protein
Adenylate kinase 4, mitochondrial
Gene
AK4
Organism
Homo sapiens(9606)
Length
223 aa
Mass
25,268 Da
Adenylate kinase 4 (AK4) is a mitochondrial nucleoside phosphate kinase that catalyzes phosphorylation of nucleoside monophosphates, particularly AMP, to maintain cellular nucleotide homeostasis (UniProt: P27144). The enzyme also exhibits diphosphate kinase activity and plays a protective role in oxidative stress responses by regulating activation of the energy sensor AMPK. AK4 is localized to mitochondria, where it influences cellular ATP levels and energy metabolism.
AK4 shows downregulation in Alzheimer's Disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain compared to age-matched controls detected a mean log2 fold-change of −0.31 across subcellular fractions, indicating reduced AK4 abundance in AD (Chaparral AD proteomics). This downregulation may reflect impaired mitochondrial energy metabolism and nucleotide homeostasis in the AD brain, processes critical for neuronal function and stress resilience.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.309
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3094 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
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Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Broad-specificity mitochondrial nucleoside phosphate kinase involved in cellular nucleotide homeostasis by catalyzing nucleoside-phosphate interconversions (PubMed:19073142, PubMed:19766732, PubMed:23416111, PubMed:24767988). Similar to other adenylate kinases, preferentially catalyzes the phosphorylation of the nucleoside monophosphate AMP with ATP as phosphate donor to produce ADP (PubMed:19766732). Phosphorylates only AMP when using GTP as phosphate donor (PubMed:19766732). In vitro, can also catalyze the phosphorylation of CMP, dAMP and dCMP and use GTP as an alternate phosphate donor (PubMed:19766732, PubMed:23416111). Moreover, exhibits a diphosphate kinase activity, producing ATP, CTP, GTP, UTP, TTP, dATP, dCTP and dGTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donors (PubMed:23416111). Plays a role in controlling cellular ATP levels by regulating phosphorylation and activation of the energy sensor protein kinase AMPK (PubMed:24767988, PubMed:26980435). Plays a protective role in the cellular response to oxidative stress (PubMed:19130895, PubMed:23474458, PubMed:26980435)
Sources
Last updated 5/8/2026, 6:35:17 AM