Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

• HOME
• SETUP
• FAQ
• ABOUT
• GLOSSARY
• WHAT'S NEW
• FEEDBACK

FTO_NTD FTO catalytic domain

SMART accession number:	SM01223
Description:	This domain is the catalytic AlkB-like domain from the FTO protein (PUBMED:20376003). This domain catalyses a demethylase activity with a preference for 3-methylthymidine.
Interpro abstract (IPR024367):	This domain is the catalytic AlkB-like domain from the FTO protein [ (PUBMED:20376003) ]. This domain catalyses a demethylase activity with a preference for 3-methylthymidine. Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation [ (PUBMED:17991826) ]. FTO activity is highest towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine [ (PUBMED:18775698) ]. FTO has no activity towards 1-methylguanine. It has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. It contributes to the regulation of body size and body fat accumulation as well [ (PUBMED:19234441) ].
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 418 FTO_NTD domains in 418 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing FTO_NTD domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with FTO_NTD domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing FTO_NTD domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Cellular role: metabolism
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Han Z et al.
  • Crystal structure of the FTO protein reveals basis for its substrate specificity.
  • Nature. 2010; 464: 1205-9
  • Display abstract

  • Recent studies have unequivocally associated the fat mass and obesity-associated (FTO) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNAdemethylase with a strong preference for 3-methylthymidine (3-meT) insingle-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA. Here wereport the crystal structure of FTO in complex with the mononucleotide 3-meT. FTOcomprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with anovel fold. Biochemical assays show that these two domains interact with eachother, which is required for FTO catalytic activity. In contrast with thestructures of other AlkB members, FTO possesses an extra loop covering one sideof the conserved jelly-roll motif. Structural comparison shows that this loopselectively competes with the unmethylated strand of the DNA duplex for bindingto FTO, suggesting that it has an important role in FTO selection againstdouble-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meUfrom other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these resultsprovide a structural basis for understanding FTO substrate-specificity, and serveas a foundation for the rational design of FTO inhibitors.

• Structure (3D structures containing this domain)

• 3D Structures of FTO_NTD domains in PDB

  PDB code	Main view	Title
  3lfm		Crystal structure of the fat mass and obesity associated (FTO) protein reveals basis for its substrate specificity
  4cxw		4CXW
  4cxx		4CXX
  4cxy		4CXY
  4idz		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with N-oxalylglycine (NOG)
  4ie0		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with pyridine-2,4-dicarboxylate (2,4-PDCA)
  4ie4		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with 5-carboxy-8-hydroxyquinoline (IOX1)
  4ie5		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with N-[(3-hydroxypyridin-2-yl)carbonyl]glycine (MD6)
  4ie6		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)
  4ie7		Crystal structure of the human fat mass and obesity associated protein (FTO) in complex with citrate and rhein (RHN)
  4qho		4QHO
  4qkn		4QKN
  4zs2		4ZS2
  4zs3		4ZS3
  5dab		5DAB

• Links (links to other resources describing this domain)

• PFAM	FTO_NTD
  INTERPRO	IPR024367

Send comments to Ivica Letunic