYNE2, ACTN1, MBB1A, OTUB1, LPP, FLNA, BRI3B, LACC1, SYEP, EIF3B, MATR3, ABLM1, ERF3A, MYH9, CPIN1, WBP11, TRXR3, NPM3, CYBP, GARS, EF1G, CALR3, CP4V2, PUR6, ANM1, DDX21, DEST, CDYL, KHDR2, VAPA, TAGL2, SAE2, TRIP6, TULP1
Species: Homo sapiens, Mus musculus
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