Reactome | UniProt:P34897 SHMT2

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UniProt:P34897 SHMT2 Show undefined attributes

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.
crossReference	[DatabaseIdentifier:12207801] PDB:6M5O [DatabaseIdentifier:12334322] RefSeq:NP_005403.2 [DatabaseIdentifier:12334321] RefSeq:NP_001159829.1 [DatabaseIdentifier:12334320] RefSeq:NP_001159828.1 [DatabaseIdentifier:12334319] RefSeq:NP_001159830.1 [DatabaseIdentifier:12334323] RefSeq:NP_001159831.1 [DatabaseIdentifier:12289196] Pharos - Targets:P34897 [DatabaseIdentifier:12250731] PRO:P34897 [DatabaseIdentifier:12207817] PDB:8SSJ [DatabaseIdentifier:12207819] PDB:8GKS [DatabaseIdentifier:12207813] PDB:8T4P [DatabaseIdentifier:12207804] PDB:8TLC [DatabaseIdentifier:12207812] PDB:8GKT [DatabaseIdentifier:12207799] PDB:8FJT [DatabaseIdentifier:12207816] PDB:8GKY [DatabaseIdentifier:12207822] PDB:8AQL [DatabaseIdentifier:12207811] PDB:8GKW [DatabaseIdentifier:12207802] PDB:6QVL [DatabaseIdentifier:12207805] PDB:8XNA [DatabaseIdentifier:11457095] ENSEMBL:ENSG00000182199 [DatabaseIdentifier:11548485] ENSEMBL:ENSP00000413770 [DatabaseIdentifier:11548484] ENSEMBL:ENSP00000406881 [DatabaseIdentifier:11548481] ENSEMBL:ENSP00000452315 [DatabaseIdentifier:11548483] ENSEMBL:ENSP00000333667 [DatabaseIdentifier:11548482] ENSEMBL:ENSP00000452419 [DatabaseIdentifier:11671184] ENSEMBL:ENST00000449049 [DatabaseIdentifier:11671182] ENSEMBL:ENST00000328923 [DatabaseIdentifier:11671181] ENSEMBL:ENST00000414700 [DatabaseIdentifier:11671183] ENSEMBL:ENST00000553474 [DatabaseIdentifier:11671180] ENSEMBL:ENST00000557487 [DatabaseIdentifier:11791356] GeneCards:SHMT2 [DatabaseIdentifier:11807353] GlyGen:P34897 [DatabaseIdentifier:11832860] HMDB Protein:HMDBP00792 [DatabaseIdentifier:11844359] HPA:ENSG00000182199-SHMT2 [DatabaseIdentifier:12128984] OpenTargets:ENSG00000182199 [DatabaseIdentifier:12207814] PDB:8GKU [DatabaseIdentifier:12207806] PDB:6DK3 [DatabaseIdentifier:12207807] PDB:4PVF [DatabaseIdentifier:12140366] PDB:6H3C [DatabaseIdentifier:12207820] PDB:8T4O [DatabaseIdentifier:12207818] PDB:5V7I [DatabaseIdentifier:12141378] PDB:6R8F [DatabaseIdentifier:12207808] PDB:6QVG [DatabaseIdentifier:12207800] PDB:8FJU [DatabaseIdentifier:12207821] PDB:8QI7 [DatabaseIdentifier:12207809] PDB:5X3V [DatabaseIdentifier:12207810] PDB:7BYI [DatabaseIdentifier:12207803] PDB:9BOX [DatabaseIdentifier:12207815] PDB:8GKZ
databaseName	UniProt
dbId	55748
description	recommendedName: Serine hydroxymethyltransferase, mitochondrial shortName: SHMT ecNumber evidence="5 6 9 11"2.1.2.1 alternativeName: Glycine hydroxymethyltransferase alternativeName: Serine methylase
displayName	UniProt:P34897 SHMT2
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:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	SHMT2
