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Vang S, Helton ES, Guo Y, Burpee B, Rose E, Easter M, Bollenbecker S, Hirsch MJ, Matthews EL, Jones LI, Howze PH 4th, Rajasekaran V, Denson R, Cochran P, Attah IK, Olson H, Clair G, Melkani G, Krick S, Barnes JW. O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis. Frontiers in immunology 2024 15 38665916
Abstract:
Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is characterized by an excessive accumulation of extracellular matrix (ECM) proteins (e.g. collagens) in the parenchyma, which ultimately leads to respiratory failure and death. While current therapies exist to slow the progression, no therapies are available to resolve fibrosis.
O-GlcNAc proteins:
NUD4B, GAL3B, UBA6, HACL2, SPD2B, NBAS, SBNO1, VP37C, CNOT1, ZN316, DDTL, ZSWM8, P121C, GNAT3, EIFCL, C2D4D, IGLL5, NACAM, DNS2A, ADAS, PDLI1, BACH, MYO1C, AIP, GTPB1, AP3B1, PSD11, PSD12, PSMD9, ATOX1, CBX4, PGRC1, SPT5H, TAF4, DFFA, CLIC1, TR11B, EIF3F, ODPX, MATN2, QSOX1, WASL, IPO5, EMAL1, IF2B3, DNM1L, MANBA, PLOD2, MEIS1, PSDE, ZN593, IMA4, BCL9, PESC, NOP56, DDX3X, CCN1, IMA3, MA2B1, SCD, PLPP3, ARI1A, TRAD1, HSPB6, COPE, IF1AY, CCS, DVL2, TOR1A, P5I11, ANM5, NHRF1, TPP1, TCRG1, NRP1, PSA7, SCAM3, ML12B, HGS, MYPT1, GAK, HNRDL, XPO1, ZN609, SC16A, PLXB2, SR140, SET1A, SYNJ2, PUR4, NPC1, TBX3, ARC1B, ARPC2, ARPC3, TIF1A, NKRF, CASC3, RER1, SURF4, SPTC1, SPTC2, OGT1, PMM2, PPM1G, SHIP2, EIF3D, EIF3H, IPO8, STX7, MOT4, MRP4, P4HA2, NUP42, ARPC5, CLOCK, TPSN, KDM6A, DHX15, ASAP2, PRP4, SERA, DC1L2, PSMD3, RFOX2, PAPS1, SNUT1, DAPK3, TGFI1, CTIF, M3K7, MCA3, HNRPR, PRPF3, TXNL1, TPD54, EMC8, SYNJ1, IF4G3, ARK72, E41L2, B4GA1, FOXO3, RNF13, DENR, XPOT, PLRG1, ZN207, NDUA2, BUB3, ACTN4, AP1G1, SNG2, SGTA, SYNC, KRT86, MYO1B, CPSF5, LANC1, U3IP2, AKAP8, NRDC, CALU, EDIL3, SAHH2, EXTL3, MED14, SMCA5, TRAK2, GANP, FADS1, PEPL, NRP2, MA1A2, ACSL4, SNX3, OGA, HNRPQ, TPST1, NEMF, GREM1, PLOD3, SEP15, TSN3, PLIN3, MAFK, UGDH, CTND1, DPM1, USO1, RT14, H2B1K, PRAF2, DKC1, IF2P, DNJA2, BRD4, MITF, SRGP2, WDR1, ROCK2, CPNE3, PHF2, T22D2, PP6R2, CREST, ANR17, GGCT, NDUS2, ZPR1, DUS11, NIPS2, SEM7A, LX12B, TBCA, VATG1, H2AY, FLNB, NCOR1, NDUS6, CISY, SPAG7, SC22B, DEAF1, PR40A, MPPB, PSIP1, ERLN1, CLN5, CLD11, SF3B1, CSDE1, WBP4, PRKRA, LYPA1, ERAL1, U520, TIPRL, CRTAP, EIF3G, EIF3J, CBR3, FACE1, IDHC, ATRN, STAM2, PIAS1, PIAS2, DNJC8, SPF30, ATP5H, TRIO, CBPD, KT33A, KRT34, KRT36, RL1D1, WFS1, CLPX, STC2, PDE5A, SRP72, DDAH1, B3GA3, MTA2, AL1A2, TOM70, TOX4, SC24D, PHF14, CSCL1, TOX, SUN1, ERLN2, PRP6, NFAT5, GLSK, SC31A, CSTN1, YIF1A, AGFG2, SCAF4, ZFPL1, ELP1, NDUB8, LETM1, ZRAB2, LC7L3, VAPB, MPZL1, NDUAA, FKBP9, 6PGL, PAPS2, SMC2, IPO7, AGM1, SVIL, AHSA1, PSMG1, NSA2, G6PE, SC24A, SC24B, ETHE1, ACSL3, CNOT4, EYA4, K2C75, OXSR1, AP2A1, WIZ, STAU1, BAG2, BAG3, AIFM1, LATS1, BPNT1, FADS2, DDAH2, ABHGA, TXD12, FBLN4, RECK, NUDT3, NDUBA, CLPT1, TOM40, ACL6A, CYB5, LDHA, DHE3, NB5R3, GSHR, COX2, PNPH, HPRT, AATM, EGFR, PGK1, C1R, PLMN, UROK, TPA, ANT3, A2MG, CO3, CO5, TIMP1, CYTA, RASN, LDLR, TGFB1, IGHG1, IGHA1, HLAB, CO1A1, CO3A1, CRYAB, K1C14, K2C6A, LMNA, APOA1, APOC3, FIBA, FIBB, FINC, AMBP, FETUA, FETA, VTDB, TFR1, TRFE, TRFL, CATA, RAF1, GBA1, FUCO, ALDOA, ANXA1, APOB, GCR, PRIO, SODM, OAT, HRG, THY1, K2C6B, K2C1, G3P, HLAA, CPNS1, AMYP, HSPB1, RPN1, RPN2, GNAI2, AT1A1, A4, ARGI1, APOD, ALDH2, ITB3, S10A8, PAI1, ADT2, IF2A, RLA2, RLA0, JUN, LA, HEP2, ITB1, K1C18, K2C8, CO5A2, DCUP, LCK, GELS, PTMA, CDK1, ATPB, S10A9, S10A6, IF4E, ENOA, G6PI, NPM, TPM3, ITAV, HEXA, H2B1J, GDN, HYEP, LDHB, PGK2, PDIA1, H10, CATD, ANXA2, CAN1, TBB5, TRY1, PGS2, SAP, HEXB, CATL1, PROF1, APT, SYEP, CATB, HS90A, HNRPC, LAMB1, TPM2, FUMH, TSP1, SP1, CO1A2, ANXA6, 4F2, PFKAM, HS90B, SRPRA, ASNS, ODPA, CY1, RU2B, RU17, ITA5, NFIC, VIME, A2AP, RS17, GNAI3, ANXA5, K1C16, STS, RSSA, CD63, FGF2, GSTP1, RU1C, LEG1, DHPR, HMGB1, SPRC, TPM1, CLCA, ANXA4, CN37, PGFRB, DLDH, ROA1, PARP1, UCHL1, LKHA4, ALDOC, CO4A, H2AZ, UCRIL, ATX1L, POTEI, ZN865, ZN888, INAM2, HS71A, GLI2, LYAG, HLAC, H14, ODP2, THIO, PPGB, MGST1, KAP0, ESTD, CH60, CLUS, BIP, LAMC1, PPAL, HSP7C, UMPS, ODPB, ODB2, PYGB, RALA, LAMP1, ACADM, FGFR1, TOP1, G6PD, PYC, C1TC, MPRI, ADHX, SRF, PABP1, PCNA, HARS1, CO6A1, CO6A2, CO6A3, ADT3, IMDH2, TPR, ACTN1, PEPD, XRCC6, XRCC5, COX41, IFM1, LAMP2, RINI, CSPG2, EF2, K1C13, K2C5, PDIA4, P4HA1, TCTP, HLAE, PLST, ACPH, ETFA, KAP2, ENOB, CD59, MIF, CD99, GLU2B, FPPS, NID1, AK1A1, KPYM, ENPL, RSMB, IDE, PO2F1, HNRPL, SYDC, PLAK, ALDR, AMPN, PVR, ERF3A, B4GT1, EZRI, ATF2, UCHL3, FOSL1, FOSL2, NDKA, GNS, ZEP1, ARSB, RS2, ITF2, TFE2, DESP, RFA2, CD44, CBR1, CREB1, PGFRA, BGAL, H15, H13, H12, NCPR, AT2A2, FAAA, STMN1, NAGAB, AATC, KPCA, JUNB, ITA2, ASM, UBF1, HXB6, ATF7, CAN2, DESM, CEBPB, PYRG1, EGLN, DDX5, LEG3, IBP3, TCPA, PTN1, IBP2, RL35A, ARF4, RL7, EGR1, VINC, SON, RL17, PGAM1, RCC1, ATF1, NUCL, HXK1, E2AK2, SPEE, CSK22, RXRA, ITIH2, ITIH1, NFKB1, FST, IF2B, ANXA7, CD22, RAB3B, RAB5A, PSB1, MPRD, COX5A, LMNB1, HXA5, IMDH1, CO5A1, FILA, GSTM3, VATB2, CSRP1, FLNA, ACOHC, 