RASF1_HUMAN
ID RASF1_HUMAN Reviewed; 344 AA.
AC Q9NS23; B7ZLL1; O14571; O60539; O60710; Q0VGC6; Q5TZT2; Q9HB04; Q9HB18;
AC Q9NS22; Q9UND4; Q9UND5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ras association domain-containing protein 1;
GN Name=RASSF1 {ECO:0000312|EMBL:AAF35128.2};
GN Synonyms=RDA32 {ECO:0000312|EMBL:AAC16001.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD44174.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), FUNCTION, TISSUE
RP SPECIFICITY, VARIANT GLN-21, AND INTERACTION WITH XPA.
RX PubMed=10888881; DOI=10.1038/77083;
RA Dammann R., Li C., Yoon J.-H., Chin P.L., Bates S., Pfeifer G.P.;
RT "Epigenetic inactivation of a RAS association domain family protein from
RT the lung tumour suppressor locus 3p21.3.";
RL Nat. Genet. 25:315-319(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF35128.2}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C; D; E; F AND G), FUNCTION, TISSUE
RP SPECIFICITY, AND VARIANTS GLN-21; CYS-53; GLU-133; SER-137 AND CYS-329.
RC TISSUE=Heart {ECO:0000312|EMBL:AAF35128.2},
RC Lung {ECO:0000312|EMBL:AAF35127.2}, and
RC Pancreas {ECO:0000312|EMBL:AAF35129.2};
RX PubMed=11333291; DOI=10.1093/jnci/93.9.691;
RA Burbee D.G., Forgacs E., Zochbauer-Muller S., Shivakumar L., Fong K.,
RA Gao B., Randle D., Kondo M., Virmani A., Bader S., Sekido Y., Latif F.,
RA Milchgrub S., Toyooka S., Gazdar A.F., Lerman M.I., Zabarovsky E.,
RA White M., Minna J.D.;
RT "Epigenetic inactivation of RASSF1A in lung and breast cancers and
RT malignant phenotype suppression.";
RL J. Natl. Cancer Inst. 93:691-699(2001).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAB67312.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAB67312.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC TISSUE=Blood, and Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7] {ECO:0000305}
RP FUNCTION, VARIANT PHE-135, AND CHARACTERIZATION OF VARIANTS PHE-135 AND
RP SER-137.
RX PubMed=12024041; DOI=10.1128/mcb.22.12.4309-4318.2002;
RA Shivakumar L., Minna J., Sakamaki T., Pestell R., White M.A.;
RT "The RASSF1A tumor suppressor blocks cell cycle progression and inhibits
RT cyclin D1 accumulation.";
RL Mol. Cell. Biol. 22:4309-4318(2002).
RN [8]
RP SELF-ASSOCIATION, AND INTERACTION WITH RSSF5 AND HRAS.
RX PubMed=11857081; DOI=10.1038/sj.onc.1205192;
RA Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R.,
RA Pfeifer G.P., Avruch J.;
RT "The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes
RT with the Ras-GTP binding protein Nore1.";
RL Oncogene 21:1381-1390(2002).
RN [9]
RP ERRATUM OF PUBMED:11857081.
RA Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.F., Dammann R.,
RA Pfeifer G.P., Avruch J.;
RL Oncogene 21:1943-1943(2002).
RN [10]
RP INTERACTION WITH E4F1.
RX PubMed=14729613; DOI=10.1158/0008-5472.can-03-2622;
RA Fenton S.L., Dallol A., Agathanggelou A., Hesson L., Ahmed-Choudhury J.,
RA Baksh S., Sardet C., Dammann R., Minna J.D., Downward J., Maher E.R.,
RA Latif F.;
RT "Identification of the E1A-regulated transcription factor p120 E4F as an
RT interacting partner of the RASSF1A candidate tumor suppressor gene.";
RL Cancer Res. 64:102-107(2004).
RN [11]
RP INTERACTION WITH MAP1S.
