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MGP001779

UniProt Annotations

Entry Information
Gene Namekaryopherin alpha 2 (RAG cohort 1, importin alpha 1)
Protein EntryIMA1_HUMAN
UniProt IDP52292
SpeciesHuman
Comments
Comment typeDescription
DomainConsists 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. {ECO:0000269|PubMed:8617227}.
DomainThe 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). {ECO:0000250}.
DomainThe 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). {ECO:0000250}.
FunctionFunctions 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.
InteractionP38398:BRCA1; NbExp=3; IntAct=EBI-349938, EBI-349905; P05412:JUN; NbExp=2; IntAct=EBI-349938, EBI-852823; P03101:L1 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362698; P03107:L2 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362531; Q6GQG6:npm2 (xeno); NbExp=2; IntAct=EBI-349938, EBI-8469111; P46063:RECQL; NbExp=2; IntAct=EBI-349938, EBI-2823728; P29034:S100A2; NbExp=5; IntAct=EBI-349938, EBI-752230; P06703:S100A6; NbExp=3; IntAct=EBI-349938, EBI-352877; Q9UH99:SUN2; NbExp=3; IntAct=EBI-349938, EBI-1044964;
Mass SpectrometryMass=57861.92; Method=MALDI; Range=1-529; Evidence={ECO:0000269|PubMed:11840567};
SimilarityBelongs to the importin alpha family. {ECO:0000305}.
SimilarityContains 10 ARM repeats. {ECO:0000255|PROSITE- ProRule:PRU00259}.
SimilarityContains 1 IBB domain. {ECO:0000255|PROSITE- ProRule:PRU00561}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:7604027}. Nucleus {ECO:0000269|PubMed:7604027}.
SubunitHeterodimer; 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 FRG1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc fingers). {ECO:0000250, ECO:0000269|PubMed:10980193, ECO:0000269|PubMed:11882654, ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:16188882, ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:21454664, ECO:0000269|PubMed:21699900, ECO:0000269|PubMed:7604027, ECO:0000269|PubMed:9323134, ECO:0000269|PubMed:9463369, ECO:0000269|PubMed:9786944}.
Tissue SpecificityExpressed ubiquitously.
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