5NTD, VDAC1, PGS1, SDHB, COMT, TGM2, PIMT, FBRL, PUR2, PUR6, SCP2, UBA1, NDKB, SPR1B, SPR2E, ROA2, RFX1, CBL, IBP4, QCR2, TGM1, FBLN1, PGH1, ITA6, SFPQ, PPIB, MAOM, SYWC, RS3, SAHH, COF1, IF4B, AT2B4, DGKA, GATA2, CPT2, KTHY, RIR1, EF1B, IBP5, PPAC, THIL, TENA, MYL9, RPB1, PAR1, MCM3, NFYB, ZA2G, THTM, RS12, TYY1, DNJB1, DNJB2, ATPA, PSA1, PSA2, PSA3, PSA4, ITA3, MOES, DDX6, DNMT1, U2AF2, RL13, IVD, HMGB2, PTBP1, SYTC, SYVC, EF1G, FKBP2, STOM, 1433T, DPP4, ARNT, RL10, APEX1, PYR1, CALR, MAP4, CALX, PSB8, PSA5, PSB4, PSB6, PSB5, ABCD3, ITPI2, LYOX, ELK4, NDUS1, MK01, GRN, AMPL, TPP2, IMPA1, CCN2, EPHA2, EPHB2, TKT, SPB3, RBMS1, PML, EF1D, MARCS, GNA11, AL4A1, ERP29, PRDX6, BLVRB, PRDX5, PRDX3, ATPD, RL12, ECHM, PEBP1, PDIA3, 2AAA, CDC27, T4S1, NMT1, PURA2, UFO, AMRP, TSPO, PUR8, CLIP1, SORCN, CTR1, AL1B1, RPB2, LCN1, SDHA, GDIA, S10A7, METK2, RIR2, TIA1, ZEP2, DNJA1, AKT1, QCR1, 3HIDH, PUR9, HNRH3, HNRH1, CASPE, 1433B, STIP1, S10AB, PRDX2, P5CR1, GBP1, ELF1, RL9, KINH, DUT, MRP1, MCM4, MCM5, MCM7, CD68, GLYM, HSP74, PROF2, CTNA1, CTNB1, PHB1, RADI, RFA3, RFC2, RL22, CBS, K1C9, FBN1, FBN2, IRS1, MYH9, MYH10, COPB2, ADDA, BASI, TIMP3, FUS, NU214, DEK, SOX5, GLRX1, PRS7, MP2K2, ATPG, RL4, LONM, PGM1, PP1G, PEDF, ODO2, GPX4, SRP14, NUP62, TAGL2, TALDO, ETFB, RBMX, VKGC, VATA, GRP75, IF4A3, RS19, RL3, COIA1, OST48, AN32A, FEN1, CAPG, IL6RB, TXLNA, TCPZ, NNMT, RL13A, STAT3, MDHC, MDHM, ECHA, IF2G, ETV6, WNT5A, BUD31, NAA10, CSK, GARS, SYIC, KPCI, LAP2A, LAP2B, STAT1, MTREX, HUTH, CASP3, RS27, HELZ, LPPRC, THIM, RL35, PCP, ECE1, LIS1, MUC18, MATR3, SSRA, RANG, PRS6B, PPIC, VDAC2, CBX5, UBP5, RAGP1, RECQ1, NOP2, CRKL, BAG6, NSF, NOTC1, MP2K3, RL27A, RL5, RL21, RL28, RS9, RS5, RS10, MAP1B, YAP1, UTRN, IQGA1, STT3A, CAZA2, CAPZB, SYQ, RL29, LEG7, TISD, ATPO, LIMS1, PPCE, MAOX, RFX2, RFX5, SOX9, COPD, LSS, PP2BC, CD151, PRC2A, TCPE, NEST, HSP13, KC1D, IDHP, PIPNB, PAXI, NR2C2, AL9A1, RL34, LMAN1, NASP, FAS, CDK8, TCPG, EFTU, AL7A1, SRP09, PCY1A, SYAC, SYCC, SYSC, MA2A2, PSB2, MCM2, COMP, ACADV, YLPM1, TMEDA, RBM25, NUMB, HINT1, NU153, RBP2, GSK3A, TAF6, 5NTC, SEPP1, GUAA, IDH3A, MMP14, GDIB, EMD, CPT1A, SERPH, PDLI4, F10A1, VASP, DYN2, MAP2, TOB1, CDK9, BCAM, PPT1, RL14, TCPQ, TCPD, ANX11, PAPOA, RAB5C, RAB7A, RAB9A, DAP1, RT29, SMCA4, IDH3G, SSRD, BAP31, HCFC1, DHB4, PSMD7, SPHM, CLCN5, KS6A3, HDGF, LUM, CNN1, NDUA8, ROA3, 6PGD, HNRPM, IMA1, NCBP2, GDIR1, AGFG1, HNRPF, STAT2, TF2AA, MSH6, ZN143, RBM5, SPSY, THOP1, CAZA1, CRIP2, NUP98, BIEA, TXTP, PPP5, ACLY, FOSB, MAP11, SUCA, PGTB2, COPB, COPA, CATC, RPAB4, MOT1, SC24C, TCP4, SYRC, ATX1, ATN1, CA2D1, SYYC, UBP14, AAKG1, HSP72, BCAT1, AT1B3, RD23A, RD23B, ANAG, KAD2, P5CS, SNAA, IF5, PSMD4, DRG2, XPO2, TERA, ECHB, MANF, AF10, DSRAD, LAMB2, CAD11, CAD13, SEC13, NH2L1, PSA, HNRH2, SCOT1, EIF3B, BID, SYMC, ITA1, MAZ, ATP5E, ATP5I, HDAC4, IF6, CTBP2, BCAR1, TMM33, PCBP3, NU107, MTPN, ARPC4, TPIS, EIF3E, SC61B, PP4C, GBRL2, MYL6, ACTB, IF4A1, RS20, PRPS1, PSA6, S10AA, CDC42, DEST, SPCS3, SRP54, RAB2A, RAB10, UBC12, UBE2K, UBE2N, RAB14, ARP3, ARP2, ARF3, ABCE1, RAP1B, RS3A, RL26, RL15, MGN, RL27, VA0D1, RL37A, RHOA, CH10, S61A1, LYSC, STXB1, B2MG, DAD1, NPC2, COPZ1, SUMO2, UFM1, NTF2, HNRPK, 1433G, RS7, PP1A, PP1B, PRS4, PRS8, RS8, RS15A, RS16, 1433E, RS14, RS23, RS18, RS29, RS13, RS11, RUXE, RUXF, SMD1, SMD2, PRS10, RL7A, RB11A, ERF1, CNBP, YPEL5, RS4X, PP2AB, ACTA, RL23A, RS6, H4, RAB1A, RAN, RL23, RS15, RS25, RS26, RS28, RS30, GBB1, RBX1, GBB2, RL30, RL31, RL10A, RL32, RL11, RL8, PPIA, FKB1A, RS27A, GRB2, RAC1, AP2B1, VAMP2, GNAS2, 1433Z, SUMO1, RL38, SKP1, RS21, IF5A1, RACK1, ACTG, ACTH, PP2AA, YBOX1, SC11A, CSK2B, TPM4, UB2L3, EF1A1, TBA4A, TBB4B, CSK21, HBB, NOMO3, HBA, F193A, IGBP1, SHPS1, SERB, PITX1, IF4G2, GTF2I, CNTP1, PHC1, TCPB, RAE1L, GSTO1, PRKDC, MAP1A, NUCB2, DCD, SSBP2, SARNP, RL24, RL36A, SMAD3, ERH, RHOG, RL19, SRSF3, FOXK1, DAB2, FBLN2, PGBM, XIAP, RBM10, RBM3, CYC, S25A3, VIGLN, PURA, BORG5, CLH1, FKBP3, REEP5, DHSO, HNRPU, U2AF1, SPTB2, TIAR, SET, SRSF2, FOXK2, RUNX1, AMPD2, FABP5, CAP1, K22O, HMCS1, LAT1, EXOSX, OTUD4, PFKAP, EWS, PLCB3, ROR2, TAGL, MEF2A, ODO1, DSG1, SP3, RL18A, FKBP4, PLOD1, NUCB1, RL6, TOP2B, CREB5, AKA12, M2OM, DYST, CAV1, KMT2A, LMNB2, UPAR, TF65, GLGB, IF4G1, K1C17, NOTC2, TLE3, TLE4, LGUL, AK1C1, 