Recombinant Human SHMT1 protein (His tag N-Terminus)

일반 정보

기능

Pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylene THF, serving as a critical component of the folate cycle and facilitating one-carbon biosynthetic reactions essential for methionine, purine, and pyrimidine synthesis (PubMed : 24698160, PubMed : 30035852, PubMed : 38996576). While its central activity involves serine cleavage, the detailed catalytic mechanisms remain under study, including both retro-aldol cleavage of the PLP-serine C(alpha)-C(beta) bond followed by formaldehyde condensation with THF, and alternative nucleophilic displacement mechanisms of the C(alpha) atom of PLP-serine aldimine involving THF's N5 atom (By similarity). Also catalyzes the cleavage of various 3-hydroxy amino acids, such as L-allo-threonine, L-threonine and 3-phenylserine, forming glycine and the corresponding aldehyde through a retro-aldol process; additionally, it catalyzes the formation of 5-formyltetrahydrofolate from 5,10-methenyltetrahydrofolate (PubMed : 38615009). Also functions as a hydroxytrimethyllysine aldolase (HTMLA) catalyzing the second step of the carnitine biosynthesis pathway and exhibits substrate preference with the erythro (S,S) configuration, and more efficiency with L-allo-threonine (PubMed : 38615009). In the nucleus, first functions as a lamin-binding scaffold protein that is essential for assembling the de novo thymidylate synthesis complex by co-localizing DHFR and TYMS with the nuclear lamina and anchoring the complex to DNA replication sites (PubMed : 22235121). Subsequently, provides one-carbon substrates, specifically (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, in situ for de novo dTMP synthesis to sustain DNA replication and repair during cell proliferation (PubMed : 30035852). Importantly, possesses RNA-binding capability, forming complexes that selectively regulate SHMT2 mRNA translation and dynamically modulate cytosolic and mitochondrial serine and glycine concentrations, thus influencing cellular metabolic status (PubMed : 38996576).

서열 유사성

Belongs to the SHMT family.

Post-translational modifications

Ubiquitination at Lys-39 leads to proteasomal degradation (PubMed:22194612). UBE2N/UBC13-mediated ubiquitination stabilize SHMT1 within the nucleus and signals nuclear export of SHMT1 through 'Lys-63'-specific ubiquitin linkage (PubMed:22194612). 'Lys-63' polyubiquitination is cell cycle- and compartment-specific (PubMed:22194612). Modification by UBE2I/UBC9 or UBE2N/UBC13 compete for SHMT1 modification, leading to either degradation in the nucleus or nuclear export, respectively (PubMed:22194612). In the cytoplasm, SHMT1 degradation is facilitated by 'Lys-48' ubiquitin linkages, whereas in the nucleus, 'Lys-63'-linked ubiquitination prevents degradation (PubMed:22194612).. Sumoylated at either Lys-38 or Lys-39 (PubMed:17446168). SUMO1 conjugation by UBE2I/UBC9 occurs at the nuclear pore during S,G2/M phases of the cell cycle and triggers the RAN-dependent nuclear import of SHMT1 (PubMed:17446168, PubMed:22194612). UBE2I-mediated conjugation to SUMO2/3 in the nucleus allows nuclear degradation (PubMed:22194612).. Deamidation of asparagine produces alternatively aspartate or isoaspartate, which in turn can be converted to aspartate through carboxylmethylation/demethylation.