The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.
Open accessAbstract
The von Recklinghausen neurofibromatosis locus, NF1, encodes a protein with homology restricted to the catalytic region of the RAS GTPase-activating protein, GAP, and with extensive homology to the IRA1 and IRA2 gene products of the yeast S. cerevisiae. A segment of the NF1 cDNA gene, expressed in yeast, can complement loss of IRA function and can inhibit both wild-type and mutant activated human H-ras genes that are coexpressed in yeast. Yeast expressing the NF1 segment have increased H-ras GTPase-stimulating activity. These studies indicate that the NF1 gene product can interact with RAS proteins and demonstrate structural and functional similarities and differences among the GAP, IRA1, IRA2, and NF1 proteins.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nf1 is a 2818-amino acid protein with Ras-GAP activity encoded by the NF1 gene.
“Neurofibromin 1 (Nf1) is 2818-amino acid protein with Ras-GAP activity encoded by the NF1 gene (1).”
From PU.1, Interferon Regulatory Factor (IRF) 2, and the Interferon Consensus Sequence-binding Protein (ICSBP/IRF8) Cooperate to Activate NF1 Transcription in Differentiating Myeloid Cells (2007) · cites this paper as [1]
The Complementation section reports increased H-ras GTPase-stimulating activity in lysates expressing an NF1 segment, supporting the Ras-GAP activity attributed to the NF1 gene product. The Experimental Procedures describe a 2,484-residue partial NF1 sequence, not a 2,818-amino-acid full-length protein; the paper does not substantiate the claimed length. (LLM, conf=0.90)
Experimental — accuracy not yet measuredRET and NF1 are linked by their common ability to activate the RAS/RAF/MAP kinase signaling cascade.
“The two prototype genes of Cluster 2 (RET and NF1) are linked by their common ability to activate the RAS/RAF/MAP kinase signaling cascade [16,17].”
From A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas (2005) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
Transformation of intact yeast cells treated with alkali cations
Ito, H., Fukuda, Y., Murata, K., & Kimura, A. (1983) · Journal of Bacteriology · doi:10.1128/jb.153.1.163-168.1983 · Cited by 7,518 · see citing works
Barbacid, M. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.004023 · Cited by 3,885 · see citing works
[12] One-step gene disruption in yeast
Rothstein, R. J. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01015-0 · Cited by 3,282 · see citing works
MAGOUN, H. N. (1965) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-196504000-00011 · Cited by 2,931 · see citing works
[1] Production of single-stranded plasmid DNA
Vieira, J., & Messing, J. W. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)53044-0 · Cited by 2,636 · see citing works
Karlin, S., & Altschul, S. F. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.6.2264 · Cited by 1,535 · see citing works
Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients
Wallace, M. R., Marchuk, D. A., Andersen, L. B., Letcher, R., Odeh, H. M., Saulino, A. M., Fountain, J. W., Brereton, A., Nicholson, J. M., Mitchell, A. L., et al. (1990) · Science · doi:10.1126/science.2134734 · Cited by 1,476 · see citing works
Self-citationLaboratory course manual for methods in yeast genetics
Sherman, F., Fink, G. R., & Hicks, J. B. (1986) · Cold Spring Harbor Laboratory eBooks · Cited by 1,301 · see citing works
Trahey, M., & McCormick, F. (1987) · Science · doi:10.1126/science.2821624 · Cited by 1,211 · see citing works
In yeast, RAS proteins are controlling elements of adenylate cyclase
Toda, T., Uno, I., Ishikawa, T., Powers, S., Kataoka, T., Broek, D., Cameron, S., Broach, J. R., Matsumoto, K., & Wigler, M. H. (1985) · Cell · doi:10.1016/0092-8674(85)90305-8 · Cited by 1,108 · see citing works
Self-citationThe neurofibromatosis type 1 gene encodes a protein related to GAP
Xu, G., O'Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90024-9 · Cited by 1,095 · cited 7× · see citing works
“Under our assay conditions, NF1 lysates have less activity than lysates from cells expressing GAP Discussion The NFl locus encodes a protein that is structurally related to the IRA proteins of yeast and to the GAP protein of mammalian cells (Xu et al., 1990; Buchberg et al., 1990).”
