Protein Summary

ALKBH8 from Homo sapiens

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

Comments:

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.

Protein sequence:

MDSNHQSNYKLSKTEKKFLRKQIKAKHTLLRHEGIETVSYATQSLVVANG
GLGNGVSRNQLLPVLEKCGLVDALLMPPNKPYSFARYRTTEESKRAYVTL
NGKEVVDDLGQKITLYLNFVEKVQWKELRPQALPPGLMVVEEIISSEEEK
MLLESVDWTEDTDNQNSQKSLKHRRVKHFGYEFHYENNNVDKDKPLSGGL
PDICESFLEKWLRKGYIKHKPDQMTINQYEPGQGIPAHIDTHSAFEDEIV
SLSLGSEIVMDFKHPDGIAVPVMLPRRSLLVMTGESRYLWTHGITCRKFD
TVQASESLKSGIITSDVGDLTLSKRGLRTSFTFRKVRQTPCNCSYPLVCD
SQRKETPPSFPESDKEASRLEQEYVHQVYEEIAGHFSSTRHTPWPHIVEF
LKALPSGSIVADIGCGNGKYLGINKELYMIGCDRSQNLVDICRERQFQAF
VCDALAVPVRSGSCDACISIAVIHHFATAERRVAALQEIVRLLRPGGKAL
IYVWAMEQEYNKQKSKYLRGNRNSQGKKEEMNSDTSVQRSLVEQMRDMGS
RDSASSVPRINDSQEGGCNSRQVSNSKLPVHVNRTSFYSQDVLVPWHLKG
NPDKGKPVEPFGPIGSQDPSPVFHRYYHVFREGELEGACRTVSDVRILQS
YYDQGNWCVILQKA

Enzymatic activities

Reaction Substrate Type Position
cm5U:mcm5U tRNA (t) Arg/UCG/cytosolic 34
cm5U:mcm5U tRNA (t) Gly/UCC/cytosolic 34
mcm5U:mchm5U tRNA (t) Gly/UCC/cytosolic 34
cm5s2U:mcm5s2U tRNA (t) unknown/unknown/cytosolic 34
ncm5U:nchm5U tRNA (t) Gly/UCC/unknown 34

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 -
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

_Wikipedia - AlkB_
_PubMed_

Last modification of this entry: 2012-08-24 15:32:04.182285
Edited by a user: magda
Edited content: Changed comments and papers.