The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Human RAS Superfamily Proteins and Related GTPases
Abstract
The tumor oncoproteins HRAS, KRAS, and NRAS are the founding members of a larger family of at least 35 related human proteins. Using a somewhat broader definition of sequence similarity reveals a more extended superfamily of more than 170 RAS-related proteins. The RAS superfamily of GTP (guanosine triphosphate) hydrolysis–coupled signal transduction relay proteins can be subclassified into RAS, RHO, RAB, and ARF families, as well as the closely related Gα family. The members of each family can, in turn, be arranged into evolutionarily conserved branches. These groupings reflect structural, biochemical, and functional conservation. Recent findings have provided insights into the signaling characteristics of representative members of most RAS superfamily branches. The analysis presented here may serve as a guide for predicting the function of numerous uncharacterized superfamily members. Also described are guanosine triphosphatases (GTPases) distinct from members of the RAS superfamily. These related proteins employ GTP binding and GTPase domains in diverse structural contexts, expanding the scope of their function in humans.
Overview
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
Verification
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?
In the citing paper
“The subcellular localization and function of Rho GTPases can be regulated by C-terminal prenylation at the CAAX motif.40–42”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
The GTPase superfamily: conserved structure and molecular mechanism
Bourne, H. R., Sanders, D. A., & McCormick, F. (1991) · Nature · doi:10.1038/349117a0 · Cited by 3,392
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911
The 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
The Rab5 effector EEA1 is a core component of endosome docking
Christoforidis, S., McBride, H. M., Burgoyne, R. D., & Zerial, M. (1999) · Nature · doi:10.1038/17618 · Cited by 854
Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47
MacMicking, J. D., Taylor, G. A., & McKinney, J. D. (2003) · Science · doi:10.1126/science.1088063 · Cited by 685
Ras signalling on the endoplasmic reticulum and the Golgi
Chiu, V. K., Bivona, T., Hach, A., Sajous, J. B., Silletti, J., Wiener, H., Johnson, R. L., Cox, A. D., & Philips, M. R. (2002) · Nature Cell Biology · doi:10.1038/ncb783 · Cited by 594
Komiyama, N. H., Watabe, A. M., Carlisle, H. J., Porter, K., Charlesworth, P., Monti, J., Strathdee, D. J. C., O'Carroll, C. M., Martin, S. J., Morris, R. G. M., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09721.2002 · Cited by 382
Castro, A. F., Rebhun, J. F., Clark, G. J., & Quilliam, L. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300226200 · Cited by 381
Research works printed but not linked: 263
- 10.1073/pnas.84.7.1814 · DOI
- 10.1002/j.1460-2075.1982.tb01276.x · DOI · Paper page
- 10.1016/0092-8674(95)90507-3 · DOI
- 10.1126/science.271.5250.810 · DOI
- 10.1016/S0092-8674(00)80226-3 · DOI
- 10.1126/science.1062023 · DOI · Paper page
- 10.1074/jbc.271.12.6794 · DOI
- 10.1126/science.2406906 · DOI
- 10.1016/S0021-9258(19)77694-7 · DOI
- 10.1159/000136714 · DOI
- 10.1126/science.8493579 · DOI
- 10.1016/S0079-6603(02)71047-7 · DOI
- L. A. Feig, G. M. Cooper, Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol. Cell. Biol. 8, 3235–3243 (1988).
- S. Y. Chen, S. Y. Huff, C. C. Lai, C. J. Der, S. Powers, Ras-15A protein shares highly similar dominant-negative biological properties with Ras-17N and forms a stable, guanine-nucleotide resistant complex with CDC25 exchange factor. Oncogene 9, 2691–2698 (1994).
- 10.1126/science.1087761 · DOI
- 10.1016/S0898-6568(98)00063-1 · DOI
- 10.1016/S0968-0004(96)10062-1 · DOI
- 10.1016/S0960-9822(98)70257-X · DOI
- 10.1038/366643a0 · DOI
- F. Tamanoi D. S. Sigman Eds. Protein Lipidation vol. 21 (Academic Press San Diego CA 2001).
- 10.1074/jbc.271.9.4671 · DOI
- 10.1016/S0021-9258(17)31698-8 · DOI
- 10.1074/jbc.270.44.26347 · DOI
- 10.1046/j.1432-1327.1999.00815.x · DOI
- 10.1074/jbc.M000397200 · DOI
- 10.1074/jbc.M104658200 · DOI
- 10.1021/bi00083a001 · DOI
- 10.1073/pnas.90.8.3675 · DOI
- 10.1016/0014-5793(94)80406-0 · DOI
- W. H. Kirsten, L. A. Mayer, Malignant lymphomas of extrathymic origin induced in rats by murine erythroblastosis virus. J. Natl. Cancer Inst. 43, 735–746 (1969).
