protein
GTP:AMP phosphotransferase AK3, mitochondrial
Gene
AK3
Organism
Homo sapiens(9606)
Length
227 aa
Mass
25,565 Da
AK3 is a mitochondrial adenylate kinase that catalyzes GTP:AMP phosphotransferase activity, recycling GTP into GDP within the mitochondrial matrix to support the TCA cycle (UniProt: Q9UIJ7). The enzyme can also utilize ITP as an alternative phosphate donor and is localized to the mitochondria where energy metabolism is tightly regulated.
AK3 expression is upregulated in Alzheimer's Disease brain tissue. Analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) revealed increased AK3 levels with a mean log2 fold-change of 0.30 (Chaparral AD proteomics). This upregulation may reflect compensatory metabolic responses to mitochondrial dysfunction observed in AD pathology.
The functional role of AK3 in mitochondrial energy metabolism suggests its upregulation could represent an attempt to sustain ATP and GTP production under the bioenergetic stress characteristic of Alzheimer's Disease neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
not detected
S3
+0.296
Mean log₂FC across detected fractions: +0.2963 (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
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
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
Mitochondrial adenylate kinase with a specific GTP:AMP phosphotransferase activity (PubMed:11485571, PubMed:32822537). Could also use ITP as phosphate donor (PubMed:11485571). Its physiological function is to recycle GTP into GDP which is necessary for the TCA cycle in the mitochondrial matrix (Probable)
Sources
Last updated 5/8/2026, 6:35:22 AM