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Protein

Alkylated DNA repair protein alkB homolog 8

Gene

Alkbh8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (By similarity). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:20583019). Required for normal survival after DNA damage (By similarity). May inhibit apoptosis and promote cell survival and angiogenesis (By similarity).By similarity2 Publications

Catalytic activityi

S-adenosyl-L-methionine + carboxymethyluridine(34) in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA.

Cofactori

Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi238Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi240Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi242Zinc; via pros nitrogenBy similarity1
Metal bindingi292Iron; catalyticPROSITE-ProRule annotation1
Binding sitei328Alpha-ketoglutarateBy similarity1
Binding sitei334Alpha-ketoglutarateBy similarity1
Metal bindingi341ZincBy similarity1
Metal bindingi343ZincBy similarity1
Metal bindingi349ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • tRNA methylation Source: UniProtKB
  • tRNA wobble uridine modification Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Oxidoreductase, Transferase

Keywords - Ligandi

Iron, Metal-binding, RNA-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BRENDAi2.1.1.229. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Alkylated DNA repair protein alkB homolog 8 (EC:1.14.11.-)
Alternative name(s):
Probable alpha-ketoglutarate-dependent dioxygenase ABH8
S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8
tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ABH8 (EC:2.1.1.-, EC:2.1.1.229)
Gene namesi
Name:Alkbh8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1914917. Alkbh8.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Predominantly cytoplasmic.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi238H → A: Abolishes hydroxylation of 5-methylcarboxymethyl uridine. 1 Publication1
Mutagenesisi240D → A: Abolishes hydroxylation of 5-methylcarboxymethyl uridine. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003371271 – 664Alkylated DNA repair protein alkB homolog 8Add BLAST664

Proteomic databases

PaxDbiQ80Y20.
PeptideAtlasiQ80Y20.
PRIDEiQ80Y20.

PTM databases

PhosphoSitePlusiQ80Y20.

Expressioni

Gene expression databases

BgeeiENSMUSG00000025899.
GenevisibleiQ80Y20. MM.

Interactioni

Subunit structurei

Interacts with TRMT112.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061511.

Structurei

3D structure databases

ProteinModelPortaliQ80Y20.
SMRiQ80Y20.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini45 – 120RRMPROSITE-ProRule annotationAdd BLAST76
Domaini220 – 337Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 229Alpha-ketoglutarate bindingBy similarity3
Regioni411 – 664Methyltransferase domainBy similarityAdd BLAST254

Domaini

The Fe2OG dioxygenase domain does not have demethylase activity with methylated nucleotides.1 Publication

Sequence similaritiesi

Belongs to the alkB family.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation
Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1331. Eukaryota.
KOG4176. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00530000063536.
HOGENOMiHOG000007984.
HOVERGENiHBG067234.
InParanoidiQ80Y20.
KOiK10770.
OMAiPCNCSYP.
OrthoDBiEOG091G03UR.
PhylomeDBiQ80Y20.
TreeFamiTF316056.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
3.30.70.330. 1 hit.
3.40.50.150. 2 hits.
InterProiIPR027450. AlkB-like.
IPR015095. AlkB_hom8_N.
IPR032863. ALKBH8.
IPR013216. Methyltransf_11.
IPR012677. Nucleotide-bd_a/b_plait.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR000504. RRM_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR13069:SF28. PTHR13069:SF28. 2 hits.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
SSF54928. SSF54928. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS50102. RRM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80Y20-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNINHKGVLK LTKMEKKFLR KQSKARHVLL KHEGIQAVSY PTQSLVIANG
60 70 80 90 100
GLGNGVSRKQ LLLTLEKCGP VEALLMPPNK PYAFVIFQTI EESKKAYFTL
110 120 130 140 150
NGKEIIDDLG QKIFLYLNFV EKAQWKNMGL EALPPGLLVV EEIISSEEEK
160 170 180 190 200
KLLESVNWTE DTGNQNFQRS LKHRRVKHFG YEFHYESNTV DKDKPLPGGL
210 220 230 240 250
PEVCSSILEK LLKEGYIKHK PDQLTINQYE PGHGIPAHID THSAFEDEII
260 270 280 290 300
SLSLGSAIVM DFKHPEGVTV QVMLPRRSLL VMTGESRYLW THGITPRKFD
310 320 330 340 350
TVQASEQFKG GIITSDIGDL TLSKRGMRTS FTFRKVRRMP CNCSYSSVCD
360 370 380 390 400
RQRKATPPSL TESSKEALEL EQKHVHQVYN EIASHFSSTR HSPWPRIVEF
410 420 430 440 450
LKALPSGSIV ADIGCGNGKY LGINKDLYMI GCDRSQNLVD ICRERQFQAL
460 470 480 490 500
VCDALAVPVR SGSCDACISI AVIHHFATAE RRVEALQELA RLLRPGGQAL
510 520 530 540 550
IYVWAMEQEY KNQKSKYLRG KRISQGDKDE LNSATSTEEF LVNQTPEGVN
560 570 580 590 600
EDPALSVNSS SITKEEEYKS RKVPNSELPI HINRTCFHSQ DVLVPWHLKR
610 620 630 640 650
NPGKDKAIEP SGVAGCPDPS PVFHRYYHVF CDGELEASCQ AVGDVSILQS
660
YYDQGNWCVV LQKV
Length:664
Mass (Da):74,768
Last modified:June 1, 2003 - v1
Checksum:i624A9F48768A903E
GO
Isoform 2 (identifier: Q80Y20-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     199-233: Missing.

