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Jia L, Zheng H, Feng J, Ding Y, Sun X, Yu Y, Hao X, Wang J, Zhang X, Tian Y, Chen F, Cui J. Upregulation of protein O-GlcNAcylation levels promotes zebrafish fin regeneration. Molecular & cellular proteomics : MCP 2025 40044042
Abstract:
As one of the most important post-translational modifications, glycosylation participates in various cellular activities in organisms and is closely associated with many pathogeneses. It has been reported that glycosylation affects liver, spinal cord, and heart tissue regeneration. The zebrafish fin has become a valuable model due to its high regenerative capacity. The molecular mechanism of regeneration has been a hot research topic in the field for a long time. However, studies on the influence of glycosylation during limb regeneration in zebrafish are relatively scarce. We discovered that O-GlcNAc expression, identified by WGA, was elevated during the regeneration of the injured fin in zebrafish using lectin microarray. This phenomenon is due to the upregulation of the expression of OGT enzymes and elevated O-GlcNAcylation levels. To investigate the effects on the fin regeneration when O-GlcNAcylation changes, we used OSMI-1 or Alloxan unilateral microinjection to decrease O-GlcNAcylation and observed that it prevented the fin regeneration. Conversely, the O-GlcNAcylation was impressed by a unilateral microinjection of Thiamet-G or Glucose into the fin, leading to a stimulation of the fin regeneration. To further understand the role of O-GlcNAcylation in fin regeneration, LC-MS/MS was performed to identify O-GlcNAc-glycoproteins. The results demonstrated that the O-GlcNAc glycoproteins, such as THBS4 and HSPG, were involved in the regulation of zebrafish fin regeneration process and were closely associated with certain biological processes, such as stem cell differentiation, ECM-receptor interaction pathway, tissue remodeling, etc. We demonstrated that O-GlcNAc glycoproteins are crucial for zebrafish fin regeneration, during which OGT promotes the process by upregulating the O-GlcNAcylation levels in the zebrafish fin.
