|Protein Name||Serine hydroxymethyltransferase, cytosolic|
|Ref Sequence ID||NP_001015553.1|
|Protein Existence Status||Reviewed: Experimental evidence at transcript level|
|Protein Function||Catalyzes the reversible conversion of L-serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate; plays a pivotal role in one-carbon metabolism; is involved in cancer metabolic reprogramming and is a recognized target of chemotherapy intervention|
|Biochemical Properties||pH optimum of SHMT mitochondrial is 0.5 unit higher with respect to that of SHMTcytosolic; cytosolic SHMT shows a marked decrease in the level of substrate inhibition at high pH values; in the case of SHMT1, below 20 μM Tetrahydrofolate, the enzyme activity decreases as the pH is increased from 6.9 to 8.4|
|Significance in milk||May be related to stage-specific expression, varying throughout gestation and rising after birth as found in swines|
|PTMs||Ubiquitinated at the small ubiquitin-like modifier (SUMO) consensus motif ; SUMO-1 modification occurs at either Lys-38 or Lys-39|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||NA|
|TM Helix Prediction||No TM helices|
|Significance of PTMs||As found in vivo, ubiquitinationis required for SHMT1 degradation; SUMOylation is required for nuclear transport|
|Bibliography||1. Vallée, M. et al. (2002) ‘Effects of Breed, Parity, and Folic Acid Supplement on the Expression of Folate Metabolism Genes in Endometrial and Embryonic Tissues from Sows in Early Pregnancy1’, Biology of Reproduction, 67(4), pp. 1259–1267. doi: 10.1095/biolreprod67.4.1259. |
2. Anderson, D. D., Eom, J. Y. and Stover, P. J. (2012) ‘Competition between Sumoylation and Ubiquitination of Serine Hydroxymethyltransferase 1 Determines Its Nuclear Localization and Its Accumulation in the Nucleus’, Journal of Biological Chemistry, 287(7), pp. 4790–4799. doi: 10.1074/jbc.M111.302174.
3. Tramonti, A. et al. (2018) ‘Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties.’, Biochemistry, 57(51), pp. 6984–6996. doi: 10.1021/acs.biochem.8b01074.