Shmt1
entrez
20425
canonical
uniprot
P50431
canonical
ensembl
ENSMUSG00000020534
resolver
ensp
ENSMUSP00000018744
resolver
ensp
ENSMUSP00000134318
resolver
ensp
ENSMUSP00000270757
resolver
enst
ENSMUST00000018744
resolver
enst
ENSMUST00000174719
resolver
genesymbol
Shmt1
resolver
genesymbol_syn
Shmt
resolver
uniprot
G3UZ26
resolver
uniprot
Q64508
resolver
uniprot
Q8R0X9
resolver
uniprot_entry
G3UZ26_MOUSE
resolver
uniprot_entry
GLYC_MOUSE
resolver
uniprot_sec
Q64508
resolver
uniprot_sec
Q8R0X9
resolver
amino_acid_sequence
MADRDATLWASHEKMLSQPLKDSDAEVYSIIKKESNRQRVGLELIASENFASRAVLEALGSCLNNKYSEGYPGQRYYGGTEFIDELEMLCQKRALQAYHLDPQCWGVNVQPYSGSPANFAVYTALVEPHGRIMGLDLPDGGHLTHGFMTDKKKISATSIFFESMPYKVYPETGYINYDQLEENASLFHPKLIIAGTSCYSRNLDYARLRKIADDNGAYLMADMAHISGLVAAGVVPSPFEHCHVVTTTTHKTLRGCRAGMIFYRKGVRSVDPKTGKETYYELESLINSAVFPGLQGGPHNHAIAGVAVALKQAMTTEFKIYQLQVLANCRALSDALTELGYKIVTGGSDNHLILMDLRSKGTDGGRAEKVLEACSIACNKNTCPGDKSALRPSGLRLGTPALTSRGLLEEDFQKVAHFIHRGIELTLQIQSHMATKATLKEFKEKLAGDEKIQSAVATLREEVENFASNFSLPGLPDF
uniprot
proteins
ec_number
2.1.2.1
uniprot
proteins
function
FUNCTION: 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 (By similarity). 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. 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 (By similarity). 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. 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. 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 (By similarity). {ECO:0000250|UniProtKB:P07511, ECO:0000250|UniProtKB:P34896}.
uniprot
proteins
mass_dalton
52601
uniprot
proteins
pathway_participation
PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. {ECO:0000250|UniProtKB:P34896}.; PATHWAY: Amino-acid degradation. {ECO:0000250|UniProtKB:P34896}.
uniprot
proteins
post_translational_modification
PTM: Ubiquitination at Lys-33 leads to proteasomal degradation. UBE2N/UBC13-mediated ubiquitination stabilize SHMT1 within the nucleus and signals nuclear export of SHMT1 through 'Lys-63'-specific ubiquitin linkage. 'Lys-63' polyubiquitination is cell cycle- and compartment-specific. Modification by UBE2I/UBC9 or UBE2N/UBC13 compete for SHMT1 modification, leading to either degradation in the nucleus or nuclear export, respectively. In the cytoplasm, SHMT1 degradation is facilitated by 'Lys-48' ubiquitin linkages, whereas in the nucleus, 'Lys-63'-linked ubiquitination prevents degradation. {ECO:0000250|UniProtKB:P34896}.; PTM: Sumoylated at either Lys-32 or Lys-33. 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. UBE2I-mediated conjugation to SUMO2/3 in the nucleus allows nuclear degradation. {ECO:0000250|UniProtKB:P34896}.; PTM: Deamidation of asparagine produces alternatively aspartate or isoaspartate, which in turn can be converted to aspartate through carboxylmethylation/demethylation. {ECO:0000250|UniProtKB:P07511}.
uniprot
proteins
protein_family
SHMT family
uniprot
proteins
pubmed
11063567
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
8863732
uniprot
proteins
sequence_length
478
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P34896}. Nucleus {ECO:0000250|UniProtKB:P34896}. Note=Nuclear translocation is RAN-dependent and is independent from both the oligomerization state and the catalytic activity. In the cytoplasm, SHMT1 degradation is facilitated by 'Lys-48'-linked ubiquitination, whereas in the nucleus, 'Lys-63'-linked ubiquitination prevents degradation. Predominantly sumoylated and localized to the nucleus in S phase cells and remains in the nucleus during the G2/M phase of the cell cycle. Sumoylation occurs at the nuclear pore and is linked to nuclear import. As a component of the de novo thymidylate synthesis complex, localizes specifically to replication forks during DNA synthesis (By similarity). {ECO:0000250|UniProtKB:P34896}.
uniprot
proteins