O-GlcNAc proteins:
A0A096X788, A0A097, A0A0B4P4A4, A0A0F7EVQ6, A0A0H4LGZ0, RECK, A0A0S2I7K2, A0A2I4KBP1, A0A2U9DQQ6, A0A8M1N0E2, A0A8M1N4I9, A0A8M1N6R0, A0A8M1N6S0, A0A8M1N743, A0A8M1N7Z8, A0A8M1N8U6, A0A8M1NAN4, A0A8M1NE33, A0A8M1NF66, A0A8M1NF67, A0A8M1NG90, A0A8M1NHL5, A0A8M1NTE7, A0A8M1NUS6, A0A8M1NXE0, A0A8M1NXI0, A0A8M1NXK7, A0A8M1NZC4, A0A8M1NZG6, A0A8M1P182, A0A8M1P1C1, A0A8M1P3F9, A0A8M1P4I3, A0A8M1P526, A0A8M1P6F7, A0A8M1P6M4, A0A8M1P6T1, A0A8M1P706, A0A8M1P748, A0A8M1P758, A0A8M1P7C1, A0A8M1P825, A0A8M1P861, A0A8M1P8B8, A0A8M1P8J0, A0A8M1PAD4, A0A8M1PAH1, A0A8M1PAV5, A0A8M1PCM8, A0A8M1PE71, A0A8M1PS86, A0A8M1PSG8, A0A8M1PU45, A0A8M1PZW5, A0A8M1Q134, A0A8M1Q1U4, A0A8M1Q1V3, A0A8M1Q2B3, A0A8M1QHB2, A0A8M1QHN7, A0A8M1QLT2, A0A8M1QUS6, A0A8M1QVB8, A0A8M1RDD4, A0A8M1RI06, A0A8M1RKG7, A0A8M1RMK1, A0A8M1RMK2, A0A8M1RN22, A0A8M1RN68, A0A8M1RN75, A0A8M1RR96, A0A8M1RRH3, A0A8M1RSB9, A0A8M1RTG2, A0A8M2B1U6, A0A8M2B227, A0A8M2B329, A0A8M2B3L9, A0A8M2B3S2, A0A8M2B3Z8, A0A8M2B473, A0A8M2B4A5, A0A8M2B4F9, A0A8M2B4G7, A0A8M2B4I2, A0A8M2B4P5, A0A8M2B594, A0A8M2B5L7, A0A8M2B5R0, A0A8M2B5Z8, A0A8M2B614, A0A8M2B6H9, A0A8M2B6P3, A0A8M2B6Z2, A0A8M2B6Z8, A0A8M2B705, A0A8M2B744, A0A8M2B749, A0A8M2B7E3, A0A8M2B7H0, A0A8M2B7L2, A0A8M2B7R8, A0A8M2B7S3, A0A8M2B7U5, A0A8M2B7V9, A0A8M2B7Y0, A0A8M2B804, A0A8M2B846, A0A8M2B8C3, A0A8M2B8N4, A0A8M2B8Q3, A0A8M2B8Y2, A0A8M2B8Z6, A0A8M2B926, A0A8M2B9A3, A0A8M2B9A6, A0A8M2B9E7, A0A8M2B9L5, A0A8M2B9V8, A0A8M2BA07, A0A8M2BA31, A0A8M2BA63, A0A8M2BA70, A0A8M2BA79, A0A8M2BA87, A0A8M2BAB1, A0A8M2BAQ6, A0A8M2BAV2, A0A8M2BAV5, A0A8M2BAZ5, A0A8M2BB16, A0A8M2BB24, A0A8M2BBC0, A0A8M2BC86, A0A8M2BC90, A0A8M2BCF1, A0A8M2BCI4, A0A8M2BCU9, A0A8M2BCY6, A0A8M2BD91, A0A8M2BDI8, A0A8M2BDJ6, A0A8M2BDV8, A0A8M2BDX2, A0A8M2BDX9, A0A8M2BDY0, A0A8M2BE58, A0A8M2BEB1, A0A8M2BF40, A0A8M2BF86, A0A8M2BFY9, A0A8M2BG24, A0A8M2BG33, A0A8M2BG68, A0A8M2BGC2, A0A8M2BGK8, A0A8M2BGP7, A0A8M2BH45, A0A8M2BH70, A0A8M2BHC1, A0A8M2BHF1, A0A8M2BHQ8, A0A8M2BHS0, A0A8M2BHZ6, A0A8M2BI30, A0A8M2BI56, A0A8M2BI58, A0A8M2BJH3, A0A8M2BJN0, A0A8M2BJR8, A0A8M2BJY6, A0A8M2BKD5, A0A8M2BKF1, A0A8M2BKJ7, A0A8M2BKN1, A0A8M2BKR2, A0A8M2BKS1, A0A8