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Protein

Alkylated DNA repair protein alkB homolog 8

Gene

ALKBH8

Organism
Homo sapiens (Human)
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, PubMed:20308323). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). 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:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182).4 Publications

Catalytic activityi

S-adenosyl-L-methionine + carboxymethyluridine(34) in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine(34) in tRNA.1 Publication

Cofactori

Fe2+1 Publication1 PublicationNote: Binds 1 Fe2+ ion per subunit.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi238Iron; catalyticPROSITE-ProRule annotationCurated1
Metal bindingi240Iron; catalyticPROSITE-ProRule annotationCurated1
Metal bindingi242Zinc; via pros nitrogen1 Publication1
Metal bindingi292Iron; catalyticPROSITE-ProRule annotationCurated1
Binding sitei328Alpha-ketoglutarate1 Publication1
Binding sitei334Alpha-ketoglutarate1 Publication1
Metal bindingi341Zinc1 Publication1
Metal bindingi343Zinc1 Publication1
Metal bindingi349Zinc1 Publication1

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

BioCyciZFISH:ENSG00000137760-MONOMER.
BRENDAi2.1.1.229. 2681.
ReactomeiR-HSA-6782315. tRNA modification in the nucleus and cytosol.

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:2.1.1.229)
Gene namesi
Name:ALKBH8
Synonyms:ABH8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:25189. ALKBH8.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • microtubule cytoskeleton Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi91801.
OpenTargetsiENSG00000137760.
PharmGKBiPA143485296.

Polymorphism and mutation databases

BioMutaiALKBH8.
DMDMi189027650.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003371251 – 664Alkylated DNA repair protein alkB homolog 8Add BLAST664

Proteomic databases

EPDiQ96BT7.
MaxQBiQ96BT7.
PaxDbiQ96BT7.
PeptideAtlasiQ96BT7.
PRIDEiQ96BT7.

PTM databases

iPTMnetiQ96BT7.
PhosphoSitePlusiQ96BT7.

Expressioni

Tissue specificityi

Widely expressed, with highest expression in spleen, followed by pancreas and lung.1 Publication

Inductioni

Up-regulated after DNA damage. Induction is mediated via ATM.1 Publication

Gene expression databases

BgeeiENSG00000137760.
CleanExiHS_ALKBH8.
ExpressionAtlasiQ96BT7. baseline and differential.
GenevisibleiQ96BT7. HS.

Organism-specific databases

HPAiHPA038724.
HPA038725.
HPA061514.

Interactioni

Subunit structurei

Interacts with TRMT112.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TRMT112Q9UI305EBI-10825637,EBI-373326

Protein-protein interaction databases

BioGridi124880. 3 interactors.
IntActiQ96BT7. 11 interactors.
STRINGi9606.ENSP00000374219.

Structurei

Secondary structure

1664
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 28Combined sources3
Turni30 – 34Combined sources5
Beta strandi38 – 40Combined sources3
Beta strandi43 – 48Combined sources6
Helixi52 – 54Combined sources3
Helixi58 – 66Combined sources9
Beta strandi71 – 75Combined sources5
Beta strandi81 – 89Combined sources9
Helixi90 – 99Combined sources10
Turni100 – 102Combined sources3
Beta strandi104 – 106Combined sources3
Beta strandi112 – 114Combined sources3
Beta strandi116 – 119Combined sources4
Beta strandi121 – 129Combined sources9
Beta strandi137 – 140Combined sources4
Helixi146 – 153Combined sources8
Beta strandi175 – 177Combined sources3
Helixi202 – 214Combined sources13
Beta strandi222 – 229Combined sources8
Beta strandi235 – 238Combined sources4
Turni242 – 244Combined sources3
Beta strandi249 – 256Combined sources8
Beta strandi258 – 263Combined sources6
Beta strandi269 – 274Combined sources6
Beta strandi278 – 282Combined sources5
Helixi285 – 288Combined sources4
Beta strandi290 – 294Combined sources5
Beta strandi298 – 304Combined sources7
Beta strandi307 – 309Combined sources3
Beta strandi315 – 318Combined sources4
Beta strandi320 – 324Combined sources5
Beta strandi328 – 334Combined sources7
Turni346 – 348Combined sources3
Turni350 – 355Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CQ2NMR-A25-125[»]
3THPX-ray3.20A25-355[»]
3THTX-ray3.01A/B/C/D25-355[»]
ProteinModelPortaliQ96BT7.
SMRiQ96BT7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96BT7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 120RRMAdd BLAST78
Domaini220 – 337Fe2OG dioxygenasePROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 229Alpha-ketoglutarate binding1 Publication3
Regioni411 – 664Methyltransferase domainAdd BLAST254