RX PubMed=15205320; DOI=10.1158/0008-5472.can-04-0267;
RA Dallol A., Agathanggelou A., Fenton S.L., Ahmed-Choudhury J., Hesson L.,
RA Vos M.D., Clark G.J., Downward J., Maher E.R., Latif F.;
RT "RASSF1A interacts with microtubule-associated proteins and modulates
RT microtubule dynamics.";
RL Cancer Res. 64:4112-4116(2004).
RN [12] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDC20.
RX PubMed=14743218; DOI=10.1038/ncb1091;
RA Song M.S., Song S.J., Ayad N.G., Chang J.S., Lee J.H., Hong H.K., Lee H.,
RA Choi N., Kim J., Kim H., Kim J.W., Choi E.-J., Kirschner M.W., Lim D.-S.;
RT "The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-
RT Cdc20 complex.";
RL Nat. Cell Biol. 6:129-137(2004).
RN [13] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH STK3/MST2 AND STK4/MST1.
RX PubMed=15109305; DOI=10.1042/bj20040025;
RA Praskova M., Khoklatchev A., Ortiz-Vega S., Avruch J.;
RT "Regulation of the MST1 kinase by autophosphorylation, by the growth
RT inhibitory proteins, RASSF1 and NORE1, and by Ras.";
RL Biochem. J. 381:453-462(2004).
RN [14]
RP INTERACTION WITH MAP1S.
RX PubMed=15753381; DOI=10.1158/0008-5472.can-04-3896;
RA Liu L., Vo A., McKeehan W.L.;
RT "Specificity of the methylation-suppressed A isoform of candidate tumor
RT suppressor RASSF1 for microtubule hyperstabilization is determined by cell
RT death inducer C19ORF5.";
RL Cancer Res. 65:1830-1838(2005).
RN [15]
RP INTERACTION WITH MOAP1, AND FUNCTION.
RX PubMed=15949439; DOI=10.1016/j.molcel.2005.05.010;
RA Baksh S., Tommasi S., Fenton S., Yu V.C., Martins L.M., Pfeifer G.P.,
RA Latif F., Downward J., Neel B.G.;
RT "The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to
RT Bax conformational change and cell death.";
RL Mol. Cell 18:637-650(2005).
RN [16]
RP FUNCTION, AND INTERACTION WITH STK3/MST2 AND STK4/MST1.
RX PubMed=16510573; DOI=10.1158/0008-5472.can-05-2951;
RA Oh H.J., Lee K.-K., Song S.J., Jin M.S., Song M.S., Lee J.H., Im C.R.,
RA Lee J.-O., Yonehara S., Lim D.-S.;
RT "Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis.";
RL Cancer Res. 66:2562-2569(2006).
RN [17]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH MDM2; DAXX AND USP7, INTERACTION
RP WITH DAXX AND MDM2, AND SUBCELLULAR LOCATION.
RX PubMed=18566590; DOI=10.1038/emboj.2008.115;
RA Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.;
RT "The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by
RT disrupting the MDM2-DAXX-HAUSP complex.";
RL EMBO J. 27:1863-1874(2008).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [19]
RP FUNCTION, AND INTERACTION WITH STK3/MST2 AND STK4/MST1.
RX PubMed=21199877; DOI=10.1074/jbc.m110.178210;
RA Guo C., Zhang X., Pfeifer G.P.;
RT "The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian
RT STE20-like kinases MST1 and MST2.";
RL J. Biol. Chem. 286:6253-6261(2011).
RN [20]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-36, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [21]
RP STRUCTURE BY NMR (ISOFORM C/H) IN COMPLEX WITH DAXX.
RX PubMed=21134643; DOI=10.1016/j.str.2010.09.016;
RA Escobar-Cabrera E., Lau D.K., Giovinazzi S., Ishov A.M., McIntosh L.P.;
RT "Structural characterization of the DAXX N-terminal helical bundle domain
RT and its complex with Rassf1C.";
RL Structure 18:1642-1653(2010).
