Importin subunit alpha-3 (KPNA4)
The protein contains 521 amino acids for an estimated molecular weight of 57887 Da.
Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. (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.
- 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.
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Biological Process
Cytokine-mediated signaling pathway
Intracellular transport of virus
Modulation by virus of host cellular process
NLS-bearing protein import into nucleus
Response to hydrogen peroxide
Cellular Component
Cytosol
Extracellular exosome
Host cell
Host cell nucleus
Nuclear membrane
Nuclear pore
Nucleoplasm
Nucleus
The reference OMIM entry for this protein is 602970
Karyopherin alpha-4; kpna4
Importin alpha-3
Qip1
DESCRIPTION
The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, such as KPNA4, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex (summary by Seki et al., 1997).CLONING
Using a yeast 2-hybrid system to identify proteins that interact with the DNA helicase Q1 (RECQL; 600537), Seki et al. (1997) isolated HeLa cell cDNAs encoding QIP1. The predicted 521-amino acid QIP1 protein contains the conserved N-terminal binding site for karyopherin-beta (see KPNB1; 602738) and a series of 7 degenerate 'armadillo' repeats, which are 42-amino acid motifs implicated in protein-protein interactions. Human QIP1 has 50% amino acid identity with human KPNA2 (600685), 49% with Xenopus importin-alpha, 47% with human KPNA1 (600686), and 46% with S. cerevisiae Srp1. Kohler et al. (1997) isolated a human KPNA4 cDNA. The predicted KPNA4 protein contains an N-terminal importin-beta-binding (IBB) domain, 8 armadillo repeats, and a C-terminal acidic region, all of which are characteristics of importin-alphas. Of the known human importin-alphas, KPNA4 shares the highest sequence identity with KPNA3 (601892). Northern blot analysis detected a 4.4-kb KPNA4 transcript in all tissues tested. However, expression levels varied considerably among tissues, with the highest expression in testis, ovary, small intestine, and pancreas, and the lowest expression in kidney, thymus, colon, and peripheral blood leukocytes.GENE FUNCTION
Seki et al. (1997) demonstrated that QIP1 interacted with the NLSs of DNA helicase Q1 and SV40 T antigen. Using an in vitro import assay based on permeabilized HeLa cells to study the import substrate specificity of all ubiquitously expressed importins, including KPNA4, Kohler et al. (1999) found that all importins tested were able to transport HNRNPK (600712) and PCAF (602303), in addition to the standard test substrates, but only KPNA4 showed a strong preference for the import of GDP/GTP exchange factor RCC1 (179710), which is exclusively located inside the nucleus. When HNRNPK, PCAF, and RCC1 were offered with a competing substrate nucleoplasmin (164040), they found that substrate binding was diminished or abolished in some importins and retained in others.MAPPING
By fluorescence in situ hybridization, Ayala-Madrigal et al. (2000) mapped the KPNA4 gene to chromosome 11q22. However, Gross (2011) mapped the KPNA4 gene to chromosome 3q25.33 based on an alignment of the KPNA4 sequence (GenBank GENBANK AB002533) 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602970 was added.