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    KPNA5 karyopherin subunit alpha 5 [ Homo sapiens (human) ]

    Gene ID: 3841, updated on 3-Nov-2024

    Summary

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    Official Symbol
    KPNA5provided by HGNC
    Official Full Name
    karyopherin subunit alpha 5provided by HGNC
    Primary source
    HGNC:HGNC:6398
    See related
    Ensembl:ENSG00000196911 MIM:604545; AllianceGenome:HGNC:6398
    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
    SRP6; IPOA6
    Summary
    The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC) which consists of 60-100 proteins and is probably 120 million daltons in molecular size. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion; larger molecules are transported by an active process. Most nuclear proteins contain short basic amino acid sequences known as nuclear localization signals (NLSs). KPNA5 protein belongs to the importin alpha protein family and is thought to be involved in NLS-dependent protein import into the nucleus. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in testis (RPKM 10.4), ovary (RPKM 8.3) and 24 other tissues See more
    Orthologs
    all
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    Genomic context

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    See KPNA5 in Genome Data Viewer
    Location:
    6q22.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (116681211..116741867)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (117864908..117925542)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (117002374..117063030)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901386 Neighboring gene radial spoke head component 4A Neighboring gene zinc finger containing ubiquitin peptidase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17497 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24999 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:117001971-117002954 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:117002955-117003936 Neighboring gene uncharacterized LOC124901560 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_88226 Neighboring gene family with sequence similarity 162 member B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:117085903-117086417 Neighboring gene uncharacterized LOC105377963

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Xu W, et al. Cell Host Microbe, 2014 Aug 13. PMID 25121748, Free PMC Article
    2. Probing the specificity of binding to the major nuclear localization sequence-binding site of importin-alpha using oriented peptide library screening. Yang SN, et al. J Biol Chem, 2010 Jun 25. PMID 20406804, Free PMC Article
    3. Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5. Sun M, et al. Endocr J, 2017 Oct 28. PMID 28835592
    4. Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein. Melen K, et al. J Biol Chem, 2003 Jul 25. PMID 12740372
    5. A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway. Lischka P, et al. J Virol, 2003 Mar. PMID 12610148, Free PMC Article

    See all (116) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Data suggest that IGFBP5 nuclear import is mediated by KPNA5/KPNB1 complex; nuclear localization sequence of IGFBP5 is critical domain in this nuclear translocation. (IGFBP5 = insulin-like growth factor binding protein-5; KPNA5 = karyopherin subunit alpha-5; KPNB1 = karyopherin subunit beta-1/importin-beta)
      Title: Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5.
    2. BIG3 may block the KPNAs (KPNA1, KPNA5, and KPNA6) binding region(s) of PHB2.
      Title: BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells.
    3. eVP24 recognizes a unique nonclassical nuclear localization signal binding site on KPNA5 that is necessary for efficient phosphoryated STAT1 nuclear transport.
      Title: Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1.
    4. 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.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility for bladder cancer.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 NL4-3 replication requires KPNA5 as replication is inhibited when KPNA5 is deleted through CRISPR/Cas9 genome editing PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    integrase 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
    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 Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables nuclear import signal receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables nuclear localization sequence binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NLS-bearing protein import into nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein import into nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    part_of NLS-dependent protein nuclear import complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    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
    		  
    is_active_in nucleoplasm IBA
    Inferred from Biological aspect of Ancestor
    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

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    Preferred Names
    importin subunit alpha-6
    Names
    importin alpha 6
    karyopherin alpha 5 (importin alpha 6)

    NCBI Reference Sequences (RefSeq)

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    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_001366304.1 → NP_001353233.1  importin subunit alpha-6 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a). Variants 1 and 2 both encode the same isoform (a).
      Source sequence(s)
      AL132795, AL354716, KF458260
      Consensus CDS
      CCDS93992.1
      UniProtKB/TrEMBL
      A0A8V8TMV2
      Conserved Domains (2) summary
      sd00043
      Location:354 → 386
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:56 → 541
      Arm_3; Atypical Arm repeat

