ALKBH8 alkB homolog 8, tRNA methyltransferase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALKBH8provided by HGNC
Official Full Name: alkB homolog 8, tRNA methyltransferaseprovided by HGNC
Primary source: HGNC:HGNC:25189
See related: Ensembl:ENSG00000137760 MIM:613306; AllianceGenome:HGNC:25189
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ABH8; TRM9; MRT71; TRMT9; TRMT9A
Summary: Enables tRNA (uracil) methyltransferase activity; tRNA binding activity; and zinc ion binding activity. Involved in cellular response to DNA damage stimulus; tRNA methylation; and tRNA wobble uridine modification. Located in cytosol and nuclear body. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in thyroid (RPKM 3.3), lymph node (RPKM 3.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q22.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (107502727..107565735, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (107509865..107572838, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (107373453..107436461, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.
Title: The first Turkish family with a novel biallelic missense variant of the ALKBH8 gene: A study on the clinical and variant spectrum of ALKBH8-related intellectual developmental disorders.
HITS-CLIP analysis of human ALKBH8 reveals interactions with fully processed substrate tRNAs and with specific noncoding RNAs.
Title: HITS-CLIP analysis of human ALKBH8 reveals interactions with fully processed substrate tRNAs and with specific noncoding RNAs.
Insight into ALKBH8-related intellectual developmental disability based on the first pathogenic missense variant.
Title: Insight into ALKBH8-related intellectual developmental disability based on the first pathogenic missense variant.
Neurodevelopmental disorder in an Egyptian family with a biallelic ALKBH8 variant.
Title: Neurodevelopmental disorder in an Egyptian family with a biallelic ALKBH8 variant.
Loss of epitranscriptomic control of selenocysteine utilization engages senescence and mitochondrial reprogramming().
Title: Loss of epitranscriptomic control of selenocysteine utilization engages senescence and mitochondrial reprogramming(☆).
Recessive Truncating Mutations in ALKBH8 Cause Intellectual Disability and Severe Impairment of Wobble Uridine Modification.
Title: Recessive Truncating Mutations in ALKBH8 Cause Intellectual Disability and Severe Impairment of Wobble Uridine Modification.
findings suggest that the high expression of ALKBH8 is critical for the growth and progression of bladder cancer
Title: ALKBH8 promotes bladder cancer growth and progression through regulating the expression of survivin.
Many eukaryotic tRNAs contain the wobble modification 5-methoxycarbonylmethyl-uridine (mcm5U). It is demonstrated that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U), hydroxylated forms of mcm(5)U, are present in mammalian tRNA-Arg(UCG), and tRNA-Gly(UCC), respectively. It is shown that the hydroxylation reaction leading to the formation of (S)-mchm5U is catalyzed by the oxygenase (AlkB) domain of ALKBH8.
Title: ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA.
The methyltransferase domain of ALKBH8 is demonstrated to be a functional homologue of the Saccharomyces cerevisiae Trm9 protein, mediating the last step in the formation of the wobble uridine modification 5-methoxycarbonylmethyl-uridine in tRNA. This modification is shown to be important for efficient selenoprotein synthesis. ALKBH8 knock-out mice are generated and described.
Title: Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.
Data show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5)U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival.
Title: Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual developmental disorder, autosomal recessive 71 MedGen: C5193133 OMIM: 618504 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of alkB, alkylation repair homolog 8 (ALKBH8) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G66900 (e-PCR)
- UniSTS:166969

D11S3957 (e-PCR)
- UniSTS:153666

G17588 (e-PCR)
- UniSTS:63816

D11S4571 (e-PCR)
- UniSTS:59005

RH93706 (e-PCR)
- UniSTS:86497

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 2-oxoglutarate-dependent dioxygenase activity	IEA Inferred from Electronic Annotation more info
enables S-adenosylmethionine-dependent methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables iron ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tRNA (5-carboxymethyluridine(34)-5-O)-methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables tRNA (uridine) methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables tRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables tRNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in tRNA methylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in tRNA methylation	IDA Inferred from Direct Assay more info	PubMed
involved_in tRNA methylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tRNA wobble uridine modification	IBA Inferred from Biological aspect of Ancestor more info
involved_in tRNA wobble uridine modification	IDA Inferred from Direct Assay more info	PubMed
involved_in tRNA wobble uridine modification	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: alkylated DNA repair protein alkB homolog 8

