Descriptions
Importin-α is a nuclear import receptor that facilitates the transport of proteins with nuclear localization sequences (NLSs) into the nucleus. It is autoinhibited by its N-terminal region, which occupies the NLS-binding site, preventing unnecessary binding and import activity. Importin-α is autoinhibited in the absence of importin-β and the binding of importin-β alleviates this autoinhibition, which displaces the autoinhibitory sequence.
Autoinhibitory domains (AIDs)
Target domain |
149-241 (Major NLS-binding site);318-406 (Minor NLS-binding site) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Fontes MR et al. (2000) "Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha", Journal of molecular biology, 297, 1183-94
- Fontes MR et al. (2003) "Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha", The Journal of biological chemistry, 278, 27981-7
- Catimel B et al. (2001) "Biophysical characterization of interactions involving importin-alpha during nuclear import", The Journal of biological chemistry, 276, 34189-98
- Pumroy RA et al. (2015) "Molecular determinants for nuclear import of influenza A PB2 by importin α isoforms 3 and 7", Structure (London, England : 1993), 23, 374-84
- Kimoto C et al. (2015) "Functional characterization of importin α8 as a classical nuclear localization signal receptor", Biochimica et biophysica acta, 1853, 2676-83
- Miyatake H et al. (2015) "Crystal structure of human importin-α1 (Rch1), revealing a potential autoinhibition mode involving homodimerization", PloS one, 10, e0115995
- Kobe B (1999) "Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha", Nature structural biology, 6, 388-97
Autoinhibited structure
Activated structure
1 structures for P83953
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P83953-F1 | Predicted | AlphaFoldDB |
No variants for P83953
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P83953 | |||||
No associated diseases with P83953
9 regional properties for P83953
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| repeat | Armadillo | 115 - 198 | IPR000225-1 |
| repeat | Armadillo | 200 - 241 | IPR000225-2 |
| repeat | Armadillo | 244 - 283 | IPR000225-3 |
| repeat | Armadillo | 285 - 325 | IPR000225-4 |
| repeat | Armadillo | 327 - 369 | IPR000225-5 |
| repeat | Armadillo | 369 - 409 | IPR000225-6 |
| repeat | Armadillo | 412 - 452 | IPR000225-7 |
| domain | Importin-alpha, importin-beta-binding domain | 1 - 104 | IPR002652 |
| repeat | Atypical Arm repeat | 466 - 515 | IPR032413 |
7 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| dendrite | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| NLS-dependent protein nuclear import complex | A dimer consisting of an alpha and a beta-subunit that imports proteins with an NLS into the nucleus through a nuclear pore. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| postsynaptic density | An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| nuclear import signal receptor activity | Combining with a nuclear import signal (NIS) on a cargo to be transported, to mediate transport of the cargo through the nuclear pore, from the cytoplasm to the nuclear lumen. The cargo can be either a RNA or a protein. |
| nuclear localization sequence binding | Binding to a nuclear localization sequence, a specific peptide sequence that acts as a signal to localize the protein within the nucleus. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| NLS-bearing protein import into nucleus | The directed movement of a protein bearing a nuclear localization signal (NLS) from the cytoplasm into the nucleus, across the nuclear envelope. |
| postsynapse to nucleus signaling pathway | The series of molecular signals that conveys information from the postsynapse to the nucleus via cytoskeletal transport of a protein from a postsynapse to the component to the nucleus where it affects biochemical processes that occur in the nucleus (e.g DNA transcription, mRNA splicing, or DNA/histone modifications). |
| regulation of apoptotic process | Any process that modulates the occurrence or rate of cell death by apoptotic process. |
| regulation of canonical Wnt signaling pathway | Any process that modulates the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. |