Sequence similaritiesi

Belongs to the alkB family.Curated
Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1331. Eukaryota.
KOG4176. Eukaryota.
COG0500. LUCA.
COG3145. LUCA.
GeneTreeiENSGT00530000063536.
HOGENOMiHOG000007984.
HOVERGENiHBG067234.
InParanoidiQ96BT7.
KOiK10770.
OMAiPCNCSYP.
OrthoDBiEOG091G03UR.
PhylomeDBiQ96BT7.
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.
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.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
SSF54928. SSF54928. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96BT7-1) [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
MDSNHQSNYK LSKTEKKFLR KQIKAKHTLL RHEGIETVSY ATQSLVVANG
60 70 80 90 100
GLGNGVSRNQ LLPVLEKCGL VDALLMPPNK PYSFARYRTT EESKRAYVTL
110 120 130 140 150
NGKEVVDDLG QKITLYLNFV EKVQWKELRP QALPPGLMVV EEIISSEEEK
160 170 180 190 200
MLLESVDWTE DTDNQNSQKS LKHRRVKHFG YEFHYENNNV DKDKPLSGGL
210 220 230 240 250
PDICESFLEK WLRKGYIKHK PDQMTINQYE PGQGIPAHID THSAFEDEIV
260 270 280 290 300
SLSLGSEIVM DFKHPDGIAV PVMLPRRSLL VMTGESRYLW THGITCRKFD
310 320 330 340 350
TVQASESLKS GIITSDVGDL TLSKRGLRTS FTFRKVRQTP CNCSYPLVCD
360 370 380 390 400
SQRKETPPSF PESDKEASRL EQEYVHQVYE EIAGHFSSTR HTPWPHIVEF
410 420 430 440 450
LKALPSGSIV ADIGCGNGKY LGINKELYMI GCDRSQNLVD ICRERQFQAF
460 470 480 490 500
VCDALAVPVR SGSCDACISI AVIHHFATAE RRVAALQEIV RLLRPGGKAL
510 520 530 540 550
IYVWAMEQEY NKQKSKYLRG NRNSQGKKEE MNSDTSVQRS LVEQMRDMGS
560 570 580 590 600
RDSASSVPRI NDSQEGGCNS RQVSNSKLPV HVNRTSFYSQ DVLVPWHLKG
610 620 630 640 650
NPDKGKPVEP FGPIGSQDPS PVFHRYYHVF REGELEGACR TVSDVRILQS
660
YYDQGNWCVI LQKA
Length:664
Mass (Da):75,208
Last modified:May 20, 2008 - v2
Checksum:i4BE595D6757C2A43
GO
Isoform 2 (identifier: Q96BT7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     234-238: GIPAH → DCHGF
     239-664: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:238
Mass (Da):27,440
Checksum:i24EF6A3A66DCC2F7
GO
Isoform 3 (identifier: Q96BT7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     215-224: GYIKHKPDQM → AEKNLEVGIH
     225-664: Missing.

Note: No experimental confirmation available.
Show »
Length:224
Mass (Da):25,742
Checksum:i6FD66E832509EE87
GO
Isoform 4 (identifier: Q96BT7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MFAM

Note: May be due to competing donor splice site. No experimental confirmation available.
Show »
Length:667
Mass (Da):75,558
Checksum:iBF6DB408A2B1B39C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti210K → R in BAC04566 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0391591M → MFAM in isoform 4. 1 Publication1
Alternative sequenceiVSP_033925215 – 224GYIKHKPDQM → AEKNLEVGIH in isoform 3. 1 Publication10
Alternative sequenceiVSP_033926225 – 664Missing in isoform 3. 1 PublicationAdd BLAST440
Alternative sequenceiVSP_033927234 – 238GIPAH → DCHGF in isoform 2. 1 Publication5
Alternative sequenceiVSP_033928239 – 664Missing in isoform 2. 1 PublicationAdd BLAST426

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB218768 mRNA. Translation: BAG16270.1.
AK095523 mRNA. Translation: BAC04566.1.
AK293603 mRNA. Translation: BAG57067.1.
AK304413 mRNA. Translation: BAG65244.1.
AP001823 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67089.1.
CH471065 Genomic DNA. Translation: EAW67090.1.
BC015183 mRNA. Translation: AAH15183.1.
CCDSiCCDS73376.1. [Q96BT7-4]
CCDS8337.2. [Q96BT7-1]
RefSeqiNP_001287939.1. NM_001301010.1. [Q96BT7-4]
NP_620130.2. NM_138775.2. [Q96BT7-1]
UniGeneiHs.503763.

