Table 1.
O-GlcNAc modified proteins in heart, erythrocytes, and vascular tissue*
| Protein and Site | Potential Role of O-GlcNAc | Tissue/Organism | Reference |
|---|---|---|---|
| α-Actin | None | Neonatal cardiomyocytes | (70) |
| Actin (Ser54, Ser157, Ser201, Ser234, Ser325, Ser370) | Unknown, although O-GlcNAc levels appear elevated in diabetic models (STZ treated rats and ob/ob mice). | Heart | (138) |
| Akt§ | O-GlcNAcylation is associated with reduced phosphorylation of Akt and is implicated in reducing angiogenesis. | Aorta | (95, 96, 106) |
| Ankyrin-1 (Ser288, Ser794, Ser960, Ser1162) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes (Ser794 and Ser1162). | Erythrocytes | (169) |
| Aquaporin-1 (Ser236) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes. | Erythrocytes | (169) |
| Band-3 anion transport protein (Ser162, Ser224, Ser745) | Unknown, but O-GlcNAc levels are reduced in patients with diabetes (Ser162 and Ser224). | Erythrocytes | (169) |
| Carbonic anhydrase (Ser130, Ser218) | Unknown, but O-GlcNAc levels are reduced in patients with diabetes (Ser30 and Ser218). | Erythrocytes | (169) |
| Catalase (Ser114, Ser254) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes (Ser254). | Erythrocytes | (169) |
| Complex II, core 1† | Increased O-GlcNAcylation is linked to mitochondrial dysfunction in diabetes. | Neonatal cardiomyocytes | (64) |
| Complex III, core 2† | Increased O-GlcNAcylation is linked to mitochondrial dysfunction in diabetes. | Neonatal cardiomyocytes | (64) |
| Cox1† | Increased O-GlcNAcylation is linked to mitochondrial dysfunction in diabetes. | Neonatal cardiomyocytes | (64) |
| Desmin | Unknown | Neonatal cardiomyocytes | (70) |
| eNOS | Enhanced O-GlcNAc modification is associated with a reduction in phosphorylation at Ser1177 and a subsequent reduction in NO production. | Aorta | (95, 119) |
| Increased O-GlcNAcylation in DOCA-salt treated rats is associated with reduced phosphorylation at Ser1177. This may alter vascular relaxation contributing to hypertension. | |||
| Equilibrative nucleoside transporter 1 (Ser63) | Unknown. | Erythrocytes | (169) |
| Erythrocyte membrane protein band 4.2 (Ser82) | Unknown, but O-GlcNAc levels are reduced in patients with diabetes. | Erythrocytes | (169) |
| Fructose-bisphosphate aldolase | Unknown | Neonatal cardiomyocytes | (70) |
| Glut1 (Ser465) | Unknown | Erythrocytes | (169) |
| Glutathione S-transferase ω-1 (Ser13) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes. | Erythrocytes | (169) |
| Glyceraldehyde-3-phosphate | Unknown | Neonatal cardiomyocytes | (70) |
| Hemoglobin subunit-α (Ser4, Ser36, Ser134) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes (Ser 4, Ser 36). | Erythrocytes | (169) |
| Hemoglobin subunit-β (Ser50, Ser73, Thr85) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes (Ser50 and Ser73). | Erythrocytes | (169) |
| HSP27 | Unknown | Neonatal cardiomyocytes | (70) |
| HSP60 | Unknown | Neonatal cardiomyocytes | (70) |
| Malate dehydrogenase | Unknown | Neonatal cardiomyocytes | (70) |
| Myosin heavy chain 6 (Ser172 Ser179, Ser196, Ser392, Ser622, Ser626, Ser644, Ser645, Ser749, Ser880, Ser1038, Ser1148, Ser1159, Thr1189, Ser1200, Ser1308, Ser1336, Ser1470, Ser1471, Ser1597, Thr1600, Thr1606, Ser1711, Ser1777, Ser19161) | Unknown | Heart | (138) |
