SHMT2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004372 glycine hydroxymethyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core catalytic molecular function. SHMT2 is the mitochondrial serine hydroxymethyltransferase (EC 2.1.2.1); this phylogenetic inference matches abundant experimental IDA/IMP support for the human protein. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt Catalyzes the cleavage of serine to glycine accompanied with
GO:0006545 glycine biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: SHMT2 interconverts serine and glycine; in the serine-catabolic (physiological) direction it produces glycine, so glycine biosynthesis is defensible. However the better-supported experimental framing for the human enzyme is the broader glycine metabolic process (GO:0006544, IDA). Keep as non-core.
GO:0030170 pyridoxal phosphate binding	IBA GO_REF:0000033	ACCEPT	Summary: Core cofactor-binding molecular function. SHMT2 is PLP-dependent; PLP binds Lys-280 via a Schiff base and is required for tetramerization. Directly supported for the human protein by IDA (PMID:25619277). Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt Name=pyridoxal 5'-phosphate
GO:0046653 tetrahydrofolate metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Correct: SHMT2 consumes/interconverts tetrahydrofolate (THF + serine to glycine + 5,10-methylene-THF). Well supported experimentally (IDA PMID:24075985, PMID:25619277) and by the UniProt one-carbon/THF-interconversion pathway. Subsumed under the core one-carbon metabolic process; keep non-core.
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Correct and core localization. SHMT2 carries an N-terminal mitochondrial transit peptide (residues 1-29) and acts mainly in the mitochondrion. Redundant with the more specific mitochondrial matrix; accept. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt Mainly localizes in the
GO:0004372 glycine hydroxymethyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Correct core catalytic MF, electronically inferred; redundant with the experimental IDA/IMP annotations of the same term.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Minor localization. SHMT2 is found in the nucleus/cytoplasm as part of the BRISC complex, not in its metabolic role. IEA from the UniProt subcellular-location mapping; real but non-core (moonlighting-associated).
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Minor localization tied to the cytoplasmic BRISC complex (moonlighting), not the core mitochondrial metabolic role. Experimentally supported (IDA PMID:24075985). Keep as non-core.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Correct core localization; redundant with experimental IDA/EXP annotations.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: SHMT2 is a matrix enzyme that also associates with the inner membrane (IDA PMID:21876188, in the context of the mitochondrial thymidylate synthesis complex). The matrix is the principal compartment; keep this inner-membrane call as non-core.
GO:0006544 glycine metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Correct; redundant with experimental IDA/IMP annotations of the same term.
GO:0006545 glycine biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Same as the IBA glycine biosynthetic process call; defensible in the serine-catabolic direction but glycine metabolic process is better supported. Keep non-core.
GO:0006563 L-serine metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Correct; redundant with experimental IDA/IMP annotations of the same term.
GO:0006730 one-carbon metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Core biological process; redundant with experimental IDA/IMP annotations. SHMT2 is the entry point of mitochondrial one-carbon (folate) metabolism.
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000120	ACCEPT	Summary: Correct core cofactor binding; redundant with experimental IDA (PMID:25619277).
GO:0035999 tetrahydrofolate interconversion	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Correct and precise. Matches the UniProt PATHWAY one-carbon metabolism / tetrahydrofolate interconversion (UPA00193). Subsumed under core one-carbon metabolism; keep non-core. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt One-carbon metabolism; tetrahydrofolate interconversion.
GO:0042645 mitochondrial nucleoid	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: SHMT2 associates with mtDNA/the mitochondrial nucleoid (IDA PMID:18063578). Real but a minor, non-core localization within the mitochondrion.
GO:0046653 tetrahydrofolate metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Correct; redundant with experimental IDA annotations. Keep non-core.
GO:0051289 protein homotetramerization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: SHMT2 assembles into a PLP-dependent homotetramer (IDA PMID:29180469, PMID:25619277). This is a self-assembly property rather than a distinct biological process the gene is involved in; real but non-core.
GO:0120567 hydroxytrimethyllysine aldolase activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Promiscuous secondary aldolase activity (PMID:38615009): SHMT1/2 can catalyze the hydroxytrimethyllysine aldolase reaction of carnitine biosynthesis, but a threonine aldolase is the more efficient enzyme and SHMT only partially compensates. This ARBA IEA duplicates the FlyBase IDA (PMID:38615009); a genuine but secondary/promiscuous side activity, not the core SHMT function. Keep as non-core (consistent with the IDA).
