From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Importin subunit alpha-1 is a
protein that in humans is encoded by the KPNA2
gene .
[5]
[6]
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-1. 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
[7]
Interactions
Karyopherin alpha 2 has been shown to
interact with:
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000182481 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000018362 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Cuomo CA, Kirch SA, Gyuris J, Brent R, Oettinger MA (Jun 1994).
"Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein" . Proceedings of the National Academy of Sciences of the United States of America . 91 (13): 6156–60.
Bibcode :
1994PNAS...91.6156C .
doi :
10.1073/pnas.91.13.6156 .
PMC
44157 .
PMID
8016130 .
^ Weis K, Mattaj IW, Lamond AI (May 1995). "Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences". Science . 268 (5213): 1049–53.
Bibcode :
1995Sci...268.1049W .
doi :
10.1126/science.7754385 .
PMID
7754385 .
^
"Entrez Gene: KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1)" .
^ Lin CY, Huang PH, Liao WL, Cheng HJ, Huang CF, Kuo JC, Patton WA, Massenburg D, Moss J, Lee FJ (Dec 2000).
"ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli" . The Journal of Biological Chemistry . 275 (48): 37815–23.
doi :
10.1074/jbc.M002470200 .
PMID
10980193 .
^ Perez-Villar JJ, O'Day K, Hewgill DH, Nadler SG, Kanner SB (Oct 2001).
"Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)" .
International Immunology . 13 (10): 1265–74.
doi :
10.1093/intimm/13.10.1265 .
PMID
11581171 .
^ Nagoshi E, Yoneda Y (Apr 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" . Molecular and Cellular Biology . 21 (8): 2779–89.
doi :
10.1128/MCB.21.8.2779-2789.2001 .
PMC
86908 .
PMID
11283257 .
^ Köhler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Görlich D, Hartmann E (Nov 1999).
"Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import" . Molecular and Cellular Biology . 19 (11): 7782–91.
doi :
10.1128/mcb.19.11.7782 .
PMC
84838 .
PMID
10523667 .
^ Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D (Sep 1997).
"Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor" . Cell . 90 (6): 1061–71.
doi :
10.1016/s0092-8674(00)80372-4 .
PMID
9323134 .
S2CID
16092404 .
^ Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven WJ, Voz ML (May 2002).
"Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal" . The Journal of Biological Chemistry . 277 (22): 19673–8.
doi :
10.1074/jbc.M112112200 .
PMID
11882654 .
^ 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". Biochemical and Biophysical Research Communications . 234 (1): 48–53.
doi :
10.1006/bbrc.1997.6535 .
PMID
9168958 .
^ Maiyar AC, Leong ML, Firestone GL (Mar 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" . Molecular Biology of the Cell . 14 (3): 1221–39.
doi :
10.1091/mbc.E02-03-0170 .
PMC
151592 .
PMID
12631736 .
Further reading
Bukrinsky MI, Haffar OK (Dec 1997).
"HIV-1 nuclear import: in search of a leader" . Frontiers in Bioscience . 2 (4): d578-87.
doi :
10.2741/A213 .
PMID
9366553 .
Bukrinsky MI, Haffar OK (Mar 1998).
"HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr" . Molecular Medicine . 4 (3): 138–43.
doi :
10.1007/BF03401911 .
PMC
2230352 .
PMID
9562972 .
Kino T, Pavlakis GN (Apr 2004).
"Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1" . DNA and Cell Biology . 23 (4): 193–205.
doi :
10.1089/104454904773819789 .
PMID
15142377 .
Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L (Sep 2006). "Importin KPNA2, NBS1, DNA repair and tumorigenesis". Journal of Molecular Histology . 37 (5–7): 293–9.
doi :
10.1007/s10735-006-9032-y .
PMID
16752129 .
S2CID
7281949 .
Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M (Jul 1992).
"Active nuclear import of human immunodeficiency virus type 1 preintegration complexes" . Proceedings of the National Academy of Sciences of the United States of America . 89 (14): 6580–4.
Bibcode :
1992PNAS...89.6580B .
doi :
10.1073/pnas.89.14.6580 .
PMC
49545 .
PMID
1631159 .
Sharova N, Bukrinskaya A (Mar 1991). "p17 and p17-containing gag precursors of input human immunodeficiency virus are transported into the nuclei of infected cells". AIDS Research and Human Retroviruses . 7 (3): 303–6.
doi :
10.1089/aid.1991.7.303 .
PMID
2064827 .
Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau NR (Dec 1995).
"Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr" . Journal of Virology . 69 (12): 7909–16.
doi :
10.1128/JVI.69.12.7909-7916.1995 .
