Transmembrane protein 237 (TMEM237)
The protein contains 408 amino acids for an estimated molecular weight of 45526 Da.
Component of the transition zone in primary cilia. Required for ciliogenesis. (updated: Feb. 22, 2012)
Protein identification was indicated in the following studies:
- 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.
This protein is predicted to be membranous by TOPCONS.
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Cellular Component
Ciliary transition zone
Cone photoreceptor outer segment
Integral component of membrane
Membrane
Photoreceptor connecting cilium
Rod photoreceptor outer segment
Molecular Function
The reference OMIM entry for this protein is 614423
Transmembrane protein 237; tmem237
Als2 chromosome region gene 4; als2cr4
DESCRIPTION
TMEM237 is a tetraspanin protein localized to the ciliary transition zone that is predicted to function with other transition zone proteins in canonical and noncanonical Wnt (see 164820) signaling (Huang et al., 2011).CLONING
Huang et al. (2011) identified 2 TMEM237 splice variants that include either exon 1 or exon 2 and are translated into 2 different protein isoforms. Transcript-1 contains exon 1 and encodes a deduced 408-amino acid protein, designated isoform A, that has a long N-terminal domain, followed by 4 transmembrane domains and a short C-terminal tail. Both the N- and C-terminal domains are intracellular. The N-terminal domain and the intracellular loops between the transmembrane helices contain short repetitive motifs of basic (arg and/or lys) and acidic (asp and/or glu) residues that are highly conserved in metazoans. Immunocytochemical staining of polarized ciliated mouse inner medullary collecting duct (IMCD3) cells revealed that Tmem237 localized to the transition zone at the proximal region of primary cilia. Zuniga and Craft (2010) cloned mouse Tmem237, which they called Als2cr4, and identified variants encoding 2 protein isoforms that differ only at the extreme N terminus. The deduced 403-amino acid protein encoded by Als2cr4 transcript-2 has a calculated molecular mass of about 45 kD and shares 81% and 82% identity with isoforms A and B of human ALS2CR4, respectively. Mouse Als2cr4 has a long N-terminal domain containing a tetratricopeptide motif, followed by 4 transmembrane segments and a short C-terminal tail. Zuniga and Craft (2010) noted that previous in situ hybridization and gene expression profiles revealed high Als2cr4 expression in eye, hippocampus, cerebellum, and olfactory bulb. By immunohistochemical analysis of retina, Zuniga and Craft (2010) found Als2cr4 enriched in retina and localized to photoreceptor outer segments, ciliary complex, and horizontal cells in the outer plexiform layer. Immunoelectron microscopy verified Als2cr4 expression in the discs of photoreceptor outer segments.GENE FUNCTION
By yeast 2-hybrid analysis of mouse retina, Zuniga and Craft (2010) found that Als2cr4 interacted with Arr4 (ARR3; 301770). Immunoprecipitation analysis of light-adapted mouse retinas showed that Als2cr4 associated with cytoskeletal components. Als2cr4 interacted directly with myosin Va (MYO5A; 160777), myosin VI (MYO6; 600970), and Arr3. Huang et al. (2011) found that knockdown of Tmem237 in IMCD3 cells via small interfering RNA impaired ciliogenesis and caused mislocalization of RhoA (165390) to peripheral regions of the basal body and to basolateral cell-cell contacts. Similarly, fibroblasts from a patient with Joubert syndrome-14 (JBTS14; 614424) and a null mutation in TMEM237 (R18X; 614423.0001) showed deregulation of canonical and noncanonical Wnt signaling and mislocalization of RHOA. Morpholino-mediated knockdown of Tmem237 in zebrafish caused gastrulation defects consistent with ciliary dysfunction that were similar to defects resulting from knockdown of other transition zone proteins, including Mks3 (TMEM67; 609884) and Tmem216 (613277). These defects in zebrafish were partially reversed by expression of human TMEM237, MKS3, or TMEM216. In both IMCD3 cells and C. elegans, transition zone localization of Tmem237 was dependent upon other transition zone proteins. Huang et al. (2011) hypothesized that TMEM237, TMEM216, and MKS3 function as a module to regul ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614423 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).