1433F, PLP2, CSTF1, UBE3A, FAK1, CALD1, COEA1, PUR1, GFPT1, SUH, MEF2C, GABPA, GABP1, PRDX1, RL18, CKAP4, ZO1, KHDR1, BAX, KLC1, ACK1, LRP1, SRSF1, RHG01, TLE5, TGM3, PP2BA, DHX9, QOR, GOGA3, GOGA2, LG3BP, DSC1, CD47, PPID, SSRP1, NSUN2, RBBP4, NCBP1, MGT5A, EP300, AHNK, IFFO1, INCA1, NEXN, MGAT2, GALT2, GALT1, AP1B1, CPSF1, MPPA, SCRN1, NU160, SCAP, SRBP2, TWF1, ASPH, FBLN3, TROP, BPTF, FSTL1, GRSF1, NFIA, SFSWA, SF3A3, SEPR, TP53B, AIMP1, ILF3, LMAN2, EPS8, TRAP1, TAF10, ECH1, STRN3, CDC16, FLII, CSN1, MTAP, AAPK1, EI2BE, TADBP, ROA0, AIMP2, PRDX4, PAK2, CBX3, PSMD2, TBX2, SRSF9, SRSF5, SRSF6, TIF1B, G3BP1, SG2A2, PTK7, PABP4, EIF3I, CTBP1, UB2V1, DC1I2, ILK, NNTM, TCOF, S39A6, SF3B2, ADAM9, TMED1, LSAMP, MYO9B, GAB1, SMAD4, PICAL, MAMD1, SQSTM, TBB3, ASAH1, PRP4K, PIN1, RIPK1, HDAC1, KCC2D, DCTN2, TRA2A, SNX1, CUL1, CUL4A, CUL4B, DYR1A, FCL, FHL1, FHL3, CD166, RUNX3, SPTN1, PKP1, DX39B, BLMH, TBB2A, IDI1, RUNX2, PEBB, NFYC, CDK13, CKAP5, COTL1, HNRPD, SCRB2, NID2, DAG1, VEZF1, EIF3A, UBP2L, SCRIB, GIT2, MLEC, TTL12, FHL2, DPYL3, DCTN1, DYHC1, SRC8, RCN2, TRI25, FLNC, FKBP8, FZD2, GAS6, CAPR1, RBM39, FAT1, SEM3A, MCM6, DSC3, PUM1, EPN4, SMC1A, RRP1B, NCOA6, GSE1, GANAB, 2A5D, LBR, MVP, LTBP1, LTBP2, MEF2D, CHD4, LASP1, ARI5B, PTGR1, NC2A, ZN638, IMB1, NOLC1, NUMA1, K2C72, CND2, PSMD6, SEPT2, SART3, CND1, U5S1, R3HD1, TRAM2, RB3GP, SYK, IF4H, BRD3, POSTN, OXA1L, EEA1, PDIA6, PA1B3, PCOC1, PLEC, IPYR, TEBP, NONO, RBBP5, RCN1, PCBP1, PCBP2, RHEB, DHC24, SF3B3, PUM3, DLGP5, RSU1, CNN3, SF3B4, SF3A2, RBMS2, SC23A, SF3A1, CDSN, SSXT, BGH3, NCOA2, TRAM1, SF01, MED1, JHD2C, TRIP6, MARE1, T22D1, ELAV1, ELF2, NAB2, MYLK, TAB1, AAAT, MLF2, ITSN1, TBCC, VAS1, ZFHX3, ZYX, ETFD, SEPT7, ADRM1, UAP1, IBP7, AINX, LAMA4, EXT1, PSMD5, CSRP2, DDB1, CDC37, DPYL2, KCC4, RBBP7, TAF9, ECM1, SRSF7, CPSF6, DREB, NRF1, FSCN1, IF16, DECR, GLO2, H2A2C, NDUA9, PCKGM, DDR2, HCDH, UGPA, TRXR1, MIC60, CPEB4, HNRL2, INF2, RFX7, QSER1, AAK1, PRSR3, QRIC1, LRRF1, P3H1, MA7D1, AL1L2, K2C71, TIM50, FUT11, TB10B, ANO6, FIL1L, SVEP1, AMOT, EPC2, FND3B, CRTC2, QORX, DHB12, CYBR1, IN80D, PAN3, YIF1B, F133B, ZN326, FILA2, MEST, HERC4, PIGG, BCORL, FA76B, TGO1, PREP, PRC2B, RRP12, TOIP1, PCID2, EOGT, TTC38, TM201, NU188, HP1B3, CE170, ZN362, FBP1L, FKB15, ZEP3, ZC3HD, LRIF1, UBR4, STXB5, RHG21, RM02, UBAP2, KPRP, KPLCE, RBM26, WLS, TUT4, H37, NT5D1, AHDC1, MRCKA, RPRD2, MYOME, ZN318, BROX, TASO2, PEAR1, MBNL2, ZMYM4, FHI2A, CD276, TSH3, TENS2, KANK2, AR6P4, OLM2A, HGNAT, ARID2, TENS3, CRBG3, RHG17, BICRL, AMERL, ATLA3, NXN, IQEC1, VASN, CPIN1, PTRD1, ELP2, LTOR1, TWF2, ADNP2, K2C80, LIN54, SCMC1, TM214, PPR18, CAVN1, CDC73, RM14, TATD1, EDC4, PRP8, SCYL2, GOLM2, NFRKB, RL22L, ALKB5, NCEH1, MDEAS, ZC3HE, OGFD3, LARP1, C1TM, FIP1, CRTC1, CSPG4, ARAID, LRSM1, TMCO3, LCLT1, CREL2, PAMR1, FAT4, MCAF1, CP2R1, PACS1, BCOR, MPRIP, HACD2, GGYF2, HSDL2, KAT3, CERS6, THSD4, MEX3B, ZN574, RN111, BAKOR, SRCAP, RIPR1, YJ005, TSH1, BGIN, UBN2, TMTC3, RAPH1, MOB2, IKIP, H32, LARP4, TBA1A, RS27L, HAKAI, ASXL2, CCD80, SPT6H, SND1, DDX46, 5MP2, DHX30, EIF3M, CYFP1, TAOK1, KDM3B, PHF5A, ERMP1, ZCCHV, NUP54, POGZ, MON2, K1C27, NUFP2, MAVS, CLAP1, DHX29, PLGT3, LIMS2, HDGR2, DCXR, EMSY, RAI1, I2BP2, RBBP6, SH3R1, RABEK, HUWE1, YTHD3, K2C1B, KHDC4, TMED4, COXM1, CENPV, GALT5, PHLB2, GLT10, MYPN, SYVN1, ACOT1, PABP2, LDB1, LYRIC, ZN598, KTN1, BCL9L, PHLB1, LUZP1, GP180, CAND1, HOOK3, TSYL5, CARM1, PRSR1, MEX3D, DDX42, P66A, HORN, RB6I2, RELL1, PLD3, FOXP4, P3H2, P3H3, CCD50, SPA12, CTL2, WDFY1, TEX2, NXP20, MGAP, Z3H7A, CHERP, ANKH1, SUGP1, CCAR1, DJC10, MSRB3, PLPL6, MILK2, SPB1, SMAP1, P20D2, PHAR4, ZNF34, ELMD2, DCP1B, XRN1, MAML2, ABI1, SELH, SPART, RPTOR, CCAR2, SIX5, NUP93, K2C78, ZCH24, LTBP4, ASCC3, SYNPO, FNBP4, AFAP1, CERS5, NKAP, CPSF7, ARFG2, ARFG1, LRC17, EMC1, ENAH, RM43, YP023, ANR52, GT251, SUMF2, SUMF1, PGLT1, PCYXL, TXND5, SCPDL, SERB1, LEMD2, NECP1, FA98A, CHSTE, APCDL, RN214, LS14A, TNR6A, PHC3, ABCF1, SP20H, ZNT7, NAV1, VP37A, FBX22, PCAT1, ZMIZ2, ARI1B, NUP35, NEUA, PLBL2, MFSD8, NEDD1, ZNT5, G45IP, SMRC2, NPL4, PUM2, KISHA, RDH11, STT3B, SPP2B, HM13, ALMS1, NEK9, PKHO2, DDX54, DLG5, NEK7, GPX8, GEMI5, IPO4, ZN384, SETD7, F222B, SMAP2, CHUR, CEMIP, PDC6I, FBLI1, PHLA1, NUDC2, SCFD1, POF1B, LMO7, ATX2L, SELM, PALLD, SREK1, PSPC1, P66B, AUTS2, ZCH14, IRGQ, DDB2, ASM3A, DDX1, S39A7, FAM3C, GBF1, SMG7, RTF1, NICA, TM9S4, TM131, RT27, F168A, PHF3, MAML1, HS105, LAR4B, GCN1, ZN516, NU205, PXDN, AN32B, NECT2, TFG, ARC1A, STAM1, REQU, SC65, CBP, GGH, NELL1, DDX17, TANK, CELF1, GSLG1, RENT1, CSN5, GATA6, SMRC1, FUBP2, TNPO1, ARHG2, UBP13, USP9X, UBP7, LPP, RBPMS, SMCE1, CAVN3, MYDGF, YIPF5, PIGT, RL36L, ZN622, WBP2, NCLN, MRTFA, ERGI1, RFT1, FERM2, FUBP1, TTC17, LRC59, PBIP1, FKB10, AKTS1, PF21A, EFHD2, GALM, INT12, CTHR1, KLH29, OPTN, AP2M1, RCN3, REPS1, KBP, DAZP1, RBM33, CK024, ZN503, I17RA, OTUB1, PGM2, CERS2, ZC21A, P121A, PDLI5, CREL1, ERO1A, PGAM5, FUBP3, SUCB2, GMPPA, KIRR1, WNK4, TMX3, CHAP1, ZFP91, PDLI2, ZC3HA, CLP1L, SCYL1, Z512B, CNDP2, ZFR, B3GT6, EP400, VATG3, PRRC1, ZN512, NOL4L, MBOA7, DOCK7, TOX2, SPB12, ARHGH, RBM14, QKI, LENG8, GSDMA, PP1RA, S38A2, VPS35, PHF12, SNX18, CIC, MED15, ERGI2, NUDC1, ERBIN, PIGS, WRIP1, RANB9, CLCC1, UBL7, MYADM, SIN3A, RUFY1, MINT, MMS19, UHRF1, NIBA2, HTF4, TBCB, NELL2, PSB7, CNN2, SEC62, PCY2, K1C12, CDC5L, PSMD1, SDF2, PARK7, EYA3, NEUR1, VAT1, LGMN, PLIN2, NUP88, MNT, SCAFB, DNJC7, PHB2, RGPD5, PITX2, ATX2, HCD2, COCA1, SMAD5, ROAA, LITAF, NP1L4, ACON, TM9S2, TS101, CPNE1, TCPH, EBP2, ANM1, SH3G1, CND3, DDX50, MEP50, VKOR1, TBA1C, SELS, MBB1A, COR1B, TXD17, VPS25, RM45, MXRA8, CAB45, ADPGK, PELO, ERP44, LXN, ESYT1, CNPY3, LIMD2, CSN4, WAC, DIDO1, DCTN5, AASD1, TMM43, TBCD, TBB6, HNRL1, HTAI2, DDX23, DHRS6, CA050, WDR18, THUM3, RN126, TBB2B, TM109, TMED9, NUP58, ELOV1, THIC, REPI1, RBM4, SFXN3, SSBP3, NAA15, KLF16, SRRT, TGT, HDHD5, EIF2A, CADM1, MK67I, YTHD1, WNK3, NEUL, RM37, GTPB4, UACA, RAB34, TBL1R, UBL5, EDEM3, API5, K1C23, UNK, FTO, TB182, AMRA1, TTYH3, ADSSP, PITH1, SKI8, SLIRP, WWTR1, TWSG1, NAA50, MKRN2, PAIP1, LSG1, NAT10, XRN2, SP130, BRD8, DDX47, MAGT1, LMA2L, SIL1, I2BPL, NUCKS, EHD4, VPS16, SH3L3, EPC1, SLK, S38A1, PDCL3, RBGPR, ADNP, DPH5, HIPK2, FOXP1, CK068, BOLA2, TMX1, NELFA, GCP60, PTN23, UN45A, OFUT1, WNK1, AMPB, GAPR1, ZHX3, EHD1, ZN768, SG196, CC134, PEAK1, AAMDC, WDR26, PKHG2, ZN703, ACAD9, GORS2, JUPI2, SYP2L, SFXN1, FKRP, ELP3, KT3K, FBRS, MLXIP, PKHA5, GBB4, XPO5, GRPE1, MYG1, RC3H2, TENS1, TAF9B, EMAL4, GLOD4, ZBT20, NCOA5, TANC2, MOV10, ZN532, ZN160, TNR6C, CHD8, SDF2L, CD248, SEC12, S10AE, AT131, RM47, CHM1A, TM9S3, APMAP, TRXR2, ARFG3, RAB18, VTA1, CD320, UBN1, DCP1A, TF7L2, RTN4, NIT2, NECT3, EXOS3, ANLN, XPP1, GEPH, PDLI7, DDX21, SAR1A, SIAS, SHLB2, MBNL1, 4ET, AAAS, STRN4, UBQL4, HEBP1, ABC3C, PHP14, F1142, TM7S3, KRT84, SYFB, SYIM, BMP2K, ATG3, SMC4, SAC1, OLA1, ZF64B, RBM12, ABHDA, SHFL, T106B, SPS2L, DD19A, TBC23, CC50A, SEP11, MED17, DJC11, INT7, ATD3A, ARL8B, DDX18, RT18A, NLE1, ZN358, RBM22, ARGL1, RM22, CZIB, GEMI8, F120C, OCAD1, IMPA3, MIC19, CKLF6, P4HTM, TOR4A, TRM1, CARF, DPP3, DDX56, BCLF1, TAB2, M3K20, UGGG2, UGGG1, CDK12, TECR, ERAP1, GGA3, F120A, GDE1, IF2B1, MAT2B, MYOF, ITSN2, BICRA, EHD2, CNOT2, CALL5, CRIM1, HACD3, KCMF1, RAI14, RM27, SENP1, SH3B4, PHRF1, RCC2, SLAI2, TEN3, CT2NL, RRBP1, SYLC, RBM27, KANL3, ANFY1, RERE, SUCB1, LRIT1, DPM3, SAE1, COPG2, MRC2, GBG12, DHCR7, DKK3, VPS29, EIF3K, GRHPR, CATZ, SAE2, NXF1, B4GT7, PEF1, FBLN5, CLIP2, ZO2, DNJB4, ADDG, ABCF2, TES, LIMD1, Z3H7B, TCF20, SUN2, LIMA1, SRP68, CHRD1, SEPT9, UBQL2, PCYOX, DDX20, ATS1, DPP2, CEIP2, NB5R1, S30BP, MED13, PUF60, NRBP, VATH, CBPA4, XPO7, BAZ2B, SIX4, GGT7, MSRA, NAGK, DBNL, DCTN4, CDC23, STML2, DBR1, AKA11, GMEB2, CPSF3, PARP4, RALY, ITA11, NUP50, ZHX1, ZN346, DNPEP, MCTS1, S39AA, ASAP1, MRTFB, HEG1, ZMIZ1, PRR12, YETS2, HECD1, ZMYD8, COR1C, NOTC3, SPAT2, PPT2, PRP19, UBQL1, SNX12, SYNRG, G3BP2, CHIP, PACN2, MAGD2, SNX6, PSD13, FAF1, PPIE, CSN3, MINP1, S12A4, MACF1, SCAF8, TRI33, TNR6B, SMAG1, CE164, FOXJ3, SHAN2, COR2B, SRRM2, PA2G4, ZN148, RTRAF, RUVB2, CLC11, EIF3L, PLAP, RUVB1, NUDC, VDAC3, COF2, ERGI3, SYFA, DRG1, NCKP1, PLAK2, ZN652, MA2B2, OFUT2, FND3A, E41L3, R3HD2, RRP44, LRCH1, GSTK1, DDX52, RT07, TMA7, MAN1, CHSP1, TR150, NOP58, ZN281, SGT1, ACOT9, NOSIP, MEMO1, SHLB1, LC7L2, SBDS, TMED7, ORN, UFC1, STRAP, RTCB, ZN330, RL36, SAMH1, TLN1, ARIP4, MTCL1, TCAF1, UBP15, LOXL2, CRBG1, HYOU1, TBL2, KLF12, ARI1, LSM4, RN114, PRC2C, RBM7, YTHD2, SP16H, SRPRB, MRCKB, ZN706, MAGD1, SNX5, HCFC2, FHOD1, SERC, NCOR2, NPTN, CBPQ, SOX21, RT18B, COPG1, FKBP7, GMEB1, CLIC4, EMIL1, MTCH2, 5MP1, DC1L1, EPN1, NEMO, IF2B2, ZNT1, NCOA3, NUMBL, PIAS3, ZHX2, S23IP
Species: Homo sapiens, Bos taurus
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Joiner CM, Hammel FA, Janetzko J, Walker S. Protein Substrates Engage the Lumen of O-GlcNAc Transferase's Tetratricopeptide Repeat Domain in Different Ways. Biochemistry 2021 60(11) 33709700
Abstract:
Glycosylation of nuclear and cytoplasmic proteins is an essential post-translational modification in mammals. O-GlcNAc transferase (OGT), the sole enzyme responsible for this modification, glycosylates more than 1000 unique nuclear and cytoplasmic substrates. How OGT selects its substrates is a fundamental question that must be answered to understand OGT's unusual biology. OGT contains a long tetratricopeptide repeat (TPR) domain that has been implicated in substrate selection, but there is almost no information about how changes to this domain affect glycosylation of individual substrates. By profiling O-GlcNAc in cell extracts and probing glycosylation of purified substrates, we show here that ladders of asparagines and aspartates that extend the full length of OGT's TPR lumen control substrate glycosylation. Different substrates are sensitive to changes in different regions of OGT's TPR lumen. We also found that substrates with glycosylation sites close to the C-terminus bypass lumenal binding. Our findings demonstrate that substrates can engage OGT in a variety of different ways for glycosylation.
