6ECR

The human methylenetetrahydrofolate dehydrogenase/cyclohydrolase (FolD) complexed with NADP

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d6ecra2	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Aminoacid dehydrogenase-like, C-terminal domain	Methylenetetrahydrofolate dehydrogenase/cyclohydrolase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d6ecra1	Alpha and beta proteins (a/b)	Aminoacid dehydrogenase-like, N-terminal domain	Aminoacid dehydrogenase-like, N-terminal domain	Tetrahydrofolate dehydrogenase/cyclohydrolase	Tetrahydrofolate dehydrogenase/cyclohydrolase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d6ecrb2	Alpha and beta proteins (a/b)	NAD(P)-binding Rossmann-fold domains	NAD(P)-binding Rossmann-fold domains	Aminoacid dehydrogenase-like, C-terminal domain	Methylenetetrahydrofolate dehydrogenase/cyclohydrolase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d6ecrb1	Alpha and beta proteins (a/b)	Aminoacid dehydrogenase-like, N-terminal domain	Aminoacid dehydrogenase-like, N-terminal domain	Tetrahydrofolate dehydrogenase/cyclohydrolase	Tetrahydrofolate dehydrogenase/cyclohydrolase	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	MtdA-like	8056181	3000046	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	MtdA-like	8056181	3000046	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	THF_DHG_CYH_C	e6ecrA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: THF_DHG_CYH_C	ECOD (1.6)
A	THF_DHG_CYH	e6ecrA2	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: Aminoacid dehydrogenase-like, N-terminal domain	F: THF_DHG_CYH	ECOD (1.6)
B	THF_DHG_CYH_C	e6ecrB2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: NAD(P)-binding Rossmann-fold domains	F: THF_DHG_CYH_C	ECOD (1.6)
B	THF_DHG_CYH	e6ecrB1	A: a/b three-layered sandwiches	X: Flavodoxin-like	H: Class I glutamine amidotransferase-like	T: Aminoacid dehydrogenase-like, N-terminal domain	F: THF_DHG_CYH	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02882	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain (THF_DHG_CYH_C)	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain	-	Domain
A, B	PF00763	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain (THF_DHG_CYH)	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	methylenetetrahydrofolate dehydrogenase cyclohydrolase	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines cyclohydrolase activity methenyltetrahydrofolate cyclohydrolase activity hydrolase activity catalytic activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds methylenetetrahydrofolate dehydrogenase (NADP+) activity oxidoreductase activity oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on the CH-NH group of donors methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity binding adenyl ribonucleotide binding nucleotide binding hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines cyclohydrolase activity methenyltetrahydrofolate cyclohydrolase activity hydrolase activity catalytic activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds methylenetetrahydrofolate dehydrogenase (NADP+) activity oxidoreductase activity oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor oxidoreductase activity, acting on the CH-NH group of donors methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding methylenetetrahydrofolate dehydrogenase (NAD+) activity formate-tetrahydrofolate ligase activity ligase activity, forming carbon-nitrogen bonds ligase activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development embryonic organ morphogenesis embryonic viscerocranium morphogenesis embryonic cranial skeleton morphogenesis chordate embryonic development embryonic morphogenesis embryo development developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development embryonic organ morphogenesis embryonic viscerocranium morphogenesis embryonic cranial skeleton morphogenesis chordate embryonic development embryonic morphogenesis embryo development anatomical structure morphogenesis embryo development ending in birth or egg hatching skeletal system development cranial skeletal system development animal organ morphogenesis embryonic skeletal system development skeletal system morphogenesis embryonic organ development embryonic skeletal system morphogenesis ribose phosphate metabolic process nucleotide biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process phosphate-containing compound metabolic process small molecule metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process carbohydrate derivative biosynthetic process cellular metabolic process primary metabolic process nucleotide metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process metabolic process cellular process purine ribonucleotide metabolic process purine nucleotide biosynthetic process folic acid-containing compound metabolic process tetrahydrofolate interconversion tetrahydrofolate metabolic process pteridine-containing compound metabolic process cellular modified amino acid metabolic process one-carbon metabolic process oxoacid metabolic process sulfur amino acid metabolic process aspartate family amino acid metabolic process carboxylic acid metabolic process amino acid metabolic process methionine metabolic process organic acid metabolic process alpha-amino acid metabolic process L-amino acid metabolic process proteinogenic amino acid metabolic process sulfur compound metabolic process cellular biosynthetic process organic acid biosynthetic process carboxylic acid biosynthetic process dicarboxylic acid biosynthetic process 10-formyltetrahydrofolate metabolic process folic acid-containing compound biosynthetic process small molecule biosynthetic process dicarboxylic acid metabolic process 10-formyltetrahydrofolate biosynthetic process cellular modified amino acid biosynthetic process pteridine-containing compound biosynthetic process tetrahydrofolate biosynthetic process embryonic epithelial tube formation tube formation epithelial tube formation tube morphogenesis primary neural tube formation epithelial tube morphogenesis morphogenesis of embryonic epithelium epithelium development neural tube development tube development morphogenesis of an epithelium nervous system development tissue development tissue morphogenesis neural tube closure neural tube formation anatomical structure formation involved in morphogenesis tube closure homocysteine metabolic process serine family amino acid metabolic process transsulfuration cysteine metabolic process non-proteinogenic amino acid metabolic process homoserine metabolic process aspartate family amino acid biosynthetic process methionine biosynthetic process L-amino acid biosynthetic process amino acid biosynthetic process sulfur compound biosynthetic process proteinogenic amino acid biosynthetic process sulfur amino acid biosynthetic process alpha-amino acid biosynthetic process embryonic neurocranium morphogenesis multicellular organismal-level homeostasis leukocyte homeostasis homeostatic process immune system process homeostasis of number of cells myeloid cell homeostasis neutrophil homeostasis serine family amino acid biosynthetic process somite development	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR046346	Aminoacid dehydrogenase-like, N-terminal domain superfamily	Homologous Superfamily
A, B	IPR020630	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain	Domain
A, B	IPR000672	Tetrahydrofolate dehydrogenase/cyclohydrolase	Family
A, B	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, B	IPR020631	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain	Domain
A, B	IPR000559	Formate-tetrahydrofolate ligase, FTHFS	Family
A, B	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily
A, B	IPR020628	Formate-tetrahydrofolate ligase, FTHFS, conserved site	Conserved Site
A, B	IPR020867	Tetrahydrofolate dehydrogenase/cyclohydrolase, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P11586	neural tube defect neural tube defects, folate-sensitive schizophrenia Spinal Cord Myelodysplasia tuberculosis colorectal cancer diastematomyelia iniencephaly pancreatic ductal adenocarcinoma combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia ductal breast carcinoma in situ lung cancer neurenteric cyst placental abruption tethered spinal cord syndrome neural tube defect neural tube defects, folate-sensitive schizophrenia Spinal Cord Myelodysplasia tuberculosis colorectal cancer diastematomyelia iniencephaly pancreatic ductal adenocarcinoma combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia ductal breast carcinoma in situ lung cancer neurenteric cyst placental abruption tethered spinal cord syndrome bipolar disorder craniorachischisis lymphoplasmacytic lymphoma ovarian cancer

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.