CC -!- FUNCTION: Potential tumor suppressor. Required for death receptor-
CC dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1
CC during Fas-induced apoptosis by preventing their dephosphorylation.
CC When associated with MOAP1, promotes BAX conformational change and
CC translocation to mitochondrial membranes in response to TNF and TNFSF10
CC stimulation. Isoform A interacts with CDC20, an activator of the
CC anaphase-promoting complex, APC, resulting in the inhibition of APC
CC activity and mitotic progression. Inhibits proliferation by negatively
CC regulating cell cycle progression at the level of G1/S-phase transition
CC by regulating accumulation of cyclin D1 protein. Isoform C has been
CC shown not to perform these roles, no function has been identified for
CC this isoform. Isoform A disrupts interactions among MDM2, DAXX and
CC USP7, thus contributing to the efficient activation of TP53 by
CC promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in
CC response to DNA damage. {ECO:0000269|PubMed:10888881,
CC ECO:0000269|PubMed:11333291, ECO:0000269|PubMed:12024041,
CC ECO:0000269|PubMed:14743218, ECO:0000269|PubMed:15109305,
CC ECO:0000269|PubMed:15949439, ECO:0000269|PubMed:16510573,
CC ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:21199877}.
CC -!- SUBUNIT: Interacts with MAP1S (PubMed:15205320, PubMed:15753381).
CC Interacts with XPA (PubMed:10888881). Binds to the N-terminal of CDC20
CC during prometaphase (PubMed:14743218). Binds to STK3/MST2 and STK4/MST1
CC (PubMed:15109305, PubMed:16510573, PubMed:21199877). Recruited to the
CC TNFRSF1A and TNFRSF10A complexes in response to their respective
CC cognate ligand, after internalization (PubMed:15949439). Can self-
CC associate (PubMed:11857081). Part of a complex with MDM2, DAXX, RASSF1
CC and USP7 (PubMed:18566590). Interacts with ECM2 (By similarity).
CC {ECO:0000250|UniProtKB:Q99MK9, ECO:0000269|PubMed:10888881,
CC ECO:0000269|PubMed:11857081, ECO:0000269|PubMed:14729613,
CC ECO:0000269|PubMed:14743218, ECO:0000269|PubMed:15109305,
CC ECO:0000269|PubMed:15205320, ECO:0000269|PubMed:15753381,
CC ECO:0000269|PubMed:15949439, ECO:0000269|PubMed:16510573,
CC ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:21199877}.
CC -!- SUBUNIT: [Isoform A]: Interacts with MOAP1 (PubMed:15949439). Interacts
CC with E4F1 (PubMed:14729613). Interacts with RSSF5 and probably
CC associates with HRAS via a RSSF1 isoform A-RSSF5 heterodimer
CC (PubMed:11857081). Interacts (via C-terminus) with DAXX (via N-
CC terminus); the interaction is independent of MDM2 and TP53
CC (PubMed:18566590). Interacts (via N-terminus) with MDM2 (via C-
CC terminus); the interaction is independent of TP53 (PubMed:18566590).
CC Interacts with RAB39A (By similarity). Interacts with RAB39B; the
CC interaction is weak (By similarity). {ECO:0000250|UniProtKB:Q99MK9,
CC ECO:0000269|PubMed:11857081, ECO:0000269|PubMed:14729613,
CC ECO:0000269|PubMed:15949439, ECO:0000269|PubMed:18566590}.
CC -!- SUBUNIT: [Isoform C]: Interacts (via N-terminus) with DAXX
CC (PubMed:18566590). Interacts with RAB39B; the interaction is strong (By
CC similarity). Does not interact with RAB39A (By similarity).
CC {ECO:0000250|UniProtKB:Q99MK9, ECO:0000269|PubMed:18566590}.
CC -!- SUBUNIT: [Isoform H]: Interacts (via N-terminus) with DAXX.
