Transportin-1 (TNPO1)
The protein contains 898 amino acids for an estimated molecular weight of 102355 Da.
Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:24753571). Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin 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 the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. 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 (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Appears also to be involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones, and SRP19 (By similarity). Mediates nuclear import of ADAR/ADAR1 isoform 1 and isoform 5 in a RanGTP-dependent manner (PubMed:19124606, PubMed:24753571).', '(Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear im (updated: March 28, 2018)
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.
- 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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs25661 |
Biological Process
Gene expression
Intraciliary transport involved in cilium assembly
NLS-bearing protein import into nucleus
Obsolete protein import into nucleus, translocation
Organelle organization
Protein import into nucleus
Regulation of mRNA stability
Ribosomal protein import into nucleus
Viral process
Cellular Component
Cilium
Cytoplasm
Cytosol
Extracellular exosome
Nuclear membrane
Nuclear periphery
Nucleus
Primary cilium
The reference OMIM entry for this protein is 602901
Transportin 1; tnpo1
Transportin
Karyopherin beta-2; kpnb2
M9-interacting protein; mip1
Importin beta-2
CLONING
Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the protein's nuclear localization signal (NLS) and the importin, or karyopherin, receptor complex. An importin heterodimer recognizes the NLS protein in the cytoplasm via its alpha subunit and, via its beta subunit, docks the complex to a subset of peptide repeat-containing proteins known as nucleoporins. See importin beta-1 (KPNB1; 602738). Michael et al. (1995) determined that the C terminus of HNRNPA1 (164017) contains a 38-amino acid domain, termed M9, that confers bidirectional transport across the nuclear envelope. Pollard et al. (1996) found that M9-mediated nuclear import occurs by a novel pathway independent of the importin-mediated NLS pathway. Using a yeast 2-hybrid system, they identified a HeLa cell cDNA encoding a protein that interacts with an M9-containing sequence. The predicted 890-amino acid protein was designated M9-interacting protein (MIP1), or transportin. Transportin contains 2 leucine zipper motifs and a 19-amino acid highly acidic domain, and has an estimated pI of 4.6. Pollard et al. (1996) demonstrated that transportin mediated the nuclear import of M9-bearing proteins. Bonifaci et al. (1997) isolated cDNAs encoding transportin, which they designated karyopherin beta-2, or KPNB2. They reported that the predicted protein sequence is 34% identical to that of the yeast beta-karyopherin Kap104p. Using overlay blots, Bonifaci et al. (1997) demonstrated that KPNB2 also functions as a docking factor that binds to peptide repeat-containing nucleoporins. In an assay using permeabilized HeLa cells, KPNB2 inhibited KPNB1-mediated import of an NLS-containing substrate and KPNB1 inhibited KPNB2-mediated import of recombinant HNRNPA1. These results led Bonifaci et al. (1997) to suggest that the distinct KPNB1- and KPNB2-mediated nuclear import pathways merge at least partially at the level of docking to nucleoporins.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the KPNB2 gene to chromosome 5 (TMAP WI-13973).BIOCHEMICAL FEATURES
- Crystal Structure Lee et al. (2003) showed the crystal structure of importin-beta complexed with the active form of SREBP2 (600481). Importin-beta uses characteristic long helices like a pair of chopsticks to interact with an SREBP2 dimer. Importin-beta changes its conformation to reveal a pseudo-2-fold symmetry on its surface structure so that it can accommodate a symmetric dimer molecule. ... More on the omim web site
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602901 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed