Erlin-2 (ERLIN2)
The protein contains 339 amino acids for an estimated molecular weight of 37840 Da.
Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 (PubMed:19240031, PubMed:17502376). Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex (PubMed:21343306). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (PubMed:24217618). (updated: Oct. 25, 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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs2032066 |
Biological Process
Cholesterol metabolic process
Negative regulation of cholesterol biosynthetic process
Negative regulation of fatty acid biosynthetic process
SREBP signaling pathway
Transmembrane transport
Ubiquitin-dependent ERAD pathway
Cellular Component
Cytoplasm
Cytosol
Endoplasmic reticulum
Endoplasmic reticulum membrane
Extracellular exosome
Integral component of membrane
Membrane raft
Plasma membrane
Protein complex
Protein-containing complex
Molecular Function
Cholesterol binding
Protein tyrosine kinase activity
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 611225
Spastic paraplegia 18, autosomal recessive; spg18
Intellectual disability, motor dysfunction, and joint contractures; idmdc
A number sign (#) is used with this entry because of evidence that autosomal recessive spastic paraplegia-18 (SPG18) is caused by homozygous mutation in the ERLIN2 gene (611605) on chromosome 8p11.
DESCRIPTION
Spastic paraplegia-18 is a severe autosomal recessive neurologic disorder characterized by onset in early childhood of progressive spastic paraplegia resulting in motor disability. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures (summary by Alazami et al., 2011 and Yildirim et al., 2011).CLINICAL FEATURES
Al-Yahyaee et al. (2006) reported 2 unrelated consanguineous Omani families with autosomal recessive complicated SPG. In 1 family (family B), 3 affected individuals presented with walking difficulties between ages 4 and 6 years. Physical examination showed lower limb spasticity primarily affecting the hamstring and posterior tibial muscles. Two of the children also had epilepsy; all had normal brain CT scans and normal mental development. Affected individuals from the second family (family A) had early-onset spasticity, mental retardation, and thin corpus callosum on brain MRI. Family A was later found by Schuurs-Hoeijmakers et al. (2012) to have SPG54 (615033), caused by mutation in the DDHD2 gene (615003) on chromosome 8p11. Alazami et al. (2011) reported a consanguineous Saudi family with a complicated form of SPG. One of 2 affected sibs was described in detail. At age 30 months, he developed progressive tightening of the lower extremities with later involvement of the upper extremities, rendering him wheelchair-bound at age 4 years. He had a history of delayed early motor development and intellectual disability, and failed to acquire language. He also developed seizures at age 7 years, and EEG was severely abnormal, with generalized slowing of background and generalized slow spike and wave activities compatible with atypical absence epilepsy. Brain MRI was normal. His younger sister had a similar disease course, except without seizures. Three maternal uncles, who were not examined, reportedly had severe intellectual disability, aphasia, and marked hypertonia, all without seizures. Yildirim et al. (2011) reported a very large, highly consanguineous family from eastern Turkey with a neurologic disorder that the authors termed 'intellectual disability, motor dysfunction, and joint contractures' (IDMDC). Affected individuals presented between ages 6 months and 2 years with an arrest and regression of motor function. Nine patients had infantile febrile seizures. Distal limb deformities became evident after the age of 1 or 2 years and progressed very slowly, but each child finally assumed a specific fixed position. Contractures seemed to begin from the feet and spread in an ascending manner, involving the ankles, knees, and elbows, and finally involving the spine and the neck. Examination of 11 patients between ages 4 and 22 years revealed that none of the patients could walk or crawl; only 2 were still able to sit. All had severe intellectual disability, and none could speak, read, or write. Features suggestive of spasticity included hyperactive reflexes, ankle clonus, and extensor plantar responses, but the neurologic examination was difficult to perform in most. Muscle biopsy of 2 patients, EMG of 4 patients, and brain imaging of 3 patients were all normal. Electron microscopy of white blood cells from 2 affected sibs showed large membrane-boun ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611225 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed