ORM1-like protein 1 (ORMDL1)
The protein contains 153 amino acids for an estimated molecular weight of 17371 Da.
Negative regulator of sphingolipid synthesis. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
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
Cellular sphingolipid homeostasis
Ceramide metabolic process
Negative regulation of ceramide biosynthetic process
Cellular Component
Endoplasmic reticulum
Endoplasmic reticulum membrane
Integral component of membrane
Obsolete cell
SPOTS complex
Molecular Function
The reference OMIM entry for this protein is 610073
Orm1-like protein 1; ormdl1
CLONING
By sequencing clones mapped to the RP26 locus (608380) on chromosome 2, followed by screening a retina cDNA library and 3-prime and 5-prime RACE of placenta RNA, Hjelmqvist et al. (2002) cloned ORMDL1. The deduced 153-amino acid protein has a calculated molecular mass of 17.4 kD. ORMDL1 contains 4 putative transmembrane domains and shares 83%, 84%, and 99% amino acid identity with ORMDL2 (610074), ORMDL3 (610075), and mouse Ormdl1, respectively. It also share significant homology with its yeast orthologs, Orm1 and Orm2. RT-PCR showed ORMDL1 expression in all adult and fetal tissues examined. Northern blot analysis detected transcripts of 1.4, 2.5, and 3.3 kb in all tissues tested, with moderately high levels in pancreas, placenta, and brain and lowest levels in skeletal muscle and lung. Fluorescence-tagged ORMDL1 localized with an endoplasmic reticulum marker following transfection into COS-7 cells.GENE STRUCTURE
Hjelmqvist et al. (2002) determined that the ORMDL1 gene contains 5 exons and spans at least 17 kb. The first exon is untranslated. The promoter region has no TATA box, but it has several SP1 (189906)-binding sites. A CpG island covers part of the upstream region, the first exon, and part of the first intron.GENE FUNCTION
Starting from an unbiased functional genomic approach in S. cerevisiae, Breslow et al. (2010) identified ORM proteins as negative regulators of sphingolipid synthesis that form a conserved complex with serine palmitoyltransferase (605712), the first and rate-limiting enzyme in sphingolipid production. Breslow et al. (2010) also defined a regulatory pathway in which phosphorylation of ORM proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Breslow et al. (2010) concluded that their work identified the ORM proteins as critical mediators of sphingolipid homeostasis and raised the possibility that sphingolipid misregulation contributes to the development of childhood asthma.MAPPING
By genomic sequence analysis, Hjelmqvist et al. (2002) mapped the ORMDL1 gene to chromosome 2q32.2. They identified a putative ORMDL1 pseudogene on chromosome 10p14. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 610073 was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).