- J. J. Harvey, An unidentified virus which causes the rapid production of tumours in mice. Nature 204, 1104–1105 (1964).
- 10.1016/0092-8674(81)90388-3 · DOI
- 10.1073/pnas.78.2.1181 · DOI
- 10.1038/290261a0 · DOI
- 10.1038/346754a0 · DOI
- L. A. Feig, G. M. Cooper, Relationship among guanine nucleotide exchange, GTP hydrolysis, and transforming potential of mutated ras proteins. Mol. Cell. Biol. 8, 2472–2478 (1988).
- G. Patel, M. J. MacDonald, R. Khosravi-Far, M. M. Hisaka, C. J. Der, Alternate mechanisms of ras activation are complementary and favor and formation of ras-GTP. Oncogene 7, 283–288 (1992).
- 10.1002/ajmg.10692 · DOI
- 10.1146/annurev.genom.3.022502.103043 · DOI
- 10.1016/S1535-6108(02)00093-4 · DOI
- 10.1200/JCO.2003.10.130 · DOI
- 10.1016/0304-3835(96)04372-8 · DOI
- 10.1023/A:1006491619920 · DOI
- 10.1016/0092-8674(90)90149-9 · DOI
- 10.1016/0092-8674(90)90150-D · DOI
- 10.1016/0092-8674(90)90151-4 · DOI · Paper page
- 10.1016/S0022-5347(01)64362-3 · DOI
- 10.1007/s00232-002-1026-4 · DOI
- 10.1016/S0092-8674(00)80607-8 · DOI · Paper page
- 10.1128/MCB.20.7.2475-2487.2000 · DOI
- 10.1128/MCB.22.14.5128-5140.2002 · DOI
- 10.1091/mbc.01-11-0552 · DOI
- 10.1038/35070050 · DOI
- 10.1038/nrm1105 · DOI · Paper page
- 10.1074/jbc.M105888200 · DOI
- 10.1016/S0021-9258(18)61562-5 · DOI
- 10.1042/bj3550145 · DOI
- 10.1074/jbc.M001813200 · DOI
- 10.1073/pnas.1037299100 · DOI
- 10.1073/pnas.96.24.13813 · DOI
- 10.1074/jbc.M103133200 · DOI
- 10.1038/304497a0 · DOI
- 10.1038/304501a0 · DOI
- S. Guil, N. de La Iglesia, J. Fernandez-Larrea, D. Cifuentes, J. C. Ferrer, J. J. Guinovart, M. Bach-Elias, Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras family protein that trafficks to cytoplasm and nucleus. Cancer Res. 63, 5178–5187 (2003).
- 10.1016/0092-8674(85)90280-6 · DOI
- 10.1016/0092-8674(91)90065-7 · DOI
- 10.1016/0092-8674(90)90495-Z · DOI
- 10.1038/36849 · DOI
- 10.1016/S0896-6273(00)80471-7 · DOI · Paper page
- 10.1016/S0896-6273(00)81008-9 · DOI · Paper page
- 10.1523/JNEUROSCI.23-03-00748.2003 · DOI
- 10.1073/pnas.90.13.6213 · DOI
- 10.1016/0092-8674(93)90307-C · DOI
- 10.1038/364352a0 · DOI
- 10.1038/364308a0 · DOI
- 10.1073/pnas.90.18.8683 · DOI
- 10.1042/bj3510289 · DOI
- 10.1016/S0955-0674(97)80060-9 · DOI
- 10.1073/pnas.93.14.6924 · DOI
- 10.1073/pnas.212516099 · DOI
- 10.1038/ncb833 · DOI
- 10.1038/nature00848 · DOI
- 10.1002/j.1460-2075.1996.tb00602.x · DOI
- 10.1073/pnas.91.26.12609 · DOI
- A. Kikuchi, S. D. Demo, Z. H. Ye, Y. W. Chen, L. T. Williams, ralGDS family members interact with the effector loop of ras p21. Mol. Cell. Biol. 14, 7483–7491 (1994).
- 10.1074/jbc.271.47.29903 · DOI
- 10.1038/sj.onc.1204053 · DOI
- 10.1002/j.1460-2075.1996.tb00416.x · DOI
- 10.1128/MCB.21.17.5958-5969.2001 · DOI
- 10.1101/gad.993902 · DOI
- 10.1128/MCB.22.3.916-926.2001 · DOI
- 10.1073/pnas.94.10.4954 · DOI
- 10.1016/S1534-5807(01)00008-9 · DOI · Paper page
- 10.1016/S1074-7613(00)80452-5 · DOI
- 10.1016/S0960-9822(02)00683-8 · DOI
- 10.1093/emboj/20.4.743 · DOI
- 10.1073/pnas.97.16.9064 · DOI
- 10.1074/jbc.M312867200 · DOI
- 10.1038/nature02237 · DOI
- 10.1128/MCB.23.3.933-949.2003 · DOI
- 10.1242/jcs.00689 · DOI
- 10.1073/pnas.91.16.7558 · DOI
- S. M. Graham, A. D. Cox, G. Drivas, M. G. Rush, P. D’Eustachio, C. J. Der, Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation. Mol. Cell. Biol. 14, 4108–4115 (1994).