otherIdentifier	11746438_a_at 11747537_x_at 11750992_x_at 11756615_x_at 16752834 214095_PM_at 214095_at 214096_PM_s_at 214096_s_at 214437_3p_s_at 214437_PM_s_at 214437_s_at 3418008 3418009 3418010 3418011 3418012 3418013 3418014 3418015 3418016 3418017 3418018 3418019 3418020 3418021 3418022 3418023 3418024 3418025 3418026 3418027 3418028 3418029 3418030 3418031 3418032 3418033 3418034 3418035 3418036 3418037 3418038 3418039 3418040 3418041 3418042 36178_at 50836_i_at 6472 7956401 A_14_P122852 A_23_P158239 A_23_P169629 A_33_P3363245 GE59018 GO:0002082 GO:0003682 GO:0004372 GO:0005515 GO:0005634 GO:0005737 GO:0005739 GO:0005743 GO:0005759 GO:0005856 GO:0006231 GO:0006417 GO:0006520 GO:0006544 GO:0006545 GO:0006563 GO:0006564 GO:0006575 GO:0006730 GO:0008168 GO:0008284 GO:0008732 GO:0015630 GO:0015943 GO:0016020 GO:0016597 GO:0016740 GO:0019264 GO:0030170 GO:0032259 GO:0034340 GO:0035999 GO:0042645 GO:0042802 GO:0046653 GO:0051262 GO:0051289 GO:0055086 GO:0065003 GO:0070013 GO:0070062 GO:0070129 GO:0070536 GO:0070552 GO:1901135 GO:1903715 HMNXSV003011419 HMNXSV003058149 Hs.120911.0.S1_3p_at Hs.2186.4.A1_3p_a_at Hs.2186.4.A1_3p_x_at Hs.75069.0.S1_3p_x_at ILMN_1661264 PH_hs_0004269 PH_hs_0031312 TC12000525.hg TC12002398.hg U23143_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5694086] PXLP-K280-SHMT2 [mitochondrial inner membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9714752] SHMT2 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000182199] ENSEMBL:ENSG00000182199 SHMT2 [ReferenceDNASequence:12729149] UCSC:P34897 SHMT2 [ReferenceDNASequence:11321874] BioGPS Gene:6472 SHMT2 [ReferenceDNASequence:11398257] COSMIC - genes:SHMT2 SHMT2 [ReferenceDNASequence:11419058] CTD Gene:6472 SHMT2 [ReferenceDNASequence:11435052] dbSNP Gene:6472 SHMT2 [ReferenceDNASequence:11823027] HGNC:10852 SHMT2 [ReferenceDNASequence:11864582] KEGG:hsa:6472 SHMT2 [ReferenceDNASequence:11951663] Monarch:6472 SHMT2 [ReferenceDNASequence:12035756] NCBI Gene:6472 SHMT2 [ReferenceDNASequence:12113682] OMIM:138450 SHMT2
referenceTranscript	[ReferenceRNASequence:12516204] RefSeq:NM_001166356.2 SHMT2 [ReferenceRNASequence:12516205] RefSeq:NM_001166357.1 SHMT2 [ReferenceRNASequence:12516206] RefSeq:NM_001166358.2 SHMT2 [ReferenceRNASequence:12516203] RefSeq:NM_005412.5 SHMT2 [ReferenceRNASequence:12516207] RefSeq:NM_001166359.1 SHMT2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	GLYM_HUMAN B7Z9F1 E7EQ19 E7EU43 O00740 Q8N1A5
sequenceLength	504
species	[Species:48887] Homo sapiens
stId	uniprot:P34897
url	http://purl.uniprot.org/uniprot/P34897

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-5694086] PXLP-K280-SHMT2 [mitochondrial inner membrane] [EntityWithAccessionedSequence:R-HSA-9714752] SHMT2 [cytosol]
(referenceSequence)	[ModifiedResidue:9644815] N6-pyridoxal phosphate-L-lysine at 280
(interactor)	[UndirectedInteraction:11148125] UniProt:P13569 <-> UniProt:P34897 (IntAct) [UndirectedInteraction:11216221] UniProt:Q9NXR7 <-> UniProt:P34897 (IntAct) [UndirectedInteraction:11286153] UniProt:P46736 <-> UniProt:P34897 (IntAct) [UndirectedInteraction:11295543] UniProt:Q9NWV8 <-> UniProt:P34897 (IntAct)