Pantothenate kinase 2, mitochondrial (PANK2)
The protein contains 570 amino acids for an estimated molecular weight of 62681 Da.
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).Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis. (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Aerobic respiration
Angiogenesis
Coenzyme A biosynthetic process
Mitochondrion morphogenesis
Obsolete coenzyme biosynthetic process
Pantothenate metabolic process
Phosphorylation
Regulation of bile acid metabolic process
Regulation of fatty acid metabolic process
Regulation of mitochondrial membrane potential
Regulation of triglyceride metabolic process
Small molecule metabolic process
Spermatid development
Vitamin metabolic process
Water-soluble vitamin metabolic process
The reference OMIM entry for this protein is 234200
Neurodegeneration with brain iron accumulation 1; nbia1
Pantothenate kinase-associated neurodegeneration; pkan
Pkan neuroaxonal dystrophy, juvenile-onset
Hallervorden-spatz disease
A number sign (#) is used with this entry because neurodegeneration with brain iron accumulation-1 (NBIA1), also known as Hallervorden-Spatz disease, is caused by homozygous or compound heterozygosity mutation in the pantothenate kinase-2 gene (PANK2; 606157) on chromosome 20p13. HARP syndrome (607236) is a rare allelic disorder with a less severe phenotype and the presence of hypobetalipoproteinemia and acanthocytosis.
DESCRIPTION
Neurodegeneration with brain iron accumulation is a genetically heterogeneous disorder characterized by progressive iron accumulation in the basal ganglia and other regions of the brain, resulting in extrapyramidal movements, such as parkinsonism and dystonia. Age at onset, severity, and cognitive involvement are variable (review by Gregory et al., 2009). PKAN has been classified clinically as 'classic,' 'atypical,' or 'intermediate.' In the classic form, patients present within the first decade of life with rapidly progressing disease and loss of ambulation approximately 15 years later. In the atypical form, patients have onset in the second decade with slow progression and maintain independent ambulation after 15 years. In the intermediate form, patients have early onset and slow progression or later onset and rapid progression. Patients with early onset tend to develop pigmentary retinopathy, whereas those with later onset tend to have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI (Hayflick et al., 2003; Pellecchia et al., 2005). Kumar et al. (2006) noted that the 'eye of the tiger' sign is not pathognomonic for PANK2 mutations. They reported 2 unrelated adult patients with cognitive dysfunction who had the characteristic sign on MRI but did not have mutations in the PANK2 gene. Gregory et al. (2009) provided a detailed review of the different forms of neurodegeneration with brain iron accumulation. In addition, some patients with Kufor-Rakeb syndrome (606693), also known as Parkinson disease-9 (PARK9), have iron deposition in the basal ganglia. - Genetic Heterogeneity of Neurodegeneration with Brain Iron Accumulation Neurodegeneration with brain iron accumulation is an umbrella term that encompasses a group of genetically heterogeneous disorders. See also NBIA2A (256600) and NBIA2B (610217), both caused by mutation in the PLA2G6 gene (603604); NBIA3 (606159), caused by mutation in the FTL gene (134790); NBIA4 (614298), caused by mutation in the C19ORF12 gene (614297); NBIA5 (300894), caused by mutation in the WDR45 gene (300526); and NBIA6 (615643), caused by mutation in the COASY gene (609855). See review of Schneider and Bhatia (2012) on syndromes of neurodegeneration with brain iron accumulation, including Kufor-Rakeb disease (606693) and aceruloplasminemia (604290).CLINICAL FEATURES
The original description of this syndrome by Hallervorden and Spatz (1922) concerned a sibship of 12 in which 5 sisters showed clinically increasing dysarthria and progressive dementia, and at autopsy brown discoloration of the globus pallidus and substantia nigra. Familial cases have been reported by others as well. About 30 cases were reported by Meyer (1958). Clinically the condition is characterized by progressive rigidity, first in the lower and later in the upper extremities. An equinovarus deformity of the foot has been the first sign in several cases. Involuntary movements of choreic or athetoid type sometimes precede or accompany rigidi ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PANK2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 234200 was added.