nuclear localization signals


Summary: Short, predominantly basic amino acid sequences identified as nuclear import signals for some proteins. These sequences are believed to interact with specific receptors at the NUCLEAR PORE.

Top Publications

  1. Chang C, Couñago R, Williams S, Boden M, Kobe B. Distinctive conformation of minor site-specific nuclear localization signals bound to importin-?. Traffic. 2013;14:1144-54 pubmed publisher
    b>Nuclear localization signals (NLSs) contain one or two clusters of basic residues and are recognized by the import receptor importin-?...
  2. Shuai J, Fu L, Zhang X, Zhu B, Li X, He Y, et al. Functional exchangeability of the nuclear localization signal (NLS) of capsid protein between PCV1 and PCV2 in vitro: Implications for the role of NLS in viral replication. Virol J. 2011;8:341 pubmed publisher
    ..Further studies are required to determine the in vivo viral replication and pathogenicity of the NLS chimeric DNA clones...
  3. Redrejo Rodríguez M, Muñoz Espín D, Holguera I, Mencía M, Salas M. Functional eukaryotic nuclear localization signals are widespread in terminal proteins of bacteriophages. Proc Natl Acad Sci U S A. 2012;109:18482-7 pubmed publisher
    A number of prokaryotic proteins have been shown to contain nuclear localization signals (NLSs), although its biological role remains sometimes unclear...
  4. Teng A, Al Montashiri N, Cheng B, Lou P, Ozmizrak P, Chen H, et al. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2. PLoS ONE. 2011;6:e24100 pubmed publisher
    ..Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status likely control nucleocytoplasmic localization of IRF2BP2 during muscle differentiation. ..
  5. García Santisteban I, Zorroza K, Rodriguez J. Two nuclear localization signals in USP1 mediate nuclear import of the USP1/UAF1 complex. PLoS ONE. 2012;7:e38570 pubmed publisher
    ..Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex...
  6. Dzijak R, Yildirim S, Kahle M, Novak P, Hnilicová J, Venit T, et al. Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner. PLoS ONE. 2012;7:e30529 pubmed publisher
    ..This opens a new field for exploring functions of this molecular motor in nuclear processes, and for exploring the signals between cytoplasm and the nucleus. ..
  7. Cardarelli F, Tosti L, Serresi M, Beltram F, Bizzarri R. Fluorescent recovery after photobleaching (FRAP) analysis of nuclear export rates identifies intrinsic features of nucleocytoplasmic transport. J Biol Chem. 2012;287:5554-61 pubmed publisher
    ..These findings suggest differential gating at the NPC level. ..
  8. Ganesh K, Adam S, Taylor B, Simpson P, Rada C, Neuberger M. CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31. J Biol Chem. 2011;286:17091-102 pubmed publisher
    ..Thus, CTNNBL1 is a novel NLS-binding protein, distinct from karyopherin ?s, with the results suggesting a possible role in the selective intranuclear targeting or interactions of some splicing-associated complexes. ..
  9. Cherezova L, Burnside K, Rose T. Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV. PLoS ONE. 2011;6:e18920 pubmed publisher

More Information


  1. Zhang Z, Satterly N, Fontoura B, Chook Y. Evolutionary development of redundant nuclear localization signals in the mRNA export factor NXF1. Mol Biol Cell. 2011;22:4657-68 pubmed publisher
  2. Hu Q, Wang J, Shen J, Liu M, Jin X, Tang G, et al. Intracellular pathways and nuclear localization signal peptide-mediated gene transfection by cationic polymeric nanovectors. Biomaterials. 2012;33:1135-45 pubmed publisher
    ..Compared to PC/pDNA, PC-NLS/pDNA, and PC/pDNA/NLS can effectively improve gene transfection in dividing and non-dividing cells. ..
  3. Yi W, Yang J, Li C, Wang H, Liu C, Tao L, et al. Enhanced nuclear import and transfection efficiency of TAT peptide-based gene delivery systems modified by additional nuclear localization signals. Bioconjug Chem. 2012;23:125-34 pubmed publisher
    ..In order to evaluate whether additional nuclear localization signals (NLSs) can improve gene transfection efficiency, we introduced different kinds of NLSs to TAT-based ..
