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Details on Person UniProt:P34897 SHMT2
| Class:Id | ReferenceGeneProduct:55748 |
|---|---|
| _chainChangeLog | transit peptide:1-29 added on Fri February 6 2015;chain:30-504 added on Fri February 6 2015 |
| _displayName | UniProt:P34897 SHMT2 |
| _timestamp | 2024-11-03 20:19:16 |
| chain | transit peptide:1-29 chain:30-504 |
| checksum | 7A13AF741C68FFD6 |
| comment | 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).CATALYTIC ACTIVITY (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O = (6S)-5,6,7,8-tetrahydrofolate + L-serineCOFACTOR Hydroxymethyltransferase is inhibited by succinylation at Lys-280.BIOPHYSICOCHEMICAL PROPERTIES One-carbon metabolism; tetrahydrofolate interconversion.SUBUNIT Homotetramer; in the presence of bound pyridoxal 5'-phosphate (PubMed:25619277, PubMed:29180469). Homodimer; in the absence of bound pyridoxal 5'-phosphate (PubMed:25619277, PubMed:29180469). Pyridoxal 5'-phosphate binding mediates an important conformation change that is required for tetramerization (PubMed:25619277). Interacts with ABRAXAS2; the interaction is direct. Identified in a complex with ABRAXAS2 and the other subunits of the BRISC complex, at least composed of the ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with ABRAXAS2 and IFNAR1 (PubMed:24075985). Interacts with KIRREL3 (PubMed:25902260).INTERACTION Mainly localizes in the mitochondrion. Also found in the cytoplasm and nucleus as part of the BRISC complex (PubMed:24075985).ALTERNATIVE PRODUCTS Succinylation at Lys-280 inhibits the hydroxymethyltransferase activity. Desuccinylation by SIRT5 restores the activity, leading to promote cell proliferation.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS In eukaryotes there are two forms of the enzymes: a cytosolic one and a mitochondrial one.SIMILARITY Belongs to the SHMT family. |
| description | recommendedName: Serine hydroxymethyltransferase, mitochondrial shortName: SHMT ecNumber evidence="5 6 9 11"2.1.2.1 alternativeName: Glycine hydroxymethyltransferase alternativeName: Serine methylase |
| geneName | SHMT2 |
| identifier | P34897 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Cardiomyopathy Cytoplasm Disease variant Intellectual disability Membrane Mitochondrion Mitochondrion inner membrane Mitochondrion nucleoid Nucleus One-carbon metabolism Phosphoprotein Proteomics identification Pyridoxal phosphate Reference proteome Transferase Transit peptide |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | SHMT2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9001786] ENSEMBL:ENSG00000182199 SHMT2 [Homo sapiens] |
| secondaryIdentifier | GLYM_HUMAN B7Z9F1 E7EQ19 E7EU43 O00740 Q8N1A5 |
| sequenceLength | 504 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8969669] UniProt:P34897-1 SHMT2 [Homo sapiens] [ReferenceIsoform:8969670] UniProt:P34897-2 SHMT2 [Homo sapiens] [ReferenceIsoform:8969671] UniProt:P34897-3 SHMT2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:5694086] PXLP-K280-SHMT2 [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:9714752] SHMT2 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:9644815] N6-pyridoxal phosphate-L-lysine at 280 |
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No pathways have been reviewed or authored by UniProt:P34897 SHMT2 (55748)