Genome annotation databases

EnsembliENST00000260318; ENSP00000260318; ENSG00000137760. [Q96BT7-2]
ENST00000389568; ENSP00000374219; ENSG00000137760. [Q96BT7-1]
ENST00000417449; ENSP00000397673; ENSG00000137760. [Q96BT7-4]
ENST00000428149; ENSP00000415885; ENSG00000137760. [Q96BT7-1]
ENST00000429370; ENSP00000391225; ENSG00000137760. [Q96BT7-3]
GeneIDi91801.
KEGGihsa:91801.
UCSCiuc009yxp.4. human. [Q96BT7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB218768 mRNA. Translation: BAG16270.1.
AK095523 mRNA. Translation: BAC04566.1.
AK293603 mRNA. Translation: BAG57067.1.
AK304413 mRNA. Translation: BAG65244.1.
AP001823 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67089.1.
CH471065 Genomic DNA. Translation: EAW67090.1.
BC015183 mRNA. Translation: AAH15183.1.
CCDSiCCDS73376.1. [Q96BT7-4]
CCDS8337.2. [Q96BT7-1]
RefSeqiNP_001287939.1. NM_001301010.1. [Q96BT7-4]
NP_620130.2. NM_138775.2. [Q96BT7-1]
UniGeneiHs.503763.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CQ2NMR-A25-125[»]
3THPX-ray3.20A25-355[»]
3THTX-ray3.01A/B/C/D25-355[»]
ProteinModelPortaliQ96BT7.
SMRiQ96BT7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124880. 3 interactors.
IntActiQ96BT7. 11 interactors.
STRINGi9606.ENSP00000374219.

PTM databases

iPTMnetiQ96BT7.
PhosphoSitePlusiQ96BT7.

Polymorphism and mutation databases

BioMutaiALKBH8.
DMDMi189027650.

Proteomic databases

EPDiQ96BT7.
MaxQBiQ96BT7.
PaxDbiQ96BT7.
PeptideAtlasiQ96BT7.
PRIDEiQ96BT7.

Protocols and materials databases

DNASUi91801.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260318; ENSP00000260318; ENSG00000137760. [Q96BT7-2]
ENST00000389568; ENSP00000374219; ENSG00000137760. [Q96BT7-1]
ENST00000417449; ENSP00000397673; ENSG00000137760. [Q96BT7-4]
ENST00000428149; ENSP00000415885; ENSG00000137760. [Q96BT7-1]
ENST00000429370; ENSP00000391225; ENSG00000137760. [Q96BT7-3]
GeneIDi91801.
KEGGihsa:91801.
UCSCiuc009yxp.4. human. [Q96BT7-1]

Organism-specific databases

CTDi91801.
DisGeNETi91801.
GeneCardsiALKBH8.
HGNCiHGNC:25189. ALKBH8.
HPAiHPA038724.
HPA038725.
HPA061514.
MIMi613306. gene.
neXtProtiNX_Q96BT7.
OpenTargetsiENSG00000137760.
PharmGKBiPA143485296.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1331. Eukaryota.
KOG4176. Eukaryota.
COG0500. LUCA.
COG3145. LUCA.
GeneTreeiENSGT00530000063536.
HOGENOMiHOG000007984.
HOVERGENiHBG067234.
InParanoidiQ96BT7.
KOiK10770.
OMAiPCNCSYP.
OrthoDBiEOG091G03UR.
PhylomeDBiQ96BT7.
TreeFamiTF316056.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137760-MONOMER.
BRENDAi2.1.1.229. 2681.
ReactomeiR-HSA-6782315. tRNA modification in the nucleus and cytosol.

Miscellaneous databases

ChiTaRSiALKBH8. human.
EvolutionaryTraceiQ96BT7.
GenomeRNAii91801.
PROiQ96BT7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137760.
CleanExiHS_ALKBH8.
ExpressionAtlasiQ96BT7. baseline and differential.
GenevisibleiQ96BT7. HS.

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.
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.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
SSF54928. SSF54928. 1 hit.
PROSITEiPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALKB8_HUMAN
AccessioniPrimary (citable) accession number: Q96BT7
Secondary accession number(s): B1Q2M0, B4DEF6, Q8N989
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.