  4. Umemoto T, Fujiki Y. Ligand-dependent nucleo-cytoplasmic shuttling of peroxisome proliferator-activated receptors, PPAR? and PPAR?. Genes Cells. 2012;17:576-96 pubmed publisher
    ..a series of truncation mutants, we identify that PPAR nuclear transport is mediated by at least two nuclear localization signals (NLSs) in DNA-binding domain (DBD)-hinge and activation function 1 (AF1) regions and their respective ..
  5. Moon D, Choi C, Lee S, Lee J, Kim S, Kim D, et al. Nuclear translocation of Acinetobacter baumannii transposase induces DNA methylation of CpG regions in the promoters of E-cadherin gene. PLoS ONE. 2012;7:e38974 pubmed publisher
    ..Tnp of A. baumannii ATCC 17978 possesses nuclear localization signals (NLSs), (225)RKRKRK(230). Transient expression of A...
  6. Brandariz Nuñez A, Valle Casuso J, White T, Laguette N, Benkirane M, BROJATSCH J, et al. Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac. Retrovirology. 2012;9:49 pubmed publisher
    ..The viral accessory protein Vpx overcomes the SAMHD1-mediated lentiviral block by inducing its proteasomal degradation...
  7. Li S, Qi Y, Zhao J, Li Y, Liu X, Chen X, et al. Characterization of nuclear localization signals (NLSs) and function of NLSs and phosphorylation of serine residues in subcellular and subnuclear localization of transformer-2? (Tra2?). J Biol Chem. 2013;288:8898-909 pubmed publisher
    ..mutation analysis, we showed that the nuclear localization of Tra2? was determined by multiple nuclear localization signals (NLSs) in the RS domains...
  8. Kumar D, Kumar D, Saha S. A highly basic sequence at the N-terminal region is essential for targeting the DNA replication protein ORC1 to the nucleus in Leishmania donovani. Microbiology. 2012;158:1775-82 pubmed publisher
    ..b>Nuclear localization signals (NLSs) have been reported in only a few Leishmania proteins...
  9. Chang C, Couñago R, Williams S, Boden M, Kobe B. Crystal structure of rice importin-? and structural basis of its interaction with plant-specific nuclear localization signals. Plant Cell. 2012;24:5074-88 pubmed publisher
    In the classical nucleocytoplasmic import pathway, nuclear localization signals (NLSs) in cargo proteins are recognized by the import receptor importin-?...
  10. Gu Z, Zhou L, Gao S, Wang Z. Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77. PLoS ONE. 2011;6:e22395 pubmed publisher
    ..These results provide a basis for understanding subcellular transport of p44/WDR77 during prostate development and tumorigenesis. ..
  11. Weinthal D, Barash I, Tzfira T, Gaba V, Teper D, Sessa G, et al. Characterization of nuclear localization signals in the type III effectors HsvG and HsvB of the gall-forming bacterium Pantoea agglomerans. Microbiology. 2011;157:1500-8 pubmed publisher
    ..Sequence analysis of these effectors did not detect canonical nuclear localization signals (NLSs), but two basic amino acid clusters designated putative NLS1 and NLS2 were detected in their N-..
  12. Gassman N, Clodfelter J, McCauley A, Bonin K, Salsbury F, Scarpinato K. Cooperative nuclear localization sequences lend a novel role to the N-terminal region of MSH6. PLoS ONE. 2011;6:e17907 pubmed publisher
    ..We demonstrate that a cluster of three nuclear localization signals (NLS) in the NTR direct nuclear import...
  13. Che M, Jiang Y, Xie Y, Jiang L, Hu H. Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing. FASEB J. 2011;25:2344-53 pubmed publisher
    ..This suggests that fragmentation of TDP-43 leads to cellular redistribution, inclusion body formation, and altered RNA processing, which are implicated in the molecular pathogenesis of ALS and FTLD. ..
  14. Hutchinson E, Orr O, Man Liu S, Engelhardt O, Fodor E. Characterization of the interaction between the influenza A virus polymerase subunit PB1 and the host nuclear import factor Ran-binding protein 5. J Gen Virol. 2011;92:1859-69 pubmed publisher
    ..Furthermore, mutations affecting RanBP5 binding are incompatible with or severely attenuate viral growth, providing further support for a key role for RanBP5 in the influenza A virus life cycle. ..
