Seroatlas · Human Serome Atlas

MTHFD2

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Also known as: MTDC_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
P13995
Gene
MTHFD2
Ensembl
ENSG00000065911
Chromosome
2
Canonical length
350 aa
Protein class
Enzymes, Metabolic proteins, Predicted intracellular proteins
Subcellular location
Mitochondria
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]

Canonical amino-acid sequenceUniProt

350 residues, UniProt reviewed canonical sequence.

>P13995|MTHFD2
     1  MAATSLMSAL AARLLQPAHS CSLRLRPFHL AAVRNEAVVI SGRKLAQQIK QEVRQEVEEW
    61  VASGNKRPHL SVILVGENPA SHSYVLNKTR AAAVVGINSE TIMKPASISE EELLNLINKL
   121  NNDDNVDGLL VQLPLPEHID ERRICNAVSP DKDVDGFHVI NVGRMCLDQY SMLPATPWGV
   181  WEIIKRTGIP TLGKNVVVAG RSKNVGMPIA MLLHTDGAHE RPGGDATVTI SHRYTPKEQL
   241  KKHTILADIV ISAAGIPNLI TADMIKEGAA VIDVGINRVH DPVTAKPKLV GDVDFEGVRQ
   301  KAGYITPVPG GVGPMTVAML MKNTIIAAKK VLRLEEREVL KSKELGVATN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MTHFD2 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)
0.3
Highest tissue expression
111 nTPM

Expression across tissuesHPA

Tissue

  • blood vessel: 111 nTPM
  • pancreas: 62 nTPM
  • tonsil: 54 nTPM
  • skeletal muscle: 52 nTPM
  • tongue: 52 nTPM
  • appendix: 51 nTPM

Single-cell type

  • vascular smooth muscle cells: 227 nCPM
  • pancreatic acinar cells: 178 nCPM
  • plasma cells: 153 nCPM
  • decidual stromal cells: 152 nCPM
  • cdc: 148 nCPM
  • pericytes: 144 nCPM

Immune cell

  • non-classical monocyte: 57 nTPM
  • intermediate monocyte: 57 nTPM
  • basophil: 45 nTPM
  • T-reg: 37 nTPM
  • myeloid DC: 35 nTPM
  • eosinophil: 31 nTPM

Brain region

  • hypothalamus: 25 nTPM
  • medulla oblongata: 25 nTPM
  • midbrain: 24 nTPM
  • white matter: 22 nTPM
  • pons: 22 nTPM
  • spinal cord: 21 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)
0.81
gnomAD pLI
0
gnomAD missense Z
0.48
DepMap mean gene effect
-0.06
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

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MTHFD2 as an antibody target. Whether an autoantibody or antibody against MTHFD2 could matter depends on whether native MTHFD2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MTHFD2 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 MTHFD2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MTHFD2. 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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