Importin subunit beta-1 (KPNB1)

The protein contains 876 amino acids for an estimated molecular weight of 97170 Da.

 

Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor. Acting autonomously, serves itself as NLS receptor. 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. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In association with IPO7 mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Imports SNAI1 and PRKCI into the nucleus. (updated: April 1, 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. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

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: 100
No model available.

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The reference OMIM entry for this protein is 602738

Karyopherin beta-1; kpnb1
Importin beta-1

The import of proteins into the nucleus proceeds through the nuclear pore complex. Cytoplasmic proteins with a nuclear localization signal (NLS) bind to an importin-alpha (see 600685)/importin-beta heterodimer. The trimeric complex docks to the cytoplasmic periphery of the nuclear pore complex and is subsequently translocated through as a single entity. The import reaction is terminated by the direct binding of RAN (601179) to KPNB, which dissociates the importin heterodimer.

CLONING

Gorlich et al. (1995) purified a 90-kD subunit of importin (importin-90) from Xenopus egg extracts and obtained a 188-amino acid partial protein sequence from internal peptides. Using the partial amino acid sequence, they isolated cDNAs encoding human importin-90, or KPNB1, from a HeLa cell cDNA library. The sequence of the predicted 876-amino acid human KPNB1 protein is 93% identical to the 188-amino acid partial sequence of Xenopus importin-90. Gorlich et al. (1995) showed that Xenopus importin-60 and importin-90 cooperate to form an import receptor that distinguishes functional NLSs from nonfunctional ones and selectively binds import substrates to the nuclear envelope. Independently, Chi et al. (1995) identified cDNAs encoding human KPNB1. Based on the 97-kD product of in vitro translation, they designated the protein p97. Using a monoclonal antibody against bovine p97, Chi et al. (1995) localized p97 to the cytoplasm and nuclear envelope of bovine kidney cells. These authors found that recombinant human p97 binds zinc and that a bound metal ion is required for nuclear envelope-binding activity. Kutay et al. (1997) identified the regions of KPNB1 that interact with RAN, importin-alpha, and the nuclear pore complex.

GENE FUNCTION

The guanosine triphosphatase Ran (601179) stimulates assembly of microtubule asters and spindles in mitotic Xenopus egg extracts. A carboxy-terminal region of the nuclear mitotic apparatus protein (NUMA; 164009), a nuclear protein required for organizing mitotic spindle poles, mimics Ran's ability to induce asters. This NUMA fragment also specifically interacted with importin-beta. Wiese et al. (2001) showed that importin-beta is an inhibitor of microtubule aster assembly in Xenopus egg extracts and that Ran regulates the interaction between importin-beta and NUMA. Importin-beta therefore links NUMA to regulation by Ran. Wiese et al. (2001) concluded that this suggests that similar mechanisms regulate nuclear import during interphase and spindle assembly during mitosis. The survival of motor neuron (SMN1; 600354) protein is mutated in patients with spinal muscular atrophy. SMN is part of a multiprotein complex required for biogenesis of the Sm class of small nuclear ribonucleoproteins (snRNPs). Following assembly of the Sm core domain, snRNPs are transported to the nucleus via importin-beta. Sm snRNPs contain a nuclear localization signal (NLS) consisting of a 2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin-1 (607902) is the adaptor protein that recognizes both the TMG cap and importin-beta. Narayanan et al. (2002) reported that a mutant snurportin construct lacking the importin-beta-binding (IBB) domain, but containing an intact TMG cap-binding domain, localized primarily to the nucleus, whereas full-length snurportin localized to the cytoplasm. Snurportin interacted with SMN, Gemin3 (606168), Sm snRNPs, and importin-beta. In the presence of ribonucleases, the interactions with SMN and Sm pr ... 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602738 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed