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    KPNA1 karyopherin alpha 1 (importin alpha 5) [ Homo sapiens ]

    Gene ID: 3836, updated on 11-May-2012
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    Summary

    Official Symbol
    KPNA1provided by HGNC
    Official Full Name
    karyopherin alpha 1 (importin alpha 5)provided by HGNC
    Primary source
    HGNC:6394
    See related
    Ensembl:ENSG00000114030; HPRD:02819; MIM:600686; Vega:OTTHUMG00000159487
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RCH2; SRP1; IPOA5; NPI-1
    Summary
    Recombination activating proteins RAG1 and RAG2 regulate and mediate V(D)J recombination, the process by which genes for immunoglobulins and T-cell receptors are generated. Several other ubiquitously expressed proteins are thought to be recruited in the recombination process. Among these are the genes affected in severe combined immune deficiency and genes involved in ds-DNA break repair. The protein encoded by this gene interacts with RAG1 and may play a role in V(D)J recombination. Two transcript variants, one protein-coding and the other not, have been found for this gene. [provided by RefSeq, Jan 2009]
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    Genomic context

    Location :
    3q21
    Sequence :
    Chromosome: 3; NC_000003.11 (122140748..122233786, complement)
    See KPNA1 in Epigenomics, MapViewer

    Chromosome 3 - NC_000003.11Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 162, member A Neighboring gene WD repeat domain 5B Neighboring gene poly (ADP-ribose) polymerase family, member 9 Neighboring gene deltex 3-like (Drosophila) Neighboring gene poly (ADP-ribose) polymerase family, member 14 pseudogene Neighboring gene poly (ADP-ribose) polymerase family, member 15

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin α5. Pumroy RA, et al. J Biol Chem, 2012 Jan 13. PMID 22130666.
    2. Nuclear exportin receptor CAS regulates the NPI-1-mediated nuclear import of HIV-1 Vpr. Takeda E, et al. PLoS One, 2011. PMID 22110766.
    3. The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import. Shabman RS, et al. J Infect Dis, 2011 Nov. PMID 21987768.
    4. Global identification of modular cullin-RING ligase substrates. Emanuele MJ, et al. Cell, 2011 Oct 14. PMID 21963094.
    5. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.

