ORM1-like protein 3 (ORMDL3)
The protein contains 153 amino acids for an estimated molecular weight of 17495 Da.
Negative regulator of sphingolipid synthesis. May indirectly regulate endoplasmic reticulum-mediated Ca(+2) signaling. (updated: Oct. 1, 2002)
Protein identification was indicated in the following studies:
- 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.
- 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, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
No binding partner found
Biological Process
Cellular sphingolipid homeostasis
Ceramide metabolic process
Motor behavior
Myelination
Negative regulation of B cell apoptotic process
Negative regulation of ceramide biosynthetic process
Negative regulation of serine C-palmitoyltransferase activity
Neutrophil degranulation
Positive regulation of autophagy
Positive regulation of protein localization to nucleus
Regulation of smooth muscle contraction
Sphingomyelin biosynthetic process
Cellular Component
Endoplasmic reticulum
Integral component of membrane
Obsolete cell
Plasma membrane
Secretory granule membrane
Specific granule membrane
SPOTS complex
Molecular Function
The reference OMIM entry for this protein is 600807
Asthma, susceptibility to
Asthma, bronchial
Asthma-related traits, susceptibility to asthma, protection against, included
Asthma, diminished response to antileukotriene treatment in, included
A number sign (#) is used with this entry because multiple loci and candidate genes have been implicated in the causation of asthma and asthma-related traits (ASRT). See, e.g., ASRT1 (607277), associated with a mutation in the PTGDR gene (604687) on chromosome 14q24; ASRT2 (608584), associated with mutation in the GPRA gene (608595) on 7p15-p14; ASRT3 (609958), which has been mapped to chromosome 2p; ASRT4 (610906), which has been mapped to chromosome 1p31; and ASRT5 (611064), associated with variation in the IRAK3 gene (604459) on 12q14.3. ASRT6 (611403) is associated with markers on chromosome 17q21 and transcript levels of ORMDL3 (610075). ASRT7 (611960) is associated with polymorphism in the CHI3L1 gene (601525) on chromosome 1q32.1, and ASRT8 (613207) has been mapped to chromosome 9q33. Polymorphisms in the HNMT gene (605238) and the ADRB2 gene (109690) have also been associated with susceptibility to asthma. Balaci et al. (2007) stated that in the previous decade several loci and more than 100 genes had been found to be associated with asthma in at least 1 population.
DESCRIPTION
Bronchial asthma is the most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002; Pillai et al., 2006). See 147050 for information on the asthma-associated phenotype atopy.CLINICAL FEATURES
A critical phenotypic characteristic of human asthma and an important feature of animal models of asthma is airway hyperresponsiveness (Hirshman et al., 1984; Levitt and Mitzner, 1988; Levitt and Mitzner, 1989).INHERITANCE
Longo et al. (1987) postulated that asthma can be inherited as a mendelian dominant disorder (with incomplete penetrance); Townley et al. (1986) supported polygenic inheritance. Longo et al. (1987) found that among the healthy parents of asthmatic children, tests of airway responsiveness to carbachol showed a bimodal distribution of responsiveness; in 85% of couples who had an asthmatic child, one or both parents had normal airway responsiveness consistent with an autosomal dominant trait. Townley et al. (1986) demonstrated a unimodal distribution of airway responsiveness in normal subjects from nonasthmatic and nonallergic families and confirmed a bimodal distribution of bronchial reactivity to methacholine (MCh) in families with and without asthma. - Association with BMI In a study of 1,001 monozygotic and 383 dizygotic same-sex twin pairs, Hallstrand et al. (2005) analyzed self-reports of a physician diagnosis of asthma and BMI (see 606641) calculated using self-reported height and weight, and found a strong association between asthma and BMI (p less than 0.001). Substantial heritability was detected for asthma (53%) and obesity (77%), indicating additive genetic influences on each disorder. The best-fitting model of shared components of variance indicated that 8% of the genetic component of obesity is shared with asthma.PATHOGENESIS
Xiang et al. (2007) reported that an excitatory rather than inhibitory GABAergic system exists in airway epithelial cells. Both GABA ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600807 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).