BackgroundMethodResultInfluentialCawthon, R., Weiss, R. B., Xu, G., Viskochil, D. H., Culver, M., Stevens, J., Robertson, M. A., Dunn, D. M., Gesteland, R. F., O'Connell, P., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90253-b · Cited by 1,093 · see citing works
Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus
Viskochil, D. H., Buchberg, A. M., Xu, G., Cawthon, R., Stevens, J., Wolff, R. K., Culver, M., Carey, J. C., Copeland, N. G., Jenkins, N. A., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90252-a · Cited by 1,082 · see citing works
A workbench for multiple alignment construction and analysis
Schuler, G. D., Altschul, S. F., & Lipman, D. J. (1991) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.340090304 · Cited by 985 · see citing works
Furth, M. E., Davis, L. J., Fleurdelys, B. E., & Scolnick, E. M. (1982) · Journal of Virology · doi:10.1128/jvi.43.1.294-304.1982 · Cited by 800 · see citing works
Neurofibromatosis, Phenotype, Natural History, and Pathogenesis
Riccardi, V. M., & Smirniotopoulos, J. G. (1992) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199211000-00009 · Cited by 789 · see citing works
Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation
Bar‐Sagi, D., & Feramisco, J. R. (1985) · Cell · doi:10.1016/0092-8674(85)90280-6 · Cited by 733 · see citing works
Gene for von Recklinghausen Neurofibromatosis Is in the Pericentromeric Region of Chromosome 17
Barker, D. F., Wright, E., Nguyen, K., Cannon, L. A., Fain, P. R., Goldgar, D., Bishop, D. T., Carey, J. C., Baty, B. J., Kivlin, J., et al. (1987) · Science · doi:10.1126/science.3107130 · Cited by 695 · see citing works
Cloning of bovine GAP and its interaction with oncogenic ras p21
Vogel, U. S., Dixon, R. A. F., Schaber, M. D., Diehl, R. E., Marshall, M. S., Scolnick, E. M., Sigal, I. S., & Gibbs, W. W. (1988) · Nature · doi:10.1038/335090a0 · Cited by 649 · see citing works
A Clinical, Pathological, and Genetic Study of Multiple Neurofibromatosis
(1956) · JAMA · doi:10.1001/jama.1956.02970230087029 · Cited by 525 · see citing works
Autoradiography using storage phosphor technology
Johnston, R. F., Pickett, S. C., & Barker, D. L. A. (1990) · Electrophoresis · doi:10.1002/elps.1150110503 · Cited by 525 · see citing works
A tool for multiple sequence alignment.
Lipman, D. J., Altschul, S. F., & Kececioglu, J. D. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.12.4412 · Cited by 506 · see citing works
Guanosine Triphosphatase Activating Protein (GAP) Interacts with the p21 ras Effector Binding Domain
Adari, H. Y., Lowy, D. R., Willumsen, B. M., Der, C. J., & McCormick, F. P. (1988) · Science · doi:10.1126/science.2833817 · Cited by 506 · see citing works
Predictive motifs derived from cytosine methyltransferases
Pósfai, J., Bhagwat, A. S., Pósfai, G., & Roberts, R. J. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.7.2421 · Cited by 491 · see citing works
The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway
Broek, D., Toda, T., Michaeli, T., Levin, L. R., Birchmeier, C., Zoller, M. J., Powers, S., & Wigler, M. H. (1987) · Cell · doi:10.1016/0092-8674(87)90076-6 · Cited by 478 · see citing works
Self-citationMolecular Cloning of Two Types of GAP Complementary DNA from Human Placenta
Trahey, M., Wong, G. A., Halenbeck, R., Rubinfeld, B., Martin, G. A., Ladner, M. B., Long, C. M., Crosier, W. J., Watt, K., Koths, K. E., et al. (1988) · Science · doi:10.1126/science.3201259 · Cited by 468 · see citing works
Noda, M., Ko, M. S. H., Ogura, A., Liu, D. G., Amano, T., Takano, T., & Ikawa, Y. (1985) · Nature · doi:10.1038/318073a0 · Cited by 449 · see citing works
Hagag, N. G., Halegoua, S., & Viola, M. V. (1986) · Nature · doi:10.1038/319680a0 · Cited by 419 · see citing works
Three human transforming genes are related to the viral ras oncogenes.
Shimizu, K., Goldfarb, M. P., Suard, Y. M. L., Perucho, M., Li, Y., Kamata, T., Feramisco, J. R., Stavnezer, E., Fogh, J. M., & Wigler, M. H. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2112 · Cited by 389 · see citing works
Self-citationThe cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product
Calés, C., Hancock, J. F., Marshall, C. J., & Hall, A. (1988) · Nature · doi:10.1038/332548a0 · Cited by 386 · see citing works
Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene
Seizinger, B. R., Rouleau, G. A., Ozelius, L. J., Lane, A., Faryniarz, A. G., Chao, M. V., Huson, S., Korf, B. R., Parry, D. M., Pericak‐Vance, M. A., et al. (1987) · Cell · doi:10.1016/0092-8674(87)90534-4 · Cited by 369 · see citing works
Self-citationMutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma.