    See all (118) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. the requirement for and the regulation of CAS in the functioning of the Vpr-Impalpha complex
      Title: Nuclear exportin receptor CAS regulates the NPI-1-mediated nuclear import of HIV-1 Vpr.
    2. Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin alpha5.
      Title: Nucleoporin Nup50 stabilizes closed conformation of armadillo repeat 10 in importin α5.
    3. The ability of hnRNP C1/C2 to bind KPNA1 is diminished in the presence of VP24, and cells transiently expressing VP24 redistribute hnRNP C1/C2 from the nucleus to the cytoplasm.
      Title: The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import.
    4. This study reports the identification and classification of importin alpha 5 -interacting proteins in brain cells.
      Title: Proteomic analysis of importin α-interacting proteins in adult mouse brain.
    5. The mammalian E1 subunits can be imported separately, identify nuclear localization signals (NLSs) in Aos1 and in Uba2, and demonstrate that their import is mediated by importin alpha/beta in vitro and in intact cells.
      Title: Importin α/β mediates nuclear import of individual SUMO E1 subunits and of the holo-enzyme.
    6. Impalpha5 acts as a chaperone until Influenza a virus nucleoprotein (NP) is delivered in the nucleus for viral RNA encapsidation.
      Title: Human importin alpha and RNA do not compete for binding to influenza A virus nucleoprotein.
    7. Study identified the sequences KKKRR, KKKRK, and KKRKK as the optimal sequences for binding to this site for mouse importin-alpha2, human importin-alpha1, and human importin-alpha5, respectively.
      Title: Probing the specificity of binding to the major nuclear localization sequence-binding site of importin-alpha using oriented peptide library screening.
    8. The papillomavirus E2 proteins preferentially interacted with alpha importins 3 and 5, and showed very weak or no interaction with the other three widely expressed alpha importins (alpha1, alpha 4, and alpha 7).
      Title: Common importin alpha specificity for papillomavirus E2 proteins.
    9. The VP24 IFN antagonist function of ebolavirus requires the ability of VP24 to interact with KPNalpha.
      Title: Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling.
    10. Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase.
      Title: Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase.
    Submit: New GeneRIF Correction See all (19)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr interacts with importin-alpha through alphaH1 (residues 17-34) and alphaH2 (residues 46-74); the interaction via alphaH1 is indispensable for the nuclear entry of Vpr, and residues 393-462 of importin-alpha promote entry of Vpr into the nucleus PubMed
    vpr HIV-1 Vpr interacts with both karyopherin alpha 1 and alpha 2 to facilitate nuclear import of the HIV-1 preintegration complex, however conflicting reports indicate it may also be imported by other mechanisms independently of karyopherin alpha 1 and 2 PubMed
    integrase gag-pol Some reports indicate a possible role for the interactions between karyopherin alpha and beta with HIV-1 integrase in the nuclear import of HIV-1 preintegration complexes (PIC), while other reports indicate integrase is not involved in PIC nuclear import PubMed
    gag-pol Karyopherin alpha binds to a bipartite nuclear localization signal in HIV-1 integrase (amino acids 186-189 and 211-219) PubMed
    gag-pol Karyopherin alpha and beta are reported to interact with HIV-1 integrase (IN) to facilitate nuclear import of IN, however a conflicting report indicates nuclear accumulation of IN does not involve karyopherin alpha, beta 1, or beta 2 mediated pathways PubMed
    matrix gag Nuclear import of HIV-1 preintegration complexes by karyopherin alpha is governed by phosphorylation of HIV-1 Matrix on tyrosine and serine, however the exact role of phosphorylation of the C-terminal tyrosine of Matrix has been debated PubMed
    gag HIV-1 Matrix increases intracellular ATP content, an effect hypothesized to support the ATP-dependent nuclear import of HIV-1 preintegration complexes by karyopherin alpha PubMed
    gag HIV-1 Vpr increases the affinity of karyopherin alpha to the HIV-1 Matrix nuclear localization signal, thereby mediating the nuclear import of HIV-1 preintegration complexes PubMed
    gag Hsp70 stimulates the binding of HIV-1 matrix to karyopherin alpha PubMed
    gag The role of HIV-1 Matrix during nuclear import of the HIV-1 preintegration complex has been controversial, however recent understanding indicates HIV-1 Matrix and Vpr proteins act in concert to facilitate nuclear import by binding to karyopherin alpha PubMed
    gag HIV-1 Matrix contains two nuclear localization signals (NLS) spanning amino acids 24-33 and 110-114 that are recognized by karyopherin alpha and mediate the nuclear import of HIV-1 preintegration complexes PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P52294 P39687 ANP32A    HPRD  PubMed  
    P52294 Q15717 ELAVL1    HPRD  PubMed  
    P52294 Q16778 HIST2H2BE    HPRD  PubMed  
    P52294 Q16695 HIST3H3    HPRD  PubMed  
    P52294 Q9UJU2 LEF1    HPRD  PubMed  
    P52294 P61968 LMO4    HPRD  PubMed  
    P52294 Q02548 PAX5    HPRD  PubMed  
    P52294 P15918 RAG1    HPRD  PubMed  
    P52294 Q06455 RUNX1T1    HPRD  PubMed  
    P52294 P09132 SRP19    HPRD  PubMed  
    P52294 P42224 STAT1    HPRD  PubMed  
    P52294 P40763 STAT3    HPRD  PubMed  
    P52294 Q16594 TAF9    HPRD  PubMed  
    P52294 O95071 UBR5    HPRD  PubMed  
    BioGRID:110034 BioGRID:121497 AICDA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:107461 CDKN1B    BioGRID  PubMed Affinity Capture-Western; Protein-peptide; Reconstituted Complex 