M2BKT2, A0A8M2BKU1, A0A8M2BKV1, A0A8M2BKX2, A0A8M2BKY8, A0A8M2BL32, A0A8M2BLP7, A0A8M2BLY6, A0A8M3AI36, A0A8M3AI90, A0A8M3AJA6, A0A8M3AJX0, A0A8M3AKJ3, A0A8M3AKU9, A0A8M3ALQ9, A0A8M3ANV7, A0A8M3APK5, A0A8M3APN2, A0A8M3AQ77, A0A8M3AQ81, A0A8M3AQE8, A0A8M3AQJ2, A0A8M3ARN6, A0A8M3AS23, A0A8M3ASD1, A0A8M3AU14, A0A8M3AUM8, A0A8M3AUT7, A0A8M3AV68, A0A8M3AV96, A0A8M3AVG6, A0A8M3AVI2, A0A8M3AWE5, A0A8M3AWF2, A0A8M3AXV0, A0A8M3AYV9, A0A8M3AYZ1, A0A8M3AZU1, A0A8M3B081, A0A8M3B088, A0A8M3B0Y8, A0A8M3B1Z0, A0A8M3B295, A0A8M3B3W4, A0A8M3B448, A0A8M3B464, A0A8M3B4R7, A0A8M3B4W9, A0A8M3B5S9, A0A8M3B7N0, A0A8M3B808, A0A8M3B814, A0A8M3B826, A0A8M3B882, A0A8M3BAQ1, A0A8M3BBK0, A0A8M6YU37, A0A8M6YUI4, A0A8M6YWS7, A0A8M6YZ95, A0A8M6YZW1, A0A8M6Z047, A0A8M6Z050, A0A8M6Z0P5, A0A8M6Z121, A0A8M6Z1R1, A0A8M6Z250, A0A8M6Z2M1, A0A8M6Z2N0, A0A8M6Z319, A0A8M6Z367, A0A8M6Z3L7, A0A8M6Z447, A0A8M6Z5L8, A0A8M6Z641, A0A8M6Z7Z5, A0A8M6Z8C5, A0A8M6Z8R4, A0A8M6Z9Q6, A0A8M9NZB7, A0A8M9P366, A0A8M9P4Q6, A0A8M9P595, A0A8M9P5B3, A0A8M9P5U3, A0A8M9P8V5, A0A8M9P9Q7, A0A8M9PAR6, A0A8M9PBF2, A0A8M9PBG3, A0A8M9PBU2, A0A8M9PCC2, A0A8M9PCH5, A0A8M9PCW9, A0A8M9PD82, A0A8M9PDD8, A0A8M9PDY1, A0A8M9PEL4, A0A8M9PFH0, A0A8M9PFM1, A0A8M9PFX7, A0A8M9PGI2, A0A8M9PHD2, A0A8M9PI83, A0A8M9PII1, A0A8M9PIJ0, A0A8M9PJQ1, A0A8M9PJX3, A0A8M9PK39, A0A8M9PKI9, A0A8M9PLA6, A0A8M9PM15, A0A8M9PMA1, A0A8M9PMJ5, A0A8M9PN10, A0A8M9PNE8, A0A8M9PNK3, A0A8M9PNK8, A0A8M9PPG9, A0A8M9PPV8, DESPB, A0A8M9PQP7, A0A8M9PQR9, A0A8M9PRV2, A0A8M9PSQ1, A0A8M9PSZ1, A0A8M9PTJ2, A0A8M9PTR2, A0A8M9PTY1, A0A8M9PUC7, A0A8M9PVP6, A0A8M9PW65, A0A8M9PX21, A0A8M9PX41, A0A8M9PXA5, A0A8M9PXN7, A0A8M9PYN8, A0A8M9PYS6, A0A8M9PYT5, A0A8M9PZ17, A0A8M9PZG9, A0A8M9PZU3, A0A8M9Q078, A0A8M9Q0X5, A0A8M9Q165, A0A8M9Q352, A0A8M9Q4F0, A0A8M9Q590, A0A8M9Q5C3, A0A8M9Q5Q4, A0A8M9Q5S4, A0A8M9Q6A0, A0A8M9Q7C2, A0A8M9Q7D5, A0A8M9Q7K5, A0A8M9Q812, A0A8M9Q8S4, A0A8M9Q945, A0A8M9Q9I4, A0A8M9Q9J2, A0A8M9Q9M9, A0A8M9QA09, A0A8M9QA62, A0A8M9QAA0, A0A8M9QB10, A0A8M9QB73, A0A8M9QBK3, A0A8M9QBU3, A0A8M9QCI5, A0A8M9QDG6, A0A8M9QDJ7, A0A8M9QDP1, A0A8M9QDU6, A0A8M9QE16, A0A8M9QE52, A0A8M9QFE6, A0A8M9QFL0, A0A8M9QFQ9, A0A8M9QGE4, A0A8M9QGJ8, A0A8M9QGR2, A0A8M9QIL1, A0A8M9QJL3, A0A8M9QKC3, A0A8M9QKH6, A0A8M9QMN2, A0A8N1TT16, A0A8N7T5L8, A0A8N7T6E8, A0A8N7T6S1, A0A8N7T7N7, A0A8N7T801, A0A8N7T837, A0A8N7T8M6, A0A8N7T8N4, A0A8N7TFA0, A0A8N7UR03, A0A8N7URF7, A0A8N7URI5, A0A8N7UTE7, A0A8N7UVR1, A0A8N7UW22, A0A8N7UZ95, A0A8N7UZX0, A0A8N7V0N1, A0AUP8, A0AUR8, A0AUR9, A0JMB8, A0JMG3, A0JMJ1, A0JMK7, A0JMN4, CNOT1, YES, EFTS, A1IH01, A1L1S0, A1L1S8, A1L1W1, A1L257, A2AR64, GLTP, A2RQR3, ZN346, A2TJ25, A3FKT8, GPT3L, A3KMS0, A3KMS4, A3KNN5, A3KNW4, A3KP44, A3KP84, JAM3B, A4FVJ5, A4IG19, A4IG87, A4IGC2, A4JYP0, A4JYP8, A4QN64, A4QNX8, A4QP04, A4QP06, A4QP10, A4QP67, CNO11, SAC1A, VP35L, A5A4L9, A5D6U4, LEG1A, A5PL48, SDHB, LHPP, A5PN62, MED22, ITPA, A6QL59, A7E2G2, A7MBU4, A7MBY2, A7MCE3, A8E7F4, A8KAZ3, A8KB50, A8KB80, A8KBB1, A8KBI4, A8WFS1, A8WFV1, A8WG65, A8WG75, A8WGR0, MLEC, A9JR82, MTNA, A9JRZ4, B0S641, B1H1M2, B2CZB8, B2XCL9, B3DFP9, B3DFQ1, B3DGG4, B3DGV1, B3DH18, B3DHC5, B3DHG0, B3DIC7, B3DID0, B3DJ34, B3DJF3, B3DK73, B3DKC0, B3DKC5, YBOX1, B6CS38, B8A5G0, B8JHU4, C1IHU9, C5H5I1, D3XD60, D3XD61, D3XD84, D3XD97, D3XDB2, D7RVS2, E2FHP4, E3NZ06, E7F3D4, HARS1, F1Q8B0, PABPA, GAL3A, HDA10, PS11B, IF2G, NU133, RPZ, F1QUY3, ST6B1, F1QYU7, SPAG1, F1RC25, PTGIS, SMYD5, PS11A, FLII, DSG21, NEUAB, GBLP, APOA1, APOEB, O57330, O57332, HS90B, O93598, PA24A, RL36A, RS7, RS8, RIR2, RAN, RUVB2, B2MG, Q05AK3, Q05AL9, Q05AP2, Q08BF1, Q08BF2, MCU, Q08BN2, Q08C21, Q08C31, ISOC1, Q08C42, Q08C80, Q08C89, Q08CA5, Q08CB4, Q08CE4, Q08CQ0, Q08CV8, Q0D284, Q0H0R9, Q0IIP9, Q0MSH9, LTOR4, Q0P463, Q0P4C2, Q0PWB9, Q0V973, SELS, Q0ZBR7, Q1ED16, Q1JPU8, SYFA, Q1JPZ2, SRC, PRP39, Q1L907, Q1LUT0, EDC4, I2BP1, Q1LVD7, LAMC1, Q1LWH1, ARPIN, Q1LWP9, Q1LWU4, Q1LXF9, Q1LXJ1, M10B1, PSMG2, Q1LY62, Q1LY92, Q1LYQ0, Q1LYQ9, Q1MT41, MCES, ARL3, Q24JV1, OLF3A, Q2LEK1, Q2TJF5, IMPA3, Q31365, BHMT1, Q32LR0, Q32LT0, MIRO2, PP1R7, Q32PQ5, Q32PR4, Q32PS6, Q32PT3, Q32PT4, Q32Q51, Q3B738, Q3B7F0, Q3B7G2, Q3B7P7, Q3LTM3, Q3LTM4, Q3LTM5, Q3MU74, Q3S344, SELN, Q3YA99, Q3YAA0, Q3YMK9, Q498Q0, Q499A0, Q4G000, Q4KM20, Q4KMD4, Q4KME8, Q4KMH7, Q4KMK4, EIF2A, MAP11, DDX46, Q4V916, Q4V9A4, Q4V9C6, Q4V9D8, Q