O-GlcNAc proteins:
TAB1, KCC4, CARM1
Species: Homo sapiens
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Ramirez DH, Yang B, D'Souza AK, Shen D, Woo CM. Truncation of the TPR domain of OGT alters substrate and glycosite selection. Analytical and bioanalytical chemistry 2021 413(30) 34725712
Abstract:
O-GlcNAc transferase (OGT) is an essential enzyme that installs O-linked N-acetylglucosamine (O-GlcNAc) to thousands of protein substrates. OGT and its isoforms select from these substrates through the tetratricopeptide repeat (TPR) domain, yet the impact of truncations to the TPR domain on substrate and glycosite selection is unresolved. Here, we report the effects of iterative truncations to the TPR domain of OGT on substrate and glycosite selection with the model protein GFP-JunB and the surrounding O-GlcNAc proteome in U2OS cells. Iterative truncation of the TPR domain of OGT maintains glycosyltransferase activity but alters subcellular localization of OGT in cells. The glycoproteome and glycosites modified by four OGT TPR isoforms were examined on the whole proteome and a single target protein, GFP-JunB. We found the greatest changes in O-GlcNAc on proteins associated with mRNA splicing processes and that the first four TPRs of the canonical nucleocytoplasmic OGT had the broadest substrate scope. Subsequent glycosite analysis revealed that alteration to the last four TPRs corresponded to the greatest shift in the resulting O-GlcNAc consensus sequence. This dataset provides a foundation to analyze how perturbations to the TPR domain and expression of OGT isoforms affect the glycosylation of substrates, which will be critical for future efforts in protein engineering of OGT, the biology of OGT isoforms, and diseases associated with the TPR domain of OGT.
O-GlcNAc proteins:
UBA6, SBNO1, CNOT1, SMHD1, ADAS, DX39A, BACH, MYO1C, PSD11, PSD12, TAF4, CLIC1, EIF3F, IPO5, DNM1L, AGRIN, PLOD2, IMA4, NOP56, DDX3X, PDXK, ANM5, TCRG1, PSA7, SCAM3, HAT1, HGS, MYPT1, HNRDL, XPO1, PUR4, NPC1, SCAM2, ARC1B, ARPC2, ARPC3, RPAC1, GNPAT, ZN185, SURF4, OGT1, PPM1G, EIF3D, EIF3H, P4HA2, MAGB2, NUP42, DHX15, MCES, SERA, PSMD3, PAPS1, ZW10, HNRPR, TXNL1, E41L2, XPOT, TIM44, PLRG1, ZN207, GET3, BUB3, ACTN4, AP1G1, SNG1, SNG2, SYNC, MYO1B, NRDC, CALU, EDIL3, SAHH2, DHX16, SMCA5, KDM1A, OGA, HNRPQ, PLOD3, DIAP1, TSN3, PLIN3, CTND1, MAGC1, USO1, DKC1, IF2P, DNJA2, WDR1, CPNE3, T22D2, ANR17, H2AY, FLNB, CISY, SC22B, PR40A, ERLN1, SF3B1, CSDE1, U520, NU155, EIF3G, FACE1, IDHC, ATRN, STAM2, PRAF3, FLOT1, RL1D1, WFS1, MTA2, TOX4, SC24D, SUN1, FRYL, NFAT5, GLSK, SC31A, UBR5, LC7L3, FKBP9, SMC2, IPO7, AHSA1, SGPL1, SC24B, ACSL3, CDS2, AP2A1, BAG2, AIFM1, FADS2, CLPT1, TOM40, ACL6A, LDHA, COX2, PNPH, AATM, PGK1, ASSY, FOS, LMNA, FINC, TFR1, NU4M, NU5M, GBA1, FUCO, ALDOA, ANXA1, OAT, TBB4A, G3P, CPNS1, HSPB1, TYSY, RPN1, RPN2, GNAI2, AT1A1, AT1B1, ALDH2, ADT2, PCCA, IF2A, RLA2, RLA0, LA, ITB1, ATPB, IF4E, ENOA, G6PI, NPM, ITAV, HYEP, LDHB, PDIA1, H10, CATD, ANXA2, CAN1, TBB5, TRY1, SAP, PROF1, SYEP, CATB, HS90A, HNRPC, LAMB1, YES, FUMH, TSP1, ANXA6, MDR1, 4F2, PFKAM, HS90B, SRPRA, ASNS, ODPA, RU17, GNAI3, ANXA5, RSSA, CD63, SNRPA, GSTP1, LEG1, CN37, DLDH, ROA1, PARP1, LKHA4, ALDOC, GPHRB, HS71B, LYAG, RRAS, H14, ODP2, THIO, ESTD, CH60, CLUS, BIP, LAMC1, PPAL, HSP7C, GTR1, GTR3, ODPB, PYGB, LAMP1, TOP1, TOP2A, G6PD, PYC, C1TC, MPRI, ADHX, PABP1, PCNA, HARS1, IMDH2, TPR, KCRB, ACTN1, PEPD, XRCC6, XRCC5, LAMP2, RINI, EF2, PDIA4, P4HA1, TCTP, ACPH, ETFA, GLU2B, FPPS, KPYM, ENPL, IDE, HNRPL, SYDC, ALDR, B4GT1, EZRI, FOSL2, NDKA, GNS, RS2, RFA2, BGAL, H12, AT2A2, FAAA, AATC, JUNB, ITA2, CAN2, PYRG1, DDX5, PFKAL, PRS6A, TCPA, RL35A, ARF4, RL7, VINC, SON, RL17, PGAM1, DNLI1, PLCG1, NUCL, HXK1, RPB3, E2AK2, TFE3, SPEE, IF2B, ANXA7, PSB1, MPRD, LMNB1, VATB2, FLNA, VDAC1, TGM2, FBRL, PUR2, PUR6, UBA1, NDKB, ADRO, ROA2, RFX1, QCR2, SFPQ, PPIB, SYWC, RS3, SAHH, COF1, IF4B, PPAC, RPB1, MCM3, RS12, DNJB1, ATPA, PSA1, PSA2, PSA3, PSA4, ITA3, MOES, DDX6, DNMT1, U2AF2, RL13, PTBP1, SYTC, SYVC, EF1G, STOM, RL10, RFA1, APEX1, CD82, PYR1, CALR, MAP4, CALX, PSB8, PSA5, PSB4, PSB6, PSB5, DPOD1, TEAD1, MK01, AMPL, IMPA1, EPHA2, TKT, EF1D, PRDX6, BLVRB, PRDX5, PRDX3, RL12, ECHM, PEBP1, PDIA3, 2AAA, CDC27, PURA2, AMRP, PUR8, CLIP1, CTR1, RPB2, SDHA, GDIA, METK2, DNJA1, QCR1, PUR9, HNRH3, HNRH1, 1433B, 