Search Results

Overview

Uniprot IDP34896
Protein NameSerine hydroxymethyltransferase, cytosolic
Gene NameSHMT1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
20 DLWSSHDKMLAQPLK
274 IFYRKGVKSVDPKTG
279 GVKSVDPKTGKEILY
375 TDGGRAEKVLEACSI
38 VEVYNIIKKESNRQR
386 ACSIACNKNTCPGDR
420 LLEKDFQKVAHFIHR
456 KERLAGDKYQAAVQA
72 LGSCLNNKYSEGYPG

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 (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)

Protein Sequence

10 MTMPVNGAHK 20 DADLWSSHDK 30 MLAQPLKDSD 40 VEVYNIIKKE 50 SNRQRVGLEL 60 IASENFASRA 70 VLEALGSCLN 80 NKYSEGYPGQ 90 RYYGGTEFID 100 ELETLCQKRA 110 LQAYKLDPQC 120 WGVNVQPYSG 130 SPANFAVYTA 140 LVEPHGRIMG 150 LDLPDGGHLT 160 HGFMTDKKKI 170 SATSIFFESM 180 PYKVNPDTGY 190 INYDQLEENA 200 RLFHPKLIIA 210 GTSCYSRNLE 220 YARLRKIADE 230 NGAYLMADMA 240 HISGLVAAGV 250 VPSPFEHCHV 260 VTTTTHKTLR 270 GCRAGMIFYR 280 KGVKSVDPKT 290 GKEILYNLES 300 LINSAVFPGL 310 QGGPHNHAIA 320 GVAVALKQAM 330 TLEFKVYQHQ 340 VVANCRALSE 350 ALTELGYKIV 360 TGGSDNHLIL 370 VDLRSKGTDG 380 GRAEKVLEAC 390 SIACNKNTCP 400 GDRSALRPSG 410 LRLGTPALTS 420 RGLLEKDFQK 430 VAHFIHRGIE 440 LTLQIQSDTG 450 VRATLKEFKE 460 RLAGDKYQAA 470 VQALREEVES 480 FASLFPLPGL PDF

Gene Ontology

Classification GO ID Description
Biological Process GO:0006565 L-serine catabolic process
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0070013 intracellular organelle lumen
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005657 replication fork
Molecular Function GO:0016832 aldehyde-lyase activity
Molecular Function GO:0004372 glycine hydroxymethyltransferase activity
Molecular Function GO:0120567 hydroxytrimethyllysine aldolase activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0008732 L-allo-threonine aldolase activity
Molecular Function GO:0005521 lamin binding
Molecular Function GO:0048027 mRNA 5'-UTR binding
Molecular Function GO:0000900 mRNA regulatory element binding translation repressor activity
Molecular Function GO:0050179 phenylserine aldolase activity
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0030170 pyridoxal phosphate binding
Molecular Function GO:0070905 serine binding
Molecular Function GO:0036094 small molecule binding
Molecular Function GO:0004793 threonine aldolase activity
Biological Process GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
Biological Process GO:0045329 carnitine biosynthetic process
Biological Process GO:1904482 cellular response to tetrahydrofolate
Biological Process GO:0006260 DNA replication
Biological Process GO:0006231 dTMP biosynthetic process
Biological Process GO:0046655 folic acid metabolic process
Biological Process GO:0019264 glycine biosynthetic process from L-serine
Biological Process GO:0006544 glycine metabolic process
Biological Process GO:0006563 L-serine metabolic process
Biological Process GO:0017148 negative regulation of translation
Biological Process GO:0006730 one-carbon metabolic process
Biological Process GO:0051289 protein homotetramerization
Biological Process GO:0009113 purine nucleobase biosynthetic process
Biological Process GO:0035999 tetrahydrofolate interconversion
Biological Process GO:0046653 tetrahydrofolate metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.