| Tbio | Importin subunit alpha-1 |
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.
The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
Comments
| Disease | Target Count |
|---|---|
| IGA Glomerulonephritis | 454 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6685 | 3.96747914393869E-262 |
| non-small cell lung carcinoma | 413 | 6.28472998257903E-19 |
| lung adenocarcinoma | 2714 | 7.75618062904858E-11 |
| acute myeloid leukemia | 785 | 0.0387058112335379 |
| Disease | log2 FC | p |
|---|---|---|
| lung adenocarcinoma | 1.300 | 0.000 |
| non-small cell lung carcinoma | 1.300 | 0.000 |
| acute myeloid leukemia | 1.100 | 0.039 |
| psoriasis | 1.800 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA EggNOG Inparanoid |
| Horse | OMA Inparanoid |
| Cow | OMA Inparanoid |
| Pig | OMA Inparanoid |
| Platypus | OMA Inparanoid |
| Chicken | OMA Inparanoid |
| Anole lizard | OMA Inparanoid |
| Xenopus | OMA Inparanoid |
| AID | Type | Active / Inconclusive / Inactive | Description |
|---|---|---|---|
| 435026 | confirmatory |
407 / 3 / 606 | Fluorescence Cell-Free Homogeneous Counterscreen to Identify Inhibitors of the RanGTP-Importin-beta complex. |
| 493094 | confirmatory |
13 / 0 / 27 | Conterscreen for target specificity Measured in Cell-Free Homogeneous System Using Plate Reader - 2041-02_Inhibitor_Dose_DryPowder_Activity |
| PMID | Text |
|---|---|
| 26884852 | The combination of low nuclear and cytoplasmic KPNA2 expression is associated with adverse outcome in head and neck squamous cell carcinoma treated with radio(chemo)therapy. |
| 26663089 | High KPNA2 expression was found to be associated with poor prognosis and resistance to hyperthermochemoradiation therapy (HCRT). |
| 26626145 | KPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer. |
| 26553592 | provided support for a link between autophagy and epithelial-to-mesenchymal (-like) transition status in WT TP53 glioblastoma cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy |
| 26491019 | RBBP4 functions as a novel regulatory factor to increase the efficiency of importin alpha/beta-mediated nuclear import |
| 26209501 | High KPNA2 expression is associated with osteoarthritis. |
| 26135850 | Suggest that KPNA2 may play a key role in the inflammation process of rheumatoid arthritis via NF-kappaB P65 signal transduction pathway. |
| 25989275 | This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function. |
| 25956057 | High KPNA2 immunoreactivity is a predictor of bladder recurrence and poor survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. |
| 25862856 | OPN, SPINK1, GPC3 and KNPA2 were significantly over-expressed in HCC tissues. These genes may be useful in developing future biomarkers and therapeutic strategies for HCC |
| More... |
MSTNENANTPAARLHRFKNKGKDSTEMRRRRIEVNVELRKAKKDDQMLKRRNVSSFPDDATSPLQENRNN 1 - 70 QGTVNWSVDDIVKGINSSNVENQLQATQAARKLLSREKQPPIDNIIRAGLIPKFVSFLGRTDCSPIQFES 71 - 140 AWALTNIASGTSEQTKAVVDGGAIPAFISLLASPHAHISEQAVWALGNIAGDGSVFRDLVIKYGAVDPLL 141 - 210 ALLAVPDMSSLACGYLRNLTWTLSNLCRNKNPAPPIDAVEQILPTLVRLLHHDDPEVLADTCWAISYLTD 211 - 280 GPNERIGMVVKTGVVPQLVKLLGASELPIVTPALRAIGNIVTGTDEQTQVVIDAGALAVFPSLLTNPKTN 281 - 350 IQKEATWTMSNITAGRQDQIQQVVNHGLVPFLVSVLSKADFKTQKEAVWAVTNYTSGGTVEQIVYLVHCG 351 - 420 IIEPLMNLLTAKDTKIILVILDAISNIFQAAEKLGETEKLSIMIEECGGLDKIEALQNHENESVYKASLS 421 - 490 LIEKYFSVEEEEDQNVVPETTSEGYTFQVQDGAPGTFNF 491 - 529 //
| PMID | Year | Title |
|---|---|---|
| 26884852 | 2015 | Low cytoplasmic and nuclear KPNA2 expression in radiotherapy-treated head and neck squamous cell cancer is associated with an adverse outcome. |
| 26663089 | 2016 | KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients. |
| 26626145 | 2015 | Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer. |
| 26553592 | 2015 | MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation. |
| 26496610 | 2015 | A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| 26491019 | 2015 | Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence. |
| 26420826 | 2015 | Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins. |
| 26209501 | 2015 | KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis. |
| 26135850 | 2015 | KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells. |
| 25989275 | 2015 | KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. |
| More... |