GO:0005515 protein binding	IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a DUB-interactome screen (interaction with BRCC3/BRCC36), which reflects BRISC-complex association. Uninformative as a molecular function per curation policy; flag as over-annotated (do not remove the IPI).
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a high-throughput interactome map (interactions with ARL6IP1, CMTM5). Uninformative MF; flag as over-annotated.
GO:0005515 protein binding	IPI PMID:25902260 Autism and Intellectual Disability-Associated KIRREL3 Intera...	MARK AS OVER ANNOTATED	Summary: Bare protein binding for the KIRREL3 interaction. Reported by UniProt SUBUNIT but uninformative as an MF; flag as over-annotated.
GO:0005515 protein binding	IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an alternative-splicing interactome map; uninformative MF.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an interactome-perturbation screen; uninformative MF.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the HuRI binary interactome map; uninformative MF.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a proteome-scale interactome (BRCC3 interaction, i.e. BRISC association). Uninformative MF; flag as over-annotated.
GO:0005515 protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an AI-guided PPI pipeline (BRCC3 interaction). Uninformative MF; flag as over-annotated.
GO:0042802 identical protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	KEEP AS NON CORE	Summary: Reflects SHMT2 self-interaction (homodimer/homotetramer), consistent with UniProt SUBUNIT and the IntAct self-interaction. Informative and real, but a property of oligomerization rather than a core catalytic function; keep as non-core.
GO:0002082 regulation of oxidative phosphorylation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based IEA; redundant with human experimental IMP (PMID:29364879, PMID:29452640). SHMT2 catalytic output is required for OXPHOS via mitochondrial translation. Downstream pleiotropic consequence of the one-carbon function; keep non-core.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000107	ACCEPT	Summary: Correct and core compartment; redundant with experimental IDA (PMID:21876188, PMID:11516159).
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based IEA. SHMT2 supports proliferation of cancer cells (PMID:29180469), but this is an indirect metabolic consequence, not a core function; keep non-core.
GO:0008732 L-allo-threonine aldolase activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ortholog-based IEA for a promiscuous threonine-aldolase side activity of SHMTs. Not the core function and not experimentally established for the human enzyme in vivo; over-annotation.
GO:0016597 amino acid binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic ortholog-based IEA. Substrate (serine/glycine) binding is already captured by the catalytic MF and PLP binding; this uninformative binding term is an over-annotation.
GO:0042802 identical protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based IEA reflecting self-interaction/homo-oligomerization; redundant with the IPI identical-protein-binding annotation. Real but non-core.
GO:0070129 regulation of mitochondrial translation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based IEA; redundant with human experimental IMP (PMID:29364879, PMID:29452640). SHMT2-derived 5,10-methylene-THF is required for taurinomethyluridine tRNA wobble modification and thus mitochondrial translation. Downstream consequence of the core function; keep non-core.
GO:1903715 regulation of aerobic respiration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based IEA; redundant with human experimental IMP (PMID:29364879, PMID:29452640). Downstream physiological consequence (via OXPHOS/mitochondrial translation); keep non-core.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Correct core localization (immunofluorescence, HPA). Redundant with other IDA calls.
GO:0120567 hydroxytrimethyllysine aldolase activity	IDA PMID:38615009 One substrate many enzymes virtual screening uncovers missin...	KEEP AS NON CORE	Summary: Experimentally demonstrated promiscuous aldolase side activity (PMID:38615009): SHMT1/2 catalyze the hydroxytrimethyllysine aldolase reaction, only partially compensating for a missing dedicated threonine aldolase in carnitine biosynthesis. A genuine secondary activity, not the core SHMT function; keep as non-core (experimental IDA, not removed). Supporting Evidence: PMID:38615009 serine hydroxymethyl transferase (SHMT) 1 and 2, catalyze the HTMLA reaction
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: Correct core localization (high-throughput mitochondrial proteome). Redundant; accept.
GO:0005739 mitochondrion	EXP PMID:21876188 Identification of a de novo thymidylate biosynthesis pathway...	ACCEPT	Summary: Correct core localization; SHMT2 localized to mitochondria in the de novo mitochondrial thymidylate biosynthesis study.
