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

Gene ID: 3838, updated on 21-Apr-2019

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
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; 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

Genomic context

See KPNA2 in Genome Data Viewer
Location:
17q24.2
Exon count:
12
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 17 NC_000017.11 (68035602..68046859)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (66031848..66042970)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene chromosome 17 open reading frame 58 Neighboring gene transfer RNA-Arg (CCG) 2-1 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 FunctionsWhat'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 BioSystems

  • 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.
  • 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...
  • DNA Double Strand Break Response, organism-specific biosystem (from REACTOME)
    DNA Double Strand Break Response, organism-specific biosystemDNA double strand break (DSB) response involves sensing of DNA DSBs by the MRN complex which triggers ATM activation. ATM phosphorylates a number of proteins involved in DNA damage checkpoint signali...
  • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
    DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • 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 ...
  • Host Interactions with Influenza Factors, organism-specific biosystem (from REACTOME)
    Host Interactions with Influenza Factors, organism-specific biosystemInfection of a human host cell with influenza virus triggers an array of host processes that interfere with viral replication, notably the production of type I interferon. The viral NS1 protein plays...
  • 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...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • 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...
  • 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...
  • NS1 Mediated Effects on Host Pathways, organism-specific biosystem (from REACTOME)
    NS1 Mediated Effects on Host Pathways, organism-specific biosystemViral NS1 protein is a nuclear, dimeric protein that is highly expressed in infected cells and has dsRNA-binding activity. The RNA-binding domain lies within the N-terminal portion of the protein. Th...
  • Regulation of cytoplasmic and nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of cytoplasmic and nuclear SMAD2/3 signaling, organism-specific biosystem
    Regulation of cytoplasmic and nuclear SMAD2/3 signaling
  • Role of Calcineurin-dependent NFAT signaling in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
    Role of Calcineurin-dependent NFAT signaling in lymphocytes, organism-specific biosystem
    Role of Calcineurin-dependent NFAT signaling in lymphocytes
  • Sensing of DNA Double Strand Breaks, organism-specific biosystem (from REACTOME)
    Sensing of DNA Double Strand Breaks, organism-specific biosystemDetection of DNA double-strand breaks (DSBs) involves sensor proteins of the MRN complex, composed of MRE11A, RAD50 and NBN (NBS1). Binding of the MRN complex to DNA DSBs activates ATM-dependent DNA ...
  • Signaling events mediated by TCPTP, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by TCPTP, organism-specific biosystem
    Signaling events mediated by TCPTP

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
RNA binding HDA PubMed 
histone deacetylase binding IPI
Inferred from Physical Interaction
more info
PubMed 
nuclear import signal receptor activity IEA
Inferred from Electronic Annotation
more info
 
nuclear localization sequence binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Component Evidence Code Pubs
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
extrinsic component of postsynaptic specialization membrane IDA
Inferred from Direct Assay
more info
PubMed 
glutamatergic synapse EXP
Inferred from Experiment
more info
PubMed 
glutamatergic synapse IDA
Inferred from Direct Assay
more info
PubMed 
host cell IEA
Inferred from Electronic Annotation
more info
 
membrane HDA PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
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)
pendulin

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_001320611.1NP_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)
    AA744568, AC134407, BC005978, BC067848, DA636948
    Consensus CDS
    CCDS32713.1
    UniProtKB/Swiss-Prot
    P52292
    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
    P52292
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p12 Primary Assembly

    Range
    68035602..68046859
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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