Annotations: 6S4A

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	e6s4aA1	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	e6s4aA2	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	e6s4aB1	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	e6s4aB2	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	Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial	cation binding magnesium ion binding ion binding binding metal ion binding small molecule 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 cation binding magnesium ion binding ion binding binding metal ion binding small molecule 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 methylenetetrahydrofolate dehydrogenase (NAD+) activity anion binding phosphate ion binding	folic acid-containing compound metabolic process cellular metabolic process metabolic process cellular process tetrahydrofolate metabolic process pteridine-containing compound metabolic process cellular modified amino acid metabolic process oxoacid metabolic process dicarboxylic acid metabolic process carboxylic acid metabolic process organic acid metabolic process vitamin metabolic process small molecule metabolic process amide metabolic process folic acid-containing compound metabolic process cellular metabolic process metabolic process cellular process tetrahydrofolate metabolic process pteridine-containing compound metabolic process cellular modified amino acid metabolic process oxoacid metabolic process dicarboxylic acid metabolic process carboxylic acid metabolic process organic acid metabolic process vitamin metabolic process small molecule metabolic process amide metabolic process water-soluble vitamin metabolic process folic acid metabolic process tetrahydrofolate interconversion one-carbon metabolic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle extracellular region extracellular space membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen

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	IPR020631	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain	Domain
A, B	IPR020630	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain	Domain
A, B	IPR036291	NAD(P)-binding domain superfamily	Homologous Superfamily
A, B	IPR020867	Tetrahydrofolate dehydrogenase/cyclohydrolase, conserved site	Conserved Site
A, B	IPR000672	Tetrahydrofolate dehydrogenase/cyclohydrolase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P13995	Hodgkins lymphoma Hodgkin's granuloma ulcerative colitis Hodgkin's lymphoma, lymphocytic-histiocytic predominance invasive ductal breast carcinoma lung adenocarcinoma adrenal cortex carcinoma malignant colon neoplasm astrocytic tumor malignant pancreatic neoplasm breast cancer myopathy dermatomyositis non-small cell lung carcinoma ovarian cancer Hodgkins lymphoma Hodgkin's granuloma ulcerative colitis Hodgkin's lymphoma, lymphocytic-histiocytic predominance invasive ductal breast carcinoma lung adenocarcinoma adrenal cortex carcinoma malignant colon neoplasm astrocytic tumor malignant pancreatic neoplasm breast cancer myopathy dermatomyositis non-small cell lung carcinoma ovarian cancer Emery-Dreifuss muscular dystrophy pituitary cancer head and neck cancer psoriasis Hodgkin's lymphoma, mixed cellularity Huntington disease juvenile dermatomyositis lung cancer malignant glioma attention deficit hyperactivity disorder, inattentive type medulloblastoma breast carcinoma nasopharyngeal carcinoma diabetes mellitus oligodendroglioma pancreatic ductal adenocarcinoma esophageal adenocarcinoma polycystic ovary syndrome sarcoidosis Hodgkin's lymphoma, lymphocytic depletion interstitial cystitis large cell medulloblastoma amyotrophic lateral sclerosis malignant mesothelioma atypical teratoid rhabdoid tumor Crohn disease nodular lymphocyte predominant Hodgkin lymphoma ductal breast carcinoma in situ osteosarcoma pilocytic astrocytoma glioblastoma primitive neuroectodermal tumor

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.