GO:0004372 glycine hydroxymethyltransferase activity	IMP PMID:33015733 Impairment of the mitochondrial one-carbon metabolism enzyme...	ACCEPT	Summary: Core catalytic MF, supported by disease genetics: biallelic SHMT2 variants impair enzyme function (variant P499A shows decreased glycine hydroxymethyltransferase activity) and cause the NEDCASB syndrome. Accept as core. Supporting Evidence: PMID:33015733 it transfers one-carbon units from serine to tetrahydrofolate (THF), generating glycine and 5,10-methylene-THF
GO:0006563 L-serine metabolic process	IMP PMID:33015733 Impairment of the mitochondrial one-carbon metabolism enzyme...	ACCEPT	Summary: Core BP. Patient fibroblasts show altered glycine/serine ratios, confirming SHMT2's role in L-serine metabolism. Accept. Supporting Evidence: PMID:33015733 fibroblasts from affected individuals showed a significant decrease in glycine/serine ratios compared to controls
GO:0006730 one-carbon metabolic process	IMP PMID:33015733 Impairment of the mitochondrial one-carbon metabolism enzyme...	ACCEPT	Summary: Core BP. SHMT2 is described as the mitochondrial one-carbon metabolism enzyme; patient cells show impaired folate one-carbon metabolism (altered 5-methyl-THF). Accept as core. Supporting Evidence: PMID:33015733 it transfers one-carbon units from serine to tetrahydrofolate (THF), generating glycine and 5,10-methylene-THF
GO:0006544 glycine metabolic process	IMP PMID:33015733 Impairment of the mitochondrial one-carbon metabolism enzyme...	ACCEPT	Summary: Core BP; SHMT2 produces glycine and patient fibroblasts show altered glycine/serine ratios. Accept. Supporting Evidence: PMID:33015733 fibroblasts from affected individuals showed a significant decrease in glycine/serine ratios compared to controls
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-5694137	KEEP AS NON CORE	Summary: Reactome places the SHMT2 catalytic reaction at the mitochondrial inner membrane. SHMT2 is principally a matrix enzyme that associates with the inner membrane; keep this inner-membrane localization as non-core.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9837978	KEEP AS NON CORE	Summary: From a Reactome LONP1 substrate-binding reaction (SHMT2 as an inner-membrane-associated protein degraded by LONP1). Inner-membrane association is real but non-core relative to the matrix.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9838004	KEEP AS NON CORE	Summary: From a Reactome LONP1 substrate-degradation reaction; inner-membrane association, non-core.
GO:0002082 regulation of oxidative phosphorylation	IMP PMID:29364879 Mitochondrial translation requires folate-dependent tRNA met...	KEEP AS NON CORE	Summary: Experimentally supported (SHMT2 catalytic loss causes defective oxidative phosphorylation via impaired mitochondrial translation). A downstream consequence of the core one-carbon function; keep as non-core. Supporting Evidence: PMID:29364879 leads to defective oxidative phosphorylation in human cells due to impaired mitochondrial translation
GO:0002082 regulation of oxidative phosphorylation	IMP PMID:29452640 Serine Catabolism by SHMT2 Is Required for Proper Mitochondr...	KEEP AS NON CORE	Summary: Experimentally supported: SHMT2 is required for robust mitochondrial oxygen consumption. Downstream consequence of the core function; keep as non-core. Supporting Evidence: PMID:29452640 SHMT2) is required for robust mitochondrial oxygen consumption
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat...	ACCEPT	Summary: Core catalytic MF, measured directly; the paper assays SHMT2 hydroxymethyltransferase activity and its inhibition by Lys-280 succinylation. Accept as core. Supporting Evidence: PMID:29180469 The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:29364879 Mitochondrial translation requires folate-dependent tRNA met...	ACCEPT	Summary: Core catalytic MF, measured directly (active-site mutagenesis E98/Y106/K280). Accept.
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:29452640 Serine Catabolism by SHMT2 Is Required for Proper Mitochondr...	ACCEPT	Summary: Core catalytic MF, measured directly (serine catabolism by SHMT2). Accept.
GO:0006544 glycine metabolic process	IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat...	ACCEPT	Summary: Core BP; SHMT2 catabolizes serine to glycine. Accept.
GO:0006563 L-serine metabolic process	IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat...	ACCEPT	Summary: Core BP; SHMT2 catalyzes the rate-limiting step of serine catabolism. Accept. Supporting Evidence: PMID:29180469 which catalyzes the rate-limiting step in serine catabolism
GO:0006730 one-carbon metabolic process	IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat...	ACCEPT	Summary: Core BP; SHMT2 is the entry point of mitochondrial one-carbon metabolism. Accept.
