ID:IMA2_HUMAN DESCRIPTION: RecName: Full=Importin subunit alpha-2; AltName: Full=Karyopherin subunit alpha-2; AltName: Full=RAG cohort protein 1; AltName: Full=SRP1-alpha; FUNCTION: 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. SUBUNIT: Heterodimer; with KPNB1. Interacts with ANP32E (By similarity). Component of a complex containing CSE1L, RAN and KPNA2. Interacts directly with CSE1L. Interacts with HIV-1 Vpr and PLAG1. Interacts with APEX1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN. INTERACTION: P38398:BRCA1; NbExp=3; IntAct=EBI-349938, EBI-349905; P05412:JUN; NbExp=2; IntAct=EBI-349938, EBI-852823; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: Expressed ubiquitously. DOMAIN: Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import. DOMAIN: The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS- containing proteins (By similarity). DOMAIN: The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity). MASS SPECTROMETRY: Mass=57861.92; Method=MALDI; Range=1-529; Source=PubMed:11840567; SIMILARITY: Belongs to the importin alpha family. SIMILARITY: Contains 10 ARM repeats. SIMILARITY: Contains 1 IBB domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P52292
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003723 RNA binding GO:0005515 protein binding GO:0008139 nuclear localization sequence binding GO:0008565 protein transporter activity GO:0042826 histone deacetylase binding GO:0061608 nuclear import signal receptor activity
Biological Process: GO:0000018 regulation of DNA recombination GO:0006259 DNA metabolic process GO:0006606 protein import into nucleus GO:0006607 NLS-bearing protein import into nucleus GO:0015031 protein transport GO:0016032 viral process GO:0019054 modulation by virus of host process
BioCarta from NCI Cancer Genome Anatomy Project h_npcPathway - Mechanism of Protein Import into the Nucleus h_ranMSpathway - Role of Ran in mitotic spindle regulation
Reactome (by CSHL, EBI, and GO)
Protein P52292 (Reactome details) participates in the following event(s):