PANK2

This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms.

pantothenate kinase 2

Isoform 1
Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150).
Required for angiogenic activity of umbilical vein of endothelial cells (HUVEC) (PubMed:30221726).
Isoform 4
Cytoplasmic isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.

Aerobic respirationIEA:Ensembl
AngiogenesisManual Assertion Based On ExperimentIMP:UniProtKB
Coenzyme A biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Mitochondrion morphogenesisIEA:Ensembl
Pantothenate metabolic process1 PublicationNAS:ParkinsonsUK-UCL
Phosphorylation1 PublicationNAS:ParkinsonsUK-UCL
Regulation of bile acid metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of fatty acid metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Regulation of mitochondrial membrane potentialIEA:Ensembl
Regulation of triglyceride metabolic processManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Spermatid developmentIEA:Ensembl

Isoform 1
Mitochondrion
Mitochondrion intermembrane space
Nucleus
Localizes predominantly to the mitochondria and to a lesser extent to the nucleus. Found in both the mitochondria and the nucleus throughout the cell cycle, with the exception of the G2/M phase when it is restricted to mitochdondria.
Isoform 2
Cytoplasm
Isoform 3
Cytoplasm
Isoform 4
Cytoplasm

Neurodegeneration with brain iron accumulation 1 (NBIA1):
Autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. Clinical manifestations include progressive muscle spasticity, hyperreflexia, muscle rigidity, dystonia, dysarthria, and intellectual deterioration which progresses to severe dementia over several years. It is clinically classified into classic, atypical, and intermediate phenotypes. Classic forms present with onset in first decade, rapid progression, loss of independent ambulation within 15 years. Atypical forms have onset in second decade, slow progression, maintenance of independent ambulation up to 40 years later. Intermediate forms manifest onset in first decade with slow progression or onset in second decade with rapid progression. Patients with early onset tend to also develop pigmentary retinopathy, whereas those with later onset tend to also have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI.
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP):
Rare syndrome with many clinical similarities to PKAN.

Synthesized as a 62-kDa precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 59-kDa intermediate to yield the mature mitochondrial 48-kDa subunit.