DnaJ homolog subfamily C member 13 (DNAJC13)
The protein contains 2243 amino acids for an estimated molecular weight of 254415 Da.
Involved in membrane trafficking through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in degradation of EGF and EGFR (PubMed:18256511, PubMed:18307993). Involved in the regulation of endosomal membrane tubulation and regulates th dynamics of SNX1 on the endosomal membrane; via association with WASHC2 may link the WASH complex to the retromer SNX-BAR subcomplex (PubMed:24643499). (updated: Jan. 31, 2018)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- 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.
- 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 annotated as membranous in Gene Ontology.
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Biological Process
Endosome organization
Neutrophil degranulation
Osteoblast differentiation
Protein transport
Receptor-mediated endocytosis
Regulation of early endosome to late endosome transport
Regulation of early endosome to recycling endosome transport
Cellular Component
Azurophil granule membrane
Cytosol
Early endosome membrane
Endosome membrane
Extracellular exosome
Intracellular membrane-bounded organelle
Lysosomal membrane
Membrane
Plasma membrane
Secretory granule membrane
Molecular Function
The reference OMIM entry for this protein is 614334
Dnaj/hsp40 homolog, subfamily c, member 13; dnajc13
Receptor-mediated endocytosis 8, c. elegans, homolog of; rme8
Kiaa0678
DESCRIPTION
The DNAJC13 gene encodes a protein that localizes to the membrane of the endosomal system, where it plays a role in vesicle formation and trafficking (summary by Vilarino-Guell et al., 2014).CLONING
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Ishikawa et al. (1998) obtained a partial DNAJC13 clone, which they designated KIAA0678. RT-PCR detected DNAJC13 expression in all tissues examined, with highest expression in ovary and lowest expression in pancreas and spleen. By searching for genes in a region of chromosome 3 linked to adolescent nephronophthisis (NPHP3; 604387) and Senior-Loken syndrome (SLSN3; 606995), Volz et al. (2002) identified KIAA0678. The deduced protein contains a DnaJ homology domain and a conserved his-pro-asp (HPD) motif that may be involved in regulation of HSP70 (see HSPA1A; 140550) ATPase activity. By searching a database for sequences similar to rat Rme8, Girard et al. (2005) obtained the full-length sequence for human DNAJC13, which they called RME8. The deduced 2,243-amino acid protein has a central DnaJ domain flanked on either side by 2 IWN repeats. It also has 4 potential clathrin heavy chain (CHC, or CLTC; 118955) interaction motifs. Confocal immunofluorescence analysis of COS-7 cells and HeLa cells revealed that endogenous RME8 distributed in a punctate pattern that accumulated in the perinuclear region and overlapped with endosomal markers. Western blot analysis of rat tissues and several cell lines, including HEK293 and HeLa cells, detected RME8 at an apparent molecular mass of 220 kD. Fractionation of rat kidney and protein extraction experiments revealed that Rme8 is an extrinsic membrane protein associated with microsomes.GENE FUNCTION
Girard et al. (2005) showed that the isolated DnaJ domain of human RME8 bound rat kidney Hsc70 (HSPA8; 600816) in an ATP-dependent manner. Knockdown of Rme8 in COS-7 cells disrupted endocytic trafficking of Egfr (131550), Cimpr (IGF2R; 147280), and cathepsin D (CTSD; 116840).GENE STRUCTURE
Girard et al. (2005) determined that the DNAJC13 gene contains 56 exons.MAPPING
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the DNAJC13 gene to chromosome 3. Volz et al. (2002) mapped the DNAJC13 gene to chromosome 3q21-q22 by genomic sequence analysis. Girard et al. (2005) mapped the DNAJC13 gene to chromosome 3q22.1 by genomic sequence analysis.MOLECULAR GENETICS
- Parkinson Disease 21 In affected members of a large 4-generation Mennonite family of Dutch/German/Russian descent with autosomal dominant late-onset Parkinson disease-21 (PARK21; 616361), Vilarino-Guell et al. (2014) identified a heterozygous missense mutation in the DNAJC13 gene (N855S; 614334.0001). The mutation, which was found by exome sequencing, segregated with the specific phenotype in the family. Sequencing in 2,928 additional cases of Parkinson disease identified 5 more probands with the same mutation, 2 of whom had a family history of the disorder. All individuals with the mutation reported Dutch/German/Russian Mennonite ancestry, and haplotype analysis was consistent with a founder effect. In vitro functional expression assays showed that the mutation altered the cellular activity and regulation of endosomal membrane trafficking, most likely decreased exocytosis. - Associations Pending Confirmation For discussion of a possible role of variation in the DNAJC13 gene in Tourette s ... More on the omim web site
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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614334 was added.