CC {ECO:0000269|PubMed:18566590}.
CC -!- INTERACTION:
CC Q9NS23; Q9UER7: DAXX; NbExp=6; IntAct=EBI-367363, EBI-77321;
CC Q9NS23; O95166: GABARAP; NbExp=2; IntAct=EBI-367363, EBI-712001;
CC Q9NS23; P60520: GABARAPL2; NbExp=2; IntAct=EBI-367363, EBI-720116;
CC Q9NS23; O60341: KDM1A; NbExp=2; IntAct=EBI-367363, EBI-710124;
CC Q9NS23; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-367363, EBI-373144;
CC Q9NS23; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-367363, EBI-2603996;
CC Q9NS23; Q00987: MDM2; NbExp=5; IntAct=EBI-367363, EBI-389668;
CC Q9NS23; O43463: SUV39H1; NbExp=2; IntAct=EBI-367363, EBI-349968;
CC Q9NS23-2; Q12834: CDC20; NbExp=2; IntAct=EBI-438698, EBI-367462;
CC Q9NS23-2; Q66K89: E4F1; NbExp=7; IntAct=EBI-438698, EBI-1227043;
CC Q9NS23-2; Q01844: EWSR1; NbExp=3; IntAct=EBI-438698, EBI-739737;
CC Q9NS23-2; P01112: HRAS; NbExp=2; IntAct=EBI-438698, EBI-350145;
CC Q9NS23-2; Q9NS23-2: RASSF1; NbExp=2; IntAct=EBI-438698, EBI-438698;
CC Q9NS23-2; Q13188: STK3; NbExp=7; IntAct=EBI-438698, EBI-992580;
CC Q9NS23-2; Q13043: STK4; NbExp=4; IntAct=EBI-438698, EBI-367376;
CC Q9NS23-4; P02649: APOE; NbExp=3; IntAct=EBI-438710, EBI-1222467;
CC Q9NS23-4; P54252: ATXN3; NbExp=3; IntAct=EBI-438710, EBI-946046;
CC Q9NS23-4; Q9UER7: DAXX; NbExp=5; IntAct=EBI-438710, EBI-77321;
CC Q9NS23-4; G5E9A7: DMWD; NbExp=3; IntAct=EBI-438710, EBI-10976677;
CC Q9NS23-4; P50570-2: DNM2; NbExp=3; IntAct=EBI-438710, EBI-10968534;
CC Q9NS23-4; P41091: EIF2S3; NbExp=3; IntAct=EBI-438710, EBI-1054228;
CC Q9NS23-4; P22607: FGFR3; NbExp=3; IntAct=EBI-438710, EBI-348399;
CC Q9NS23-4; Q16595: FXN; NbExp=3; IntAct=EBI-438710, EBI-949340;
CC Q9NS23-4; P14136: GFAP; NbExp=3; IntAct=EBI-438710, EBI-744302;
CC Q9NS23-4; Q53GS7: GLE1; NbExp=3; IntAct=EBI-438710, EBI-1955541;
CC Q9NS23-4; P28358: HOXD10; NbExp=3; IntAct=EBI-438710, EBI-12690664;
CC Q9NS23-4; P01112: HRAS; NbExp=4; IntAct=EBI-438710, EBI-350145;
CC Q9NS23-4; P42858: HTT; NbExp=3; IntAct=EBI-438710, EBI-466029;
CC Q9NS23-4; Q8WXH2: JPH3; NbExp=6; IntAct=EBI-438710, EBI-1055254;
CC Q9NS23-4; Q99732: LITAF; NbExp=3; IntAct=EBI-438710, EBI-725647;
CC Q9NS23-4; P51608: MECP2; NbExp=3; IntAct=EBI-438710, EBI-1189067;
CC Q9NS23-4; P19404: NDUFV2; NbExp=6; IntAct=EBI-438710, EBI-713665;
CC Q9NS23-4; P49591: SARS1; NbExp=3; IntAct=EBI-438710, EBI-1053431;
CC Q9NS23-4; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-438710, EBI-5235340;
CC Q9NS23-4; Q9NUW8: TDP1; NbExp=3; IntAct=EBI-438710, EBI-2902553;
CC Q9NS23-4; Q9Y649; NbExp=3; IntAct=EBI-438710, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Cytoplasm, cytoskeleton. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Cytoplasm,
CC cytoskeleton, spindle. Cytoplasm, cytoskeleton, spindle pole. Nucleus.