- 10.1182/blood.V94.7.2433.419k31_2433_2444 · DOI · Paper page
- A. D. Cox, T. R. Brtva, D. G. Lowe, C. J. Der, R-Ras induces malignant, but not morphologic, transformation of NIH3T3 cells. Oncogene 9, 3281–3288 (1994).
- Y. Huang, R. Saez, L. Chao, E. Santos, S. A. Aaronson, A. M. Chan, A novel insertional mutation in the TC21 gene activates its transforming activity in a human leiomyosarcoma cell line. Oncogene 11, 1255–1260 (1995).
- G. J. Clark, M. S. Kinch, T. M. Gilmer, K. Burridge, C. J. Der, Overexpression of the Ras-related TC21/R-Ras2 protein may contribute to the development of human breast cancers. Oncogene 12, 169–176 (1996).
- 10.1038/bjc.1998.490 · DOI
- 10.1016/S0960-9822(06)00028-5 · DOI · Paper page
- 10.1128/MCB.21.11.3750-3762.2001 · DOI
- 10.1042/bj3000303 · DOI
- 10.1093/emboj/18.5.1270 · DOI
- 10.1083/jcb.148.6.1151 · DOI
- S. J. McLeod A. J. Shum R. L. Lee F. Takei M. R. Gold The Rap GTPases regulate integrin-mediated adhesion cell spreading actin polymerization and Pyk2 tyrosine phosphorylation in B lymphocytes. J. Biol. Chem. (2003). · DOI
- 10.1016/0092-8674(89)90985-9 · DOI
- 10.1016/S0092-8674(00)80184-1 · DOI
- 10.1038/ncb874 · DOI · Paper page
- 10.1074/jbc.M008970200 · DOI
- 10.1016/S1535-6108(03)00163-6 · DOI
- 10.1016/S0092-8674(03)00155-7 · DOI · Paper page
- 10.1128/MCB.23.3.1112-1124.2003 · DOI · Paper page
- 10.1038/sj.onc.1206003 · DOI
- 10.1038/ni950 · DOI
- 10.1016/S0962-8924(03)00152-1 · DOI · Paper page
- 10.1128/MCB.20.2.462-467.2000 · DOI
- 10.1038/sj.embor.embor899 · DOI
- 10.1128/MCB.24.13.5746-5756.2004 · DOI
- S. H. Park, R. A. Weinberg, A putative effector of Ral has homology to Rho/Rac GTPase activating proteins. Oncogene 11, 2349–2355 (1995).
- 10.1074/jbc.270.38.22473 · DOI · Paper page
- 10.1128/MCB.15.8.4578 · DOI · Paper page
- 10.1242/jcs.113.16.2837 · DOI · Paper page
- 10.1093/emboj/18.13.3629 · DOI · Paper page
- 10.1074/jbc.M302191200 · DOI
- 10.1038/ncb728 · DOI · Paper page
- 10.1074/jbc.M308702200 · DOI · Paper page
- 10.1038/ncb720 · DOI · Paper page
- 10.1083/jcb.200308070 · DOI
- 10.1242/jcs.00401 · DOI
- 10.1074/jbc.M201092200 · DOI
- 10.1523/JNEUROSCI.16-21-06784.1996 · DOI
- 10.1038/sj.onc.1203836 · DOI
- 10.1016/S0014-5793(01)03264-1 · DOI
- 10.1006/abbi.1999.1448 · DOI
- 10.1038/nature01646 · DOI
- 10.1074/jbc.M202150200 · DOI
- 10.1073/pnas.142193799 · DOI
- 10.1073/pnas.96.1.214 · DOI
- L. Wang, A. Hoque, R. Z. Luo, J. Yuan, Z. Lu, A. Nishimoto, J. Liu, A. A. Sahin, S. M. Lippman, R. C. Bast, Jr., Y. Yu, Loss of the expression of the tumor suppressor gene ARHI is associated with progression of breast cancer. Clin. Cancer Res. 9, 3660–3666 (2003).