4V9J1, Q4V9N1, Q4VBH6, Q4VBR6, Q4VBR7, Q4VBU0, Q4VBV2, Q502A6, Q502B9, GLOD5, Q502I0, PCAT2, Q502P2, Q503C0, NUDC1, Q503E3, Q503E6, IMA6, Q503H4, Q503H9, Q503J3, Q503M9, Q503P4, Q504B1, Q504C0, Q504C3, Q504F5, Q504F7, CASPB, Q52KK6, DPYL3, Q561T2, Q561T3, Q561T4, Q561T5, DHRS6, Q561Y1, Q566N7, Q566T8, Q566W6, MGN, Q567F4, Q567F8, Q567G0, Q567N5, Q567V5, EIF3K, Q567Y8, Q568C9, Q568D0, Q568D6, Q568E7, Q568F3, PURA2, Q568H0, Q568I4, Q568J6, Q568K1, Q568L9, CRLF3, Q568N1, Q568N9, Q568Q8, Q568S9, FBX50, HIBCH, Q58EC1, ERLN1, Q58EK7, Q58EM3, Q5BJ07, Q5BJ17, Q5BJB9, SPCS2, Q5BKV3, Q5BKV9, Q5BL99, Q5BLC1, RETST, Q5BLF7, Q5BLH5, Q5BU17, Q5CZP5, PFD1, Q5GA11, KAP0, Q5KTT7, G3P2, Q5PR60, NDRG2, DHTK1, Q5PRB9, Q5PRC6, 143BA, Q5RG12, HSP7E, IMDH3, Q5RHK5, PARP1, Q5RKM2, Q5RKM6, Q5RKP7, Q5RKP9, Q5RKQ3, Q5RKQ5, AGR2, WDR26, Q5SPD1, P5CR3, Q5TZG5, Q5U369, Q5U398, PPR21, Q5U3E1, Q5U3E7, Q5U3E8, Q5U3G0, Q5U3M8, Q5U3R4, Q5U3S2, Q5U3T6, CPPED, Q5XFY2, Q5XIZ3, GPD1L, Q5XJ12, Q5XJ23, PARK7, GLRX3, PRRC1, Q5XJA4, Q5XJC6, Q5XJD4, Q5XJJ3, Q5XJJ8, GILT, Q5XJP4, EXOS9, Q5XJQ6, Q5XJS8, Q5XJT9, Q5XLR3, SEP8A, RS4X, Q642J0, Q642J7, DHDH, Q64HD0, ADPRS, COPB, Q66HV5, GDAP2, CCD47, SPS3, Q66I19, Q66I20, ASSY, Q66I39, Q66I58, Q66I72, Q66I80, Q66I87, Q66IB1, Q66IB5, Q66IB6, Q66ID8, Q66IF0, SCMC1, Q66L64, Q68EH2, Q68EI7, RAB4B, Q68SP2, Q6A3P5, THIL, CPIN1, Q6AZB9, Q6AZV8, Q6AZW4, CPTP, TXD17, NAA50, Q6DBZ1, CARM1, Q6DC31, Q6DC71, PEF1, Q6DEJ0, CLPT1, UFC1, Q6DFZ8, ADA, Q6DG41, Q6DG42, Q6DG44, Q6DG67, PLST, Q6DGA0, Q6DGE2, Q6DGH3, Q6DGH7, Q6DGI6, Q6DGJ8, Q6DGL0, Q6DGQ9, Q6DGR3, Q6DGS7, Q6DGV0, Q6DGW3, TMCO1, Q6DH28, DENR, Q6DHB6, RB18B, Q6DHK5, Q6DHL6, RHOAB, ACY3B, Q6DHR4, Q6DHS3, Q6DHS7, PR38A, SUMO3, Q6DI34, MXC, SYSC, EIF3G, Q6DRD1, Q6DRD2, DPOLB, Q6DRE2, PSB1, EI3EA, RIC8B, Q6DRK2, Q6DRK5, Q6DRL7, Q6DRM4, Q6DRN5, ENOPH, Q6GML2, Q6GQM3, Q6GQN6, Q6GQN9, Q6IMW6, Q6IQ56, Q6IQ57, Q6IQ70, CHM4C, Q6IQ89, Q6IQA6, Q6IQB1, Q6IQD0, PU60B, PI42C, GET3, Q6IQI3, Q6IQI6, Q6IQJ1, Q6IQJ7, CYC, Q6IQM9, Q6IQP5, Q6IQQ7, Q6IQQ8, Q6IQR5, SAE1, Q6IQS7, Q6IQU1, Q6J0N1, Q6NSN6, Q6NUT5, Q6NUU2, Q6NUW4, AN32E, Q6NUX4, Q6NUX6, Q6NUX7, RHOAA, Q6NUY4, Q6NV07, Q6NV11, Q6