Names: AlkB homologue 8; S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8; alkB, alkylation repair homolog 8; probable alpha-ketoglutarate-dependent dioxygenase ABH8; tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ABH8; tRNA methyltransferase 9 homolog; tRNA methyltransferase 9 related

NP_001287939.2

EC 2.1.1.229

NP_001365062.1

EC 2.1.1.229

NP_620130.2

EC 2.1.1.229

XP_016874046.1

EC 2.1.1.229

XP_047283826.1

EC 2.1.1.229

XP_047283827.1

EC 2.1.1.229

XP_054226479.1

EC 2.1.1.229

XP_054226480.1

EC 2.1.1.229

XP_054226481.1

EC 2.1.1.229

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001301010.3 → NP_001287939.2 alkylated DNA repair protein alkB homolog 8 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 both encode the same isoform (1).

Source sequence(s)

AP001823

Consensus CDS

CCDS8337.2

UniProtKB/Swiss-Prot

B1Q2M0, B4DEF6, Q8N989, Q96BT7

Related

ENSP00000397673.3, ENST00000417449.6

Conserved Domains (4) summary

pfam09004
Location:1 → 37

DUF1891; Domain of unknown function (DUF1891)

pfam13649
Location:410 → 497

Methyltransf_25; Methyltransferase domain

cd12431
Location:42 → 122

RRM_ALKBH8; RNA recognition motif (RRM) found in alkylated DNA repair protein alkB homolog 8 (ALKBH8) and similar proteins

cl21496
Location:152 → 334

2OG-FeII_Oxy; 2OG-Fe(II) oxygenase superfamily
NM_001378133.1 → NP_001365062.1 alkylated DNA repair protein alkB homolog 8 isoform 3

Status: VALIDATED

Source sequence(s)

AP001823

Conserved Domains (3) summary

pfam09004
Location:1 → 37

DUF1891; Domain of unknown function (DUF1891)

cd12431
Location:42 → 122

RRM_ALKBH8; RNA recognition motif (RRM) found in alkylated DNA repair protein alkB homolog 8 (ALKBH8) and similar proteins

cl21496
Location:152 → 334

2OG-FeII_Oxy; 2OG-Fe(II) oxygenase superfamily
NM_138775.3 → NP_620130.2 alkylated DNA repair protein alkB homolog 8 isoform 1

See identical proteins and their annotated locations for NP_620130.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 both encode the same isoform (1).

Source sequence(s)

AB218768, AP001823, BX649085

Consensus CDS

CCDS8337.2

UniProtKB/Swiss-Prot

B1Q2M0, B4DEF6, Q8N989, Q96BT7

Related

ENSP00000415885.2, ENST00000428149.7

Conserved Domains (4) summary

pfam09004
Location:1 → 37

DUF1891; Domain of unknown function (DUF1891)

pfam13649
Location:410 → 497

Methyltransf_25; Methyltransferase domain

cd12431
Location:42 → 122

RRM_ALKBH8; RNA recognition motif (RRM) found in alkylated DNA repair protein alkB homolog 8 (ALKBH8) and similar proteins

cl21496
Location:152 → 334

2OG-FeII_Oxy; 2OG-Fe(II) oxygenase superfamily

RNA

NR_165421.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823
NR_165422.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823
NR_165423.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823
NR_165424.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823
NR_165425.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823
NR_165426.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AP001823

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

107502727..107565735 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047427870.1 → XP_047283826.1 alkylated DNA repair protein alkB homolog 8 isoform X1
XM_047427871.1 → XP_047283827.1 alkylated DNA repair protein alkB homolog 8 isoform X3
XM_017018557.2 → XP_016874046.1 alkylated DNA repair protein alkB homolog 8 isoform X2

Conserved Domains (3) summary

pfam09004
Location:4 → 40

DUF1891; Domain of unknown function (DUF1891)

cd12431
Location:45 → 125

RRM_ALKBH8; RNA recognition motif in alkylated DNA repair protein alkB homolog 8 (ALKBH8) and similar proteins

cl21496
Location:155 → 337

2OG-FeII_Oxy; 2OG-Fe(II) oxygenase superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

107509865..107572838 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370504.1 → XP_054226479.1 alkylated DNA repair protein alkB homolog 8 isoform X1
XM_054370506.1 → XP_054226481.1 alkylated DNA repair protein alkB homolog 8 isoform X3
XM_054370505.1 → XP_054226480.1 alkylated DNA repair protein alkB homolog 8 isoform X2