GO:0006730 one-carbon metabolic process	IDA PMID:29364879 Mitochondrial translation requires folate-dependent tRNA met...	ACCEPT	Summary: Core BP; SHMT2 generates mitochondrial 5,10-methylene-THF (one-carbon units). Accept. Supporting Evidence: PMID:29364879 SHMT2, presumably by generating mitochondrial 5,10-methylenetetrahydrofolate
GO:0006730 one-carbon metabolic process	IDA PMID:29452640 Serine Catabolism by SHMT2 Is Required for Proper Mitochondr...	ACCEPT	Summary: Core BP; SHMT2 catalyzes serine-derived one-carbon metabolism. Accept.
GO:0051289 protein homotetramerization	IDA PMID:29180469 SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferat...	KEEP AS NON CORE	Summary: SHMT2 forms a PLP-dependent homotetramer (directly observed). A structural/assembly property rather than the core function; keep non-core.
GO:0070129 regulation of mitochondrial translation	IMP PMID:29364879 Mitochondrial translation requires folate-dependent tRNA met...	KEEP AS NON CORE	Summary: Experimentally supported: SHMT2-derived 5,10-methylene-THF provides methyl donors for the taurinomethyluridine wobble base of select mitochondrial tRNAs; its loss causes defective mitochondrial translation. Downstream consequence of the core one-carbon function; keep non-core. Supporting Evidence: PMID:29364879 provides methyl donors to produce the taurinomethyluridine base at the wobble position of select mitochondrial tRNAs
GO:0070129 regulation of mitochondrial translation	IMP PMID:29452640 Serine Catabolism by SHMT2 Is Required for Proper Mitochondr...	KEEP AS NON CORE	Summary: Experimentally supported: SHMT2 serine catabolism is required for proper mitochondrial translation initiation and fMet-tRNA maintenance. Downstream consequence; keep non-core.
GO:1903715 regulation of aerobic respiration	IMP PMID:29364879 Mitochondrial translation requires folate-dependent tRNA met...	KEEP AS NON CORE	Summary: Experimentally supported; SHMT2 loss impairs respiratory-chain expression via mitochondrial translation. Downstream consequence of the core function; keep non-core.
GO:1903715 regulation of aerobic respiration	IMP PMID:29452640 Serine Catabolism by SHMT2 Is Required for Proper Mitochondr...	KEEP AS NON CORE	Summary: Experimentally supported; SHMT2 required for robust mitochondrial oxygen consumption. Downstream consequence; keep non-core.
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	ACCEPT	Summary: Core catalytic MF; the BRISC-SHMT2 paper confirms SHMT2 catalytic (hydroxymethyltransferase) activity. Accept.
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	ACCEPT	Summary: Core catalytic MF, directly measured with kinetics (KM 278 uM serine, 23 uM THF) on recombinant human SHMT2. Accept.
GO:0005634 nucleus	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Nuclear localization as part of the BRISC complex (moonlighting), not the core metabolic role. Keep as non-core.
GO:0005737 cytoplasm	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Cytoplasmic localization tied to the cytoplasmic BRISC complex (moonlighting), not the core mitochondrial role. Keep as non-core. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt Also found in the cytoplasm and nucleus as part of the
GO:0005739 mitochondrion	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	ACCEPT	Summary: Correct core localization. Accept.
GO:0006544 glycine metabolic process	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	ACCEPT	Summary: Core BP. Accept.
GO:0006563 L-serine metabolic process	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	ACCEPT	Summary: Core BP; SHMT2 is central to serine metabolism. Accept. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt Serine provides the major source of
GO:0030170 pyridoxal phosphate binding	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	ACCEPT	Summary: Core cofactor binding, directly demonstrated (PLP binding controls dimer-to-tetramer transition). Accept.
GO:0034340 response to type I interferon	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Moonlighting function: as a BRISC-complex component SHMT2 deubiquitinates IFNAR1 and regulates type I interferon responses. Experimentally supported (IDA), genuine but non-core relative to the metabolic enzyme function. Keep as non-core. Supporting Evidence: PMID:24075985 BRISC-SHMT2 complexes localize to and deubiquitinate actively engaged IFNAR1
GO:0046653 tetrahydrofolate metabolic process	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Correct; THF interconversion is part of the SHMT2 reaction. Subsumed under core one-carbon; non-core.
GO:0046653 tetrahydrofolate metabolic process	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	KEEP AS NON CORE	Summary: Correct; SHMT2 interconverts THF species. Subsumed under core one-carbon metabolism; non-core.
GO:0051262 protein tetramerization	IDA PMID:25619277 How pyridoxal 5'-phosphate differentially regulates human cy...	KEEP AS NON CORE	Summary: SHMT2 undergoes a PLP-dependent dimer-to-tetramer transition (directly observed). Structural assembly property; keep non-core.