1433S, STIP1, PRDX2, RL9, KINH, MRP1, MCM4, MCM5, MCM7, GLYM, HSP74, CTNA1, CTNB1, PHB1, RADI, RFC4, RL22, FBN2, GDE, MYH9, MYH10, COPB2, SOAT1, ADDA, BASI, FUS, NU214, PRS7, MP2K2, ATPG, HEM6, RL4, PGM1, ODO2, SRP14, NUP62, FDFT, TAGL2, TALDO, RBMX, VKGC, VATA, GRP75, IF4A3, RS19, RL3, OST48, AN32A, CAP2, TCPZ, RL13A, STAT3, MDHC, MDHM, ECHA, IF2G, KDM5C, GARS, SYIC, STAT1, CASP3, LPPRC, SATT, LIS1, MUC18, MATR3, MSH2, MAGA4, RANG, NAMPT, PRS6B, PPIC, VDAC2, UBP5, KI67, RAGP1, RECQ1, NOP2, CRKL, BAG6, NSF, RL27A, RL5, RL21, RL28, RS9, RS5, MAP1B, UTRN, IQGA1, STT3A, CAPZB, SYQ, UCRI, PPCE, COPD, LSS, CD151, PSMD8, TCPE, NEST, HSP13, PIPNB, PAXI, AL9A1, RL34, LMAN1, NASP, FAS, TCPG, EFTU, AL7A1, SYAC, SYCC, SYSC, PRI2, PSB3, PSB2, MCM2, ACADV, YLPM1, TMEDA, RBM25, NU153, RBP2, NDUV1, GSK3A, TAF6, GUAA, GDIB, EMD, SERPH, VASP, TCPQ, TCPD, ANX11, PAPOA, FXR1, RAB5C, RAB7A, RT29, SMCA4, BAP31, HCFC1, DHB4, HDGF, ROA3, 6PGD, HNRPM, IMA1, GDIR1, AGFG1, HNRPF, MSH6, RBM5, SPSY, CAZA1, NUP98, BIEA, PPP5, ACLY, MAP11, COPB, COPA, SC5A3, SMTN, MOT1, IST1, SC24C, SYRC, SYYC, UBP14, BCAT1, AT1B3, RD23B, P5CS, IF5, S12A2, XPO2, TERA, ECHB, AFAD, NP1L1, DSRAD, SEC13, PSA, HNRH2, EIF3B, ATPK, SYMC, IF6, CTBP2, TMM33, GEMI4, CORO7, NU107, ARPC4, TPIS, EIF3E, PP4C, IF4A1, PSA6, CDC42, DEST, GMFB, SRP54, RAB10, UBC12, ARP3, ARP2, ABCE1, RAP2B, RS3A, RL15, RL37A, S61A1, DAD1, NPC2, HNRPK, 1433G, RS7, PRS4, PRS8, RS8, RS15A, RS16, 1433E, RS14, RS23, RS13, RS11, SMD2, SMD3, PRS10, RL7A, ERF1, CNBP, RS4X, PP2AB, RS6, H4, RAB1A, RAN, RL23, RS25, RS28, RL30, RL31, RL10A, RL32, RL11, RL8, PPIA, TRA2B, AP2B1, 1433Z, IF5A1, RACK1, YBOX1, UB2L3, TBA4A, IF4G2, GTF2I, TCPB, PRKDC, RL24, SRSF3, FOXK1, DAB2, RBM10, S25A3, VIGLN, CLH1, FKBP3, HNRPU, U2AF1, SPTB2, AMPD2, CAP1, HMCS1, LAT1, EXOSX, PFKAP, EWS, PLCB3, ODO1, RL18A, MP2K1, FKBP4, PLOD1, RL6, TOP2B, DYST, KMT2A, LMNB2, CEBPZ, TF65, IF4G1, LGUL, 1433F, DYN1, EF1A2, PTN11, PUR1, GFPT1, EXOS9, SUH, GABPA, PRDX1, RL18, C1QBP, CKAP4, KHDR1, LRP1, SRSF1, PP2BA, DHX9, GOGA2, LG3BP, CD47, SSRP1, NSUN2, NCBP1, EP300, AHNK, MGAT2, GALT2, AP1B1, MPPA, SCRN1, NU160, SCAP, TBL3, TF3C1, ASPH, TROP, BPTF, AIMP1, ILF2, ILF3, LMAN2, TRAP1, FLII, ACACA, CSN1, MTAP, EI2BE, TADBP, ROA0, PRDX4, PSMD2, SRSF6, TIF1B, DHRS2, G3BP1, MTA1, EIF3I, UB2V1, DC1I2, NNTM, TCOF, TMED1, VPP3, PICAL, RIPK1, CUL2, CUL4A, CUL4B, FCL, MOGS, CD166, SPTN1, DX39B, BLMH, CKAP5, COTL1, HNRPD, SCRB2, EIF3A, UBP2L, SCRIB, FHL2, DPYL3, DCTN1, DYHC1, SRC8, FLOT2, TRI25, FLNC, GALE, CAPR1, RBM39, MCM6, TRIPC, PUM1, EPN4, RRP5, BMS1, UBP10, GANAB, LBR, MVP, MEF2D, CHD4, LASP1, GPNMB, ZN638, IMB1, NUMA1, CND2, SPCS2, PSMD6, ABRX2, SEPT2, CND1, U5S1, SYK, WDR43, PDIA6, PA1B3, IPYR, TEBP, NONO, PWP2, RCN1, L2GL1, TMED2, PCBP1, PCBP2, SF3B3, SC23A, SF3A1, TSN, SF01, PCH2, MED1, MARE1, ELAV1, NSDHL, TAB1, AAAT, MLF2, VAS1, ZYX, SEPT7, ADRM1, CCDC6, UAP1, PSMD5, PKN2, DDB1, DPYL2, KCC4, SRSF7, DREB, NRF1, FSCN1, IF16, PCKGM, UPP1, UGPA, TRXR1, HNRL2, INF2, PDS5A, QSER1, QRIC1, SMU1, P3H1, K2C71, TIM50, GXLT1, TB10B, SNUT2, HERC4, P4R3B, EOGT, CE170, UBR4, SKT, UBAP2, RBM26, RPRD2, ZMYM4, TWF2, LIN54, RHBD2, MBOA5, EDC4, PRP8, SCYL2, NFRKB, SKI3, NCEH1, BRAT1, ZC3HE, C1TM, SBSN, CREL2, PACS1, GGYF2, SRCAP, TMTC3, IKIP, SPT6H, SND1, DDX46, 5MP2, DHX30, EIF3M, CYFP1, KDM3B, RIR2B, ERMP1, ZCCHV, NUP54, POGZ, MYH14, CLAP1, EMSY, SH3R1, HUWE1, TMED4, SYVN1, ZN598, PHLB1, LUZP1, CAND1, TSYL5, EZHIP, CARM1, DDX42, P66A, C2CD5, I2BP1, RB6I2, PLD3, P3H3, WDR75, Z3H7A, ANKH1, CCAR1, DJC10, SMAP1, SPART, RPTOR, NUP93, ZN687, SYNPO, FNBP4, CPSF7, EMC1, ENAH, S43A3, GT251, SUMF2, PGLT1, TXND5, SERB1, LS14A, ABCF1, FBX22, NEUA, CADM4, ATLA2, PLBL2, WDR36, SMRC2, NPL4, S35B2, UBA3, TBC15, CIP2A, STT3B, PNPT1, HM13, DTX3L, PO210, GEMI5, PARD3, IPO4, SCRB1, RAB2B, NU133, PDC6I, S20A1, ATX2L, PALLD, DDX1, GBF1, NICA, TM9S4, HS105, GCN1, PRP16, NU205, PXDN, TFG, ARC1A, HDAC2, CBP, SYMPK, DDX17, CELF1, UFD1, GSLG1, RENT1, TNPO1, GLMN, USP9X, UBP7, SCAM4, SMCE1, MYDGF, PIGT, NCLN, EXOC4, FERM2, FUBP1, FKB10, APH1A, PPWD1, AP2M1, RCN3, ELP4, SEH1, DNJA3, CYFP2, PGM2, PDLI5, ERO1A, FUBP3, ITCH, TMX3, CNDP2, ZFR, EP400, SNX27, PRRC1, ZN512, MBOA7, DOCK7, ARAP1, IPO9, RBM14, NED4L, VPS35, CIC, MED15, EFGM, MCCA, MYADM, SIN3A, MINT, PNKP, NIBA2, TBCB, PSB7, CNN2, PSMD1, EYA3, SORT, NUP88, P2RX4, DNJC7, PHB2, KIF2C, ATX2, HCD2, ROAA, NP1L4, ACON, TM9S2, S29A1, TS101, TCPH, ANM1, CND3, MBB1A, COR1B, GCP2, ESYT1, DIDO1, MCMBP, TBCD, TBB6, RPC3, HNRL1, HTAI2, TMED9, NUP58, SFXN3, OSB10, NAA15, S12A9, SRRT, EIF2A, WDR11, FTO, TTYH3, WDR12, YIPF3, PITH1, PAIP1, NAT10, XRN2, TOLIP, SP130, BRD8, DDX47, MAGT1, RAB1B, LMA2L, I2BPL, GHITM, TMX1, PTN23, OFUT1, PIGU, WNK1, AMPB, HEAT1, NOL6, WDR26, AT133, ACAD9, GORS2, MARH7, SFXN1, PKHA5, XPO5, MYG1, EMAL4, TM9S3, APMAP, ARFG3, RTN4, ANLN, XPP1, PDLI7, DDX21, EI2BG, MBNL1, HEBP1, SERC1, F1142, SYFB, SYIM, SMC4, OLA1, RBM12, T106B, CYRIB, DCA13, CC50A, SEP11, FANCI, ARL8B, DDX18, TM160, MIO, CARF, DPP3, RM39, UGGG1, ERAP1, HPBP1, MAT2B, MYOF, ITSN2, HACD3, SEP10, RCC2, DIP2B, CT2NL, RRBP1, SYLC, RBM27, SUCB1, MRC2, DHCR7, DJB11, SAE2, NXF1, SUN2, SRP68, SEPT9, UBQL2, PCYOX, CEIP2, S30BP, MED13, PUF60, NRBP, VATH, IPO11, XPO7, BAZ2A, GGT7, NAGK, DBNL, CDC23, STML2, PARP4, NUDT5, TF3C4, ACINU, RAB21, DNPEP, ASAP1, MRTFB, MED23, HECD1, ZMYD8, COR1C, MYO6, PRP19, MAGD2, PSD13, MINP1, NOVA2, WDR3, S12A4, MACF1, SCAF8, TRI33, SMAG1, XCT, SRRM2, PA2G4, SMC3, RUVB2, EIF3L, PLAP, RUVB1, VDAC3, ERGI3, SC5A6, DRG1, NCKP1, AT11B, E41L3, CHSP1, NOP58, ZN281, SYYM, TMX2, SHLB1, SBDS, TMED7, STRAP, RTCB, FBX7, RBGP1, NOC2L, TLN1, DCAF1, HYOU1, PRC2C, YTHD2, SP16H, TNPO3, MAGD1, SNX8, PUS1, NPTN, S12A7, COPG1, BIG1, 5MP1, DC1L1, IF2B2, ZNT1, S4A7, ZHX2, S23IP
