Seroatlas · Human Serome Atlas

SHMT2

Serine hydroxymethyltransferase, mitochondrial

Also known as: GLYM_HUMAN, mSHMT, SHMT

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P34897
Gene
SHMT2
Ensembl
ENSG00000182199
Chromosome
12
Canonical length
504 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Microtubules,Mitochondria
Quaternary structure
Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

504 residues, UniProt reviewed canonical sequence.

>P34897|SHMT2
     1  MLYFSLFWAA RPLQRCGQLV RMAIRAQHSN AAQTQTGEAN RGWTGQESLS DSDPEMWELL
    61  QREKDRQCRG LELIASENFC SRAALEALGS CLNNKYSEGY PGKRYYGGAE VVDEIELLCQ
   121  RRALEAFDLD PAQWGVNVQP YSGSPANLAV YTALLQPHDR IMGLDLPDGG HLTHGYMSDV
   181  KRISATSIFF ESMPYKLNPK TGLIDYNQLA LTARLFRPRL IIAGTSAYAR LIDYARMREV
   241  CDEVKAHLLA DMAHISGLVA AKVIPSPFKH ADIVTTTTHK TLRGARSGLI FYRKGVKAVD
   301  PKTGREIPYT FEDRINFAVF PSLQGGPHNH AIAAVAVALK QACTPMFREY SLQVLKNARA
   361  MADALLERGY SLVSGGTDNH LVLVDLRPKG LDGARAERVL ELVSITANKN TCPGDRSAIT
   421  PGGLRLGAPA LTSRQFREDD FRRVVDFIDE GVNIGLEVKS KTAKLQDFKS FLLKDSETSQ
   481  RLANLRQRVE QFARAFPMPG FDEH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SHMT2 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
Other membrane
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.27
Highest tissue expression
223 nTPM

Expression across tissuesHPA

Tissue

  • liver: 223 nTPM
  • pancreas: 74 nTPM
  • esophagus: 57 nTPM
  • tonsil: 55 nTPM
  • lymph node: 49 nTPM
  • stomach: 43 nTPM

Single-cell type

  • hepatocytes: 205 nCPM
  • esophageal basal cells: 123 nCPM
  • esophageal suprabasal cells: 78 nCPM
  • migrating cytotrophoblasts: 73 nCPM
  • plasma cells: 67 nCPM
  • hofbauer cells: 65 nCPM

Immune cell

  • T-reg: 203 nTPM
  • naive B-cell: 139 nTPM
  • memory B-cell: 128 nTPM
  • myeloid DC: 60 nTPM
  • total PBMC: 54 nTPM
  • intermediate monocyte: 51 nTPM

Brain region

  • white matter: 23 nTPM
  • thalamus: 22 nTPM
  • medulla oblongata: 20 nTPM
  • hippocampal formation: 20 nTPM
  • pons: 19 nTPM
  • midbrain: 19 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SHMT2.

Disease | AllUniProt

Conditions SHMT2 is implicated in, by any mechanism.

  • Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB) MIM:619121

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 111 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.86
gnomAD pLI
0
gnomAD missense Z
1.52
DepMap mean gene effect
-0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SHMT2 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 SHMT2 as an antibody target. Whether an autoantibody or antibody against SHMT2 could matter depends on whether native SHMT2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SHMT2 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 SHMT2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SHMT2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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