GO:0070536 protein K63-linked deubiquitination	IMP PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Moonlighting function: SHMT2 is required for BRISC-mediated K63-linked deubiquitination of IFNAR1 (it directs the BRISC DUB to its substrate; the catalytic DUB is BRCC3/BRCC36). Experimentally supported (IMP), genuine but catalysis-independent and non-core. Keep as non-core. Supporting Evidence: PMID:24075985 SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1
GO:0070552 BRISC complex	IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in...	KEEP AS NON CORE	Summary: Moonlighting: SHMT2 is a bona fide component of the cytoplasmic BRISC deubiquitinase complex (with ABRAXAS2, BRCC3/BRCC36, BABAM1/2). Experimentally supported and captured by ComplexPortal (CPX-9341 BRISC-SHMT2 complex). Genuine complex membership but non-core relative to the metabolic role; keep as non-core. Supporting Evidence: file:human/SHMT2/SHMT2-uniprot.txt required for IFNAR1 deubiquitination by the BRISC complex
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput exosome proteomics (urinary exosomes). A mitochondrial matrix enzyme detected in exosome preparations is a common proteomics catch-all; not a functional localization for SHMT2. Over-annotation.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	MARK AS OVER ANNOTATED	Summary: High-throughput exosome proteomics (B-cell exosomes). Same catch-all concern; not a functional localization for a mitochondrial matrix enzyme. Over-annotation.
GO:0005743 mitochondrial inner membrane	IDA PMID:21876188 Identification of a de novo thymidylate biosynthesis pathway...	KEEP AS NON CORE	Summary: SHMT2 localizes to the matrix and inner membrane in the de novo mitochondrial thymidylate biosynthesis study. Inner-membrane association is real but non-core relative to the matrix.
GO:0005759 mitochondrial matrix	IDA PMID:21876188 Identification of a de novo thymidylate biosynthesis pathway...	ACCEPT	Summary: Correct and core compartment (directly observed). Accept.
GO:0003682 chromatin binding	IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids.	KEEP AS NON CORE	Summary: From a mitochondrial DNA nucleoid proteomics/cross-linking study; SHMT2 associates with mtDNA in the nucleoid. Chromatin binding is a poor fit for mtDNA/nucleoid association; the specific and appropriate term is mitochondrial nucleoid (GO:0042645, also annotated). Better captured by that localization; keep this MF as non-core rather than removing an experimental annotation. Proposed replacements: mitochondrial nucleoid
GO:0042645 mitochondrial nucleoid	IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids.	KEEP AS NON CORE	Summary: SHMT2 associates with the mitochondrial nucleoid/mtDNA (nucleoid proteomics). Real but a minor, non-core localization within the mitochondrion.
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:17482557 Effect of vitamin B6 availability on serine hydroxymethyltra...	ACCEPT	Summary: Core catalytic MF; SHMT (mitochondrial isozyme) activity measured in MCF-7 cells under varying vitamin B6/PLP availability. Accept.
GO:0004372 glycine hydroxymethyltransferase activity	IDA PMID:8505317 Cloning of human cDNAs encoding mitochondrial and cytosolic ...	ACCEPT	Summary: Core catalytic MF; the human mitochondrial SHMT cDNA functionally complemented an E. coli glyA (SHMT-deficient) mutant, directly demonstrating hydroxymethyltransferase activity. Accept. Supporting Evidence: PMID:8505317 cloned by functional complementation of an Escherichia coli glyA
GO:0005739 mitochondrion	IDA PMID:17482557 Effect of vitamin B6 availability on serine hydroxymethyltra...	ACCEPT	Summary: Correct core localization (mitochondrial isozyme). Accept.
GO:0005759 mitochondrial matrix	IDA PMID:11516159 The role of serine hydroxymethyltransferase isozymes in one-...	ACCEPT	Summary: Correct and core compartment. Accept.
GO:0006730 one-carbon metabolic process	IDA PMID:11516159 The role of serine hydroxymethyltransferase isozymes in one-...	ACCEPT	Summary: Core BP; 13C-NMR tracing shows mitochondrial serine (C3) is the major source of the cellular one-carbon pool via mitochondrial SHMT. Accept. Supporting Evidence: PMID:11516159 Formate is formed in the mitochondria from carbon 3 of serine

Gene Description

Existing Annotations Review

Core Functions

Binds the cofactor pyridoxal 5'-phosphate (PLP), which is required for catalysis and mediates the conformational change driving assembly of the active homotetramer.

References

📚 Additional Documentation

Notes

📄 View Raw YAML