  15. Shin S, Lee E, Chun J, Hyun S, Kim Y, Kang S. The nuclear localization of glycogen synthase kinase 3? is required its putative PY-nuclear localization sequences. Mol Cells. 2012;34:375-82 pubmed publisher
    ..Thus, our observations indicated that Kap ?2 imports GSK-3? through its putative PY NLS motif from the cytoplasm to the nucleus and increases its kinase activity. ..
  16. Hofmann H, Logue E, Bloch N, Daddacha W, Polsky S, Schultz M, et al. The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus. J Virol. 2012;86:12552-60 pubmed publisher
    ..The inhibition of nuclear export with leptomycin B did not impair the ability of Vpx to degrade SAMHD1. These findings suggest that SAMHD1 is targeted by Vpx for ubiquitination and degradation in the nucleus. ..
  17. Zhang Z, Chook Y. Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS). Proc Natl Acad Sci U S A. 2012;109:12017-21 pubmed publisher
    ..5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kap?2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated. ..
  18. Zeineldin M, Cunningham J, McGuinness W, Alltizer P, Cowley B, Blanchat B, et al. A knock-in mouse model reveals roles for nuclear Apc in cell proliferation, Wnt signal inhibition and tumor suppression. Oncogene. 2012;31:2423-37 pubmed publisher
    ..APC in the context of a whole organism, we generated a mouse model with mutations that inactivate the nuclear localization signals (NLSs) of Apc (Apc(mNLS))...
  19. Miao D, Su H, He B, Gao J, Xia Q, Zhu M, et al. Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein. Proc Natl Acad Sci U S A. 2008;105:20309-14 pubmed publisher
    ..These findings provide in vivo experimental proof that substantiates the biologic relevance of the NLS and C-terminal portion of PTHrP, a polypeptide ligand that signals mainly via a cell surface G protein-coupled receptor. ..
  20. Yang F, Lin Y, Hu M. Identification of two functional nuclear localization signals mediating nuclear import of liver receptor homologue-1. Cell Mol Life Sci. 2011;68:1241-53 pubmed publisher
    ..We characterized two functional nuclear localization signals (NLSs) in LRH-1. NLS1 (residues 117-168) overlaps the second zinc finger in the DNA binding domain...
  21. Muha V, Zagyva I, Venkei Z, Szabad J, Vertessy B. Nuclear localization signal-dependent and -independent movements of Drosophila melanogaster dUTPase isoforms during nuclear cleavage. Biochem Biophys Res Commun. 2009;381:271-5 pubmed publisher
    ..The observed dynamic localization character showed strict timing to the nuclear cleavage phases and explained how both isoforms can be present within the nuclear microenvironment, although at different stages of cell cycle. ..
  22. Mingot J, Vega S, Maestro B, Sanz J, Nieto M. Characterization of Snail nuclear import pathways as representatives of C2H2 zinc finger transcription factors. J Cell Sci. 2009;122:1452-60 pubmed publisher
    ..Importantly, the identified basic residues are also conserved in other families of C(2)H(2) transcription factors whose nuclear localization requires the zinc finger region. ..
  23. Mehta T, Lu H, Wang X, Urvalek A, Nguyen K, Monzur F, et al. A unique sequence in the N-terminal regulatory region controls the nuclear localization of KLF8 by cooperating with the C-terminal zinc-fingers. Cell Res. 2009;19:1098-109 pubmed publisher
    ..Taken together, these results suggest that KLF8 has two NLSs, one surrounding S165 and K171 and the other being two tandem ZFs, which are critical for the regulation of KLF8 nuclear localization and its cellular functions. ..
  24. Thirkettle H, Girling J, Warren A, Mills I, Sahadevan K, Leung H, et al. LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals. Clin Cancer Res. 2009;15:3003-13 pubmed publisher
    ..LYRIC/AEG-1 contains three uncharacterized nuclear localization signals (NLS), which may regulate its distribution and, ultimately, function in cells...
  25. Kroetz M, Su D, Hochstrasser M. Essential role of nuclear localization for yeast Ulp2 SUMO protease function. Mol Biol Cell. 2009;20:2196-206 pubmed publisher
  26. Turgay Y, Ungricht R, Rothballer A, Kiss A, Csucs G, Horvath P, et al. A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane. EMBO J. 2010;29:2262-75 pubmed publisher
    ..Together, SUN2 represents the first mammalian INM protein relying on a functional cNLS, a Golgi retrieval signal and a perinuclear domain to mediate targeting to the INM. ..