    BioGRID:110034 BioGRID:107821 CSE1L    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:121123 CTNNBL1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:114028 CUL4B    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:207838 Ddx21    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:109540 HSPA4    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110034 BioGRID:110035 KPNB1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:120780 LYAR    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:121122 MEPCE    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:201430 Mki67    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:119759 NUP54    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:117165 NUP62    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:203509 Nhp2l1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:214531 Nipbl    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:111370 PLRG1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:118151 PRPF19    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:117563 PRPF31    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:111832 RAG1    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:110034 BioGRID:111833 RAG2    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:110034 BioGRID:111839 RANBP2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:107310 RUNX1T1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:124097 SLX4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:112649 STAT1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110034 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:116624 TPX2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110034 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:110034 BioGRID:119501 UBR5    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:110034 BioGRID:113241 USP1    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Activation of DNA fragmentation factor, organism-specific biosystem (from REACTOME)
      Activation of DNA fragmentation factor, organism-specific biosystemDNA fragmentation in response to apoptotic signals is achieved, in part, through the activity of apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) (reviewed ...
    • Antiviral mechanism by IFN-stimulated genes, organism-specific biosystem (from REACTOME)
      Antiviral mechanism by IFN-stimulated genes, organism-specific biosystemThe ISG proteins generated by IFN pathways plays key roles in the induction of innate and adaptive immune responses.
    • Apoptosis, organism-specific biosystem (from REACTOME)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Apoptosis induced DNA fragmentation, organism-specific biosystem (from REACTOME)
      Apoptosis induced DNA fragmentation, organism-specific biosystemDNA fragmentation in response to apoptotic signals is achieved through the activity of two apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) and endonuclease...
    • Apoptotic execution phase, organism-specific biosystem (from REACTOME)
      Apoptotic execution phase, organism-specific biosystemIn the execution phase of apoptosis, effector caspases cleave vital cellular proteins leading to the morphological changes that characterize apoptosis. These changes include destruction of the nucle...
    • Class I PI3K signaling events mediated by Akt, organism-specific biosystem (from Pathway Interaction Database)
      Class I PI3K signaling events mediated by Akt, organism-specific biosystem
      Class I PI3K signaling events mediated by Akt
    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • HIV Infection, organism-specific biosystem (from REACTOME)
      HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
    • Host Interactions of HIV factors, organism-specific biosystem (from REACTOME)
      Host Interactions of HIV factors, organism-specific biosystemLike all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewis...
    • ISG15 antiviral mechanism, organism-specific biosystem (from REACTOME)
      ISG15 antiviral mechanism, organism-specific biosystemInterferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. On...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Influenza A, organism-specific biosystem (from KEGG)
      Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Influenza A, conserved biosystem (from KEGG)
      Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Influenza Infection, organism-specific biosystem (from REACTOME)
      Influenza Infection, organism-specific biosystemFor centuries influenza epidemics have plagued man, and influenza was probably the disease described by Hippocrates in 412 BC. Today it remains a major cause of morbidity and mortality worldwide with...
    • Influenza Life Cycle, organism-specific biosystem (from REACTOME)
      Influenza Life Cycle, organism-specific biosystemThe virus particle initially associates with a human host cell by binding to sialic acid-containing receptors on the host cell surface. The bound virus is endocytosed by one of four distinct mechanis...
    • Interactions of Vpr with host cellular proteins, organism-specific biosystem (from REACTOME)
      Interactions of Vpr with host cellular proteins, organism-specific biosystemVpr has been implicated in multiple processes during HIV-1 replication, including nuclear import of the pre-integration complex (PIC)(Heinzinger et al., 1994), apoptosis (Stewart et al., 1997) and in...
    • Interferon Signaling, organism-specific biosystem (from REACTOME)
      Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
    • Transport of Ribonucleoproteins into the Host Nucleus, organism-specific biosystem (from REACTOME)
      Transport of Ribonucleoproteins into the Host Nucleus, organism-specific biosystemAn unusual characteristic of the influenza virus life cycle is its dependence on the nucleus. Trafficking of the viral genome into and out of the nucleus is a tightly regulated process with all viral...
    • Vpr-mediated nuclear import of PICs, organism-specific biosystem (from REACTOME)
      Vpr-mediated nuclear import of PICs, organism-specific biosystemVpr appears to function in anchoring the PIC to the nuclear envelope. This anchoring likely involves interactions between Vpr and host nucleoporins.

