Importin subunit alpha-7 (KPNA6)

The protein contains 536 amino acids for an estimated molecular weight of 60030 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. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 50
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 610563

Karyopherin alpha-6; kpna6
Importin alpha-7

DESCRIPTION

Importin alpha proteins, such as KPNA6, play a pivotal role in the classical nuclear protein import pathway. Importin alpha shuttles between the nucleus and cytoplasm, binds nuclear localization signal-bearing proteins, and functions as an adaptor to access the importin beta (see KPNB1, 602738)-dependent import pathway (Kohler et al., 1999).

CLONING

By searching a database for sequences similar to mouse importin alpha-S2, followed by 5-prime RACE of a HeLa cell cDNA library, Kohler et al. (1999) cloned KPNA6, which they called importin alpha-7. The deduced 536-amino acid protein shares a high degree of identity with KPNA5 (604545). Northern blot analysis detected an 8-kb transcript in all tissues examined except thymus, with highest expression in skeletal muscle. Western blot analysis detected the protein in all tissues examined.

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 KPNA6, 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. By Western blot analysis and in vitro binding assays, Ma and Cao (2006) found that nuclear translocation of STAT3 (102582) and STAT1 (600555) is mediated by binding of human KPNA1 (600686) and KPNA6.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the KPNA6 gene to chromosome 1 (TMAP SHGC-74534). ... More on the omim web site

Subscribe to this protein entry history

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 610563 was added.