  27. Lee J, Kim D, Moon D, Lee J, Kim M, Lee S, et al. Prediction of bacterial proteins carrying a nuclear localization signal and nuclear targeting of HsdM from Klebsiella pneumoniae. J Microbiol. 2009;47:641-5 pubmed publisher
  28. Scott M, Boisvert F, McDowall M, Lamond A, Barton G. Characterization and prediction of protein nucleolar localization sequences. Nucleic Acids Res. 2010;38:7388-99 pubmed publisher
    ..80% for randomly chosen nucleoplasmic sequences and 12% for nuclear localization signals. The predictor was used to predict NoLSs in the complete human proteome and 10 of the highest scoring ..
  29. Patenaude A, Orthwein A, Hu Y, Campo V, Kavli B, Buschiazzo A, et al. Active nuclear import and cytoplasmic retention of activation-induced deaminase. Nat Struct Mol Biol. 2009;16:517-27 pubmed publisher
    ..Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching. ..
  30. Kelley J, Talley A, Spencer A, Gioeli D, Paschal B. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors. BMC Cell Biol. 2010;11:63 pubmed publisher
    ..These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation. ..
  31. McLane L, Corbett A. Nuclear localization signals and human disease. IUBMB Life. 2009;61:697-706 pubmed publisher
  32. Kosugi S, Hasebe M, Tomita M, Yanagawa H. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A. 2009;106:10171-6 pubmed publisher
    ..prediction of CDK1-regulated nucleocytoplasmic shuttling proteins using a prediction system for nuclear localization signals (NLSs)...
  33. Wagstaff K, Jans D. Importins and beyond: non-conventional nuclear transport mechanisms. Traffic. 2009;10:1188-98 pubmed publisher
  34. Li X, ZHU F. Identification of the nuclear export and adjacent nuclear localization signals for ORF45 of Kaposi's sarcoma-associated herpesvirus. J Virol. 2009;83:2531-9 pubmed publisher
    ..These data suggest that the subcellular localization signals of ORF45 have important functional roles in KSHV lytic replication...
  35. Nguyen Ba A, Pogoutse A, Provart N, Moses A. NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction. BMC Bioinformatics. 2009;10:202 pubmed publisher
    b>Nuclear localization signals (NLSs) are stretches of residues within a protein that are important for the regulated nuclear import of the protein...
  36. Gomez Corredor A, Archambault D. The bovine immunodeficiency virus rev protein: identification of a novel lentiviral bipartite nuclear localization signal harboring an atypical spacer sequence. J Virol. 2009;83:12842-53 pubmed publisher
    ..In summary, we conclude that the nucleolar and nuclear localizations of BIV Rev are mediated via novel NLS and NoLS motifs...
  37. Leong V, Lorenowicz J, Kozij N, Guarné A. Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key. Mol Carcinog. 2009;48:742-50 pubmed publisher
    ..Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.
  38. Chen B, Mallampalli R. Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme cytidylyltransferase. Mol Cell Biol. 2009;29:3062-75 pubmed publisher
    ..These results unravel a unique molecular mechanism whereby monoubiquitination governs the trafficking and life span of a critical regulatory enzyme in vivo. ..
  39. Levin A, Armon Omer A, Rosenbluh J, Melamed Book N, Graessmann A, Waigmann E, et al. Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal. Retrovirology. 2009;6:112 pubmed publisher
    ..This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN. ..
  40. Pankiv S, Lamark T, Bruun J, Øvervatn A, Bjørkøy G, Johansen T. Nucleocytoplasmic shuttling of p62/SQSTM1 and its role in recruitment of nuclear polyubiquitinated proteins to promyelocytic leukemia bodies. J Biol Chem. 2010;285:5941-53 pubmed publisher
    ..The protein is also found in nuclear promyelocytic leukemia bodies. We show that p62 contains two nuclear localization signals and a nuclear export signal...
  41. Harrison B, Huynh K, Lundgaard G, Helmke S, Perryman M, McKinsey T. Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett. 2010;584:1103-10 pubmed publisher
    ..We provide evidence to suggest that the unique phospho-acceptor cooperates with the 14-3-3 target sites to impair HDAC nuclear import. ..
  42. Yang S, Takeda A, Fontes M, Harris J, Jans D, Kobe B. Probing the specificity of binding to the major nuclear localization sequence-binding site of importin-alpha using oriented peptide library screening. J Biol Chem. 2010;285:19935-46 pubmed publisher
  43. Reisenauer M, Wang S, Xia Y, Zhang W. Dot1a contains three nuclear localization signals and regulates the epithelial Na+ channel (ENaC) at multiple levels. Am J Physiol Renal Physiol. 2010;299:F63-76 pubmed publisher
    ..Here, we provide evidence showing that Dot1a contains at least three potential nuclear localization signals (NLSs)...
  44. Knapp A, McManus P, Bockstall K, Moroianu J. Identification of the nuclear localization and export signals of high risk HPV16 E7 oncoprotein. Virology. 2009;383:60-8 pubmed publisher
    ..The presence of both NLSs and an NES suggests that HPV16 E7 shuttles between the cytoplasm and nucleus which is consistent with E7 having functions in both of these cell compartments. ..
  45. Kahle J, Piaia E, Neimanis S, Meisterernst M, Doenecke D. Regulation of nuclear import and export of negative cofactor 2. J Biol Chem. 2009;284:9382-93 pubmed publisher
    ..Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits. ..
  46. Kanazawa T, Takashima Y, Murakoshi M, Nakai Y, Okada H. Enhancement of gene transfection into human dendritic cells using cationic PLGA nanospheres with a synthesized nuclear localization signal. Int J Pharm. 2009;379:187-95 pubmed publisher
    ..Thus, this delivery system using nanospheres combined with synthesized NLS might be applicable to DC-based gene vaccines when much non-invasive application such as needle-free injector should be required. ..
  47. Cardarelli F, Bizzarri R, Serresi M, Albertazzi L, Beltram F. Probing nuclear localization signal-importin alpha binding equilibria in living cells. J Biol Chem. 2009;284:36638-46 pubmed publisher
    The regulated process of protein import into the nucleus of a eukaryotic cell is mediated by specific nuclear localization signals (NLSs) that are recognized by protein-import receptors...
  48. Misra R, Sahoo S. Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy. Eur J Pharm Sci. 2010;39:152-63 pubmed publisher
    ..In conclusion, these results suggested that NLS conjugated doxorubicin loaded NPs could be potentially useful as novel drug delivery system for breast cancer therapy. ..
  49. Mills E, Truong K. Engineering Ca2+/calmodulin-mediated modulation of protein translocation by overlapping binding and signaling peptide sequences. Cell Calcium. 2010;47:369-77 pubmed publisher
    ..Our work demonstrates the feasibility of engineering Ca2+/calmodulin-mediated modulation of protein translocation and suggests that more natural analogs may exist. ..
  50. Van Dusen C, Yee L, McNally L, McNally M. A glycine-rich domain of hnRNP H/F promotes nucleocytoplasmic shuttling and nuclear import through an interaction with transportin 1. Mol Cell Biol. 2010;30:2552-62 pubmed publisher
    ..Collectively, the results suggest that hnRNP H and F are GYR domain-dependent shuttling proteins whose posttranslational modifications may alter nuclear localization and hence function. ..
  51. Lott K, Cingolani G. The importin ? binding domain as a master regulator of nucleocytoplasmic transport. Biochim Biophys Acta. 2011;1813:1578-92 pubmed publisher
    ..This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import. ..
  52. Guo Z, Wang D, Yao Q, Chen K, Zhang C. Identification of a novel functional nuclear localization signal in the protein encoded by open reading frame 47 of Bombyx mori nucleopolyhedrovirus. Arch Virol. 2010;155:1943-50 pubmed publisher
    ..Finally, we observed that two clusters of basic residues were conserved in BM47 homologues of group-I nucleopolyhedroviruses...
  53. Gal J, Zhang J, Kwinter D, Zhai J, Jia H, Jia J, et al. Nuclear localization sequence of FUS and induction of stress granules by ALS mutants. Neurobiol Aging. 2011;32:2323.e27-40 pubmed publisher
    ..Our results suggest that the ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism. ..