Ankyrin repeat domain-containing protein 13A (ANKRD13A)
The protein contains 590 amino acids for an estimated molecular weight of 67619 Da.
Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane. (updated: March 4, 2015)
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.
- 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 annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs2287174 |
The reference OMIM entry for this protein is 615123
Ankyrin repeat domain-containing protein 13a; ankrd13a
DESCRIPTION
Some members of the ANKRD13 family, such as ANKRD13A, have a role in regulating internalization of cell surface proteins (Tanno et al., 2012).CLONING
Tanno et al. (2012) cloned ANKRD13A from a human brain cDNA library. The deduced 590-amino acid protein contains 3 N-terminal ankyrin repeats and 4 putative C-terminal ubiquitin-interacting motifs. Immunofluorescence analysis of HeLa cells revealed that ANKRD13A localized to the plasma membrane and late endosomes.GENE FUNCTION
Monoubiquitination and/or lys63-linked polyubiquitin chains serve as endocytosis signals that are tagged to a variety of cell surface integral membrane proteins. Proteins of the endocytic machinery are also regulated by their own ubiquitination. Using immunoprecipitation and Western blot analysis of EGF (131530)-stimulated HeLa cells, Tanno et al. (2012) showed that ANKRD13A, ANKRD13B (615124), and ANKRD13D (615126), but not ANKRD13C (615125), bound to the ubiquitinated EGF receptor (EGFR; 131550). Tanno et al. (2012) found that ANKRD13A was itself monoubiquitinated, and this ubiquitination interfered with interaction between ANKRD13A and ubiquitinated EGFR. Both ubiquitination of ANKRD13A and binding of ANKRD13A to EGFR required the ubiquitin-interacting motifs of ANKRD13A. Protein binding assays revealed that ANKRD13A, ANKRD13B, and ANKRD13D bound to lys63-linked, but not lys48-linked, polyubiquitin chains. Binding affinity was higher with ubiquitin chain lengths between 4 and 7 units, with lower or no affinity for shorter ubiquitin chain lengths. Overexpression of ANKRD13A, ANKRD13B, and ANKRD13B delayed, but did not completely inhibit, ligand-induced EGFR internalization. ANKRD13 proteins had no effect on EGFR degradation. Overexpression of ANKRD13A also suppressed uptake of nonubiquitinated cargo, such as transferrin receptor (TFRC; 190010).MAPPING
Hartz (2013) mapped the ANKRD13A gene to chromosome 12q24.11 based on an alignment of the ANKRD13A sequence (GenBank GENBANK AF064604) with the genomic sequence (GRCh37). ... More on the omim web site
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 615123 was added.