Species: Homo sapiens
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Tan HY, Eskandari R, Shen D, Zhu Y, Liu TW, Willems LI, Alteen MG, Madden Z, Vocadlo DJ. Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates. Journal of the American Chemical Society 2018 140(45) 30296064
Abstract:
The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology. Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc. These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed. Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore. Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro. We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells. This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner. Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells. The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
O-GlcNAc proteins:
NU214, NUP62, NU153, KCC4
Species: Homo sapiens
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Shen DL, Liu TW, Zandberg W, Clark T, Eskandari R, Alteen MG, Tan HY, Zhu Y, Cecioni S, Vocadlo D. Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose. ACS chemical biology 2017 12(1) 27935279
Abstract:
O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. Spurred by this observation, we show that OGT transfers 2-azido-2-deoxy-d-glucose (GlcAz) in vitro from UDP-GlcAz to proteins. Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. We find that O-GlcAz is reversible within cells, and an unidentified cellular enzyme exists to cleave O-Glc that can also process O-GlcAz. We anticipate that AcGlcAz will prove to be a useful tool to study the O-GlcNAc modification. We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification.
O-GlcNAc proteins:
A0A0D9R5K0, A0A0D9SE53, NUP62, TAB1, KCC4
Species: Chlorocebus sabaeus, Homo sapiens
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Li S, Zhu H, Wang J, Wang X, Li X, Ma C, Wen L, Yu B, Wang Y, Li J, Wang PG. Comparative analysis of Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and strain-promoted alkyne-azide cycloaddition (SPAAC) in O-GlcNAc proteomics. Electrophoresis 2016 37(11) 26853435
Abstract:
O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an essential protein post-translational modification in a range of organisms. It is involved in various cellular processes such as nutrient sensing, protein degradation, gene expression, and is associated with many human diseases. Despite its importance, identifying O-GlcNAcylated proteins is a major challenge in proteomics. Here, using peracetylated N-azidoacetylglucosamine (Ac4 GlcNAz) as a bioorthogonal chemical handle, we described a gel-based mass spectrometry method for the identification of proteins with O-GlcNAc modification in A549 cells. In addition, we made a labeling efficiency comparison between two modes of azide-alkyne bioorthogonal reactions in click chemistry: copper-catalyzed azide-alkyne cycloaddition (CuAAC) with Biotin-Diazo-Alkyne and stain-promoted azide-alkyne cycloaddition (SPAAC) with Biotin-DIBO-Alkyne. After conjugation with click chemistry in vitro and enrichment via streptavidin resin, proteins with O-GlcNAc modification were separated by SDS-PAGE and identified with mass spectrometry. Proteomics data analysis revealed that 229 putative O-GlcNAc modified proteins were identified with Biotin-Diazo-Alkyne conjugated sample and 188 proteins with Biotin-DIBO-Alkyne conjugated sample, among which 114 proteins were overlapping. Interestingly, 74 proteins identified from Biotin-Diazo-Alkyne conjugates and 46 verified proteins from Biotin-DIBO-Alkyne conjugates could be found in the O-GlcNAc modified proteins database dbOGAP (http://cbsb.lombardi.georgetown.edu/hulab/OGAP.html). These results suggested that CuAAC with Biotin-Diazo-Alkyne represented a more powerful method in proteomics with higher protein identification and better accuracy compared to SPAAC. The proteomics credibility was also confirmed by the molecular function and cell component gene ontology (GO). Together, the method we reported here combining metabolic labeling, click chemistry, affinity-based enrichment, SDS-PAGE separation, and mass spectrometry, would be adaptable for other post-translationally modified proteins in proteomics.
