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AK4 adenylate kinase 4 [ Homo sapiens (human) ]

Gene ID: 205, updated on 5-Mar-2024

Summary

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Official Symbol
AK4provided by HGNC
Official Full Name
adenylate kinase 4provided by HGNC
Primary source
HGNC:HGNC:363
See related
Ensembl:ENSG00000162433 MIM:103030; AllianceGenome:HGNC:363
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AK3; AK 4; AK3L1; AK3L2
Summary
This gene encodes a member of the adenylate kinase family of enzymes. The encoded protein is localized to the mitochondrial matrix. Adenylate kinases regulate the adenine and guanine nucleotide compositions within a cell by catalyzing the reversible transfer of phosphate group among these nucleotides. Five isozymes of adenylate kinase have been identified in vertebrates. Expression of these isozymes is tissue-specific and developmentally regulated. A pseudogene for this gene has been located on chromosome 17. Three transcript variants encoding the same protein have been identified for this gene. Sequence alignment suggests that the gene defined by NM_013410, NM_203464, and NM_001005353 is located on chromosome 1. [provided by RefSeq, Jul 2008]
Annotation information
Note: On Build 36.2, AK3L1 and AK3L2 (GeneID 387851) were annotated at the same location. AK3L2 is defined as a locus on Chr12, which was annotated on Build 36.2 as GeneID 645619 on the reference assembly and 731007 on the Celera assembly. To remove the extra record, GeneID 387851 was merged into GeneID 205, and GeneID 645619 was renamed AK3L2. [13 Feb 2013]
Expression
Biased expression in kidney (RPKM 79.4), liver (RPKM 24.7) and 11 other tissues See more
Orthologs
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Genomic context

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See AK4 in Genome Data Viewer
Location:
1p31.3
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (65147552..65232145)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (65025531..65110134)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (65613235..65697828)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein S24 pseudogene Neighboring gene MPRA-validated peak272 silencer Neighboring gene mitochondrial ribosomal protein S21 pseudogene 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:65605473-65606012 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 965 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:65614416-65615134 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:65615135-65615853 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1141 Neighboring gene NANOG hESC enhancer GRCh37_chr1:65619207-65619708 Neighboring gene ribosomal protein S29 pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1142 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1143 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 968 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 969 Neighboring gene uncharacterized LOC102724416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 970 Neighboring gene DnaJ heat shock protein family (Hsp40) member C6 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:65764980-65765192 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:65769278-65769456 Neighboring gene uncharacterized LOC112268227 Neighboring gene cytochrome c oxidase subunit 6C pseudogene 13

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m(6)A-Based Epitranscriptomic Mechanism. Liu X, et al. Mol Ther, 2020 Dec 2. PMID 32956623, Free PMC Article
  2. AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion. Zhang J, et al. Dis Markers, 2019. PMID 31827645, Free PMC Article
  3. Adenylate kinase 4 promotes bladder cancer cell proliferation and invasion. Xin F, et al. Clin Exp Med, 2019 Nov. PMID 31463832
  4. Crystal structure of human adenylate kinase 4 (L171P) suggests the role of hinge region in protein domain motion. Liu R, et al. Biochem Biophys Res Commun, 2009 Jan 30. PMID 19073142
  5. Report of the committee on the genetic constitution of chromosomes 7, 8, and 9. Oslo Conference (1981): Sixth International Workshop on Human Gene Mapping. Robson EB, et al. Cytogenet Cell Genet, 1982. PMID 7140357

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3.
    Title: MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3.
  2. Adenylate Kinase 4-A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1alpha Signaling Pathways.
    Title: Adenylate Kinase 4-A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1α Signaling Pathways.
  3. Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m(6)A-Based Epitranscriptomic Mechanism.
    Title: Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m(6)A-Based Epitranscriptomic Mechanism.
  4. Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis.
    Title: Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis.
  5. A co-expressed gene status of adenylate kinase 1/4 reveals prognostic gene signature associated with prognosis and sensitivity to EGFR targeted therapy in lung adenocarcinoma.
    Title: A co-expressed gene status of adenylate kinase 1/4 reveals prognostic gene signature associated with prognosis and sensitivity to EGFR targeted therapy in lung adenocarcinoma.
  6. High AK4 expression is associated with Breast Cancer by Facilitating Cell Proliferation and Invasion.
    Title: AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion.
  7. The overexpression of AK4 stabilizes HIF-1alpha protein by increasing intracellular ROS levels and induces epithelial-to-mesenchymal transition in non-small cell lung cancer.
    Title: Adenylate kinase 4 modulates oxidative stress and stabilizes HIF-1α to drive lung adenocarcinoma metastasis.
  8. Study found that AK4 was positively correlated with poor prognosis of bladder cancer (BC) patients. Its knockdown in bladder cancer cell lines inhibited proliferation and invasion and suppressed tumor formation and metastasis in mice. AK4 may therefore represent a potential biomarker for the prognosis of bladder cancer.
    Title: Adenylate kinase 4 promotes bladder cancer cell proliferation and invasion.
  9. Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the osteosarcoma drug resistance.
    Title: MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4.
  10. Results found that AK4 was involved in hypoxia tolerance, resistance to anti-tumor drug, and the regulation of mitochondrial activity.
    Title: Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4.
Submit: New GeneRIF Correction See all GeneRIFs (15)

