Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Structure and expression of human mitochondrial adenylate kinase targeted to the mitochondrial matrix.
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Overexpressed AK3, but not AK4, gave GTP:AMP phosphotransferase activity and complemented a temperature-sensitive E. coli adenylate kinase mutant.
"Over expression of AK3, but not AK4"
Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase.
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AK4 is inactive as an adenylate kinase in vitro because Gln159 replaces a conserved active-site arginine; Q159R restores activity with GTP.
"Mutation of the glutamine residue to arginine (Q159R) restored the adenylate kinase activity"
Evidence of an intact N-terminal translocation sequence of human mitochondrial adenylate kinase 4.
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Recombinant AK4 phosphorylated AMP, dAMP, CMP and dCMP with ATP or GTP as donors, contrary to the earlier reports of no activity.
"The enzyme catalyzed the phosphorylation of AMP, dAMP, CMP and dCMP with ATP or GTP as phosphate donors"
Long-read cDNA sequencing identifies functional pseudogenes in the human transcriptome.
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AK4P3 is one of four spliced pseudogenes whose intact ORFs were amplified from human cDNA and cloned - so the locus is genuinely transcribed, not merely predicted.
"we amplified the 5′ exons and coding sequence of four spliced pseudogenes with intact ORFs (HMGB1P1, AK4P3, IFITM3P2 and RPL13AP20) and cloned them into a vector with a C-terminus 3XHA tag"
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The AK4P3 ORF is translation-competent: a tagged construct produced detectable protein in HEK293T cells.
"Transfection into HEK293T cells resulted in clear translation of the HMGB1P1 and AK4P3 transcripts"
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The figure legend states the result plainly, and equally plainly scopes it to cultured cells rather than endogenous expression.
"HMGB1P1 and AK4P3 are translated when expressed in cultured cells."
Is human AK4P3 an over-annotated pseudogene, or a functional AK4 duplicate?
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The AK4P3 ORF is 99.1% identical to AK4, differing at two conservative positions.
"| Identity to AK4 | **221/223 (99.1%)** |"
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The catalytic Walker A P-loop is intact and at the same position in both.
"| Catalytic P-loop (Walker A) | `GPPGSGK` at position 12 — **intact in both** |"
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Nothing in the protein sequence marks this locus as pseudogenised.
"The sequence gives no evidence of pseudogenisation at the protein level."
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Two fully tryptic peptides are unique to AK4P3, so the PE=1 protein-level claim is in principle attributable rather than necessarily a paralog misassignment.
"**The PE=1 is checkable, which is the useful part.**"
UniProtKB A0A8I5KW96 (AK4P3, unreviewed) flat file
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UniProt assigns protein-existence level 1, evidence at protein level, to this unreviewed entry.
"PE 1: Evidence at protein level;"
Falcon deep research report for human AK4P3
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The report's summary verdict, which this review adopts.
"Human transcribed AK4-related pseudogene with an intact, translation-competent ORF; putative adenylate-kinase-family protein whose catalytic function and localization remain unvalidated."
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It states precisely what the transcription evidence does not establish.
"It does **not** establish endogenous protein production, enzymatic activity, substrate specificity, mitochondrial localization, pathway membership, disease causality, or physiological function."