Search Results

Overview

Uniprot IDP34897
Protein NameSerine hydroxymethyltransferase, mitochondrial
Gene NameSHMT2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
103 YSEGYPGKRYYGGAE
200 MPYKLNPKTGLIDYN
269 KVIPSPFKHADIVTT
280 IVTTTTHKTLRGARS
302 GVKAVDPKTGREIPY
409 LVSITANKNTCPGDR
464 EVKSKTAKLQDFKSF
469 TAKLQDFKSFLLKDS
474 DFKSFLLKDSETSQR
95 LGSCLNNKYSEGYPG

Function

Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985)

Protein Sequence

10 MLYFSLFWAA 20 RPLQRCGQLV 30 RMAIRAQHSN 40 AAQTQTGEAN 50 RGWTGQESLS 60 DSDPEMWELL 70 QREKDRQCRG 80 LELIASENFC 90 SRAALEALGS 100 CLNNKYSEGY 110 PGKRYYGGAE 120 VVDEIELLCQ 130 RRALEAFDLD 140 PAQWGVNVQP 150 YSGSPANLAV 160 YTALLQPHDR 170 IMGLDLPDGG 180 HLTHGYMSDV 190 KRISATSIFF 200 ESMPYKLNPK 210 TGLIDYNQLA 220 LTARLFRPRL 230 IIAGTSAYAR 240 LIDYARMREV 250 CDEVKAHLLA 260 DMAHISGLVA 270 AKVIPSPFKH 280 ADIVTTTTHK 290 TLRGARSGLI 300 FYRKGVKAVD 310 PKTGREIPYT 320 FEDRINFAVF 330 PSLQGGPHNH 340 AIAAVAVALK 350 QACTPMFREY 360 SLQVLKNARA 370 MADALLERGY 380 SLVSGGTDNH 390 LVLVDLRPKG 400 LDGARAERVL 410 ELVSITANKN 420 TCPGDRSAIT 430 PGGLRLGAPA 440 LTSRQFREDD 450 FRRVVDFIDE 460 GVNIGLEVKS 470 KTAKLQDFKS 480 FLLKDSETSQ 490 RLANLRQRVE 500 QFARAFPMPG FDEH

Gene Ontology

Classification GO ID Description
Cellular Component GO:0070552 BRISC complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0042645 mitochondrial nucleoid
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Molecular Function GO:0016597 amino acid binding
Molecular Function GO:0003682 chromatin binding
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:0030170 pyridoxal phosphate binding
Biological Process GO:0015943 formate biosynthetic process
Biological Process GO:0019264 glycine biosynthetic process from L-serine
Biological Process GO:0006544 glycine metabolic process
Biological Process GO:0006564 L-serine biosynthetic process
Biological Process GO:0006563 L-serine metabolic process
Biological Process GO:0006730 one-carbon metabolic process
Biological Process GO:0008284 positive regulation of cell population proliferation
Biological Process GO:0051289 protein homotetramerization
Biological Process GO:0070536 protein K63-linked deubiquitination
Biological Process GO:0051262 protein tetramerization
Biological Process GO:1903715 regulation of aerobic respiration
Biological Process GO:0070129 regulation of mitochondrial translation
Biological Process GO:0002082 regulation of oxidative phosphorylation
Biological Process GO:0034340 response to type I interferon
Biological Process GO:0034516 response to vitamin B6
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.

[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.