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Details on Person UniProt:P52294 KPNA1

Class:IdReferenceGeneProduct:57333
_chainChangeLoginitiator methionine:1 added on Fri February 6 2015;chain:1-538 added on Fri February 6 2015;chain:2-538 added on Fri February 6 2015;initiator methionine:1 for 57333 removed on Fri Nov 03 2023;initiator methionine: for 57333 added on Fri Nov 03 2023;initiator methionine: for 57333 removed on Fri Aug 15 2025;initiator methionine:1 for 57333 added on Fri Aug 15 2025
_displayNameUniProt:P52294 KPNA1
_timestamp2025-08-15 21:00:25
chainchain:1-538
initiator methionine:1
chain:2-538
checksumE8407A3352D6051C
commentFUNCTION Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1 (PubMed:27713473, PubMed:7892216, PubMed:8692858). Binds specifically and directly to substrates containing either a simple or bipartite NLS motif (PubMed:27713473, PubMed:7892216, PubMed:8692858). 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 (PubMed:27713473, PubMed:7892216). 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 (PubMed:7892216). 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 (PubMed:7892216). Mediator of PR-DUB complex component BAP1 nuclear import; acts redundantly with KPNA2 and Transportin-1/TNPO1 (PubMed:35446349).FUNCTION (Microbial infection) In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.SUBUNIT Heterodimer; with KPNB1 (PubMed:7604027, PubMed:7892216, PubMed:8692858). Interacts with ANP32E (By similarity). Interacts with ZIC3 (By similarity). Interacts with NSMF; the interaction occurs in a calcium-independent manner after synaptic NMDA receptor stimulation and is required for nuclear import of NSMF but is competed by CABP1 (By similarity). Interacts with APEX1 (PubMed:15942031). Interacts with RAG1 (PubMed:8052633). Interacts with CTNNBL1 (via its N-terminal) (PubMed:21385873). Interacts with AICDA (via its NLS) (PubMed:21385873). Interacts with SNAI1 (via zinc fingers) (PubMed:21454664). Interacts with DCAF8 (PubMed:22500989). Interacts with ITSN1 isoform 2 (PubMed:29599122). Interacts with TALDO1 isoform 1 (By similarity). Interacts with the AMPK-mediated 'Ser-659' phosphorylated form of ACSS2; this interaction results in nuclear translocation of ACSS2 (PubMed:28552616). Interacts with BAP1 (via C-terminus); the interaction contributes to BAP1 nuclear localization (PubMed:35446349).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HCMV UL84.SUBUNIT (Microbial infection) Interacts with HIV-1 Vpr.SUBUNIT (Microbial infection) Interacts with ebolavirus protein VP24.SUBUNIT (Microbial infection) Interacts with the venezuelan equine encephalitis virus protease nsP2; this interaction probably allows the active transport of protease nsP2 into the host nucleus.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus EBNA1; this interaction allows the nuclear import of EBNA1.SUBUNIT (Microbial infection) Interacts with human parainfluenza virus type 2 proteins P and V.INTERACTION 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).PTM Polyubiquitinated in the presence of RAG1 (in vitro).SIMILARITY Belongs to the importin alpha family.
descriptionrecommendedName: Importin subunit alpha-5 alternativeName: fullName evidence="31"Karyopherin subunit alpha-1 alternativeName: fullName evidence="30"Nucleoprotein interactor 1 shortName evidence="30"NPI-1 alternativeName: RAG cohort protein 2 alternativeName: SRP1-beta component recommendedName: Importin subunit alpha-5, N-terminally processed /component
geneNameKPNA1
RCH2
identifierP52294
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Cytoplasm
Direct protein sequencing
Host-virus interaction
Nucleus
Phosphoprotein
Protein transport
Proteomics identification
Reference proteome
Repeat
Transport
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameKPNA1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9000637] ENSEMBL:ENSG00000114030 KPNA1 [Homo sapiens]
secondaryIdentifierIMA5_HUMAN
D3DN93
Q6IBQ9
Q9BQ56
sequenceLength538
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:180612] KPNA1 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:188865] KPNA1 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P52294 KPNA1 (57333)