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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi238 – 2381Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi240 – 2401Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi242 – 2421Zinc; via pros nitrogenBy similarity
Metal bindingi292 – 2921Iron; catalyticPROSITE-ProRule annotation
Binding sitei328 – 3281Alpha-ketoglutarateBy similarity
Binding sitei334 – 3341Alpha-ketoglutarateBy similarity
Metal bindingi341 – 3411ZincBy similarity
Metal bindingi343 – 3431ZincBy similarity
Metal bindingi349 – 3491ZincBy similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi238 – 2381H → A: Abolishes hydroxylation of 5-methylcarboxymethyl uridine. 1 Publication
Mutagenesisi240 – 2401D → A: Abolishes hydroxylation of 5-methylcarboxymethyl uridine. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 664664Alkylated DNA repair protein alkB homolog 8PRO_0000337127Add
BLAST

Proteomic databases

EPDiQ80Y20.
MaxQBiQ80Y20.
PaxDbiQ80Y20.
PeptideAtlasiQ80Y20.
PRIDEiQ80Y20.

PTM databases

PhosphoSiteiQ80Y20.

Expressioni

Gene expression databases

BgeeiQ80Y20.
GenevisibleiQ80Y20. MM.

Interactioni

Subunit structurei

Interacts with TRMT112.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061511.

Structurei

3D structure databases

ProteinModelPortaliQ80Y20.
SMRiQ80Y20. Positions 23-354, 406-545.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini45 – 12076RRMPROSITE-ProRule annotationAdd
BLAST
Domaini220 – 337118Fe2OG dioxygenasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni227 – 2293Alpha-ketoglutarate bindingBy similarity
Regioni411 – 664254Methyltransferase domainBy similarityAdd
BLAST

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.
OrthoDBiEOG780RMC.
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 BAC38223.1 differs from that shown. Reason: Frameshift at position 121. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti88 – 881Q → H in BAC38223 (PubMed:16141072).Curated
Sequence conflicti132 – 1321A → T in BAC38223 (PubMed:16141072).Curated
Sequence conflicti151 – 1511K → R in BAC38223 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei123 – 16947AQWKN…QNFQR → GTLTLASFNLLFLCEFSSYR ESLSIILYVWEVCAGVLDHA VPVGVKG in isoform 3. 1 PublicationVSP_033929Add
BLAST
Alternative sequencei170 – 664495Missing in isoform 3. 1 PublicationVSP_033930Add
BLAST
Alternative sequencei199 – 23335Missing in isoform 2. 1 PublicationVSP_033931Add
BLAST

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_006509880.2. [Q80Y20-1]
UniGeneiMm.116968.
Mm.440994.

Genome annotation databases

EnsembliENSMUST00000053407; ENSMUSP00000061511; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000165105; ENSMUSP00000125996; ENSMUSG00000025899. [Q80Y20-1]
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_006509880.2. [Q80Y20-1]
UniGeneiMm.116968.
Mm.440994.

3D structure databases

ProteinModelPortaliQ80Y20.
SMRiQ80Y20. Positions 23-354, 406-545.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061511.

PTM databases

PhosphoSiteiQ80Y20.

Proteomic databases

EPDiQ80Y20.
MaxQBiQ80Y20.
PaxDbiQ80Y20.
PeptideAtlasiQ80Y20.
PRIDEiQ80Y20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053407; ENSMUSP00000061511; ENSMUSG00000025899. [Q80Y20-1]
ENSMUST00000165105; ENSMUSP00000125996; ENSMUSG00000025899. [Q80Y20-1]
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.
OrthoDBiEOG780RMC.
PhylomeDBiQ80Y20.
TreeFamiTF316056.

Enzyme and pathway databases

BRENDAi2.1.1.229. 3474.

Miscellaneous databases

PROiQ80Y20.
SOURCEiSearch...

Gene expression databases

BgeeiQ80Y20.
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...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Strain: C57BL/6J.
    Tissue: Head and Testis.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Embryo.
  3. "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. 49:8885-8888(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, COFACTOR, LACK OF DEMETHYLASE ACTIVITY, DOMAIN, MUTAGENESIS OF HIS-238 AND ASP-240.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.
  5. "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 C.B., Kristoffersen T., Krokan H.E., Kirpekar F., Falnes P.O., Klungland A.
    Mol. Cell. Biol. 30:1814-1827(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.

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: July 6, 2016
This is version 108 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.