Patatin-like phospholipase domain-containing protein 6 (PNPLA6)
The protein contains 1366 amino acids for an estimated molecular weight of 149995 Da.
Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho). This deacylation occurs at both sn-2 and sn-1 positions of PtdCho. Catalyzes the hydrolysis of several naturally occurring membrane-associated lipids (PubMed:11927584). Hydrolyzes lysophospholipids and monoacylglycerols, preferring the 1-acyl to the 2-acyl isomer. Does not catalyze hydrolysis of di- or triacylglycerols or fatty acid amides (PubMed:11927584). (updated: June 17, 2020)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
This protein is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Angiogenesis
Animal organ morphogenesis
Developmental process
Glycerophospholipid catabolic process
Lipid catabolic process
Phosphatidylcholine metabolic process
The reference OMIM entry for this protein is 215470
Boucher-neuhauser syndrome; bnhs
Spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy
A number sign (#) is used with this entry because Boucher-Neuhauser syndrome (BNHS) is caused by homozygous or compound heterozygous mutation in the PNPLA6 gene (603197) on chromosome 19p13.
DESCRIPTION
Boucher-Neuhauser syndrome is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39; 612020) (summary by Synofzik et al., 2014). See also Gordon Holmes syndrome (GDHS; 212840), caused by mutation in the RNF216 gene (609948), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism.CLINICAL FEATURES
Neuhauser and Opitz (1975) described a kindred in which 2 brothers and 2 sisters with second-cousin parents had cerebellar ataxia in association with hypogonadotropic hypogonadism. In 3 sibs the onset of cerebellar ataxia was between 12 and 20 years and in the fourth, in the 30s. Hypogonadotropism was reflected in failure of secondary sexual characteristics, eunuchoidism, absence of libido, and infertility. Limber et al. (1989) provided a follow-up on the family described by Neuhauser and Opitz (1975) and demonstrated that the affected members had a syndrome that included, in addition to spinocerebellar ataxia and hypogonadotropic hypogonadism, chorioretinal dystrophy. Limber et al. (1989) also reported another family in which a brother and sister had cerebellar ataxia, hypogonadotropic hypogonadism, and choroidal dystrophy, and noted that an earlier example of this triad had been reported by Boucher and Gibberd (1969) in 2 affected sisters. Limber et al. (1989) recognized the association of spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy as an autonomous single-gene disorder and called it Boucher-Neuhauser syndrome. Fok et al. (1989) reported a Chinese male with cerebellar ataxia, hypogonadotropic hypogonadism, and peripapillary degeneration with chorioretinal atrophy. Baroncini et al. (1991) described affected brothers. A review of reported cases indicated that the neurologic signs usually develop during adolescence or early adulthood (range, early childhood to the fourth decade) and are slowly progressive or nonprogressive, whereas ophthalmologic manifestations have an age of onset that varies from the first to the sixth decade of life and a pronounced variability in progression. Salvador et al. (1995) reported the ophthalmologic findings in a 39-year-old woman with this disorder. Puberty had been delayed although menarche occurred and secondary sex characteristics developed with hormone injections at 17 years of age. Menstruation ceased when the medication was discontinued 4 years later. At 28 years of age, the patient experienced progressive deterioration of balance, and at age 32 years, scanning speech and intention tremor appeared. MRI showed diffuse atrophy of the cerebellar hemispheres. Progressive loss of vision and photophobia began at the age of 37 years. Ophthalmoscopy showed extensive atrophic changes of the retinal pigment epithelium and choriocapillaris in the posterior pole and midperiphery of both ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 25, 2020: 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 215470 was added.