Karyopherin alpha 2

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Karyopherin alpha 2 (RAG cohort 1, importin alpha 1)
Protein KPNA2 PDB 1ejl.png
PDB rendering based on 1ejl.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols KPNA2 ; IPOA1; QIP2; RCH1; SRP1alpha
External IDs OMIM600685 MGI103561 HomoloGene1708 ChEMBL: 1741187 GeneCards: KPNA2 Gene
Species Human Mouse
Entrez 3838 16647
Ensembl ENSG00000182481 ENSMUSG00000018362
UniProt P52292 P52293
RefSeq (mRNA) NM_002266 NM_010655
RefSeq (protein) NP_002257 NP_034785
Location (UCSC) Chr 17:
66.03 – 66.04 Mb
Chr 11:
106.99 – 107 Mb
PubMed search [1] [2]

Importin subunit alpha-2 is a protein that in humans is encoded by the KPNA2 gene.[1][2]

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 are members of the alpha importin family of karyopherins such as importin subunit alpha-2. 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[3]


Karyopherin alpha 2 has been shown to interact with SGK,[4] PLAG1,[5] KPNB1,[6][7][8] RECQL,[9] ARL4A[10] and ITK.[11]


  1. ^ Cuomo CA, Kirch SA, Gyuris J, Brent R, Oettinger MA (July 1994). "Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein". Proc Natl Acad Sci U S A 91 (13): 6156–60. doi:10.1073/pnas.91.13.6156. PMC 44157. PMID 8016130. 
  2. ^ Weis K, Mattaj IW, Lamond AI (June 1995). "Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences". Science 268 (5213): 1049–53. doi:10.1126/science.7754385. PMID 7754385. 
  3. ^ "Entrez Gene: KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1)". 
  4. ^ Maiyar, Anita C; Leong Meredith L L; Firestone Gary L (March 2003). "Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domain". Mol. Biol. Cell (United States) 14 (3): 1221–39. doi:10.1091/mbc.E02-03-0170. ISSN 1059-1524. PMC 151592. PMID 12631736. 
  5. ^ Braem, Caroline V; Kas Koen, Meyen Eva, Debiec-Rychter Maria, Van De Ven Wim J M, Voz Marianne L (May 2002). "Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal". J. Biol. Chem. (United States) 277 (22): 19673–8. doi:10.1074/jbc.M112112200. ISSN 0021-9258. PMID 11882654. 
  6. ^ Nagoshi, E; Yoneda Y (April 2001). "Dimerization of sterol regulatory element-binding protein 2 via the helix-loop-helix-leucine zipper domain is a prerequisite for its nuclear localization mediated by importin beta". Mol. Cell. Biol. (United States) 21 (8): 2779–89. doi:10.1128/MCB.21.8.2779-2789.2001. ISSN 0270-7306. PMC 86908. PMID 11283257. 
  7. ^ Köhler, M; Speck C; Christiansen M; Bischoff F R; Prehn S; Haller H; Görlich D; Hartmann E (November 1999). "Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7782–91. ISSN 0270-7306. PMC 84838. PMID 10523667. 
  8. ^ Kutay, U; Bischoff F R; Kostka S; Kraft R; Görlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell (UNITED STATES) 90 (6): 1061–71. doi:10.1016/S0092-8674(00)80372-4. ISSN 0092-8674. PMID 9323134. 
  9. ^ Seki, T; Tada S; Katada T; Enomoto T (May 1997). "Cloning of a cDNA encoding a novel importin-alpha homologue, Qip1: discrimination of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase Q1/RecQL". Biochem. Biophys. Res. Commun. (UNITED STATES) 234 (1): 48–53. doi:10.1006/bbrc.1997.6535. ISSN 0006-291X. PMID 9168958. 
  10. ^ Lin, C Y; Huang P H; Liao W L; Cheng H J; Huang C F; Kuo J C; Patton W A; Massenburg D; Moss J; Lee F J (December 2000). "ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli". J. Biol. Chem. (UNITED STATES) 275 (48): 37815–23. doi:10.1074/jbc.M002470200. ISSN 0021-9258. PMID 10980193. 
  11. ^ Perez-Villar, J J; O'Day K; Hewgill D H; Nadler S G; Kanner S B (October 2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. (England) 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. ISSN 0953-8178. PMID 11581171. 

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