    2. NM_001366305.2 → NP_001353234.1  importin subunit alpha-6 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a).
      Source sequence(s)
      AL132795, AL354716, KF458260
      Consensus CDS
      CCDS93992.1
      UniProtKB/TrEMBL
      A0A8V8TMV2
      Related
      ENSP00000513404.1, ENST00000697697.1
      Conserved Domains (2) summary
      sd00043
      Location:354 → 386
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:56 → 541
      Arm_3; Atypical Arm repeat

    3. NM_001366306.2 → NP_001353235.1  importin subunit alpha-6 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), as well as variant 3, encodes isoform b.
      Source sequence(s)
      AL132795, AL354716, KF458260
      Consensus CDS
      CCDS5111.1
      UniProtKB/Swiss-Prot
      B2RAI5, O15131, Q86X23
      Related
      ENSP00000357552.1, ENST00000368564.7
      Conserved Domains (2) summary
      sd00043
      Location:334 → 366
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:36 → 521
      Arm_3; Atypical Arm repeat

    4. NM_001366307.2 → NP_001353236.1  importin subunit alpha-6 isoform c

      Status: REVIEWED

      Source sequence(s)
      AL132795, AL354716, KF458260
      Consensus CDS
      CCDS93993.1
      UniProtKB/TrEMBL
      A0A8V8TL88
      Related
      ENSP00000513406.1, ENST00000697699.1
      Conserved Domains (2) summary
      sd00043
      Location:331 → 363
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:33 → 518
      Arm_3; Atypical Arm repeat

    5. NM_001366308.1 → NP_001353237.1  importin subunit alpha-6 isoform d

      Status: REVIEWED

      Source sequence(s)
      AL132795, AL354716, KF458260
      Conserved Domains (2) summary
      sd00043
      Location:334 → 366
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:36 → 476
      Arm_3; Atypical Arm repeat

    6. NM_001366309.2 → NP_001353238.1  importin subunit alpha-6 isoform e

      Status: REVIEWED

      Source sequence(s)
      AL132795
      Conserved Domains (2) summary
      sd00043
      Location:142 → 175
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:56 → 327
      Arm_3; Atypical Arm repeat

    7. NM_001366310.2 → NP_001353239.1  importin subunit alpha-6 isoform f

      Status: REVIEWED

      Source sequence(s)
      AL132795
      Conserved Domains (2) summary
      sd00043
      Location:122 → 155
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:36 → 307
      Arm_3; Atypical Arm repeat

    8. NM_002269.3 → NP_002260.2  importin subunit alpha-6 isoform b

      See identical proteins and their annotated locations for NP_002260.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), as well as variant 4, encodes isoform b.
      Source sequence(s)
      AA332147, BC047409, BG721781
      Consensus CDS
      CCDS5111.1
      UniProtKB/Swiss-Prot
      B2RAI5, O15131, Q86X23
      Related
      ENSP00000348704.1, ENST00000356348.6
      Conserved Domains (2) summary
      sd00043
      Location:334 → 366
      ARM; armadillo repeat [structural motif]
      cl25709
      Location:36 → 521
      Arm_3; Atypical Arm repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      116681211..116741867
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047418752.1 → XP_047274708.1  importin subunit alpha-6 isoform X2

    2. XM_047418751.1 → XP_047274707.1  importin subunit alpha-6 isoform X1

    3. XM_017010841.3 → XP_016866330.1  importin subunit alpha-6 isoform X1

      UniProtKB/TrEMBL
      B3KWR2, B3KXZ2
      Conserved Domains (4) summary
      cd00020
      Location:47 → 161
      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, ...
      pfam16186
      Location:260 → 304
      Arm_3; Atypical Arm repeat
      sd00044
      Location:8 → 32
      HEAT; HEAT repeat [structural motif]
      sd00043
      Location:127 → 159
      ARM; armadillo repeat [structural motif]

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      117864908..117925542
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355385.1 → XP_054211360.1  importin subunit alpha-6 isoform X2

    2. XM_054355384.1 → XP_054211359.1  importin subunit alpha-6 isoform X1

    3. XM_054355383.1 → XP_054211358.1  importin subunit alpha-6 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O15131.3 GenPept UniProtKB/Swiss-Prot:O15131

    Gene LinkOut

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