DOI: 10.1093/embo-reports/kvd092. Finding nuclear localization signals

10.1093/embo-reports/kvd092

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

Abstract

A variety of nuclear localization signals (NLSs) are experimentally known although only one motif was available for database searches through PROSITE. We initially collected a set of 91 experimentally verified NLSs from the literature. Through iterated ‘in silico mutagenesis’ we then extended the set to 214 potential NLSs. This final set matched in 43% of all known nuclear proteins and in no known non‐nuclear protein. We estimated that >17% of all eukaryotic proteins may be imported into the nucleus. Finally, we found an overlap between the NLS and DNA‐binding region for 90% of the proteins for which both the NLS and DNA‐binding regions were known. Thus, evolution seemed to have used part of the existing DNA‐binding mechanism when compartmentalizing DNA‐binding proteins into the nucleus. However, only 56 of our 214 NLS motifs overlapped with DNA‐binding regions. These 56 NLSs enabled a de novo prediction of partial DNA‐binding regions for ∼800 proteins in human, fly, worm and yeast.

Bibliography

Cokol, M., Nair, R., & Rost, B. (2000). Finding nuclear localization signals. EMBO Reports, 1(5), 411â415. Portico.

Authors 3

Murat Cokol (first)
Rajesh Nair (additional)
Burkhard Rost (additional)

References 24 Referenced 563

10.1093/nar/27.1.49
10.1093/nar/28.1.235
10.1073/pnas.94.10.5055
{'key': 'e_1_2_5_5_1', 'first-page': '193', 'article-title': 'Nuclear localization signals (NLS)', 'volume': '3', 'author': 'Boulikas T.', 'year': '1993', 'journal-title': 'Crit. Rev. Eukaryot. Gene Expr.'} / Crit. Rev. Eukaryot. Gene Expr. / Nuclear localization signals (NLS) by Boulikas T. (1993)
10.1002/jcb.240550106
10.1038/32100
10.1016/S0092-8674(00)81419-1
10.1002/1097-0134(20001001)41:1<98::AID-PROT120>3.0.CO;2-S
10.1093/bioinformatics/15.7.563
10.1093/nar/27.1.215
10.1002/(SICI)1097-4644(19980701)70:1<94::AID-JCB10>3.0.CO;2-B
10.1074/jbc.275.4.2647
{'key': 'e_1_2_5_14_1', 'first-page': '509', 'article-title': 'Efficient discovery of conserved patterns using a pattern graph', 'volume': '13', 'author': 'Jonassen I.', 'year': '1997', 'journal-title': 'Comp. Appl. Biol. Sci.'} / Comp. Appl. Biol. Sci. / Efficient discovery of conserved patterns using a pattern graph by Jonassen I. (1997)
10.1093/nar/23.10.1647
Liu J.andRost B.(2000)Analysing all proteins in entire genomes. CUBIC Columbia University Department of Biochemistry and Molecular Biophysics http://cubic.bioc.columbia.edu/genomes
10.1146/annurev.biochem.67.1.265
10.1038/380730a0
10.1016/S0014-5793(99)01446-5
10.1016/S0076-6879(96)66033-9
10.1093/protein/12.2.85
10.1016/S0968-0004(00)89080-5
10.1073/pnas.89.16.7442
10.1128/MCB.19.2.1210
10.1016/S0968-0004(98)01204-3

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 6:48 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:56 p.m.)
Indexed	3 weeks, 3 days ago (Aug. 5, 2025, 9:11 a.m.)
Issued	24 years, 9 months ago (Nov. 1, 2000)
Published	24 years, 9 months ago (Nov. 1, 2000)
Published Online	24 years, 9 months ago (Nov. 1, 2000)
Published Print	24 years, 9 months ago (Nov. 1, 2000)

