Modomics - A Database of RNA Modifications

ID Card:

Full name: Alkylated DNA repair protein alkB homolog 8
Synonym: ABH8
GI: 189027650
COG: COG3145
UniProt: Q96BT7
Structures: | 3THT | 3THP | 2CQ2 |
Alpha Fold Predicted Structure: AF-Q96BT7-F1
Complex: ALKBH8/TRM112
Enzyme type: methyltransferase, hydroxylase
Position of modification - modification: t:34 - mchm5U
t:34 - mcm5s2U
t:34 - mcm5U
t:34 - mcm5Um


PDB Structures:


3THT

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Yet to be published

Download RCSB-PDB Structures:

Pdb Files   2CQ2.pdb   3THP.pdb   3THT.pdb  
Pdbx/mmCIF Files   2CQ2.cif   3THP.cif   3THT.cif  


Protein sequence:

MDSNHQSNYKLSKTEKKFLRKQIKAKHTLLRHEGIETVSYATQSLVVANGGLGNGVSRNQLLPVLEKCGLVDALLMPPNKPYSFARYRTTEESKRAYVTLNGKEVVDDLGQKITLYLNFVEKVQWKELRPQALPPGLMVVEEIISSEEEKMLLESVDWTEDTDNQNSQKSLKHRRVKHFGYEFHYENNNVDKDKPLSGGLPDICESFLEKWLRKGYIKHKPDQMTINQYEPGQGIPAHIDTHSAFEDEIVSLSLGSEIVMDFKHPDGIAVPVMLPRRSLLVMTGESRYLWTHGITCRKFDTVQASESLKSGIITSDVGDLTLSKRGLRTSFTFRKVRQTPCNCSYPLVCDSQRKETPPSFPESDKEASRLEQEYVHQVYEEIAGHFSSTRHTPWPHIVEFLKALPSGSIVADIGCGNGKYLGINKELYMIGCDRSQNLVDICRERQFQAFVCDALAVPVRSGSCDACISIAVIHHFATAERRVAALQEIVRLLRPGGKALIYVWAMEQEYNKQKSKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGSRDSASSVPRINDSQEGGCNSRQVSNSKLPVHVNRTSFYSQDVLVPWHLKGNPDKGKPVEPFGPIGSQDPSPVFHRYYHVFREGELEGACRTVSDVRILQSYYDQGNWCVILQKA

Comments:

Alpha-Ketoglutarate-Dependent Dioxygenase AlkB homolog 8 is a member of the superfamily of alpha-ketoglutarate and Fe(II) dependent dioxygenase (Marcinkowski et al. 2020 ).Structurally, and differently from the other family members, ALKBH8 contains DNA/RNA recognition motif (RRM) and SAM-dependent methyltransferase domain, in addition to the conserved AlkB conserved domains (Fu et al. 2010 ).ALKBH8 catalyzes 5-methoxycarbonyl methyluridine (mcm5U) in the final step of its biogenesis . Noteworthy, its methyltransferases domain catalyzes the methylation of 5-carboxymethyl uridine to 5-methyl-carboxymethyl uridine on the the wobble position of the anticodon loop in different tRNAs(Songe-Møller et al. 2010 ;Fu et al. 2010 ;Monies et et al. 2019 ). It moreover shows a preference for tRNA(Arg) and tRNA(Glu), modifying different isoform (Fu et al. 2010 ). Furthermore, it catalyzes 5-methylcarboxyl-methyl-uridine to 5-S-methoxycarbonylhydroxymethyl uridine that depends on the iron and alpha-ketoglutarate dependent hydroxylation(van De Born et al. 2011 ). Exhibits two enzymatic activities: MTase domain provides the mcm5U precursor (ortholog of the yeast Trm9) while AlkB domain is a mchm5U synthesizing oxygenase (hydroxylase activity). AdoMet is the methyl group donor. Interaction with TRM112 is required for MTase activity only. Prior ALKBH8-mediated methylation is a prerequisite for sbsequent thiolation and 2'-O-ribose methylation that form 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) and 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm5Um), respectively. ABH8 depleted cells exhibit highly elevated levels of cm5U and lowered levels of mcm5U and shows an increase cellular sensitivity to DNA-damaging agents, attesting for possible regulatory role of ALKBH8 in the DNA damage response pathway. Complementary information in the case of fungi can be obtained under Trm9, Trm112 and Elongation complex Elf 1-6.




