Nicalin (NCLN)
The protein contains 563 amino acids for an estimated molecular weight of 62974 Da.
Component of a ribosome-associated translocon complex involved in multi-pass membrane protein transport into the endoplasmic reticulum (ER) membrane and biogenesis (PubMed:32820719). May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning, via its interaction with NOMO (By similarity). (updated: April 7, 2021)
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.
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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| Variant | Description |
|---|---|
| dbSNP:rs11671067 | |
| dbSNP:rs2288949 |
Biological Process
Protein stabilization
Regulation of protein complex stability
Regulation of protein-containing complex assembly
Regulation of signal transduction
The reference OMIM entry for this protein is 609156
Nicalin, zebrafish, homolog of; ncln
CLONING
By searching databases for sequences containing the ectodomain of the nicastrin (605254) family of proteins, Haffner et al. (2004) identified nicalin. The deduced type I transmembrane protein has a calculated molecular mass of 63.7 kD. Nicalin contains a region similar to an aminopeptidase domain, but it lacks amino acids necessary for catalytic activity. Northern blot analysis detected nicalin transcripts of 4.6, 4.0, and 2.3 kb. Highest expression was in pancreas and skeletal muscle, with somewhat lower expression in heart and very low expression in all other tissues examined. SDS-PAGE of enriched membrane preparations of human embryonic kidney cells and neuroblastoma cells indicated that endogenous nicalin has an apparent molecular mass of 60 kD. Nicalin was also detected in a 500- to 550-kD complex containing NOMO2 (609158). Nicalin and NOMO2 cofractionated with endoplasmic reticulum membranes.GENE FUNCTION
By coimmunoprecipitation of cotransfected cells, Haffner et al. (2004) confirmed that NOMO2 and nicalin associated in a high molecular mass complex and interacted directly. Ectopic expression of both proteins in zebrafish embryos caused cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal (601265) signaling pathway. Furthermore, Nodal- and activin (see 147290)-induced signaling was inhibited by nicalin and NOMO2 in a cell-based reporter assay. Using affinity purification and coimmunoprecipitation experiments, Dettmer et al. (2010) showed that NOMO and nicalin interacted with TMEM147 (613585). Knockdown of each of these components by RNA interference showed that they stabilized one another. Knockdown and overexpression studies suggested that nicalin is the key regulator of the complex and that it binds to NOMO prior to inclusion of TMEM147 in the complex. Mutation analysis revealed that the transmembrane domain of nicalin was required for interaction with TMEM147, but not NOMO. Coprecipitation studies with zebrafish embryos revealed conservation of the nicalin-NOMO-TMEM147 complex.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NCLN gene to chromosome 19 (TMAP WI-15783). ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 609156 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).