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    KPNA4 karyopherin subunit alpha 4 [ Homo sapiens (human) ]

    Gene ID: 3840, updated on 18-Nov-2024

    Summary

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    Official Symbol
    KPNA4provided by HGNC
    Official Full Name
    karyopherin subunit alpha 4provided by HGNC
    Primary source
    HGNC:HGNC:6397
    See related
    Ensembl:ENSG00000186432 MIM:602970; AllianceGenome:HGNC:6397
    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
    QIP1; SRP3; IPOA3
    Summary
    The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in heart (RPKM 11.7), esophagus (RPKM 9.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KPNA4 in Genome Data Viewer
    Location:
    3q25.33
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (160495007..160565571, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (163269616..163340186, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (160212795..160283359, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene TRIM59-IFT80 readthrough (NMD candidate) Neighboring gene beta-1,3-glucuronyltransferase 3 pseudogene 1 Neighboring gene RNA, U7 small nuclear 136 pseudogene Neighboring gene small Cajal body-specific RNA 7 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14856 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14857 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:160283422-160284621 Neighboring gene keratin 8 pseudogene 12 Neighboring gene ribosomal protein L6 pseudogene 8

    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
    • 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. Importin α3/Qip1 is involved in multiplication of mutant influenza virus with alanine mutation at amino acid 9 independently of nuclear transport function. Sasaki Y, et al. PLoS One, 2013. PMID 23383277, Free PMC Article
    2. Disease-specific alteration of karyopherin-α subtype establishes feed-forward oncogenic signaling in head and neck squamous cell carcinoma. Hazawa M, et al. Oncogene, 2020 Mar. PMID 31822798, Free PMC Article
    3. Human importin α3 and its N-terminal truncated form, without the importin-β-binding domain, are oligomeric species with a low conformational stability in solution. Díaz-García C, et al. Biochim Biophys Acta Gen Subj, 2020 Jul. PMID 32234409
    4. Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression. Yang W, et al. Thorac Cancer, 2023 Feb. PMID 36573325, Free PMC Article
    5. KPNA4 regulated by miR-548b-3p promotes the malignant phenotypes of papillary thyroid cancer. Feng L, et al. Life Sci, 2021 Jan 15. PMID 33188837

    See all (212) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.
      Title: Circular RNA hsa_circ_0008003 promotes the progression of non-small-cell lung cancer by sponging miR-548I and regulating KPNA4 expression.
    2. Human importin alpha3 and its N-terminal truncated form, without the importin-beta-binding domain, are oligomeric species with a low conformational stability in solution.
      Title: Human importin α3 and its N-terminal truncated form, without the importin-β-binding domain, are oligomeric species with a low conformational stability in solution.
    3. Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner.
      Title: Ginsenoside Rg3 inhibits osteosarcoma progression by reducing circ_0003074 expression in a miR-516b-5p/KPNA4-dependent manner.
    4. The nuclear localization sequence of the epigenetic factor RYBP binds to human importin alpha3.
      Title: The nuclear localization sequence of the epigenetic factor RYBP binds to human importin α3.
    5. Value of KPNA4 as a diagnostic and prognostic biomarker for hepatocellular carcinoma.
      Title: Value of KPNA4 as a diagnostic and prognostic biomarker for hepatocellular carcinoma.
    6. LINC00467 facilitates osteosarcoma progression by sponging miR217 to regulate KPNA4 expression.
      Title: LINC00467 facilitates osteosarcoma progression by sponging miR‑217 to regulate KPNA4 expression.
    7. A Phosphorylation-Induced Switch in the Nuclear Localization Sequence of the Intrinsically Disordered NUPR1 Hampers Binding to Importin.
      Title: A Phosphorylation-Induced Switch in the Nuclear Localization Sequence of the Intrinsically Disordered NUPR1 Hampers Binding to Importin.
    8. KPNA4 is involved in cataract formation via the nuclear import of p53.
      Title: KPNA4 is involved in cataract formation via the nuclear import of p53.
    9. KPNA4 regulated by miR-548b-3p promotes the malignant phenotypes of papillary thyroid cancer.
      Title: KPNA4 regulated by miR-548b-3p promotes the malignant phenotypes of papillary thyroid cancer.
    10. STAT3-induced upregulation of circCCDC66 facilitates the progression of non-small cell lung cancer by targeting miR-33a-5p/KPNA4 axis.
      Title: STAT3-induced upregulation of circCCDC66 facilitates the progression of non-small cell lung cancer by targeting miR-33a-5p/KPNA4 axis.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-Wide Association Study of Primary Dentition Pit-and-Fissure and Smooth Surface Caries.
    EBI GWAS Catalog
    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, karyopherin alpha 4 (KPNA4), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells PubMed
    Vpr vpr Full-length Vpr interacts with QIP1 through its binding to the C-terminal domain (residues 392-537) of QIP1 PubMed
    integrase gag-pol HIV-1 Integrase (IN) double mutant KK215/219AA and RK263/264AA severely impairs its binding to importin 3 alpha. W179A/N183A and W348A/N352A mutations in the major and the minor NLS binding grooves of Imp alpha3 significantly reduce its binding to IN 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 A region encompassing amino acids 251-270 in the C-terminal domain of HIV-1 IN is required for importin alpha3 binding and for nuclear localization 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

    Clone Names

    • FLJ31113, MGC12217, MGC26703

    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 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 
    Process Evidence Code Pubs
    involved_in NLS-bearing protein import into nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in NLS-bearing protein import into nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_positive_effect dopamine secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_positive_effect gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein import into nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    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 NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		  
    part_of nuclear pore IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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

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    Preferred Names
    importin subunit alpha-3
    Names
    importin alpha Q1
    importin subunit alpha-4
    karyopherin alpha 4 (importin alpha 3)

    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_002268.5 → NP_002259.1  importin subunit alpha-3

      See identical proteins and their annotated locations for NP_002259.1

      Status: REVIEWED

      Source sequence(s)
      AC078868, BC034493
      Consensus CDS
      CCDS3191.1
      UniProtKB/Swiss-Prot
      A8K4S6, D3DNM2, O00190, O00629
      UniProtKB/TrEMBL
      A0A7I2V340
      Related
      ENSP00000334373.4, ENST00000334256.9
      Conserved Domains (2) summary
      COG5064
      Location:11 → 513
      SRP1; Karyopherin (importin) alpha [Intracellular trafficking and secretion]
      sd00043
      Location:279 → 311
      ARM; armadillo repeat [structural motif]

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      160495007..160565571 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      163269616..163340186 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00629.1 GenPept UniProtKB/Swiss-Prot:O00629

    Gene LinkOut

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

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