| Myosin regulatory light chain 1 (Thr93, Thr164) | Unknown | Heart | (138) |
| Myosin regulatory light chain 2 (Ser15) | Unknown | Heart | (138) |
| NDUFA9∫† (Ser156) | Increased O-GlcNAcylation is linked to mitochondrial dysfunction in diabetes. | Neonatal cardiomyocytes | (64) |
| Peroxiredoxin-2 (Ser112, Thr18) | Unknown, but O-GlcNAc levels are reduced in patients with diabetes (Ser112 and Thr18). | Erythrocytes | (169) |
| Phospholamban† (Ser16, site identified by mutation of Ser residue to alanine) | O-GlcNAcylation is associated with reduced phosphorylation, and a subsequent increase in the association of phospholamban with SERCA2a. This association is correlated with decreased cardiac function in diabetic cardiomyopathy. | Neonatal cardiomyocytes | (189) |
| Proteasome subunit-α type-5 (Ser 198) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes. | Erythrocytes | (169) |
| Protein 4.1 (Ser 491, Ser 792) | Unknown | Erythrocytes | (169) |
| Pyruvate kinase | Unknown | Neonatal cardiomyocytes | (70) |
| Sp1† | Increased O-GlcNAcylation is associated with reduced expression of SERCA2a in models of diabetes. | Neonatal cardiomyocytes | (26) |
| Spectrin-α chain (Ser844, Ser1250, Ser1737) | Unknown | Erythrocytes | (169) |
| Spectrin-β chain (Ser671, Ser767, Ser1297, Ser1652, Ser1936) | Unknown | Erythrocytes | (169) |
| Troponin I (Ser150). | Unknown | Heart | (138) |
| VDAC§†‡ | Decreased O-GlcNAcylation correlates with increased mitochondrial permeability. | Neonatal cardiomyocytes | (70, 127) |
| α-Synuclein (S87) | Unknown, but O-GlcNAc levels are elevated in patients with diabetes. | Erythrocytes | (169) |
As more than 1,000 proteins are now known to be O-linked β-N-acetylglucosamine (O-GlcNAc) modified, we refer readers to the following 2 sites for complete lists of O-GlcNAc modified proteins and amino acids: 1) http://cbsb.lombardi.georgetown.edu/hulab/OGAP.html and 2) http://www.phosphosite.org/homeAction.do;jsessionid=D89E4F582F1A5BE65C3034BC1883CDFF. ∫O-GlcNAc modification sites were mapped by BEMAD.
Identification by immunoprecipitation of the target protein was followed by Western blot with an O-GlcNAc specific antibody.
Identification by immunoprecipitation with an O-GlcNAc specific antibody or a GlcNAc-specific lectin was followed by detection with a protein specific antibody (this technique can produce false positives).
Spots that were reactive with an O-GlcNAc specific antibody on by two-dimensional PAGE were identified by mass spectrometry (this technique can produce false positives).STZ, streptozotocin; Cox1, cyclooxygenase 1; eNOS, endothelial nitric oxide (NO) synthase; DOCA, deoxycorticosterone acetate; HSP, heat shock protein; NDUFA9, NADH dehydrogenase [ubiquitin] 1α subcomplex subunit 9, mitochondrial; SERCA2a, cardiac sarcoplasmic reticulum Ca2+-ATPase; VDAC, voltage-dependent anion-selective channel.
STZ, streptozotocin; Cox1, cyclooxygenase 1; eNOS, endothelial nitric oxide (NO) synthase; DOCA, deoxycorticosterone acetate; HSP, heat shock protein; NDUFA9, NADH dehydrogenase [ubiquitin] 1α subcomplex subunit 9, mitochondrial; SERCA2a, cardiac sarcoplasmic reticulum Ca2+-ATPase; VDAC, voltage-dependent anion-selective channel.