Note: No experimental confirmation available.
Show »
Length:629
Mass (Da):70,807
Checksum:iC26A5CE471E6F2E7
GO
Isoform 3 (identifier: Q80Y20-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     123-169: AQWKNMGLEA...EDTGNQNFQR → GTLTLASFNL...DHAVPVGVKG
     170-664: Missing.

Note: No experimental confirmation available.
Show »
Length:169
Mass (Da):18,901
Checksum:i34C66EDBDB5A6527
GO

Sequence cautioni

The sequence BAC38223 differs from that shown. Reason: Frameshift at position 121.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88Q → H in BAC38223 (PubMed:16141072).Curated1
Sequence conflicti132A → T in BAC38223 (PubMed:16141072).Curated1
Sequence conflicti151K → R in BAC38223 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033929123 – 169AQWKN…QNFQR → GTLTLASFNLLFLCEFSSYR ESLSIILYVWEVCAGVLDHA VPVGVKG in isoform 3. 1 PublicationAdd BLAST47
Alternative sequenceiVSP_033930170 – 664Missing in isoform 3. 1 PublicationAdd BLAST495
Alternative sequenceiVSP_033931199 – 233Missing in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK020197 mRNA. Translation: BAB32026.1.
AK081459 mRNA. Translation: BAC38223.1. Frameshift.
AK160783 mRNA. Translation: BAE36007.1.
BC050863 mRNA. Translation: AAH50863.1.
CCDSiCCDS22792.1. [Q80Y20-1]
RefSeqiNP_080579.1. NM_026303.1. [Q80Y20-1]
XP_006509943.1. XM_006509880.3. [Q80Y20-1]
UniGeneiMm.116968.
Mm.440994.

Genome annotation databases

EnsembliENSMUST00000053407; ENSMUSP00000061511; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000165105; ENSMUSP00000125996; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000211933; ENSMUSP00000148653; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000212294; ENSMUSP00000148380; ENSMUSG00000025899. [Q80Y20-2]
GeneIDi67667.
KEGGimmu:67667.
UCSCiuc009oat.1. mouse. [Q80Y20-1]
uc009oau.1. mouse. [Q80Y20-3]
uc012gnj.1. mouse. [Q80Y20-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK020197 mRNA. Translation: BAB32026.1.
AK081459 mRNA. Translation: BAC38223.1. Frameshift.
AK160783 mRNA. Translation: BAE36007.1.
BC050863 mRNA. Translation: AAH50863.1.
CCDSiCCDS22792.1. [Q80Y20-1]
RefSeqiNP_080579.1. NM_026303.1. [Q80Y20-1]
XP_006509943.1. XM_006509880.3. [Q80Y20-1]
UniGeneiMm.116968.
Mm.440994.

3D structure databases

ProteinModelPortaliQ80Y20.
SMRiQ80Y20.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061511.

PTM databases

PhosphoSitePlusiQ80Y20.

Proteomic databases

PaxDbiQ80Y20.
PeptideAtlasiQ80Y20.
PRIDEiQ80Y20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053407; ENSMUSP00000061511; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000165105; ENSMUSP00000125996; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000211933; ENSMUSP00000148653; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000212294; ENSMUSP00000148380; ENSMUSG00000025899. [Q80Y20-2]
GeneIDi67667.
KEGGimmu:67667.
UCSCiuc009oat.1. mouse. [Q80Y20-1]
uc009oau.1. mouse. [Q80Y20-3]
uc012gnj.1. mouse. [Q80Y20-2]

Organism-specific databases

CTDi91801.
MGIiMGI:1914917. Alkbh8.

Phylogenomic databases

eggNOGiKOG1331. Eukaryota.
KOG4176. Eukaryota.
COG3145. LUCA.
GeneTreeiENSGT00530000063536.
HOGENOMiHOG000007984.
HOVERGENiHBG067234.
InParanoidiQ80Y20.
KOiK10770.
OMAiPCNCSYP.
OrthoDBiEOG091G03UR.
PhylomeDBiQ80Y20.
TreeFamiTF316056.

Enzyme and pathway databases

BRENDAi2.1.1.229. 3474.

Miscellaneous databases

PROiQ80Y20.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025899.
GenevisibleiQ80Y20. MM.

Family and domain databases

Gene3Di2.60.120.590. 1 hit.
3.30.70.330. 1 hit.
3.40.50.150. 2 hits.
InterProiIPR027450. AlkB-like.
IPR015095. AlkB_hom8_N.
IPR032863. ALKBH8.
IPR013216. Methyltransf_11.
IPR012677. Nucleotide-bd_a/b_plait.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR000504. RRM_dom.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR13069:SF28. PTHR13069:SF28. 2 hits.
PfamiPF13532. 2OG-FeII_Oxy_2. 1 hit.
PF09004. DUF1891. 1 hit.
PF08241. Methyltransf_11. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
SSF54928. SSF54928. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
PS50102. RRM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB8_MOUSE
AccessioniPrimary (citable) accession number: Q80Y20
Secondary accession number(s): Q3TUG4, Q8BV08, Q9CX44
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.