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
cm5U:mcm5U RNA tRNA 34 ◊CG 1CG tRNAArgUCG wobble - position Cytoplasm 20308323   
cm5U:mcm5U RNA tRNA 34 ◊CC 1CC tRNAGlyUCC wobble - position Cytoplasm 20308323   
mcm5U:mchm5U RNA tRNA 34 1CC tRNAGlyUCC wobble - position Cytoplasm 20308323   
ncm5U:nchm5U RNA tRNA 34 &CC rCC tRNAGlyUCC wobble - position Cytoplasm 21285950   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M D S N H Q S N Y K L S K T E K K F L R K Q I K A K H T L L R H E G I E T V S Y A T Q S L V V A N G G L G N G V S R N Q L L P V L E K C G L V D A L L M P P N K P Y S F A R Y R T T E E S K R A Y V T L N G K E V V D D L G Q K I T L Y L N F V E K V Q W K E L R P Q A L P P G L M V V E E I I S S E E E K M L L E S V D W T E D T D N Q N S Q K S L K H R R V K H F G Y E F H Y E N N N V D K D K P L S G G L P D I C E S F L E K W L R K G Y I K H K P D Q M T I N Q Y E P G Q G I P A H I D T H S A F E D E I V S L S L G S E I V M D F K H P D G I A V P V M L P R R S L L V M T G E S R Y L W T H G I T C R K F D T V Q A S E S L K S G I I T S D V G D L T L S K R G L R T S F T F R K V R Q T P C N C S Y P L V C D S Q R K E T P P S F P E S D K E A S R L E Q E Y V H Q V Y E E I A G H F S S T R H T P W P H I V E F L K A L P S G S I V A D I G C G N G K Y L G I N K E L Y M I G C D R S Q N L V D I C R E R Q F Q A F V C D A L A V P V R S G S C D A C I S I A V I H H F A T A E R R V A A L Q E I V R L L R P G G K A L I Y V W A M E Q E Y N K Q K S K Y L R G N R N S Q G K K E E M N S D T S V Q R S L V E Q M R D M G S R D S A S S V P R I N D S Q E G G C N S R Q V S N S K L P V H V N R T S F Y S Q D V L V P W H L K G N P D K G K P V E P F G P I G S Q D P S P V F H R Y Y H V F R E G E L E G A C R T V S D V R I L Q S Y Y D Q G N W C V I L Q K A

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q96BT7-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q96BT7-F1.cif  
DSSP Secondary Structures   Q96BT7.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification. Pastore C, Topalidou I, Forouhar F, Yan AC, Levy M, Hunt JF J Biol Chem [details] 22065580 -
Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Fu D, Brophy JA, Chan CT, Atmore KA, Begley U, Paules RS, Dedon PC, Begley TJ, Samson LD Mol Cell Biol [details] 20308323 -
ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA. van den Born E, Vagbo CB, Songe-Moller L, Leihne V, Lien GF, Leszczynska G, Malkiewicz A, Krokan HE, Kirpekar F, Klungland A, Falnes PO Nat Commun [details] 21285950 doi.org/10.1038/ncomms1173
The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the wobble position of tRNA. Fu Y, Dai Q, Zhang W, Ren J, Pan T, He C Angew Chem Int Ed Engl [details] 20583019 -
Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Songe-Moller L, van den Born E, Leihne V, Vagbo CB, Kristoffersen T, Krokan HE, Kirpekar F, Falnes PO, Klungland A Mol Cell Biol [details] 20123966 -

Links:

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