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    KPNA2 karyopherin subunit alpha 2 [ Homo sapiens (human) ]

    Gene ID: 3838, updated on 17-May-2024

    Summary

    Official Symbol
    KPNA2provided by HGNC
    Official Full Name
    karyopherin subunit alpha 2provided by HGNC
    Primary source
    HGNC:HGNC:6395
    See related
    Ensembl:ENSG00000182481 MIM:600685; AllianceGenome:HGNC:6395
    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
    QIP2; RCH1; IPOA1; PTAC58; SRP1alpha; SRP1-alpha
    Summary
    The import of proteins into the nucleus is a process that involves at least 2 steps. The first is an energy-independent docking of the protein to the nuclear envelope and the second is an energy-dependent translocation through the nuclear pore complex. Imported proteins require a nuclear localization sequence (NLS) which generally consists of a short region of basic amino acids or 2 such regions spaced about 10 amino acids apart. Proteins involved in the first step of nuclear import have been identified in different systems. These include the Xenopus protein importin and its yeast homolog, SRP1 (a suppressor of certain temperature-sensitive mutations of RNA polymerase I in Saccharomyces cerevisiae), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
    Expression
    Broad expression in testis (RPKM 102.8), bone marrow (RPKM 35.5) and 20 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See KPNA2 in Genome Data Viewer
    Location:
    17q24.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (68035735..68046854)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (68911511..68922628)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (66031851..66042970)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12634 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8880 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8881 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8882 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8883 Neighboring gene chromosome 17 open reading frame 58 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:66016003-66016576 Neighboring gene tRNA-Arg (anticodon CCG) 2-1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:66031597-66032144 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12635 Neighboring gene MPRA-validated peak2956 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:66076452-66076952 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:66076953-66077453 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:66083143-66083718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12636 Neighboring gene uncharacterized LOC124904048 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:66097037-66097816 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:66097817-66098595 Neighboring gene F-box protein 36 pseudogene 1 Neighboring gene long intergenic non-protein coding RNA 674 Neighboring gene leucine rich repeat containing 37 member A16, pseudogene Neighboring gene SH3 domain containing GRB2 like 1, endophilin A2 pseudogene 3

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, karyopherin alpha 2 (KPNA2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with KPNA2 is decreased by RRE PubMed
    Tat tat Interaction of HIV-1 Tat with KPNA2 in T-cells is identified by a proteomic strategy based on affinity chromatography PubMed
    tat HIV-1 Tat peptide (amino-acids 47-57) binds to importin alpha and beta receptors PubMed
    Vpr vpr HIV-1 Vpr binds KPNA2; C-terminus changes conformation to a twisted beta-turn enabling binding to a minor KPNA2 nuclear localization. Vpr C-terminus can also bind major KPNA2 nuclear localization signal sites in an extended conformation in different ways. 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
    vpr Full-length Vpr interacts with RCH1 through its binding to the C-terminal domain (residues 404-529) of RCH1 PubMed
    vpr The nuclear import of Vpr is promoted by the addition of cytoplasmic extracts from macrophages but not of that from monocytes, and the nuclear import activity is lost with immunodepletion of importin alpha from the cytoplasmic extract PubMed
    vpr A small molecule hematoxylin, which suppresses Vpr-Importin alpha interaction, blocks Vpr nuclear entry in a dose-dependent manner PubMed
    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
    integrase 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
    gag-pol Ivermectin, an inhibitor of importin alpha/beta1, inhibits HIV-1 infection by blocking the HIV-1 Integrase interaction with importin alpha/beta1 for viral protein nuclear import PubMed
    gag-pol HIV-1 IN interacts with importin alpha by the BiFC assay and amino acids 161-173 in IN are required for the interaction with importin alpha PubMed
    gag-pol HIV-1 Rev disrupts both IN-TNPO3 and IN-importin alpha complexes PubMed
    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
    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 Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables histone deacetylase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables nuclear import signal receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables nuclear import signal receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables nuclear localization sequence binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables nuclear localization sequence binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
     
    part_of NLS-dependent protein nuclear import complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in host cell IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane HDA PubMed 
    is_active_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     

    General protein information

    Preferred Names
    importin subunit alpha-1
    Names
    RAG cohort protein 1
    importin subunit alpha-2
    importin-alpha-P1
    karyopherin alpha 2 (RAG cohort 1, importin alpha 1)
    nuclear pore-targeting complex 58kD component
    pendulin

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_001320611.3NP_001307540.1  importin subunit alpha-1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC134407
      Consensus CDS
      CCDS32713.1
      UniProtKB/Swiss-Prot
      B9EJD6, P52292, Q53YE3, Q6NVW7, Q9BRU5
      UniProtKB/TrEMBL
      A8K7D9
      Related
      ENSP00000438483.2, ENST00000537025.6
      Conserved Domains (5) summary
      COG5064
      Location:10528
      SRP1; Karyopherin (importin) alpha [Intracellular trafficking and secretion]
      cd00020
      Location:113238
      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, ...
      pfam01749
      Location:1098
      IBB; Importin beta binding domain
      pfam16186
      Location:458508
      Arm_3; Atypical Arm repeat
      sd00043
      Location:253278
      ARM; armadillo repeat [structural motif]
    2. NM_002266.4NP_002257.1  importin subunit alpha-1

      See identical proteins and their annotated locations for NP_002257.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AA744568, AK024833, U28386
      Consensus CDS
      CCDS32713.1
      UniProtKB/Swiss-Prot
      B9EJD6, P52292, Q53YE3, Q6NVW7, Q9BRU5
      UniProtKB/TrEMBL
      A8K7D9
      Related
      ENSP00000332455.3, ENST00000330459.8
      Conserved Domains (5) summary
      COG5064
      Location:10528
      SRP1; Karyopherin (importin) alpha [Intracellular trafficking and secretion]
      cd00020
      Location:113238
      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, ...
      pfam01749
      Location:1098
      IBB; Importin beta binding domain
      pfam16186
      Location:458508
      Arm_3; Atypical Arm repeat
      sd00043
      Location:253278
      ARM; armadillo repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      68035735..68046854
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      68911511..68922628
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)