Tk2 thymidine kinase 2, mitochondrial [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tk2provided by MGI
Official Full Name: thymidine kinase 2, mitochondrialprovided by MGI
Primary source: MGI:MGI:1913266
See related: Ensembl:ENSMUSG00000035824 AllianceGenome:MGI:1913266
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: mt-TK
Summary: Enables deoxycytidine kinase activity and thymidine kinase activity. Acts upstream of or within deoxyribonucleotide metabolic process and mitochondrial DNA replication. Located in mitochondrial inner membrane. Is active in mitochondrion. Used to study mitochondrial DNA depletion syndrome 2. Human ortholog(s) of this gene implicated in autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions 3 and mitochondrial DNA depletion syndrome 2. Orthologous to human TK2 (thymidine kinase 2). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in adrenal adult (RPKM 16.9), spleen adult (RPKM 13.1) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 D3; 8 53.04 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (104953323..104975224, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (104226691..104248592, complement)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Long term survival and abnormal liver fat accumulation in mice with specific thymidine kinase 2 deficiency in liver tissue.
Title: Long term survival and abnormal liver fat accumulation in mice with specific thymidine kinase 2 deficiency in liver tissue.
thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells
Title: Mitochondrial thymidine kinase 2 but not deoxyguanosine kinase is up-regulated during the stationary growth phase of cultured cells.
Data indicate that long term Dm-dNK ( nucleoside kinase from Drosophila melanogaster) expression rescued thymidine kinase 2 (Tk2)-deficient mice without lethal side effects.
Title: Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.
Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect beta-oxidation.
Title: Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.
TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle
Title: Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.
analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and severe reduction in leptin mRNA
Title: Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.
The down-regulation of Tk1 activity unmasks Tk2 deficiency in Tk2-/- mice and correlates with the onset of mtDNA depletion in the brain and the heart.
Title: Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation.
blood cells are less dependent on mitochondrial Tk2 compared with several other tissues; these cells can synthesize deoxyribonucleotides required for mtDNA replication by alternative pathways such as phosphorylation of thymidine by cytosolic Tk1
Title: Hematopoiesis in the thymidine kinase 2 deficient mouse model of mitochondrial DNA depletion syndrome.
Loss of TK2 activity leads to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain.
Title: Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.
Tk2(-/-) animals showed Tk2 deficiency, unbalanced dNTP pools, mtDNA depletion and defects of respiratory chain enzymes.
Title: Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1)
Targeted (2) 1 citation

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables deoxycytidine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxycytidine kinase activity	ISO Inferred from Sequence Orthology more info
enables deoxynucleoside kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables thymidine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables thymidine kinase activity	ISO Inferred from Sequence Orthology more info
enables thymidine kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in deoxycytidine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in deoxyribonucleoside monophosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within deoxyribonucleotide metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrial DNA metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrial DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thymidine metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial inner membrane	HDA more info	PubMed
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
is_active_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
is_active_in mitochondrion	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: thymidine kinase 2, mitochondrial

Names: 2'-deoxyuridine kinase TK2; deoxycytidine kinase TK2

NP_066356.3

EC 2.7.1.21

EC 2.7.1.74

XP_006531296.1

EC 2.7.1.21

EC 2.7.1.74

XP_006531297.1

EC 2.7.1.21

EC 2.7.1.74

XP_006531298.1

EC 2.7.1.21

EC 2.7.1.74

XP_011246763.1

EC 2.7.1.21

EC 2.7.1.74

XP_017168414.1

EC 2.7.1.21

EC 2.7.1.74

XP_030099561.1

EC 2.7.1.21

EC 2.7.1.74

XP_036010094.1

EC 2.7.1.21

EC 2.7.1.74

XP_036010095.1

EC 2.7.1.21

EC 2.7.1.74

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_021028.3 → NP_066356.3 thymidine kinase 2, mitochondrial precursor

See identical proteins and their annotated locations for NP_066356.3

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes a protein.

Source sequence(s)

AK087557, AV240875

Consensus CDS

CCDS22573.1

UniProtKB/TrEMBL

Q8BN51, Q8VCF9

Related

ENSMUSP00000053616.6, ENSMUST00000050211.7

Conserved Domains (1) summary

pfam01712
Location:58 → 265

dNK; Deoxynucleoside kinase

RNA

NR_045642.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC115718, AK051286, AK087557, AV240875, BY083126

Related

ENSMUST00000211995.2

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000074.7 Reference GRCm39 C57BL/6J

Range

104953323..104975224 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030243701.1 → XP_030099561.1 thymidine kinase 2, mitochondrial isoform X4

Conserved Domains (1) summary

cl17190
Location:26 → 136

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_006531233.5 → XP_006531296.1 thymidine kinase 2, mitochondrial isoform X1

See identical proteins and their annotated locations for XP_006531296.1

UniProtKB/TrEMBL

Q8BN51, Q8VCF9

Related

ENSMUSP00000148642.2, ENSMUST00000212275.2

Conserved Domains (1) summary

pfam01712
Location:58 → 265

dNK; Deoxynucleoside kinase
XM_006531235.4 → XP_006531298.1 thymidine kinase 2, mitochondrial isoform X3

See identical proteins and their annotated locations for XP_006531298.1

Conserved Domains (1) summary

cl17190
Location:2 → 181

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_036154201.1 → XP_036010094.1 thymidine kinase 2, mitochondrial isoform X3

Conserved Domains (1) summary

cl17190
Location:2 → 181

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_006531234.2 → XP_006531297.1 thymidine kinase 2, mitochondrial isoform X3

See identical proteins and their annotated locations for XP_006531297.1

Conserved Domains (1) summary

cl17190
Location:2 → 181

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_011248461.3 → XP_011246763.1 thymidine kinase 2, mitochondrial isoform X4

Conserved Domains (1) summary

cl17190
Location:26 → 136

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_036154202.1 → XP_036010095.1 thymidine kinase 2, mitochondrial isoform X4

Conserved Domains (1) summary

cl17190
Location:26 → 136

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...
XM_017312925.2 → XP_017168414.1 thymidine kinase 2, mitochondrial isoform X2

Conserved Domains (1) summary

cl17190
Location:30 → 192

NK; Nucleoside/nucleotide kinase (NK) is a protein superfamily consisting of multiple families of enzymes that share structural similarity and are functionally related to the catalysis of the reversible phosphate group transfer from nucleoside triphosphates ...