4IE5

Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with N-[(3-hydroxypyridin-2-yl)carbonyl]glycine (MD6)

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	FTO_NTD	e4ie5A3	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: FTO_NTD	ECOD (1.6)
A	FTO_CTD	e4ie5A2	A: alpha bundles	X: STAT-like	H: Alpha-ketoglutarate-dependent dioxygenase FTO helical domain (From Topology)	T: Alpha-ketoglutarate-dependent dioxygenase FTO helical domain	F: FTO_CTD	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.120.590	Mainly Beta	Sandwich	Jelly Rolls	Alpha-ketoglutarate-dependent dioxygenase AlkB-like	CATH (4.3.0)
A	1.20.58.1470	Mainly Alpha	Up-down Bundle	Methane Monooxygenase Hydroxylase	Chain G, domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF12934	FTO C-terminal domain (FTO_CTD)	FTO C-terminal domain	This domain is found at the C-terminus of the FTO protein which was shown to be associated with increased BMI and obesity risk in humans. The N-terminal domain of this protein is a DNA demethylase and this domain is found to associate with the N-ter ...	This domain is found at the C-terminus of the FTO protein which was shown to be associated with increased BMI and obesity risk in humans. The N-terminal domain of this protein is a DNA demethylase and this domain is found to associate with the N-terminal domain in the crystal structure [1]. This domain is alpha helical with three helices that form a bundle [1].	Domain
A	PF12933	FTO catalytic domain (FTO_NTD)	FTO catalytic domain	This domain is the catalytic AlkB-like domain from the FTO protein [1]. This domain catalyses a demethylase activity with a preference for 3-methylthymidine.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Alpha-ketoglutarate-dependent dioxygenase FTO	cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding mRNA N6-methyladenosine dioxygenase activity oxidoreductase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid oxidative RNA demethylase activity cation binding transition metal ion binding iron ion binding ion binding binding ferrous iron binding metal ion binding small molecule binding mRNA N6-methyladenosine dioxygenase activity oxidoreductase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid oxidative RNA demethylase activity catalytic activity 2-oxoglutarate-dependent dioxygenase activity demethylase activity dioxygenase activity tRNA demethylase activity catalytic activity, acting on a tRNA transferase activity DNA demethylase activity broad specificity oxidative DNA demethylase activity catalytic activity, acting on DNA	developmental process fat cell differentiation regulation of biological process regulation of cellular process cellular developmental process regulation of developmental process biological regulation regulation of cell differentiation regulation of brown fat cell differentiation brown fat cell differentiation cell differentiation cellular process regulation of fat cell differentiation oxidative demethylation developmental process fat cell differentiation regulation of biological process regulation of cellular process cellular developmental process regulation of developmental process biological regulation regulation of cell differentiation regulation of brown fat cell differentiation brown fat cell differentiation cell differentiation cellular process regulation of fat cell differentiation oxidative demethylation demethylation metabolic process connective tissue development adipose tissue development animal organ development anatomical structure development tissue development primary metabolic process DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process DNA modification organic substance metabolic process DNA demethylation DNA dealkylation macromolecule modification macromolecule metabolic process cellular response to stimulus response to stimulus DNA alkylation repair cellular response to stress DNA damage response response to stress DNA repair multicellular organismal process system process respiratory system process regulation of respiratory gaseous exchange regulation of system process regulation of multicellular organismal process regulation of respiratory system process respiratory gaseous exchange by respiratory system regulation of multicellular organism growth regulation of growth regulation of developmental growth developmental growth growth multicellular organism growth RNA metabolic process RNA repair multicellular organismal-level homeostasis homeostatic process temperature homeostasis localization regulation of localization regulation of lipid storage macromolecule localization lipid storage lipid localization maintenance of location negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process positive regulation of metabolic process post-transcriptional regulation of gene expression regulation of RNA metabolic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of biological quality RNA catabolic process mRNA catabolic process positive regulation of nucleobase-containing compound metabolic process cellular metabolic process negative regulation of metabolic process positive regulation of mRNA metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process nucleobase-containing compound catabolic process positive regulation of RNA metabolic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process nucleic acid catabolic process regulation of macromolecule biosynthetic process regulation of metabolic process catabolic process cellular biosynthetic process positive regulation of biological process mRNA destabilization macromolecule catabolic process regulation of mRNA catabolic process negative regulation of cellular process negative regulation of macromolecule metabolic process regulation of biosynthetic process RNA destabilization regulation of macromolecule metabolic process regulation of catabolic process gene expression mRNA metabolic process macromolecule biosynthetic process organic cyclic compound catabolic process regulation of cellular biosynthetic process positive regulation of catabolic process regulation of mRNA stability positive regulation of mRNA catabolic process negative regulation of biosynthetic process regulation of RNA stability regulation of mRNA metabolic process organic substance catabolic process fat cell proliferation regulation of white fat cell proliferation cell population proliferation regulation of cell population proliferation regulation of fat cell proliferation white fat cell proliferation	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen cytoplasm cytosol cell periphery plasma membrane membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR032868	Alpha-ketoglutarate-dependent dioxygenase FTO	Family
A	IPR038413	FTO, C-terminal domain superfamily	Homologous Superfamily
A	IPR024367	Alpha-ketoglutarate-dependent dioxygenase FTO, catalytic domain	Domain
A	IPR037151	Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily	Homologous Superfamily
A	IPR024366	Alpha-ketoglutarate-dependent dioxygenase FTO, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q9C0B1	obesity disorder melanoma lethal polymalformative syndrome, Boissel type breast carcinoma type 2 diabetes mellitus breast cancer psoriasis Weight Gain metabolic syndrome X monogenic obesity acquired metabolic disease bipolar disorder ovarian cancer chronic kidney disease inborn carbohydrate metabolic disorder obesity disorder melanoma lethal polymalformative syndrome, Boissel type breast carcinoma type 2 diabetes mellitus breast cancer psoriasis Weight Gain metabolic syndrome X monogenic obesity acquired metabolic disease bipolar disorder ovarian cancer chronic kidney disease inborn carbohydrate metabolic disorder leukopenia obstructive sleep apnea syndrome cutaneous melanoma X-linked mixed deafness with perilymphatic gusher heart disease intellectual disability maturity-onset diabetes of the young non-alcoholic fatty liver disease osteoarthritis polycystic ovary syndrome vitiligo depressive disorder estrogen-receptor negative breast cancer idiopathic scoliosis

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.