Tchem SHMT2 Serine hydroxymethyltransferase, mitochondrial

Protein Summary

Description

Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:29364879, PubMed:25619277). 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:29452640, PubMed:29364879). 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). This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• P34897
• B7Z9F1
• E7EQ19
• E7EU43
• O00740
• Q8N1A5
• SHMT

Gene Name

• SHMT2

Ensembl ID

• ENST00000328923
• ENSP00000333667
• ENSG00000182199
• ENST00000414700
• ENSP00000406881
• ENST00000449049
• ENSP00000413770
• ENST00000553474
• ENSP00000452419
• ENST00000557487
• ENSP00000452315

Symbol

• GLYA
• SHMT
• HEL-S-51e

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.99
transcription factor perturbation	0.99
disease perturbation	0.93
cellular component	0.87
pathway	0.87

Protein Classes

PANTHER Classes

Protein / Transferase / Methyltransferase / Serine Hydroxymethyltransferase, Mitochondrial

DTO Classes

Protein / Enzyme / Transferase / Methyltransferase / Serine Hydroxymethyltransferase, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 551.79   (req: < 5)

Gene RIFs: 49   (req: <= 3)

Antibodies: 198   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 551.79   (req: >= 5)

Gene RIFs: 49   (req: > 3)

Antibodies: 198   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 27

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2