Annotations: 6FCX

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF21895	e6fcxA2	A: a+b two layers	X: MTHFR SAM-binding regulatory domain (From Topology)	H: MTHFR SAM-binding regulatory domain (From Topology)	T: MTHFR SAM-binding regulatory domain	F: PF21895	ECOD (1.6)
A	PF02219	e6fcxA1	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PF02219	ECOD (1.6)
B	PF21895	e6fcxB1	A: a+b two layers	X: MTHFR SAM-binding regulatory domain (From Topology)	H: MTHFR SAM-binding regulatory domain (From Topology)	T: MTHFR SAM-binding regulatory domain	F: PF21895	ECOD (1.6)
B	PF02219	e6fcxB2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: PF02219	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02219	Methylenetetrahydrofolate reductase (MTHFR)	Methylenetetrahydrofolate reductase	This family includes the 5,10-methylenetetrahydrofolate reductase EC:1.7.99.5 from bacteria and methylenetetrahydrofolate reductase EC: 1.5.1.20 from eukaryotes. The structure for this domain is known [1] to be a TIM barrel.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Methylenetetrahydrofolate reductase	oxidoreductase activity methylenetetrahydrofolate reductase (NAD(P)H) 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 catalytic activity methylenetetrahydrofolate reductase (NADPH) activity binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding NADP binding oxidoreductase activity methylenetetrahydrofolate reductase (NAD(P)H) 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 catalytic activity methylenetetrahydrofolate reductase (NADPH) activity binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding adenyl nucleotide binding nucleotide binding heterocyclic compound binding NADP binding small molecule binding protein-containing complex binding FAD binding flavin adenine dinucleotide binding ion binding anion binding modified amino acid binding	response to acid chemical response to organic substance response to stimulus response to chemical response to amino acid response to xenobiotic stimulus multicellular organismal process embryonic epithelial tube formation chordate embryonic development tube formation embryo development multicellular organism development epithelial tube formation tube morphogenesis response to acid chemical response to organic substance response to stimulus response to chemical response to amino acid response to xenobiotic stimulus multicellular organismal process embryonic epithelial tube formation chordate embryonic development tube formation embryo development multicellular organism development epithelial tube formation tube morphogenesis primary neural tube formation embryo development ending in birth or egg hatching anatomical structure development epithelial tube morphogenesis system development developmental process morphogenesis of embryonic epithelium epithelium development neural tube development tube development embryonic morphogenesis morphogenesis of an epithelium nervous system development tissue development anatomical structure morphogenesis tissue morphogenesis neural tube closure neural tube formation anatomical structure formation involved in morphogenesis tube closure homocysteine metabolic process organonitrogen compound metabolic process oxoacid metabolic process sulfur amino acid metabolic process cellular metabolic process carboxylic acid metabolic process amino acid metabolic process primary metabolic process organic acid metabolic process alpha-amino acid metabolic process non-proteinogenic amino acid metabolic process organic substance metabolic process metabolic process small molecule metabolic process cellular process sulfur compound metabolic process protein-DNA complex organization cellular component organization protein-containing complex organization chromatin organization heterochromatin organization cellular component organization or biogenesis cellular biosynthetic process aspartate family amino acid biosynthetic process organonitrogen compound biosynthetic process aspartate family amino acid metabolic process organic acid biosynthetic process carboxylic acid biosynthetic process organic substance biosynthetic process methionine biosynthetic process small molecule biosynthetic process L-amino acid biosynthetic process methionine metabolic process L-amino acid metabolic process proteinogenic amino acid metabolic process amino acid biosynthetic process sulfur compound biosynthetic process biosynthetic process proteinogenic amino acid biosynthetic process sulfur amino acid biosynthetic process alpha-amino acid biosynthetic process response to decreased oxygen levels response to hypoxia response to stress response to oxygen levels response to abiotic stimulus response to nutrient levels response to organonitrogen compound response to nutrient response to oxygen-containing compound response to nitrogen compound response to vitamin response to vitamin B2 response to organic cyclic compound S-adenosylmethionine metabolic process response to folic acid response to cytokine response to interleukin-1 cellular modified amino acid metabolic process organic cyclic compound metabolic process folic acid-containing compound metabolic process tetrahydrofolate interconversion tetrahydrofolate metabolic process pteridine-containing compound metabolic process one-carbon metabolic process	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR029041	FAD-linked oxidoreductase-like	Homologous Superfamily
A, B	IPR004621	Eukaryotic-type methylenetetrahydrofolate reductase	Family
A, B	IPR003171	Methylenetetrahydrofolate reductase-like	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P42898	thrombophilia neural tube defect schizophrenia Down syndrome pulmonary embolism homocystinuria due to methylene tetrahydrofolate reductase deficiency rheumatoid arthritis spina bifida leukopenia Alzheimer disease Microvascular Angina homocystinuria hyperhomocysteinemia B-cell chronic lymphocytic leukemia neutropenia thrombophilia neural tube defect schizophrenia Down syndrome pulmonary embolism homocystinuria due to methylene tetrahydrofolate reductase deficiency rheumatoid arthritis spina bifida leukopenia Alzheimer disease Microvascular Angina homocystinuria hyperhomocysteinemia B-cell chronic lymphocytic leukemia neutropenia follicular lymphoma thrombocytopenia vascular disease endogenous depression anencephaly Crohn disease spinal cord disease malignant colon neoplasm cervical cancer graft versus host disease thyrotoxicosis allergic disease myelomeningocele coronary restenosis inherited blood coagulation disorder male infertility neural tube defects, folate-sensitive bipolar disorder breast carcinoma tethered spinal cord syndrome diabetic peripheral angiopathy melancholia alopecia prostate cancer lymphoma urinary bladder cancer colorectal cancer uterine cervix carcinoma in situ anemia endometrial carcinoma nervous system disorder female infertility intracranial sinus thrombosis brain ischemia kidney disease cardiovascular disease cerebrovascular disorder liver disease hematologic disease clubfoot colorectal carcinoma inborn errors of metabolism reticulum cell sarcoma skin disease major depressive disorder autism intellectual disability benign colon neoplasm non-Hodgkin lymphoma breast cancer osteosarcoma peripheral nervous system disease leukoencephalopathy with vanishing white matter cleft lip colonic neoplasm drug-induced liver injury androgenetic alopecia hypertensive disorder congenital heart disease endometrial cancer inborn vitamin B12 deficiency Crohn's colitis neurotic disorder cystic fibrosis non-small cell lung carcinoma isolated anencephaly/exencephaly gastric cancer ovarian cancer depressive disorder gastrointestinal mucositis cervical intraepithelial neoplasia peripheral neuropathy thrombophilia due to thrombin defect childhood acute lymphoblastic leukemia digestive system disease hemochromatosis type 1 psoriasis drug-induced hepatitis myotonic dystrophy type 1 ileocolitis coronary artery disease craniorachischisis lymphosarcoma atrial fibrillation iniencephaly neurenteric cyst nutritional deficiency disease sudden sensorineural hearing loss acute kidney failure gastric neoplasm pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia gastrointestinal stromal tumor diastematomyelia thrombotic disease lung benign neoplasm alopecia areata hemophilia B urinary bladder neoplasm hereditary diffuse gastric adenocarcinoma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.