WD repeat-containing protein 81 (WDR81)
The protein contains 1941 amino acids for an estimated molecular weight of 211697 Da.
Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). (updated: Nov. 22, 2017)
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.
- 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.
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| Variant | Description |
|---|---|
| CAMRQ2 | |
| dbSNP:rs3809870 | |
| HYC3 |
Biological Process
Aggrephagy
Early endosome to late endosome transport
Mitochondrion organization
Negative regulation of phosphatase activity
Protein stabilization
Regulation of phosphatidylinositol 3-kinase activity
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 610185
Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2; camrq2
Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 2
A number sign (#) is used with this entry because cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2 (CAMRQ2) is caused by homozygous mutation in the WDR81 gene (614218) on chromosome 17p.
DESCRIPTION
Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011). For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (224050).CLINICAL FEATURES
Turkmen et al. (2006) reported a consanguineous Turkish family of Kurdish origin in which 5 sibs had cerebellar hypoplasia, mental retardation, and an inability to walk bipedally, resulting in quadrupedal locomotion as a functional adaptation. An affected brother and sister were bipedal but had similar neurologic features and a lesser degree of cognitive impairment. One of the quadrupedal sibs died at age 26 years of unknown causes. Detailed examination of the 28-year-old male proband showed moderate thoracic kyphosis, short stature, cerebellar ataxia, dysarthria, dysmetria, and dysdiadochokinesia without pyramidal signs. He preferred to walk on his extremities with entire hands and feet touching the ground (palmigrade walking) and fully stretched knee and elbow joints. All 4 affected individuals moved about freely and participated most of the time in the family's daily work in the fields. They could understand and communicate basic words, but cognitive abilities were severely impaired. Brain MRI of affected individuals showed hypogenesis and midline clefting of the cerebellar vermis. In all cases the superior half of the vermis was formed, whereas the inferior section was not. The dentate nucleus was atrophic. Other findings included generalized brain atrophy and mild hypoplasia of the corpus callosum. Cortical dysplasia, lissencephaly, and gray matter heterotopia were not observed. Individuals who demonstrated quadrupedal locomotion did so effectively and without discomfort. As they moved, their knee and elbow joints showed almost no flexion, and their hands touched the ground mainly on their palms, distinct from knuckle walking of great apes. Tan (2006) provided a report of the same family. He noted that the affected individuals demonstrated diagonal walking seen in many animals, such as dogs, horses, and chimpanzees. Tan (2006) suggested that this syndrome may represent a live model for human evolution from quadrupedal to bipedal gait. Gulsuner et al. (2011) reported detailed neuroradiologic studies of the patients reported by Turkmen et al. (2006). Brain MRI of affected individuals showed morphologic abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural MRI showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and several Brodmann areas. Garcias and Roth (2007) reported 4 Brazilian sibs, 2 males and 2 females, born of consanguineous parents, with a clinically homogeneous syndrome in which the predominant characteristic was a quadrupedal gait. All had a normal neonatal period but did not learn to crawl normally on 4 limbs. When they learned to 'walk,' they assumed a quadrupedal position leaning on the hands and feet with erect lower limbs. Radiographic exams showed no osteoarticular changes that could justify the quadrupedal gait. A ... More on the omim web site
Feb. 10, 2018: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610185 was added.