Importin subunit alpha-4 (KPNA3)
The protein contains 521 amino acids for an estimated molecular weight of 57811 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. Recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9. (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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs1043015 |
The reference OMIM entry for this protein is 601892
Karyopherin alpha-3; kpna3
Importin alpha-4
CLONING
From a human fetal brain cDNA library, Takeda et al. (1997) isolated and characterized a novel gene, designated KPNA3, encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone contained an open reading frame encoding 521 amino acids. The predicted amino acid sequence shows 48%, 45%, and 48% identity with Xenopus importin, yeast SRP1, and human RCH1 (KPNA2; 600685), respectively. The similarities among these proteins suggested that KPNA3 may be involved in the nuclear transport system. Kohler et al. (1997) isolated a human KPNA3 cDNA. The predicted KPNA3 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, KPNA3 shares the highest sequence identity with KPNA4 (602970). Northern blot analysis detected a 4.6-kb KPNA3 transcript in all tissues tested. However, expression levels varied considerably among tissues, with the highest expression in testis and colon and the lowest expression in liver, kidney, and peripheral blood leukocytes.GENE FUNCTION
Using an in vitro import assay based on permeabilized HeLa cells to study the import substrate specificity of all ubiquitously expressed importins, including KPNA3, 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 (601892) 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. Mammalian spermiogenesis is characterized by a unique chromatin-remodeling process in which histones are replaced by transition protein-1 (TNP1; 190231), TNP2 (190232), and TNP4, which are further replaced by protamines (see 182880). Pradeepa et al. (2008) showed that importin alpha-4 was upregulated in tetraploid and haploid germ cells of rat testis and was required for nuclear import of Tnp2. In contrast, import of Tnp1 occurred by passive diffusion.MAPPING
By fluorescence in situ hybridization, Takeda et al. (1997) mapped the KPNA3 gene to chromosome 13q14.3. ... 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 601892 was added.