O-GlcNAc proteins:
AXA2L, EIFCL, MYO1C, P2Y10, IPO5, PLOD2, DDX3X, ZN197, XPO1, PPM1G, HNRPR, ACTN4, SNG2, OGA, UGDH, BRD4, FLNB, U520, IDHC, TOM70, K2C75, LDHA, AL1A1, DHE3, PGK1, PIGR, IGHA1, K1C14, K2C6A, LMNA, ALBU, TRFL, K2C6B, K2C1, AT1A1, ALDH2, S10A8, ITB1, K1C18, K2C8, ENOA, G6PI, HYEP, PDIA1, TBB5, SYEP, HS90A, 4F2, HS90B, VIME, K2C7, K1C16, RSSA, DLDH, PARP1, LIGO3, UBB, HS71A, CH60, BIP, HSP7C, PYGB, G6PD, C1TC, K2C3, ACTN1, PEPD, XRCC5, RINI, EF2, K1C10, K1C13, K2C5, PDIA4, P4HA1, GLU2B, KPYM, ENPL, HNRPL, PLAK, DESP, NCPR, AT2A2, NAGAB, HSP76, CAN2, NUCL, IF2B, ANXA7, FLNA, TGM2, PUR6, UBA1, SAHH, RPB1, ATPA, MOES, EF1G, CALR, MAP4, CALX, ITPI2, TKT, PDIA3, 2AAA, AL3A1, CPSM, QCR1, HNRH1, STIP1, HSP74, K1C9, MYH9, MYH10, K22E, PRS7, SRBP1, GRP75, IF4A3, IF2G, LPPRC, MATR3, AL3B1, NAMPT, UBP5, KI67, MAP1B, UTRN, IQGA1, TCPE, K2C6C, AL9A1, NASP, FAS, TCPG, EFTU, SYAC, F10A1, TCPQ, TCPD, 6PGD, HNRPM, ACLY, SYRC, UBP14, S12A2, TERA, ECHB, NP1L1, EIF3B, SYMC, EIF3E, ACTB, UB2D3, ARP3, HNRPK, PRS4, ACTC, EF1A1, TBA1B, TBB4B, KRT85, PRKDC, DCD, S25A3, CLH1, HNRPU, SPTB2, PFKAP, FKBP4, AKA12, IF4G1, K1C17, CKAP4, DHX9, RBBP4, TP53B, TRAP1, PSMD2, SQSTM, TBB3, SPTN1, HNRPD, EIF3A, GANAB, GOGB1, IMB1, NUMA1, PDIA6, PLEC, PCM1, K1H1, KCC4, DREB, TRXR1, HKDC1, LRRF1, FILA2, BIG3, CROCC, BROX, K2C79, K2C80, PRP8, CCD81, SPT6H, SND1, MYH14, CC190, HORN, UNC80, GHDC, CDRT4, TXND5, NDRG1, GCN1, TNPO1, SIPA1, ERO1A, ODAD4, VPS35, ERP44, EHD4, SLK, RTN4, DDX21, SYFB, MYOF, RRBP1, SRP68, ACINU, SRRM2, PA2G4, MA2B2, RTCB, TLN1
Species: Homo sapiens
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Shen DL, Gloster TM, Yuzwa SA, Vocadlo DJ. Insights into O-linked N-acetylglucosamine ([0-9]O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates. The Journal of biological chemistry 2012 287(19) 22311971
Abstract:
Cellular O-linked N-acetylglucosamine (O-GlcNAc) levels are modulated by two enzymes: uridine diphosphate-N-acetyl-D-glucosamine:polypeptidyltransferase (OGT) and O-GlcNAcase (OGA). To quantitatively address the activity of these enzymes on protein substrates, we generated five structurally diverse proteins in both unmodified and O-GlcNAc-modified states. We found a remarkably invariant upper limit for k(cat)/K(m) values for human OGA (hOGA)-catalyzed processing of these modified proteins, which suggests that hOGA processing is driven by the GlcNAc moiety and is independent of the protein. Human OGT (hOGT) activity ranged more widely, by up to 15-fold, suggesting that hOGT is the senior partner in fine tuning protein O-GlcNAc levels. This was supported by the observation that K(m,app) values for UDP-GlcNAc varied considerably (from 1 μM to over 20 μM), depending on the protein substrate, suggesting that some OGT substrates will be nutrient-responsive, whereas others are constitutively modified. The ratios of k(cat)/K(m) values obtained from hOGT and hOGA kinetic studies enable a prediction of the dynamic equilibrium position of O-GlcNAc levels that can be recapitulated in vitro and suggest the relative O-GlcNAc stoichiometries of target proteins in the absence of other factors. We show that changes in the specific activities of hOGT and hOGA measured in vitro on calcium/calmodulin-dependent kinase IV (CaMKIV) and its pseudophosphorylated form can account for previously reported changes in CaMKIV O-GlcNAc levels observed in cells. These studies provide kinetic evidence for the interplay between O-GlcNAc and phosphorylation on proteins and indicate that these effects can be mediated by changes in hOGT and hOGA kinetic activity.
O-GlcNAc proteins:
NUP62, TAB1, KCC4, CARM1
Species: Rattus norvegicus, Homo sapiens
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Dias WB, Cheung WD, Hart GW. O-GlcNAcylation of kinases. Biochemical and biophysical research communications 2012 422(2) 22564745
Abstract:
Recent evidence indicates that site-specific crosstalk between O-GlcNAcylation and phosphorylation and the O-GlcNAcylation of kinases play an important role in regulating cell signaling. However, relatively few kinases have been analyzed for O-GlcNAcylation. Here, we identify additional kinases that are substrates for O-GlcNAcylation using an in vitro OGT assay on a functional kinase array. Forty-two kinases were O-GlcNAcylated in vitro, representing 39% of the kinases on the array. In addition, we confirmed the in vivo O-GlcNAcylation of three identified kinases. Our results suggest that O-GlcNAcylation may directly regulate a substantial number of kinases and illustrates the increasingly complex relationship between O-GlcNAcylation and phosphorylation in cellular signaling.
O-GlcNAc proteins:
STK25, RIOK3, STK16, ST17B, M3K6, PAK4, PIM1, SRC, CDK2, KPYR, AKT1, MP2K3, PLK1, CSK21, CDK16, KPCZ, TWF1, MK07, KCC2B, BRD3, STK11, MK14, KCC4, AAK1, PXK, PACE1, CDK20, DYRK2, AURKB, TRIB3, SRPK1, RIOK2, TSSK1, STK33, KPCD2, NUAK2, HSPB8, STK24, RPKL1
Species: Homo sapiens
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Dias WB, Cheung WD, Wang Z, Hart GW. Regulation of calcium/calmodulin-dependent kinase IV by O-GlcNAc modification. The Journal of biological chemistry 2009 284(32) 19506079
Abstract:
Similar to phosphorylation, GlcNAcylation (the addition of O-GlcNAc to Ser(Thr) residues on polypeptides) is an abundant, dynamic, and inducible post-translational modification. GlcNAcylated proteins are crucial in regulating virtually all cellular processes, including signaling, cell cycle, and transcription. Here we show that calcium/calmodulin-dependent kinase IV (CaMKIV) is highly GlcNAcylated in vivo. In addition, we show that upon activation of HEK293 cells, hemagglutinin-tagged CaMKIV GlcNAcylation rapidly decreases, in a manner directly opposing its phosphorylation at Thr-200. Correspondingly, there is an increase in CaMKIV interaction with O-GlcNAcase during CaMKIV activation. Furthermore, we identify at least five sites of GlcNAcylation on CaMKIV. Using site-directed mutagenesis, we determine that the GlcNAcylation sites located in the active site of CaMKIV can modulate its phosphorylation at Thr-200 and its activity toward cAMP-response element-binding transcription factor. Our results strongly indicate that the O-GlcNAc modification participates in the regulation of CaMKIV activation and function, possibly coordinating nutritional signals with the immune and nervous systems. This is the first example of an O-GlcNAc/phosphate cycle involving O-GlcNAc transferase/kinase cross-talk.
O-GlcNAc proteins:
KCC4
Species: Homo sapiens
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