CC Note=Localizes to cytoplasmic microtubules during interphase, to
CC bipolar centrosomes associated with microtubules during prophase, to
CC spindle fibers and spindle poles at metaphase and anaphase, to the
CC midzone during early telophase, and to the midbody in late telophase in
CC cells. Colocalizes with MDM2 in the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform C]: Nucleus. Note=Predominantly nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=8;
CC Name=D {ECO:0000269|PubMed:11333291}; Synonyms=RASSF1D,
CC Cardiac-specific {ECO:0000269|PubMed:11333291};
CC IsoId=Q9NS23-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:10888881, ECO:0000269|PubMed:11333291};
CC Synonyms=RASSF1A;
CC IsoId=Q9NS23-2; Sequence=VSP_050771;
CC Name=B {ECO:0000269|PubMed:10888881}; Synonyms=RASSF1B;
CC IsoId=Q9NS23-3; Sequence=VSP_050770;
CC Name=C {ECO:0000269|PubMed:10888881, ECO:0000269|PubMed:11333291};
CC Synonyms=RASSF1C;
CC IsoId=Q9NS23-4; Sequence=VSP_050773, VSP_050774;
CC Name=E {ECO:0000269|PubMed:11333291}; Synonyms=RASSF1E,
CC Pancreas-specific {ECO:0000269|PubMed:11333291};
CC IsoId=Q9NS23-5; Sequence=VSP_050771, VSP_050772;
CC Name=F {ECO:0000269|PubMed:11333291}; Synonyms=RASSF1F;
CC IsoId=Q9NS23-6; Sequence=VSP_050776, VSP_050777;
CC Name=G {ECO:0000269|PubMed:11333291}; Synonyms=RASSF1G;
CC IsoId=Q9NS23-7; Sequence=VSP_050775, VSP_050778;
CC Name=H;
CC IsoId=Q9NS23-9; Sequence=VSP_050773, VSP_050774, VSP_050778;
CC -!- TISSUE SPECIFICITY: Isoform A and isoform C are ubiquitously expressed
CC in all tissues tested, however isoform A is absent in many
CC corresponding cancer cell lines. Isoform B is mainly expressed in
CC hematopoietic cells. {ECO:0000269|PubMed:10888881,
CC ECO:0000269|PubMed:11333291}.
CC -!- MISCELLANEOUS: [Isoform D]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform A]: Produced by alternative splicing of isoform
CC D. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform B]: Produced by alternative splicing of isoform
CC D. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform C]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform E]: Produced by alternative splicing of isoform
CC D. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform F]: Produced by alternative splicing of isoform
CC D. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform G]: Produced by alternative splicing of isoform
CC D. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform H]: Produced by alternative splicing of isoform
CC C. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB67312.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RASSF1ID377.html";
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DR EMBL; AF061836; AAC16001.1; -; mRNA.
DR EMBL; AF132675; AAD44174.1; -; mRNA.
DR EMBL; AF132676; AAD44175.1; -; mRNA.
DR EMBL; AF132677; AAD44176.1; -; mRNA.
DR EMBL; AF040703; AAC70910.2; -; mRNA.
DR EMBL; AF102770; AAF35127.2; -; mRNA.
DR EMBL; AF102771; AAF35128.2; -; mRNA.
DR EMBL; AF102772; AAF35129.2; -; mRNA.
