Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria.
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Identifies two PANK2 first-exon isoforms; the isoform with an N-terminal mitochondrial targeting signal localizes to mitochondria (in vitro import + in vivo immunolocalization), and PKAN is attributed to deficiency of the mitochondrial isoform.
"An in vitro import assay and in vivo immunolocalization experiments demonstrate a mitochondrial localization of this isoform."
Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
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Global 14-3-3 (zeta) affinity proteomics; source of the PANK2 IPI to YWHAZ. A broad interactome screen, not a PANK2-focused study.
"This study adds to the growing list of human 14-3-3-binding proteins"
Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2.
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PanK2 is localized to mitochondria of human brain neurons, processed by MPP to a mature 48-kDa protein that catalyzes the initial step of CoA synthesis and shows feedback inhibition by acyl-CoA species; some disease mutations reduce catalytic activity.
"The mature protein catalyzes the initial step in coenzyme A (CoA)"
Biochemical properties of human pantothenate kinase 2 isoforms and mutations linked to pantothenate kinase-associated neurodegeneration.
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Biochemical characterization of human PanK2 isoforms and 14 PKAN mutants; G521R is catalytically dead and misfolds, but many disease mutants retain wild-type activity, indicating catalytic loss is not the sole disease mechanism. PanK2 is extremely sensitive to CoA-thioester feedback inhibition.
"PanK2 was extremely sensitive to feedback inhibition by CoA thioesters (IC50 values between 250 and 500 nM)"
Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine.
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Acetyl-CoA is a competitive inhibitor of purified PanK2 with respect to ATP; palmitoylcarnitine activates PanK2 by antagonizing acetyl-CoA inhibition, coupling CoA synthesis to mitochondrial fatty-acid demand.
"Acetyl-CoA was a competitive inhibitor of purified PanK2 with"
Localization and regulation of mouse pantothenate kinase 2.
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Human PanK2 is mitochondrial whereas mouse PanK2 is cytosolic; the mitochondrial targeting signal was acquired only in primates. Both share acetyl-CoA inhibition and palmitoylcarnitine activation.
"PanK2 is a mitochondrial protein in humans"
Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations.
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Global metabolic profiling of 14 PKAN patients: elevated lactate, elevated pantothenate in premature-stop patients, and downstream defects in bile-acid conjugation and lipid metabolism, consistent with mitochondrial CoA deficiency caused by loss of PANK2 pantothenate kinase activity.
"pantothenate levels are higher in patients with premature stop mutations in PANK2"
Compartmentalization of mammalian pantothenate kinases.
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Human PanK2 localizes to the mitochondrial intermembrane space (by digitonin/protease-protection) and to the nucleus (functional NLS 82-94 and NES 268-275), shuttling nucleus->mitochondria in a cell-cycle-dependent manner; mouse PanK2 is exclusively cytosolic.
"the mature hPanK2 protein was located in the IMS of mitochondria"
Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis.
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PANK2 expression is required for normal angiogenic properties of human umbilical vein endothelial cells; pank2 knockdown perturbs zebrafish vasculature and is rescued by CoA supplementation, indicating the phenotype is a downstream consequence of CoA availability.
"PANK2 expression was required for normal angiogenetic properties of human umbilical vein endothelial cells."
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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Large-scale yeast two-hybrid interactome of neurodegenerative-disease proteins; source of multiple bare protein-binding IPIs for PANK2 isoform Q9BZ23-2.
"systematic yeast two-hybrid interaction screening of"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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High-confidence human mitochondrial proteome; PANK2 is detected as a mitochondrial protein, corroborating its experimental mitochondrial localization.
"We classified >8,000 proteins in mitochondrial preparations of human cells"
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Coenzyme A biosynthesis
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CoA is synthesized from pantothenate in five reactions occurring in the cytosol or mitochondrial intermembrane space; PANK2 catalyzes the first step.
"It is synthesized from the vitamin pantothenate in a sequence of five reactions"
PANK2 phosphorylates PanK
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PANK2 catalyzes the reaction of ATP and pantothenate to form ADP and phosphopantothenate; the enzyme is modeled in the mitochondrial intermembrane space and negatively regulated by CoA.
"Pantothenate kinase 2 (PANK2) catalyzes the reaction of ATP and pantothenate to form ADP and phosphopantothenate."