Knudson, A. G., Hethcote, H. W., & Brown, B. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.12.5116 · Cited by 351 · see citing works
Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.
Szeberényi, J., Cai, H., & Cooper, G. M. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.10.5324 · Cited by 326 · see citing works
Tanaka, K., Nakafuku, M., Satoh, T., Marshall, M. S., Gibbs, W. W., Matsumoto, K., Kaziro, Y., & Toh‐e, A. (1990) · Cell · doi:10.1016/0092-8674(90)90094-u · Cited by 323 · see citing works
Tanaka, K., Nakafuku, M., Tamanoi, F., Kaziro, Y., Matsumoto, K., & Toh‐e, A. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.8.4303 · Cited by 292 · see citing works
Sass, P. M., Field, J. M., Nikawa, J., Toda, T., & Wigler, M. H. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.24.9303 · Cited by 288 · see citing works
Self-citationIRA1, an inhibitory regulator of the RAS-cyclic AMP pathway in Saccharomyces cerevisiae.
Tanaka, K., Matsumoto, K., & Toh‐e, A. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.2.757 · Cited by 245 · see citing works
ras p21 and GAP inhibit coupling of muscarinic receptors to atrial K+ channels
Yatani, A., Okabe, K., Polakis, P. G., Halenbeck, R., McCormick, F. P., & Brown, A. M. (1990) · Cell · doi:10.1016/0092-8674(90)90187-j · Cited by 235 · see citing works
CDC25 : a Component of the RAS -Adenylate Cyclase Pathway in Saccharomyces cerevisiae
Robinson, L. C., Gibbs, W. W., Marshall, M. S., Sigal, I. S., & Tatchell, K. (1987) · Science · doi:10.1126/science.3547648 · Cited by 234 · see citing works
Camonis, J., Kalékine, M., Gondré, B., Garreau, H., Boy‐Marcotte, E., & Jacquet, M. (1986) · The EMBO Journal · doi:10.1002/j.1460-2075.1986.tb04222.x · Cited by 222 · see citing works
Genetic analysis of the role of cAMP in yeast
Matsumoto, K., Uno, I., & Ishikawa, T. (1985) · Yeast · doi:10.1002/yea.320010103 · Cited by 199 · see citing works
Buchberg, A. M., Cleveland, L. S., Jenkins, N. A., & Copeland, N. G. (1990) · Nature · doi:10.1038/347291a0 · Cited by 194 · see citing works
Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase.
Colicelli, J., Birchmeier, C., Michaeli, T., et al. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.10.3599 · Cited by 190 · see citing works
A Clinical, Pathological and Genetic Study of Multiple Neurofibromatosis
R.B.R. (1957) · Neurology · doi:10.1212/wnl.7.2.149 · Cited by 182 · see citing works
Weights for data related by a tree
Altschul, S. F., Carroll, R. J., & Lipman, D. J. (1989) · Journal of Molecular Biology · doi:10.1016/0022-2836(89)90234-9 · Cited by 177 · see citing works
Powers, S., O’Neill, K. E., & Wigler, M. H. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.2.390 · Cited by 161 · see citing works
Self-citationA C‐terminal domain of GAP is sufficient to stimulate ras p21 GTPase activity.
Marshall, M. S., Hill, W. S., Ng, A. S., Vogel, U. S., Schaber, M. D., Scolnick, E. M., Dixon, R. A., Sigal, I. S., & Gibbs, W. W. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03480.x · Cited by 159 · see citing works
Suppression of c-ras transformation by GTPase-activating protein
Zhang, K., DeClue, J. E., Vass, W. C., Papageorge, A. G., McCormick, F. P., & Lowy, D. R. (1990) · Nature · doi:10.1038/346754a0 · Cited by 157 · see citing works
Multipoint linkage analysis in neurofibromatosis type I: an international collaboration.
Goldgar, D. E., Green, P., Parry, D. M., et al. (1989) · PubMed · Cited by 142 · see citing works
Physical Mapping of a Translocation Breakpoint in Neurofibromatosis
Fountain, J. W., Wallace, M. R., BRUCE, M., et al. (1989) · Science · doi:10.1126/science.2543076 · Cited by 142 · see citing works
Genetic analysis of mammalian GAP expressed in yeast
Ballester, R., Michaeli, T., Ferguson, K. M., Xu, H., McCormick, F. P., & Wigler, M. H. (1989) · Cell · doi:10.1016/0092-8674(89)90014-7 · Cited by 133 · see citing works
Self-citationExpression of three mammalian cDNAs that interfere with RAS function in Saccharomyces cerevisiae.
Colicelli, J., Nicolette, C. A., Birchmeier, C., Rodgers, L., Riggs, M. G., & Wigler, M. H. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.7.2913 · Cited by 106 · see citing works
Self-citationPurification and Characterization of Human H-ras Proteins Expressed in Escherichia coli
Gross, M. S., Sweet, R. W., Sathe, G. M., Yokoyama, S., Fasano, O., Goldfarb, M. P., Wigler, M. H., & Rosenberg, M. J. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.5.1015-1024.1985 · Cited by 105 · see citing works
Self-citationNeurofibromatosis: Phenotype, Natural History and Pathogenesis
Huson, S. M. (1987) · Journal of Medical Genetics · doi:10.1136/jmg.24.9.574 · Cited by 93 · see citing works
Two NF1 Translocations Map Within a 600-Kilobase Segment of 17q11.2
O'Connell, P., Leach, R. J., Cawthon, R., et al. (1989) · Science · doi:10.1126/science.2543077 · Cited by 78 · see citing works
Regulatory function of the Saccharomyces cerevisiae RAS C-terminus.
Marshall, M. S., Gibbs, W. W., Scolnick, E. M., & Sigal, I. S. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.7.2309 · Cited by 69 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
RAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · see citing works
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmüller, L., Lautwein, A., Schmitz, F., & Wittinghofer, A. (1997) · Science · doi:10.1126/science.277.5324.333 · Cited by 1,543 · see citing works
Ras oncogenes: split personalities
Karnoub, A. E., & Weinberg, R. A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2438 · Cited by 1,467 · see citing works
Ras history: The saga continues
Cox, A. D., & Der, C. J. (2010) · Small GTPases · doi:10.4161/sgtp.1.1.12178 · Cited by 706 · see citing works
Brannan, C. I., Perkins, A. S., Vogel, K. S., Ratner, N., Nordlund, M. L., Reid, S. W., Buchberg, A. M., Jenkins, N. A., Parada, L. F., & Copeland, N. G. (1994) · Genes & Development · doi:10.1101/gad.8.9.1019 · Cited by 641 · see citing works
DeClue, J. E., Papageorge, A. G., Fletcher, J. A., Diehl, S. R., Ratner, N., Vass, W. C., & Lowy, D. R. (1992) · Cell · doi:10.1016/0092-8674(92)90407-4 · Cited by 580 · see citing works
A HIF1α Regulatory Loop Links Hypoxia and Mitochondrial Signals in Pheochromocytomas
Dahia, P. L. M., Ross, K. N., Wright, M. E., Hayashida, C. Y., Santagata, S., Barontini, M., Kung, A. L., Sanso, G., Powers, J. F., Tischler, A. S., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010008 · Cited by 443 · see citing works
Morrow, D. M., Tagle, D. A., Shiloh, Y., Collins, F. S., & Hieter, P. (1995) · Cell · doi:10.1016/0092-8674(95)90480-8 · Cited by 370 · see citing works
Self-citationThe interaction of Ras with GTPase‐activating proteins
Wittinghofer, A., Scheffzek, K., & Ahmadian, M. R. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00321-9 · Cited by 135 · see citing works
Huang, W., Horvath, E., & Eklund, E. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607760200 · Cited by 58 · see citing works
Huang, W., Saberwal, G., Horvath, E., Zhu, C., Lindsey, S., & Eklund, E. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00036-06 · Cited by 41 · see citing works
- Authors
- Ballester, R., Marchuk, D., Boguski, M., Saulino, A., Letcher, R., Wigler, M., & Collins, F.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1990-11
- Volume
- 63
- Issue
- 4
- Pages
- 851-859
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1971602793
- Cited by
- 847
- References
- 58
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 25 · 2023: 17 · 2022: 18 · 2021: 21 · 2020: 16 · 2019: 11 · 2018: 18 · 2017: 16 · 2016: 17 · 2015: 13 · 2014: 21 · 2013: 19 · 2012: 29
- FWCI
- 58.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- American Cancer Society
- Pfizer
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- NF1 gene, von Recklinghausen neurofibromatosis, Ras GTPase-activating protein, IRA2, yeast, H-Ras, protein homology, functional complementation, Ras signaling
- MeSH terms
- Amino Acid Sequence, Base Sequence, Fungal Proteins, Genetic Complementation Test, Genetic Vectors, Humans, Molecular Sequence Data, Neurofibromatosis 1, Plasmids, Proteins, Saccharomyces cerevisiae, Sequence Homology, Nucleic Acid, Oligonucleotide Probes, Oncogene Protein p21(ras), GTP Phosphohydrolases, GTPase-Activating Proteins, ras GTPase-Activating Proteins, Neurofibromin 1, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