| satellite cell activation involved in skeletal muscle regeneration | The process that initiates skeletal muscle satellite cell division by causing it to move from quiescence to the G1 stage of the cell cycle. The cell swells and there are a number of other small changes. The cells then start to divide. Following cell division the cells will differentiate. In adult muscle, satellite cells become activated to divide and differentiate in response to muscle damage. |
| skeletal muscle satellite cell proliferation | The multiplication or reproduction of satellite cells, resulting in the expansion of the cell population. Satellite cells are quiescent cells that are located between the basal lamina and the plasmalemma of the muscle fiber, which are the main contributors to postnatal muscle growth. In adult muscle, satellite cells become activated to divide and differentiate in response to muscle damage. |
| skeletal muscle tissue regeneration | The regrowth of skeletal muscle tissue to repair injured or damaged muscle fibers in the postnatal stage. |
30 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q02821 | SRP1 | Importin subunit alpha | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| Q0V7M0 | KPNA6 | Importin subunit alpha-7 | Bos taurus (Bovine) | SS |
| C1JZ66 | KPNA7 | Importin subunit alpha-8 | Bos taurus (Bovine) | PR |
| A2VE08 | KPNA1 | Importin subunit alpha-5 | Bos taurus (Bovine) | SS |
| Q5ZML1 | KPNA1 | Importin subunit alpha-5 | Gallus gallus (Chicken) | SS |
| P52295 | Pen | Importin subunit alpha | Drosophila melanogaster (Fruit fly) | SS |
| O00505 | KPNA3 | Importin subunit alpha-4 | Homo sapiens (Human) | SS |
| A9QM74 | KPNA7 | Importin subunit alpha-8 | Homo sapiens (Human) | EV |
| O00629 | KPNA4 | Importin subunit alpha-3 | Homo sapiens (Human) | SS |
| O15131 | KPNA5 | Importin subunit alpha-6 | Homo sapiens (Human) | SS |
| O60684 | KPNA6 | Importin subunit alpha-7 | Homo sapiens (Human) | SS |
| P52292 | KPNA2 | Importin subunit alpha-1 | Homo sapiens (Human) | EV |
| P52294 | KPNA1 | Importin subunit alpha-5 | Homo sapiens (Human) | SS |
| P52293 | Kpna2 | Importin subunit alpha-1 | Mus musculus (Mouse) | EV |
| O35344 | Kpna3 | Importin subunit alpha-4 | Mus musculus (Mouse) | SS |
| O35343 | Kpna4 | Importin subunit alpha-3 | Mus musculus (Mouse) | SS |
| O35345 | Kpna6 | Importin subunit alpha-7 | Mus musculus (Mouse) | PR |
| C0LLJ0 | Kpna7 | Importin subunit alpha-8 | Mus musculus (Mouse) | SS |
| Q60960 | Kpna1 | Importin subunit alpha-5 | Mus musculus (Mouse) | SS |
| C6K7I2 | KPNA7 | Importin subunit alpha-8 | Sus scrofa (Pig) | SS |
| Q56R16 | Kpna5 | Importin subunit alpha-6 | Rattus norvegicus (Rat) | SS |
| Q71VM4 | Os01g0253300 | Importin subunit alpha-1a | Oryza sativa subsp. japonica (Rice) | SS |
| P91276 | ima-2 | Importin subunit alpha-2 | Caenorhabditis elegans | SS |
| Q19969 | ima-3 | Importin subunit alpha-3 | Caenorhabditis elegans | SS |
| O04294 | IMPA3 | Importin subunit alpha-3 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FJ09 | IMPA5 | Importin subunit alpha-5 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9FWY7 | IMPA6 | Importin subunit alpha-6 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| Q9M9X7 | IMPA7 | Importin subunit alpha-7 | Arabidopsis thaliana (Mouse-ear cress) | SS |
| O22478 | Importin subunit alpha | Solanum lycopersicum (Tomato) (Lycopersicon esculentum) | SS | |
| Q503E9 | kpna5 | Importin subunit alpha-6 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSTPGKENFR | LKSYKNKSLN | PDEMRRRREE | EGLQLRKQKR | EEQLFKRRNV | ATAEEETEEE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| VMSDGGFHEA | QINNMEMAPG | GVITSDMTEM | IFSNSPEQQL | SATQKFRKLL | SKEPNPPIDE |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VINTPGVVAR | FVEFLKRKEN | CTLQFESAWV | LTNIASGNSL | QTRIVIQAGA | VPIFIELLSS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| EFEDVQEQAV | WALGNIAGDS | TMCRDYVLDC | NILPPLLQLF | SKQNRLTMTR | NAVWALSNLC |
| 250 | 260 | 270 | 280 | 290 | 300 |
| RGKSPPPEFA | KVSPCLNVLS | WLLFVSDTDV | LADACWALSY | LSDGPNDKIQ | AVIDAGVCRR |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LVELLMHNDY | KVVSPALRAV | GNIVTGDDIQ | TQVILNCSAL | QSLLHLLSSP | KESIKKEACW |
| 370 | 380 | 390 | 400 | 410 | 420 |
| TISNITAGNR | AQIQTVIDAN | MFPALISILQ | TAEFRTRKEA | AWAITNATSG | GSAEQIKYLV |
| 430 | 440 | 450 | 460 | 470 | 480 |
| ELGCIKPLCD | LLTVMDAKIV | QVALNGLENI | LRLGEQEAKR | NGSGINPYCA | LIEEAYGLDK |
| 490 | 500 | 510 | 520 | 530 | |
| IEFLQSHENQ | EIYQKAFDLI | EHYFGTEDED | SSIAPQVDLS | QQQYIFQQCE | APMEGSQL |