Calcium load-activated calcium channel (TMCO1)
The protein contains 188 amino acids for an estimated molecular weight of 21175 Da.
Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum (ER) overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239). Component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis (PubMed:32820719). Together with SEC61 and TMEM147, forms the lipid-filled cavity at the center of the translocon where TMEM147 may insert hydrophobic segments of mutli-pass membrane proteins from the lumen into de central membrane cavity in a process gated by SEC61, and TMCO1 may insert hydrophobic segments of nascent chains from the cytosol into the cavity (PubMed:32820719). (updated: June 2, 2021)
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 predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
Biological Process
Calcium ion transmembrane transport
Cellular calcium ion homeostasis
Endoplasmic reticulum calcium ion homeostasis
ER overload response
The reference OMIM entry for this protein is 213980
Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome; cfsmr
Cerebrofaciothoracic dysplasia
A number sign (#) is used with this entry because the craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (CFSMR) is caused by homozygous mutation in the TMCO1 gene (614123) on chromosome 1q24.
CLINICAL FEATURES
Pascual-Castroviejo et al. (1975) described a multiple congenital anomaly/mental retardation syndrome in 3 unrelated children. The features included facial dysmorphism, multiple malformations of the vertebrae and ribs, and mental retardation. Cerebrofaciothoracic dysplasia was the suggested designation. In 2 of the families, the parents were consanguineous. Philip et al. (1992) described 2 brothers, born to second-cousin parents from Morocco, who had facial dysmorphism, complex anomalies of the vertebrae and ribs, enlarged cerebral ventricles and septum pellucidum, mental retardation, and affable behavior. In the second sib reported by Philip et al. (1992), the diagnosis was suspected on ultrasound scan during pregnancy, indicating that prenatal diagnosis of this condition is possible. The costovertebral abnormalities were similar to those of spondylocostal dysplasia (277300), but mental retardation is not a feature of that condition. Guion-Almeida et al. (1996) reported a male infant who had a large septum pellucidum, hypodensity of gray matter, hypertelorism, and costovertebral anomalies. Cleft lip/palate was also present. Kanaka-Gantenbein et al. (2004) reported a brother and sister, born to nonconsanguineous parents, with cerebrofaciothoracic dysplasia. Both had severe intrauterine and postnatal growth failure, costovertebral abnormalities (hemivertebrae and fused ribs), and mental retardation. The sister, 20 years old at the time of report, had had repeated surgery for rectovaginal fistula. The brother, 8 years old at the time of report, had cleft palate. He, but not his sister, showed growth hormone deficiency. Cilliers et al. (2007) reported an Asian boy and a Turkish girl, both born to consanguineous parents, with cerebrofaciothoracic dysplasia. In addition to typical features of the disorder, the boy had bilateral colobomas of the optic nerve, a left-sided divergent strabismus, ptosis, small conical teeth, severe left-sided talipes, valgus deformity of both feet, overlapping of the toes, hypermobile joints (especially in his hands), and anterior subluxation of the shoulders. He also had right-sided renal pelvic dilation and dilated right distal ureter, and his echocardiogram showed a small patent ductus arteriosus. Xin et al. (2010) described a mental retardation syndrome in 11 patients from the Old Order Amish population of Geauga County in northeastern Ohio. Some abnormalities, such as cleft lip and palate and ventriculomegaly, could be observed from the prenatal period, although not all patients had prenatal ultrasound. Features at birth included hypotonia, poor feeding, and craniofacial dysmorphisms, including brachycephaly, flat face, low hairline, low-set ears, high-arched palate, and cleft lip and palate. Features that appeared later included highly arched bushy eyebrows, synophrys, hypertelorism, long eyelashes, wide nasal bridge, short nose with anteverted nares, microdontism, and gingival hyperplasia. Skeletal dysmorphisms tended to involve the axial skeleton, with pectus excavatum, scoliosis, vertebral fusion, and rib anomalies. Two patients had tall stature, whereas 3 had short stature. All had global developmental delay. Neurologic examination showed hyporeflexia, unstea ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 213980 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. 25, 2016: Protein entry updated
Automatic update: model status changed