NVI6, Q6NW62, Q6NWC1, CPSF6, Q6NWC8, Q6NWF2, K2C8, Q6NWF7, MRPB, Q6NWI0, Q6NWI5, DNJC2, PD10B, Q6NWL3, CNOT9, Q6NWX4, Q6NWY2, Q6NX86, Q6NX98, UBXN1, Q6NXB9, Q6NY63, Q6NY65, RFA1, Q6NY92, Q6NYD2, RCC2, Q6NYF2, Q6NYG2, Q6NYH5, Q6NYJ1, Q6NYJ7, ALAT2, Q6NYP5, Q6NYQ7, Q6NYR4, OST48, Q6NYV1, Q6NYV3, VMP1, ILF2, NCLN, Q6NZ29, AR8BA, Q6NZZ2, RBM22, EMC4, Q6P032, Q6P0B5, Q6P0I5, Q6P0V2, RL8, Q6P122, Q6P267, Q6P271, Q6P2M0, Q6P2T9, CSN3, Q6P2V1, Q6P2V4, RBBP4, EF2, MVP, Q6P3L9, Q6P5K3, Q6P5M3, Q6P607, Q6P6E0, Q6P6E4, Q6P6E7, PDLI7, GLO2, Q6PBA5, Q6PBH6, RS25, RS28, Q6PBK9, FA76B, Q6PBR3, Q6PBR5, Q6PBW0, Q6PBW4, Q6PBW6, Q6PBX1, Q6PBX6, REEP5, RS3A, EDF1, Q6PBY6, Q6PBY8, Q6PBZ1, Q6PBZ2, RL23, SSU72, CSN5, Q6PC41, Q6PC53, RL10A, Q6PC77, Q6PC90, ZFR, EIF3A, 5MP2A, MRPA, EF1G, Q6PE45, Q6PEH0, UB2V2, Q6PEI5, Q6PEI6, Q6PEI8, Q6PFJ2, Q6PFJ6, Q6PFK8, Q6PFL9, Q6PFM3, Q6PFN9, EIF3C, ATG3, Q6PFT7, AB1IP, Q6PFU7, Q6PGT6, Q6PGT7, VA0D1, DJC21, Q6PGZ2, Q6PH75, Q6PHD8, SBP1, Q6PHE4, HEMO, Q6PHG3, PD10A, Q6PHI2, Q6PHI7, Q6PHI8, Q6PHJ5, PURB, Q6PUQ3, RL36, Q6Q416, Q6Q418, RS15A, Q6Q421, DH12B, Q6R3L1, Q6RFG0, RA21A, Q6TEM5, RAP1B, Q6TGT5, Q6TGU0, Q6TGV6, OSTF1, Q6TGX3, EIF3D, DDI2, Q6TH48, Q6TLD7, RGN, Q6TNQ4, Q6TNR5, Q6TNT8, Q6U1J5, Q6U1J7, Q6XG62, Q6YLH8, Q6YLH9, Q6YMR2, Q6ZM17, IF6, Q6ZM50, Q6ZM62, Q6ZM71, H2AV, Q76C07, Q7SX58, Q7SX98, FUMH, Q7SXA1, UBL5, Q7SXJ4, Q7SXJ5, Q7SXK1, Q7SXM2, Q7SXN1, Q7SXN6, ULA1, SRS1A, GMPAB, Q7SXQ3, SETD3, Q7SXT5, EI3JA, Q7SXU3, Q7SXU4, Q7SXU7, Q7SXU9, ARP2A, Q7SXW7, AL4A1, Q7SY35, HEAT1, THOC1, CTL2, SC31A, Q7SYE1, CHID1, AATM, Q7SYN3, Q7SZ53, Q7SZ54, XPO2, Q7SZC9, Q7SZD2, Q7SZD3, SC23A, Q7SZM5, Q7SZR4, Q7SZY1, Q7T002, Q7T131, Q7T1D7, Q7T1D8, Q7T1J9, EIF3L, Q7T2C2, Q7T2C6, Q7T2D2, Q7T2E0, Q7T2E1, Q7T2F5, I2B2B, Q7T306, Q7T313, Q7T318, CISD2, Q7T341, 143BB, Q7T363, Q7T366, Q7T372, Q7T373, Q7T379, VTC1A, T179B, LIS1A, Q7T3B1, Q7T3B6, Q7T3C1, Q7T3C4, CPSF5, Q7T3D3, CHRD1, Q7T3F8, Q7T3F9, Q7T3L3, Q7ZSY3, Q7ZSZ0, Q7ZSZ9, Q7ZTH6, Q7ZTH9, Q7ZTI0, Q7ZTI4, Q7ZTR9, K1C18, Q7ZTT4, Q7ZTU4, Q7ZTW6, Q7ZTX2, Q7ZTX3, RBBP7, USE1, Q7ZTZ3, Q7ZTZ4, Q7ZU10, Q7ZU12, Q7ZU20, NUP93, Q7ZU40, Q7ZU44, Q7ZU46, Q7ZU69, Q7ZU85, Q7ZU89, Q7ZU96, TERA, Q7ZUC1, Q7ZUD3, Q7ZUD6, Q7ZUF5, Q7ZUF7, Q7ZUG1, RS21, Q7ZUG6, Q7ZUJ4, Q7ZUL8, Q7ZUM3, Q7ZUM5, Q7ZUN6, YKT6, AN32A, Q7ZUP5, Q7ZUP6, Q7ZUQ0, Q7ZUQ1, Q7ZUQ2, STK3, Q7ZUR1, Q7ZUR9, VRK1, Q7ZUS9, Q7ZUU9, HYOU1, Q7ZUW5, Q7ZUW8, Q7ZUY9, Q7ZUZ4, Q7ZV01, Q7ZV05, Q7ZV07, S22BA, Q7ZV16, Q7ZV18, Q7ZV19, MTAP, Q7ZV29, Q7ZV33, MCTS1, TOLIP, Q7ZV49, Q7ZV53, EIF3I, Q7ZV58, VPS29, Q7ZV76, Q7ZV77, RL27, RL10, SMU1, Q7ZVA3, Q7ZVA4, IF4A3, Q7ZVB0, CHM1B, A9A1A, Q7ZVB4, Q7ZVB5, Q7ZVC1, Q7ZVD2, Q7ZVD9, Q7ZVE2, Q7ZVE4, Q7ZVE7, Q7ZVF2, SDHA, Q7ZVF4, Q7ZVF8, Q7ZVG1, Q7ZVG7, ACTB1, Q7ZVI8, Q7ZVJ0, SIR2, Q7ZVK5, Q7ZVK8, Q7ZVL3, Q7ZVL6, Q7ZVL7, Q7ZVL9, Q7ZVM6, SRP54, Q7ZVP2, Q7ZVQ7, Q7ZVR3, Q7ZVS2, Q7ZVT2, Q7ZVU0, Q7ZVV5, Q7ZVV7, Q7ZVW2, Q7ZVW5, ARGLB, Q7ZVX4, REEP3, Q7ZVX9, CISY, Q7ZVY8, Q7ZVY9, PREP, Q7ZW04, Q7ZW07, Q7ZW09, Q7ZW17, Q7ZW18, CHM2A, Q7ZW32, Q7ZW65, Q7ZW72, Q7ZW75, Q7ZW80, Q7ZW92, Q7ZW96, AP2MB, Q7ZWA9, Q7ZWB4, Q7ZWD3, UAP1L, Q7ZWE5, KCY, Q7ZWF5, Q7ZWG7, SGMR1, RL18A, RL34, Q7ZYX3, Q7ZYX4, Q7ZYX7, Q7ZZA3, Q7ZZZ4, Q800S8, Q801U5, Q801Y4, Q802D5, Q802G9, Q802U8, Q802W6, Q802Y5, Q802Z1, Q802Z9, Q803A1, Q803B0, NCBP3, Q803E5, Q803F2, Q803F3, RSSA, Q803G3, CG025, Q803H5, Q803H8, ERGI3, Q803I3, Q803J2, Q803J3, Q803J6, Q803J7, Q803K3, Q803K6, Q803K8, Q803M7, Q803N5, Q803N7, Q803Q1, Q803Q7, Q803R9, Q803T1, Q803T5, Q803U3, Q803U6, Q803V2, Q803V8, Q803X6, Q803Z1, Q804C3, Q804G3, Q804G7, Q804G9, Q804H1, Q8AW07, Q8AWD0, Q8AWD9, Q8AWW3, RUVB1, Q8AX99, Q8AY63, Q8AYB9, Q8AYE2, Q8AYE3, Q8AYH1, Q8JGR1, RL24, Q8JGR8, RS18, TSP4B, MXA, ALDCB, ALDOB, Q8JHE0, Q8JHG6, Q8JHG7, Q8JHH4, Q8JHI0, Q8JHI7, RL35, Q8JHV7, TSP3A, Q8JHZ5, NACA, Q8MGW8, Q8QHA7, Q8QHI1, XPO6, CYGB1, Q8UUX0, Q8UVG7, SPT6H, CADH2, C166A, H90A1, HBB2, HBB1, HBA, Q90X41, TPISB, Q90XQ8, Q90XR6, Q90XR8, Q90XS8, CXAR, CYFP1, Q90YS5, RL13, CADH1, Q90Z77, Q90ZC5, S61A1, Q90ZZ8, CSK2B, EF1A, CAHZ, Q98UI8, UBC9B, Q9DDS8, Q9DDT0, Q9DDU5, Q9DEU1, Q9DEY8, Q9DF20, Q9DF44, Q9DGI4, TCTP, Q9DGL2, Q9I9E5, Q9I9E6, Q9I9E8, CASPA, Q9I9N4, ASC, SMAD2, Q9IAD3, Q9IB48, COX2, Q9PTH5, PCNA, DCUP, Q9PUC4, Q9PUS3, Q9PUS6, Q9PUT2, RLA0, PLAKA, LDHA, Q9W792, Q9YH60, Q9YHX5, UBA5