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    nuclear localization sequence binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    DNA fragmentation involved in apoptotic nuclear change TAS
    Traceable Author Statement
    more info
    		  
    NLS-bearing substrate import into nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    		  
    cellular component disassembly involved in apoptosis TAS
    Traceable Author Statement
    more info
    		  
    cytokine-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    interspecies interaction between organisms IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of DNA recombination TAS
    Traceable Author Statement
    more info
    		 PubMed 
    viral genome transport in host cell TAS
    Traceable Author Statement
    more info
    		  
    viral infectious cycle TAS
    Traceable Author Statement
    more info
    		  
    viral reproduction TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    nuclear pore TAS
    Traceable Author Statement
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    importin subunit alpha-1
    Names
    importin subunit alpha-1
    SRP1-beta
    importin alpha 5
    importin-alpha-S1
    RAG cohort protein 2
    nucleoprotein interactor 1
    karyopherin subunit alpha-1
    recombination activating gene cohort 2
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_002264.3 → NP_002255.3  importin subunit alpha-1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks an alternate exon compared to variant 2 and represents the protein-coding transcript.
      Source sequence(s)
      AC083798, BC003009, DA308391, U20620
      Consensus CDS
      CCDS3013.1
      UniProtKB/Swiss-Prot
      P52294
      Related
      ENSP00000343701, OTTHUMP00000215561, ENST00000344337, OTTHUMT00000355740
      Conserved Domains (3) summary
      cd00020
      Location:120 – 241
      Blast Score: 256
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      COG5064
      Location:9 – 516
      Blast Score: 1388
      SRP1; Karyopherin (importin) alpha [Intracellular trafficking and secretion]
      pfam01749
      Location:2 – 96
      Blast Score: 212
      IBB; Importin beta binding domain

    RNA

    1. NR_026698.1 RNA Sequence

      Description
      Transcript Variant: This variant (2) is the longer transcript and is likely not protein-coding.
      Source sequence(s)
      AC083798, BC003009, DA308391, DN991078, U20620

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000003.11 Reference GRCh37.p5 Primary Assembly

      Range
      122140748..122233786, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000135.1 Alternate HuRef

      Range
      119513915..119606857, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC083798.14 (136719..145604) None
    genomic AC096861.5 (2005..86015) None
    genomic CH471052.2 EAW79482.1
      EAW79483.1
    mRNA AA689229.1 None
    mRNA AF035311.1 None
    mRNA AI216375.1 None
    mRNA AK125626.1 BAG54224.1
    mRNA AK128280.1 BAG54654.1
    mRNA AK299030.1 BAG61106.1
    mRNA AK312713.1 None
    mRNA AL700464.1 None
    mRNA AL710311.1 None
    mRNA BC002374.2 AAH02374.1
    mRNA BC003009.1 AAH03009.1
    mRNA BC029937.1 None
    mRNA BC090864.1 AAH90864.1
    mRNA BG287593.1 None
    mRNA BT006959.1 AAP35605.1
    mRNA CA433573.1 None
    mRNA CR456743.1 CAG33024.1
    mRNA DA308391.1 None
    mRNA DN991078.1 None
    mRNA S75295.1 AAC60648.1
    mRNA U20620.1 None
    other-genetic DQ891406.2 ABM82332.1
    other-genetic DQ896822.2 ABM87821.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P52294.3 GenPept UniProtKB/Swiss-Prot:P52294
    Q5BKZ2 GenPept UniProtKB/TrEMBL:Q5BKZ2
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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