DR EMBL; BT020047; AAV38850.1; -; mRNA.
DR EMBL; BT020048; AAV38851.1; -; mRNA.
DR EMBL; AF286217; AAG10038.1; -; mRNA.
DR EMBL; AF291719; AAG10064.1; -; mRNA.
DR EMBL; AC002455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC002481; AAB67312.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471055; EAW65098.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW65101.1; -; Genomic_DNA.
DR EMBL; CH471055; EAW65102.1; -; Genomic_DNA.
DR EMBL; BC110412; AAI10413.1; -; mRNA.
DR EMBL; BC143879; AAI43880.1; -; mRNA.
DR CCDS; CCDS2820.1; -. [Q9NS23-1]
DR CCDS; CCDS2821.1; -. [Q9NS23-4]
DR CCDS; CCDS2822.1; -. [Q9NS23-3]
DR CCDS; CCDS43096.1; -. [Q9NS23-2]
DR RefSeq; NP_001193886.1; NM_001206957.1. [Q9NS23-3]
DR RefSeq; NP_009113.3; NM_007182.4. [Q9NS23-2]
DR RefSeq; NP_733830.1; NM_170712.2. [Q9NS23-3]
DR RefSeq; NP_733831.1; NM_170713.2. [Q9NS23-4]
DR RefSeq; NP_733832.1; NM_170714.1. [Q9NS23-1]
DR RefSeq; XP_011531617.1; XM_011533315.1.
DR RefSeq; XP_011531618.1; XM_011533316.2. [Q9NS23-3]
DR PDB; 2KZU; NMR; -; B=-.
DR PDBsum; 2KZU; -.
DR AlphaFoldDB; Q9NS23; -.
DR SMR; Q9NS23; -.
DR BioGRID; 116356; 93.
DR DIP; DIP-31270N; -.
DR IntAct; Q9NS23; 63.
DR MINT; Q9NS23; -.
DR STRING; 9606.ENSP00000349547; -.
DR iPTMnet; Q9NS23; -.
DR PhosphoSitePlus; Q9NS23; -.
DR BioMuta; RASSF1; -.
DR DMDM; 50401686; -.
DR EPD; Q9NS23; -.
DR jPOST; Q9NS23; -.
DR MassIVE; Q9NS23; -.
DR MaxQB; Q9NS23; -.
DR PaxDb; Q9NS23; -.
DR PeptideAtlas; Q9NS23; -.
DR PRIDE; Q9NS23; -.
DR ProteomicsDB; 82465; -. [Q9NS23-1]
DR ProteomicsDB; 82466; -. [Q9NS23-2]
DR ProteomicsDB; 82467; -. [Q9NS23-3]
DR ProteomicsDB; 82468; -. [Q9NS23-4]
DR ProteomicsDB; 82469; -. [Q9NS23-5]
DR ProteomicsDB; 82470; -. [Q9NS23-6]
DR ProteomicsDB; 82471; -. [Q9NS23-7]
DR ProteomicsDB; 82472; -. [Q9NS23-9]
DR Antibodypedia; 30900; 543 antibodies from 36 providers.
DR DNASU; 11186; -.
DR Ensembl; ENST00000327761.7; ENSP00000333327.3; ENSG00000068028.18. [Q9NS23-4]
DR Ensembl; ENST00000357043.6; ENSP00000349547.2; ENSG00000068028.18. [Q9NS23-1]
DR Ensembl; ENST00000359365.9; ENSP00000352323.4; ENSG00000068028.18. [Q9NS23-2]
DR Ensembl; ENST00000395117.6; ENSP00000378549.2; ENSG00000068028.18. [Q9NS23-6]
DR Ensembl; ENST00000395126.7; ENSP00000378558.3; ENSG00000068028.18. [Q9NS23-3]
DR Ensembl; ENST00000482447.1; ENSP00000433000.1; ENSG00000068028.18. [Q9NS23-7]
DR Ensembl; ENST00000616212.4; ENSP00000482696.1; ENSG00000068028.18. [Q9NS23-3]
DR GeneID; 11186; -.