- 10.1074/jbc.273.6.3129 · DOI
- 10.1038/sj.bjp.0704680 · DOI
- 10.1210/endo.142.6.8209 · DOI
- G. Vaidyanathan M. J. Cismowski G. Wang T. S. Vincent K. D. Brown S. M. Lanier The Ras-related protein AGS1/RASD1 suppresses cell growth. Oncogene 23 5858–5863 (2004). · DOI
- 10.1038/sj.onc.1207161 · DOI
- 10.1126/science.287.5454.869 · DOI
- 10.1074/jbc.M301021200 · DOI
- 10.1074/jbc.272.35.21982 · DOI
- 10.1042/bj3470223 · DOI
- 10.1126/science.8248782 · DOI · Paper page
- 10.1126/science.7912851 · DOI · Paper page
- 10.1073/pnas.2437756100 · DOI
- 10.1038/35079621 · DOI
- 10.1093/emboj/20.15.4076 · DOI
- 10.1016/j.cub.2003.08.042 · DOI
- 10.1042/bj20020829 · DOI
- 10.1016/j.bbrc.2004.02.091 · DOI
- 10.1242/jcs.00661 · DOI
- 10.1038/sj.onc.1205792 · DOI
- 10.1016/S1097-2765(03)00220-X · DOI · Paper page
- 10.1016/S0960-9822(03)00506-2 · DOI · Paper page
- 10.1038/ncb999 · DOI
- 10.1016/S0092-8674(04)00003-0 · DOI · Paper page
- 10.1242/jcs.01118 · DOI
- 10.1038/nrc725 · DOI · Paper page
- 10.1038/sj.onc.1203233 · DOI
- 10.1126/science.273.5272.245 · DOI
- 10.1038/11056 · DOI
- 10.1126/science.271.5249.648 · DOI
- 10.1126/science.271.5249.645 · DOI
- 10.1074/jbc.M306904200 · DOI
- 10.1074/jbc.M203569200 · DOI
- 10.1074/jbc.271.23.13556 · DOI
- 10.1016/S0021-9258(19)84716-6 · DOI · Paper page
- 10.1074/jbc.270.39.22731 · DOI
- 10.1074/jbc.M301418200 · DOI
- 10.1016/S0960-9822(02)00423-2 · DOI
- 10.1016/S0092-8674(00)81050-8 · DOI
- 10.1073/pnas.93.11.5615 · DOI
- 10.1016/j.cell.2004.06.027 · DOI
- 10.1093/emboj/cdg110 · DOI
- 10.1016/S0960-9822(03)00418-4 · DOI
- 10.1128/MCB.23.12.4219-4229.2003 · DOI
- 10.1016/S0092-8674(03)00315-5 · DOI
- 10.1074/jbc.M208609200 · DOI
- 10.1042/bj20031041 · DOI
- 10.1073/pnas.84.23.8210 · DOI
- E. R. Nimmo, P. G. Sanders, R. A. Padua, D. Hughes, R. Williamson, K. J. Johnson, The MEL gene: A new member of the RAB/YPT class of RAS-related genes. Oncogene 6, 1347–1351 (1991).
- N. Segev, Ypt/rab gtpases: Regulators of protein trafficking. Sci. STKE 2001, re11 (2001).
- H. Stenmark V. M. Olkkonen The Rab GTPase family. Genome Biol. 2 REVIEWS3007 (2001). · DOI
- 10.1006/jmbi.2001.5072 · DOI
- 10.1002/j.1460-2075.1996.tb00529.x · DOI
200 of 263 shown
Cited by
Ras history: The saga continues
Cox, A. D., & Der, C. J. (2010) · Small GTPases · doi:10.4161/sgtp.1.1.12178 · Cited by 706
Drugging an undruggable pocket on KRAS
Kessler, D., Gmachl, M., Mantoulidis, A., Martin, L. J., Zoephel, A., Mayer, M., Gollner, A., Covini, D., Fischer, S., Gerstberger, T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904529116 · Cited by 449
M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelett, C. C., Yeaman, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1990 · Cited by 402
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355
Chandra, A., Grecco, H. E., Pisupati, V., Perera, D., Cassidy, L., Skoulidis, F., Ismail, S. A., Hedberg, C., Hanzal-Bayer, M., Venkitaraman, A. R., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2394 · Cited by 325
Metadata
- Authors
- Colicelli, J.
- Affiliations
- Department of Biological Chemistry and Molecular Biology Institute, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
- Venue
- Science's STKE
- Published
- 2004-09-14
- Volume
- 2004
- Issue
- 250
- ISSN
- 1525-8882
- Cited by
- 582
- References
- 15
- Language
- en
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Human RAS Superfamily Proteins and Related GTPases. https://app.cochat.ai/papers/10.1126/stke.2502004re13
- The paper
- Colicelli, J. (2004). Human RAS Superfamily Proteins and Related GTPases. Science's STKE. https://doi.org/10.1126/stke.2502004re13