MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
1.5.1.15	Oxidoreductases; Acting on the CH-NH group of donors; With NAD+ or NADP+ as acceptor; methylenetetrahydrofolate dehydrogenase (NAD+)
3.5.4.9	Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In cyclic amidines; methenyltetrahydrofolate cyclohydrolase

Structure

PDB	Resolution (Å)	PDB name
5TC4	1.89	Crystal structure of human mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase (MTHFD2) in complex with LY345899 and cofactors
6JIB	2.25	Human MTHFD2 in complex with DS44960156
6JID	2.5	Human MTHFD2 in complex with Compound 1
6KG2	2.25	Human MTHFD2 in complex with Compound 18
6S4A	1.95	Structure of human MTHFD2 in complex with TH9028
6S4E	1.9	Structure of human MTHFD2 in complex with TH7299
6S4F	2.2	Structure of human MTHFD2 in complex with TH9619
7EHJ	2.16	human MTHFD2 in complex with compound 21, cofactor and phosphate.
7EHM	2.13	Human MTHFD2 in complex with compound 21 and 15
7EHN	2.25	Human MTHFD2 in complex with compound 21 and 9
7EHV	2.61	Human MTHFD2 in complex with compound 21 and 3

GO term

GO ontology	GO term	GO description
Biological Process	GO:0046655	folic acid metabolic process
Biological Process	GO:0035999	tetrahydrofolate interconversion
Biological Process	GO:0046653	tetrahydrofolate metabolic process
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0004477	methenyltetrahydrofolate cyclohydrolase activity
Molecular Function	GO:0004487	methylenetetrahydrofolate dehydrogenase (NAD+) activity
Molecular Function	GO:0004488	methylenetetrahydrofolate dehydrogenase (NADP+) activity
Molecular Function	GO:0042301	phosphate ion binding
Cellular Component	GO:0005615	extracellular space
Cellular Component	GO:0005759	mitochondrial matrix
Cellular Component	GO:0005739	mitochondrion

InterPro / Pfam

InterPro	InterPro name
IPR000672	Tetrahydrofolate dehydrogenase/cyclohydrolase
IPR020630	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
IPR020631	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain
IPR020867	Tetrahydrofolate dehydrogenase/cyclohydrolase, conserved site
IPR036291	NAD(P)-binding domain superfamily
IPR046346	Aminoacid dehydrogenase-like, N-terminal domain superfamily

Pfam	Pfam name
PF00763	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
PF02882	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-196757	Metabolism of folate and pterines	Leaf	R-HSA-1430728	Metabolism

Subcellular location

Location	ECO term	Pubmed
Mitochondrion

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
appendix	glandular cells	Low	Approved
appendix	lymphoid tissue	High	Approved
bronchus	respiratory epithelial cells	Low	Approved
caudate	glial cells	Medium	Approved
cerebellum	Purkinje cells	Medium	Approved
cerebellum	cells in granular layer	Medium	Approved
cerebral cortex	neuronal cells	Medium	Approved
cerebral cortex	neuropil	Medium	Approved
cervix	glandular cells	Medium	Approved
colon	endothelial cells	Low	Approved
colon	glandular cells	Medium	Approved
colon	peripheral nerve/ganglion	High	Approved
duodenum	glandular cells	High	Approved
endometrium 1	glandular cells	Medium	Approved
esophagus	squamous epithelial cells	Low	Approved
fallopian tube	glandular cells	Low	Approved
gallbladder	glandular cells	High	Approved
hippocampus	neuronal cells	Low	Approved
kidney	cells in tubules	High	Approved
lung	alveolar cells	Low	Approved
lung	macrophages	Low	Approved
lymph node	germinal center cells	High	Approved
lymph node	non-germinal center cells	Medium	Approved
nasopharynx	respiratory epithelial cells	Medium	Approved
pancreas	exocrine glandular cells	Medium	Approved
pancreas	pancreatic endocrine cells	Medium	Approved
parathyroid gland	glandular cells	Low	Approved
placenta	decidual cells	Low	Approved
prostate	glandular cells	Medium	Approved
rectum	glandular cells	Medium	Approved
seminal vesicle	glandular cells	Medium	Approved
skeletal muscle	myocytes	Low	Approved
skin 1	Langerhans	Medium	Approved
small intestine	glandular cells	High	Approved
stomach 1	glandular cells	Low	Approved
testis	spermatogonia cells	Low	Approved
thyroid gland	glandular cells	Low	Approved
tonsil	germinal center cells	High	Approved
tonsil	non-germinal center cells	Medium	Approved
vagina	squamous epithelial cells	Low	Approved

Summary of P13995

Gene: MTHFD2, NMDMC
Protein: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P13995

Gene: MTHFD2, NMDMC Protein: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: MTHFD2, NMDMC
Protein: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial