Low-density lipoprotein receptor class A domain-containing protein 4 (LDLRAD4)
The protein contains 306 amino acids for an estimated molecular weight of 33900 Da.
Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal. (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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Biological Process
Negative regulation of cell migration
Negative regulation of epithelial to mesenchymal transition
Negative regulation of pathway-restricted SMAD protein phosphorylation
Negative regulation of SMAD protein complex assembly
Negative regulation of transforming growth factor beta receptor signaling pathway
The reference OMIM entry for this protein is 606571
Chromosome 18 open reading frame 1; c18orf1
CLONING
By cDNA selection, Yoshikawa et al. (1997) isolated several brain-derived transcripts on chromosome 18, including C18ORF1, which maps to 18p11.2. Yoshikawa et al. (1998) further characterized C18ORF1 and identified 2 major classes of transcripts distinguished by their unique upstream regions, with the beta variants representing N-terminal-truncated versions of the alpha isoforms. The alpha-specific exons 1 to 3 are missing in beta; instead, the downstream sequence of intron C is present in the mature mRNA (exon 4a), which combines with exon 4b to create the upstream exon for beta. The differential splicing of exon 5 leads to the expression of 2 alpha and 2 beta subclasses. Alpha-1 and beta-1 share identical sequences with alpha-2 and beta-2, respectively, except for the loss of exon 5 in alpha-2 and beta-2. The differences between the alpha and the beta classes of transcripts predict 2 potentially distinct promoters for the C18ORF1 gene. Yoshikawa et al. (1998) also presented evidence of RNA editing in the 5-prime untranslated region of the beta-2 variant. Yoshikawa et al. (1998) found that the alpha-1 C18ORF1 variant encodes a deduced 306-amino acid protein. Both alpha and beta variants contain a transmembrane domain, and the alpha-specific N terminus contains a low density lipoprotein receptor class A (LDLRA) domain. Yoshikawa et al. (1998) demonstrated that the C18ORF1 transcripts display selective expression, regulated spatially and temporally. The cortical and subcortical structures of brain appear to express high levels of alpha, in both fetal and adult stages. The major 9-kb transcript of C18ORF1, detectable in early development in kidney, liver, and lung, is indiscernible in these tissues in the adult. The expression profile displayed by beta is more complex. Northern blots generated from adult tissues are devoid of hybridization signals with beta but fetal tissues exhibit a 4-kb transcript. In contrast, all subcortical areas of adult brain show relatively intense signals at 6.8 kb, implying a different mechanism of transcript processing in adult brain structures. Northern blot analysis also detected several minor bands in the alpha and beta isoforms.MAPPING
By sequence analysis, Yoshikawa et al. (1997) mapped the C18ORF1 gene to chromosome 18p11.2. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 606571 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).