SHMT2
entrez
6472
canonical
uniprot
P34897
canonical
ensembl
ENSG00000182199
resolver
ensp
ENSP00000333667
resolver
ensp
ENSP00000406881
resolver
ensp
ENSP00000413770
resolver
ensp
ENSP00000452315
resolver
ensp
ENSP00000452419
resolver
genesymbol
HEL-S-51e
resolver
genesymbol
SHMT2
resolver
genesymbol_syn
SHMT2
resolver
hgnc
HGNC:10852
resolver
uniprot
B4DJQ3
resolver
uniprot
B4DLV4
resolver
uniprot
B7Z9F1
resolver
uniprot
E7EQ19
resolver
uniprot
E7EU43
resolver
uniprot
O00740
resolver
uniprot
Q5BJF5
resolver
uniprot
Q8N1A5
resolver
uniprot
V9HW06
resolver
uniprot_entry
B4DJQ3_HUMAN
resolver
uniprot_entry
B4DLV4_HUMAN
resolver
uniprot_entry
GLYM_HUMAN
resolver
uniprot_entry
Q5BJF5_HUMAN
resolver
uniprot_entry
V9HW06_HUMAN
resolver
uniprot_sec
B7Z9F1
resolver
uniprot_sec
E7EQ19
resolver
uniprot_sec
E7EU43
resolver
uniprot_sec
O00740
resolver
uniprot_sec
Q8N1A5
resolver
activity_regulation
ACTIVITY REGULATION: Hydroxymethyltransferase is inhibited by succinylation at Lys-280. {ECO:0000269|PubMed:29180469}.
uniprot
proteins
amino_acid_sequence
MLYFSLFWAARPLQRCGQLVRMAIRAQHSNAAQTQTGEANRGWTGQESLSDSDPEMWELLQREKDRQCRGLELIASENFCSRAALEALGSCLNNKYSEGYPGKRYYGGAEVVDEIELLCQRRALEAFDLDPAQWGVNVQPYSGSPANLAVYTALLQPHDRIMGLDLPDGGHLTHGYMSDVKRISATSIFFESMPYKLNPKTGLIDYNQLALTARLFRPRLIIAGTSAYARLIDYARMREVCDEVKAHLLADMAHISGLVAAKVIPSPFKHADIVTTTTHKTLRGARSGLIFYRKGVKAVDPKTGREIPYTFEDRINFAVFPSLQGGPHNHAIAAVAVALKQACTPMFREYSLQVLKNARAMADALLERGYSLVSGGTDNHLVLVDLRPKGLDGARAERVLELVSITANKNTCPGDRSAITPGGLRLGAPALTSRQFREDDFRRVVDFIDEGVNIGLEVKSKTAKLQDFKSFLLKDSETSQRLANLRQRVEQFARAFPMPGFDEH
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB) [MIM:619121]: An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, moderate to severe intellectual disability, spastic paraparesis, ataxia, and/or peripheral neuropathy. Patients also exhibit dysmorphic features and congenital microcephaly. Most affected individuals develop progressive hypertrophic cardiomyopathy in childhood or have cardiac developmental anomalies. Brain imaging shows corpus callosum abnormalities in all patients, and perisylvian polymicrogyria-like pattern in some individuals. {ECO:0000269|PubMed:33015733}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.1.2.1
uniprot
proteins
function
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). {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}.
uniprot
proteins
mass_dalton
55993
uniprot
proteins
mutagenesis
MUTAGEN 98; /note="E->L: Abolishes serine hydroxymethyltransferase activity, leading to oxidative phosphorylation deficiency; when associated with F-106."; /evidence="ECO:0000269|PubMed:29364879"; MUTAGEN 103; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 106; /note="Y->F: Abolishes serine hydroxymethyltransferase activity, leading to oxidative phosphorylation deficiency; when associated with L-98."; /evidence="ECO:0000269|PubMed:29364879"; MUTAGEN 280; /note="K->Q: Abolishes pyridoxal phosphate-binding, leading to oxidative phosphorylation deficiency."; /evidence="ECO:0000269|PubMed:29364879"; MUTAGEN 280; /note="K->R,E: Decreased succinylation level and hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 302; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 356; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 464; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 469; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469"; MUTAGEN 474; /note="K->R,E: Does not affect succinylation level or hydroxymethyltransferase activity."; /evidence="ECO:0000269|PubMed:29180469
uniprot
proteins
pathway_participation
PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. {ECO:0000305|PubMed:25619277, ECO:0000305|PubMed:33015733}.
uniprot
proteins
post_translational_modification
PTM: Succinylation at Lys-280 inhibits the hydroxymethyltransferase activity. Desuccinylation by SIRT5 restores the activity, leading to promote cell proliferation. {ECO:0000269|PubMed:29180469}.
uniprot
proteins
protein_family
SHMT family
uniprot
proteins
pubmed
10828359
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
18063578
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21876188
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24075985
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25619277
uniprot
proteins
pubmed
25902260
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
29180469
uniprot
proteins
pubmed
29364879
uniprot
proteins
pubmed
29452640
uniprot
proteins
pubmed
33015733
uniprot
proteins
pubmed
8505317
uniprot
proteins
pubmed
8999870
uniprot
proteins
sequence_length
504
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269|PubMed:18063578}. Mitochondrion inner membrane {ECO:0000269|PubMed:21876188}. Cytoplasm {ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:24075985}. Note=Mainly localizes in the mitochondrion. Also found in the cytoplasm and nucleus as part of the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:24075985}.
uniprot
proteins