DR KEGG; hsa:11186; -.
DR MANE-Select; ENST00000359365.9; ENSP00000352323.4; NM_007182.5; NP_009113.3. [Q9NS23-2]
DR UCSC; uc003dab.2; human. [Q9NS23-1]
DR CTD; 11186; -.
DR DisGeNET; 11186; -.
DR GeneCards; RASSF1; -.
DR HGNC; HGNC:9882; RASSF1.
DR HPA; ENSG00000068028; Low tissue specificity.
DR MIM; 605082; gene.
DR neXtProt; NX_Q9NS23; -.
DR OpenTargets; ENSG00000068028; -.
DR PharmGKB; PA34245; -.
DR VEuPathDB; HostDB:ENSG00000068028; -.
DR eggNOG; KOG4239; Eukaryota.
DR GeneTree; ENSGT00940000155664; -.
DR HOGENOM; CLU_045544_1_0_1; -.
DR InParanoid; Q9NS23; -.
DR OMA; FIRKPHK; -.
DR OrthoDB; 1120975at2759; -.
DR PhylomeDB; Q9NS23; -.
DR TreeFam; TF319243; -.
DR PathwayCommons; Q9NS23; -.
DR SignaLink; Q9NS23; -.
DR SIGNOR; Q9NS23; -.
DR BioGRID-ORCS; 11186; 16 hits in 1083 CRISPR screens.
DR ChiTaRS; RASSF1; human.
DR EvolutionaryTrace; Q9NS23; -.
DR GeneWiki; RASSF1; -.
DR GenomeRNAi; 11186; -.
DR Pharos; Q9NS23; Tbio.
DR PRO; PR:Q9NS23; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NS23; protein.
DR Bgee; ENSG00000068028; Expressed in granulocyte and 128 other tissues.
DR Genevisible; Q9NS23; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IMP:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR DisProt; DP01533; -. [Q9NS23-4]
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR033600; RASSF1.
DR InterPro; IPR033614; RASSF1-6.
DR InterPro; IPR011524; SARAH_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR22738; PTHR22738; 1.
DR PANTHER; PTHR22738:SF12; PTHR22738:SF12; 1.
DR Pfam; PF16517; Nore1-SARAH; 1.
DR Pfam; PF00788; RA; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00314; RA; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50951; SARAH; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Cell cycle; Cytoplasm; Cytoskeleton; Metal-binding;
KW Methylation; Microtubule; Nucleus; Phosphoprotein; Reference proteome;
KW Tumor suppressor; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CHAIN 2..344
FT /note="Ras association domain-containing protein 1"
FT /id="PRO_0000068891"
FT DOMAIN 198..292
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 294..341
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT ZN_FING 51..105
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 2..119
FT /note="Mediates interaction with E4F1"
FT /evidence="ECO:0000269|PubMed:14729613"
FT REGION 179..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..318
FT /note="MOAP1-binding"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 36
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..155
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10888881,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_050770"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform C and isoform H)"