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

EBI GWAS Catalog

Description
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC166959

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables GTP binding IEA
Inferred from Electronic Annotation
more info
  
NOT enables adenylate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables adenylate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleoside diphosphate kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables nucleoside diphosphate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleoside monophosphate kinase activity TAS
Traceable Author Statement
more info
  
NOT enables nucleoside triphosphate adenylate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleoside triphosphate adenylate kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ADP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in AMP metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in AMP metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ATP metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in GTP metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of cellular response to hypoxia IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to hypoxia IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nucleobase-containing small molecule interconversion TAS
Traceable Author Statement
more info
  
involved_in nucleoside monophosphate phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in nucleoside triphosphate biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of oxidative phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ribonucleoside diphosphate biosynthetic process 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
  
is_active_in mitochondrial matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrial matrix ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
adenylate kinase 4, mitochondrial
Names
ATP-AMP transphosphorylase
GTP:AMP phosphotransferase AK4, mitochondrial
adenylate kinase 3-like 1
adenylate kinase isoenzyme 4, mitochondrial
epididymis secretory sperm binding protein
mitochondrial adenylate kinase-3
nucleoside-triphosphate-adenylate kinase
NP_001005353.1
NP_001317545.1
NP_037542.1
NP_982289.1
XP_016856102.1
XP_047305130.1
XP_054191032.1
XP_054191033.1

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)

  1. NM_001005353.3 → NP_001005353.1  adenylate kinase 4, mitochondrial isoform a

    See identical proteins and their annotated locations for NP_001005353.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a). Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AL356212, BC016180, BG703687, DR003868
    Consensus CDS
    CCDS629.1
    UniProtKB/Swiss-Prot
    B2R927, D3DQ62, P27144, Q6IBH4, Q6NXQ5, Q8IUU9
    UniProtKB/TrEMBL
    A0A384N647
    Related
    ENSP00000378743.2, ENST00000395334.6
    Conserved Domains (1) summary
    pfam00406
    Location:10 → 188
    ADK; Adenylate kinase

  2. NM_001330616.2 → NP_001317545.1  adenylate kinase 4, mitochondrial isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    AC099680, AL356212
    Consensus CDS
    CCDS81340.1
    UniProtKB/TrEMBL
    F8VS11
    Conserved Domains (1) summary
    pfam00406
    Location:1 → 136
    ADK; Adenylate kinase

  3. NM_013410.4 → NP_037542.1  adenylate kinase 4, mitochondrial isoform a

    See identical proteins and their annotated locations for NP_037542.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AL356212, BC040224, DB061266
    Consensus CDS
    CCDS629.1
    UniProtKB/Swiss-Prot
    B2R927, D3DQ62, P27144, Q6IBH4, Q6NXQ5, Q8IUU9
    UniProtKB/TrEMBL
    A0A384N647
    Related
    ENSP00000322175.7, ENST00000327299.8
    Conserved Domains (1) summary
    pfam00406
    Location:10 → 188
    ADK; Adenylate kinase

  4. NM_203464.3 → NP_982289.1  adenylate kinase 4, mitochondrial isoform a

    See identical proteins and their annotated locations for NP_982289.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AL356212, BC016180, BM763432
    Consensus CDS
    CCDS629.1
    UniProtKB/Swiss-Prot
    B2R927, D3DQ62, P27144, Q6IBH4, Q6NXQ5, Q8IUU9
    UniProtKB/TrEMBL
    A0A384N647
    Related
    ENSP00000445912.1, ENST00000545314.5
    Conserved Domains (1) summary
    pfam00406
    Location:10 → 188
    ADK; Adenylate kinase

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

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    65147552..65232145
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017000613.2 → XP_016856102.1  adenylate kinase 4, mitochondrial isoform X1

    UniProtKB/TrEMBL
    F8VS11
    Conserved Domains (1) summary
    pfam00406
    Location:1 → 136
    ADK; Adenylate kinase

  2. XM_047449174.1 → XP_047305130.1  adenylate kinase 4, mitochondrial isoform X1

    UniProtKB/TrEMBL
    F8VS11
    Related
    ENSP00000448458.1, ENST00000546702.5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    65025531..65110134
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054335058.1 → XP_054191033.1  adenylate kinase 4, mitochondrial isoform X1

    UniProtKB/TrEMBL
    F8VS11

  2. XM_054335057.1 → XP_054191032.1  adenylate kinase 4, mitochondrial isoform X1

    UniProtKB/TrEMBL
    F8VS11
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P27144.1 GenPept UniProtKB/Swiss-Prot:P27144

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