PMC
189735 .
PMID
7494303 .
Küssel P, Frasch M (Aug 1995). "Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis". Molecular & General Genetics . 248 (3): 351–63.
doi :
10.1007/BF02191602 .
PMID
7565597 .
S2CID
24877825 .
Gallay P, Swingler S, Song J, Bushman F, Trono D (Nov 1995).
"HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase" . Cell . 83 (4): 569–76.
doi :
10.1016/0092-8674(95)90097-7 .
PMID
7585960 .
S2CID
15536328 .
Moroianu J, Hijikata M, Blobel G, Radu A (Jul 1995).
"Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins" . Proceedings of the National Academy of Sciences of the United States of America . 92 (14): 6532–6.
Bibcode :
1995PNAS...92.6532M .
doi :
10.1073/pnas.92.14.6532 .
PMC
41552 .
PMID
7604027 .
Freed EO, Englund G, Martin MA (Jun 1995).
"Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection" . Journal of Virology . 69 (6): 3949–54.
doi :
10.1128/JVI.69.6.3949-3954.1995 .
PMC
189124 .
PMID
7745752 .
Gallay P, Swingler S, Aiken C, Trono D (Feb 1995).
"HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator" . Cell . 80 (3): 379–88.
doi :
10.1016/0092-8674(95)90488-3 .
PMID
7859280 .
S2CID
15064293 .
von Schwedler U, Kornbluth RS, Trono D (Jul 1994).
"The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes" . Proceedings of the National Academy of Sciences of the United States of America . 91 (15): 6992–6.
Bibcode :
1994PNAS...91.6992V .
doi :
10.1073/pnas.91.15.6992 .
PMC
44324 .
PMID
8041734 .
Heinzinger NK, Bukrinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA,
Gendelman HE , Ratner L, Stevenson M, Emerman M (Jul 1994).
"The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells" . Proceedings of the National Academy of Sciences of the United States of America . 91 (15): 7311–5.
Bibcode :
1994PNAS...91.7311H .
doi :
10.1073/pnas.91.15.7311 .
PMC
44389 .
PMID
8041786 .
Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M (Oct 1993).
"A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells" . Nature . 365 (6447): 666–9.
Bibcode :
1993Natur.365..666B .
doi :
10.1038/365666a0 .
PMC
9524217 .
PMID
8105392 .
S2CID
25678 .
Dubrovsky L, Ulrich P, Nuovo GJ, Manogue KR, Cerami A, Bukrinsky M (Jan 1995).
"Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention" . Molecular Medicine . 1 (2): 217–30.
doi :
10.1007/BF03401569 .
PMC
2229944 .
PMID
8529100 .
Gallay P, Stitt V, Mundy C, Oettinger M, Trono D (Feb 1996).
"Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import" . Journal of Virology . 70 (2): 1027–32.
doi :
10.1128/JVI.70.2.1027-1032.1996 .
PMC
189908 .
PMID
8551560 .
Bukrinskaya AG, Ghorpade A, Heinzinger NK, Smithgall TE, Lewis RE, Stevenson M (Jan 1996).
"Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA" . Proceedings of the National Academy of Sciences of the United States of America . 93 (1): 367–71.
Bibcode :
1996PNAS...93..367B .
doi :
10.1073/pnas.93.1.367 .
PMC
40239 .
PMID
8552640 .
PDB gallery
1ejl : MOUSE IMPORTIN ALPHA-SV40 LARGE T ANTIGEN NLS PEPTIDE COMPLEX
1ejy : MOUSE IMPORTIN ALPHA-NUCLEOPLASMIN NLS PEPTIDE COMPLEX
1ial : IMPORTIN ALPHA, MOUSE
1iq1 : CRYSTAL STRUCTURE OF THE IMPORTIN-ALPHA(44-54)-IMPORTIN-ALPHA(70-529) COMPLEX
1pjm : Mouse Importin alpha-bipartite NLS from human retinoblastoma protein Complex
1pjn : Mouse Importin alpha-bipartite NLS N1N2 from Xenopus laevis phosphoprotein Complex
1q1s : Mouse Importin alpha- phosphorylated SV40 CN peptide complex
1q1t : Mouse Importin alpha: non-phosphorylated SV40 CN peptide complex
1qgk : STRUCTURE OF IMPORTIN BETA BOUND TO THE IBB DOMAIN OF IMPORTIN ALPHA
1y2a : Structure of mammalian importin bound to the non-classical PLSCR1-NLS
2c1m : NUP50:IMPORTIN-ALPHA COMPLEX