Funders 0

None

BibTeX

@article{Cokol_2000, title={Finding nuclear localization signals}, volume={1}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kvd092}, DOI={10.1093/embo-reports/kvd092}, number={5}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Cokol, Murat and Nair, Rajesh and Rost, Burkhard}, year={2000}, month=nov, pages={411–415} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        5
      ]
    ],
    "date-time": "2025-08-05T13:11:47Z",
    "timestamp": 1754399507517
  },
  "reference-count": 24,
  "publisher": "Springer Science and Business Media LLC",
  "issue": "5",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2000,
            11,
            1
          ]
        ],
        "date-time": "2000-11-01T00:00:00Z",
        "timestamp": 973036800000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [
      "www.embopress.org"
    ],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        11
      ]
    ]
  },
  "abstract": "<jats:p>A variety of nuclear localization signals (NLSs) are experimentally known although only one motif was available for database searches through PROSITE. We initially collected a set of 91 experimentally verified NLSs from the literature. Through iterated \u2018<jats:italic>in silico</jats:italic> mutagenesis\u2019 we then extended the set to 214 potential NLSs. This final set matched in 43% of all known nuclear proteins and in no known non\u2010nuclear protein. We estimated that &gt;17% of all eukaryotic proteins may be imported into the nucleus. Finally, we found an overlap between the NLS and DNA\u2010binding region for 90% of the proteins for which both the NLS and DNA\u2010binding regions were known. Thus, evolution seemed to have used part of the existing DNA\u2010binding mechanism when compartmentalizing DNA\u2010binding proteins into the nucleus. However, only 56 of our 214 NLS motifs overlapped with DNA\u2010binding regions. These 56 NLSs enabled a <jats:italic>de novo</jats:italic> prediction of partial DNA\u2010binding regions for \u223c800 proteins in human, fly, worm and yeast.</jats:p>",
  "DOI": "10.1093/embo-reports/kvd092",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T22:48:15Z",
    "timestamp": 1027723695000
  },
  "page": "411-415",
  "update-policy": "http://dx.doi.org/10.1002/crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 563,
  "title": "Finding nuclear localization signals",
  "prefix": "10.1038",
  "volume": "1",
  "author": [
    {
      "given": "Murat",
      "family": "Cokol",
      "sequence": "first",
      "affiliation": [
        {
          "name": "CUBIC, Columbia University, Department of Biochemistry and Molecular Biophysics  630 West 168th Street New York NY 10032 USA"
        }
      ]
    },
    {
      "given": "Rajesh",
      "family": "Nair",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "CUBIC, Columbia University, Department of Biochemistry and Molecular Biophysics  630 West 168th Street New York NY 10032 USA"
        }
      ]
    },
    {
      "given": "Burkhard",
      "family": "Rost",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "CUBIC, Columbia University, Department of Biochemistry and Molecular Biophysics  630 West 168th Street New York NY 10032 USA"
        }
      ]
    }
  ],
  "member": "297",
  "published-online": {
    "date-parts": [
      [
        2000,
        11
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_5_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/27.1.49"
    },
    {
      "key": "e_1_2_5_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/28.1.235"
    },
    {
      "key": "e_1_2_5_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.10.5055"
    },
    {
      "key": "e_1_2_5_5_1",
      "first-page": "193",
      "article-title": "Nuclear localization signals (NLS)",
      "volume": "3",
      "author": "Boulikas T.",
      "year": "1993",
      "journal-title": "Crit. Rev. Eukaryot. Gene Expr."
    },
    {
      "key": "e_1_2_5_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcb.240550106"
    },
    {
      "key": "e_1_2_5_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/32100"
    },
    {
      "key": "e_1_2_5_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81419-1"
    },
    {
      "key": "e_1_2_5_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/1097-0134(20001001)41:1<98::AID-PROT120>3.0.CO;2-S"
    },
    {
      "key": "e_1_2_5_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/bioinformatics/15.7.563"
    },
    {
      "key": "e_1_2_5_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/27.1.215"
    },
    {
      "key": "e_1_2_5_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-4644(19980701)70:1<94::AID-JCB10>3.0.CO;2-B"
    },
    {
      "key": "e_1_2_5_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.275.4.2647"
    },
    {
      "key": "e_1_2_5_14_1",
      "first-page": "509",
      "article-title": "Efficient discovery of conserved patterns using a pattern graph",
      "volume": "13",
      "author": "Jonassen I.",
      "year": "1997",
      "journal-title": "Comp. Appl. Biol. Sci."
    },
    {
      "key": "e_1_2_5_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/23.10.1647"
    },
    {
      "key": "e_1_2_5_16_1",
      "unstructured": "Liu J.andRost B.(2000)Analysing all proteins in entire genomes. CUBIC Columbia University Department of Biochemistry and Molecular Biophysics http://cubic.bioc.columbia.edu/genomes"
    },
    {
      "key": "e_1_2_5_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.67.1.265"
    },
    {
      "key": "e_1_2_5_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/380730a0"
    },
    {
      "key": "e_1_2_5_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(99)01446-5"
    },
    {
      "key": "e_1_2_5_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0076-6879(96)66033-9"
    },
    {
      "key": "e_1_2_5_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/protein/12.2.85"
    },
    {
      "key": "e_1_2_5_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0968-0004(00)89080-5"
    },
    {
      "key": "e_1_2_5_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.89.16.7442"
    },
    {
      "key": "e_1_2_5_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.19.2.1210"
    },
    {
      "key": "e_1_2_5_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0968-0004(98)01204-3"
    }
  ],
  "container-title": "EMBO reports",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1093%2Fembo-reports%2Fkvd092",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1093/embo-reports/kvd092",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1093/embo-reports/kvd092",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://www.embopress.org/doi/pdf/10.1093/embo-reports/kvd092",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        12,
        18
      ]
    ],
    "date-time": "2023-12-18T20:56:30Z",
    "timestamp": 1702932990000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.embopress.org/doi/10.1093/embo-reports/kvd092"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        11
      ]
    ]
  },
  "references-count": 24,
  "journal-issue": {
    "issue": "5",
    "published-print": {
      "date-parts": [
        [
          2000,
          11
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1093/embo-reports/kvd092"
  ],
  "URL": "http://dx.doi.org/10.1093/embo-reports/kvd092",
  "relation": {},
  "ISSN": [
    "1469-221X",
    "1469-3178"
  ],
  "subject": [],
  "container-title-short": "EMBO Reports",
  "published": {
    "date-parts": [
      [
        2000,
        11
      ]
    ]
  },
  "assertion": [
    {
      "value": "2000-07-14",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2000-09-19",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2000-11-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}