FT /evidence="ECO:0000303|PubMed:10888881,
FT ECO:0000303|PubMed:11333291, ECO:0000303|Ref.3"
FT /id="VSP_050773"
FT VAR_SEQ 75..123
FT /note="VVRKGLQCARLSADCKFTCHYRCRALVCLDCCGPRDLGWEPAVERDTNV ->
FT MGEAEAPSFEMTWSSTTSSGYCSQEDSDSELEQYFTARTSLARRPRRDQ (in
FT isoform C and isoform H)"
FT /evidence="ECO:0000303|PubMed:10888881,
FT ECO:0000303|PubMed:11333291, ECO:0000303|Ref.3"
FT /id="VSP_050774"
FT VAR_SEQ 84..149
FT /note="RLSADCKFTCHYRCRALVCLDCCGPRDLGWEPAVERDTNVDEPVEWETPDLS
FT QAEIEQKIKEYNAQ -> QQGRFLHRLHQGSAEAGAPCLCALQQEATLLAGCPAGPRTG
FT HKCQAPHFLLPAQGCCQAPACAVTHKGT (in isoform G)"
FT /evidence="ECO:0000303|PubMed:11333291"
FT /id="VSP_050775"
FT VAR_SEQ 84..88
FT /note="RLSAD -> H (in isoform A and isoform E)"
FT /evidence="ECO:0000303|PubMed:10888881,
FT ECO:0000303|PubMed:11333291, ECO:0000303|PubMed:15489334"
FT /id="VSP_050771"
FT VAR_SEQ 85..91
FT /note="LSADCKF -> RACGVGD (in isoform F)"
FT /evidence="ECO:0000303|PubMed:11333291"
FT /id="VSP_050776"
FT VAR_SEQ 93..344
FT /note="Missing (in isoform F)"
FT /evidence="ECO:0000303|PubMed:11333291"
FT /id="VSP_050777"
FT VAR_SEQ 123
FT /note="V -> VPILQ (in isoform E)"
FT /evidence="ECO:0000303|PubMed:11333291"
FT /id="VSP_050772"
FT VAR_SEQ 150..344
FT /note="Missing (in isoform G and isoform H)"
FT /evidence="ECO:0000303|PubMed:11333291"
FT /id="VSP_050778"
FT VARIANT 21
FT /note="K -> Q (in dbSNP:rs4688725)"
FT /evidence="ECO:0000269|PubMed:10888881,
FT ECO:0000269|PubMed:11333291"
FT /id="VAR_019542"
FT VARIANT 53
FT /note="R -> C (in dbSNP:rs201618726)"
FT /evidence="ECO:0000269|PubMed:11333291"
FT /id="VAR_019543"
FT VARIANT 133
FT /note="D -> E (in dbSNP:rs76335415)"
FT /evidence="ECO:0000269|PubMed:11333291"
FT /id="VAR_019544"
FT VARIANT 135
FT /note="S -> F (prevents G1 cell cycle arrest; reduced
FT protein phosphorylation; dbSNP:rs934370004)"
FT /evidence="ECO:0000269|PubMed:12024041"
FT /id="VAR_019545"
FT VARIANT 137
FT /note="A -> S (prevents G1 cell cycle arrest; reduced
FT protein phosphorylation; dbSNP:rs2073498)"
FT /evidence="ECO:0000269|PubMed:11333291,
FT ECO:0000269|PubMed:12024041"
FT /id="VAR_019546"
FT VARIANT 319
FT /note="H -> R (in dbSNP:rs12488879)"
FT /id="VAR_059794"
FT VARIANT 329
FT /note="Y -> C (in dbSNP:rs782655006)"
FT /evidence="ECO:0000269|PubMed:11333291"
FT /id="VAR_019547"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:2KZU"
SQ SEQUENCE 344 AA; 39219 MW; 4071B8D044C1DB2D CRC64;
MSGEPELIEL RELAPAGRAG KGRTRLERAN ALRIARGTAC NPTRQLVPGR GHRFQPAGPA
THTWCDLCGD FIWGVVRKGL QCARLSADCK FTCHYRCRAL VCLDCCGPRD LGWEPAVERD
TNVDEPVEWE TPDLSQAEIE QKIKEYNAQI NSNLFMSLNK DGSYTGFIKV QLKLVRPVSV
PSSKKPPSLQ DARRGPGRGT SVRRRTSFYL PKDAVKHLHV LSRTRAREVI EALLRKFLVV
DDPRKFALFE RAERHGQVYL RKLLDDEQPL RLRLLAGPSD KALSFVLKEN DSGEVNWDAF
SMPELHNFLR ILQREEEEHL RQILQKYSYC RQKIQEALHA CPLG
