SHMT1
Serine hydroxymethyltransferase, cytosolic
Also known as: cSHMT, GLYC_HUMAN, MGC15229, MGC24556, SHMT
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P34896
- Gene
- SHMT1
- Ensembl
- ENSG00000176974
- Chromosome
- 17
- Canonical length
- 483 aa
- Protein class
- Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Cytosol
- Quaternary structure
- Homotetramer
OverviewNCBI Gene
This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Canonical amino-acid sequenceUniProt
483 residues, UniProt reviewed canonical sequence.
>P34896|SHMT1
1 MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA
61 VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG
121 SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY
181 INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV
241 VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGVKSVDPKT GKEILYNLES LINSAVFPGL
301 QGGPHNHAIA GVAVALKQAM TLEFKVYQHQ VVANCRALSE ALTELGYKIV TGGSDNHLIL
361 VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDRSALRPSG LRLGTPALTS RGLLEKDFQK
421 VAHFIHRGIE LTLQIQSDTG VRATLKEFKE RLAGDKYQAA VQALREEVES FASLFPLPGL
481 PDFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SHMT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.25
- Highest tissue expression
- 376 nTPM
Expression across tissuesHPA
Tissue
- liver: 376 nTPM
- kidney: 157 nTPM
- parathyroid gland: 80 nTPM
- esophagus: 55 nTPM
- breast: 35 nTPM
- adipose tissue: 35 nTPM
Single-cell type
- proximal tubule cells: 220 nCPM
- renal collecting duct principal cells: 48 nCPM
- loop of henle epithelial cells: 47 nCPM
- microglia: 32 nCPM
- papillary tip epithelial cells: 31 nCPM
- renal connecting tubule cells: 30 nCPM
Immune cell
- T-reg: 11 nTPM
- basophil: 10 nTPM
- NK-cell: 8.5 nTPM
- MAIT T-cell: 8 nTPM
- naive CD4 T-cell: 6.6 nTPM
- memory CD4 T-cell: 6.5 nTPM
Brain region
- white matter: 17 nTPM
- cerebellum: 12 nTPM
- cerebral cortex: 10 nTPM
- medulla oblongata: 9.9 nTPM
- pons: 9.7 nTPM
- basal ganglia: 9.4 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.36
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.35
- DepMap mean gene effect
- -0.19
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- carnitine biosynthetic process
- cellular response to leukemia inhibitory factor
- dTMP biosynthetic process
- folic acid metabolic process
- glycine biosynthetic process from serine
- glycine metabolic process
- L-serine catabolic process
- L-serine metabolic process
- negative regulation of translation
- one-carbon metabolic process
- protein homotetramerization
- purine nucleobase biosynthetic process
- tetrahydrofolate interconversion
- tetrahydrofolate metabolic process
- cellular response to tetrahydrofolate
Molecular functions
- glycine hydroxymethyltransferase activity
- hydroxytrimethyllysine aldolase activity
- identical protein binding
- lamin binding
- molecular adaptor activity
- mRNA 5'-UTR binding
- mRNA regulatory element binding translation repressor activity
- protein homodimerization activity
- pyridoxal phosphate binding
- serine binding
- small molecule binding
- aldehyde-lyase activity
- threonine aldolase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Serine hydroxymethyltransferase
- Pyridoxal phosphate-dependent transferase, major domain
- Pyridoxal phosphate-dependent transferase, small domain
- Pyridoxal phosphate-dependent transferase
- Serine hydroxymethyltransferase, pyridoxal phosphate binding site
- Serine hydroxymethyltransferase-like domain
- Serine hydroxymethyltransferase-like
- Serine hydroxymethyltransferase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SHMT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SHMT1 as an antibody target. Whether an autoantibody or antibody against SHMT1 could matter depends on whether native SHMT1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SHMT1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label SHMT1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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