Leucine-rich repeat-containing protein 59 (LRRC59)
The protein contains 307 amino acids for an estimated molecular weight of 34930 Da.
Required for nuclear import of FGF1, but not that of FGF2. Might regulate nuclear import of exogenous FGF1 by facilitating interaction with the nuclear import machinery and by transporting cytosolic FGF1 to, and possibly through, the nuclear pores. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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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The reference OMIM entry for this protein is 614854
Leucine-rich repeat-containing protein 59; lrrc59
P34
CLONING
By mass spectrometric analysis and peptide sequencing of proteins from human U2OS cells that bound to immobilized acidic FGF (aFGF, or FGF1; 131220), Skjerpen et al. (2002) identified LRRC59, which they called p34. They cloned the cDNA by RT-PCR of a U2OS cDNA library. The deduced 307-amino acid protein has an N-terminal domain, followed by 4 repeats of a conserved 23-amino acid leucine-rich sequence, a coiled-coil domain, a transmembrane domain, and a short C-terminal tail. Northern blot analysis detected abundant expression of a 3.8-kb transcript in all human tissues examined, with highest expression in placenta, followed by skeletal muscle, colon, kidney, liver, and lung. Transcripts of 1.4 and 1.0 kb were also observed. Database analysis revealed orthologs of p34 in mouse, rat, fruit fly, and nematode. Crosslinking experiments followed by SDS-PAGE revealed that p34 existed as a monomer but could form dimers. Zhen et al. (2012) stated that the C-terminal tail of human LRRC59 is predicted to localize to the lumen of the endoplasmic reticulum (ER). Confocal microscopy confirmed that LRRC59 localized to the ER and also detected LRRC59 at the nuclear envelope.GENE FUNCTION
Using truncation analysis, Skjerpen et al. (2002) found that the the coiled-coil domain of p34 bound aFGF. The interaction between p34 and aFGF appeared to have a 1:1 ratio, and p34 did not bind a nonmitogenic aFGF(K132E) mutant. CK2 (see CSNK2A1; 115440) competed with p34 for binding to aFGF. p34 also bound basic FGF (FGF2; 134920), but more weakly. Zhen et al. (2012) stated that FGF1 is imported into the nucleus, where it has growth regulatory activity. Nuclear FGF1 is phosphorylated by protein kinase C-delta (PRKCD; 176977), signaling FGF1 export from the nucleus for its cytosolic degradation. Using small interfering RNA directed against LRRC59, Zhen et al. (2012) found that LRRC59 was required for nuclear uptake and nuclear phosphorylation of exogenously added FGF1 in BJ human fibroblasts. Knockdown of LRRC59 did not alter FGF1 endocytic uptake or cytoplasmic accumulation. LRRC59 had no effect on nuclear import of protein kinase C-delta, suggesting that it is not a general nuclear import factor. Zhen et al. (2012) noted that LRRC34 was originally believed to be a ribosome receptor, but that this function has been rejected.MAPPING
Hartz (2012) mapped the LRRC59 gene to chromosome 17q21.33 based on an alignment of the LRRC59 sequence (GenBank GENBANK AF119857) with the genomic sequence (GRCh37). ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 614854 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).