Species: Danio rerio
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Soria LR, Makris G, D'Alessio AM, De Angelis A, Boffa I, Pravata VM, Rüfenacht V, Attanasio S, Nusco E, Arena P, Ferenbach AT, Paris D, Cuomo P, Motta A, Nitzahn M, Lipshutz GS, Martínez-Pizarro A, Richard E, Desviat LR, Häberle J, van Aalten DMF, Brunetti-Pierri N. O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis. Nature communications 2022 13(1) 36064721
Abstract:
Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis. Mechanistically, O-GlcNAcylation on specific threonine residues increased the catalytic efficiency for ammonia of carbamoyl phosphate synthetase 1 (CPS1), the rate-limiting enzyme in ureagenesis. Pharmacological inhibition of O-GlcNAcase, the enzyme removing O-GlcNAc from proteins, resulted in clinically relevant reductions of systemic ammonia in both genetic (hypomorphic mouse model of propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models of liver diseases. In conclusion, by fine-tuned control of ammonia entry into ureagenesis, hepatic O-GlcNAcylation of CPS1 increases ammonia detoxification and is a novel target for therapy of hyperammonemia in both genetic and acquired diseases.
O-GlcNAc proteins:
A0A075B5P3, A0A075B5P5, A0A075B5R4, A0A075B5V1, A0A077S9N1, A0A097PUH2, A0A0M4KM70, A0A0R4J135, A0A0R4J293, A0A1B0GT41, A0AUN0, A0JLV3, A2AA71, A5JUZ1, B1AXW5, B2RTM0, D3Z041, D3Z6F5, E9Q175, E9Q1S3, E9Q3W4, DESP, E9QNH6, E9QPE7, G5E8R3, H7BXC3, H9KV01, K3W4R2, BHMT1, IGKC, K2C1, K2C8, SPTN1, CPSM, HSPA9, KPYM, ATPB, CH60, TBA4A, WNK1, PKP1, PLAK, GSDA2, Q3TD51, Q3TH57, Q3TLH6, Q3TN99, Q3TZR8, Q3UF58, Q3UGJ7, Q3UHW2, Q3UKH3, PRRC1, SC31A, Q3UTZ4, K22O, Q3V222, Q4KL81, Q504P4, Q52L87, Q542G9, Q544B1, Q546G4, Q58E56, Q58E64, Q5FW97, Q5M9N9, Q5QNU0, MYH4, MYH1, HCFC1, DSG1A, MYH10, SPTB2, EST3A, Q68FG2, Q6ZQC2, Q71LX8, NU214, Q80WR0, Q80ZX0, ECHA, NUP54, Q8C140, Q8C153, CPSM, Q8C7S2, Q8CF71, OGT1, Q8CIF2, Q8N7N8, HUTU, MYH9, Q91V38, Q9CV13, Q9D828, ECHP, Q9DC41, MVP, Q9JJ20, Q9QZF3, MYO1C, CARM1, S4R192, S4R1W1, S4R2A9, S4R2L9
Species: Mus musculus, Homo sapiens
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