GDS1_HUMAN
ID GDS1_HUMAN Reviewed; 607 AA.
AC P52306; E9PH06; G5E9P9; Q499L7; Q4KMV2; Q4QQI8; Q9BUW9; Q9BUX6; Q9NYM2;
AC Q9NZA8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Rap1 GTPase-GDP dissociation stimulator 1 {ECO:0000305};
DE AltName: Full=Exchange factor smgGDS {ECO:0000303|PubMed:11948427};
DE AltName: Full=SMG GDS protein {ECO:0000303|PubMed:11948427};
DE AltName: Full=SMG P21 stimulatory GDP/GTP exchange protein {ECO:0000303|PubMed:1549351};
GN Name=RAP1GDS1 {ECO:0000303|Ref.3}; Synonyms=SMGGDS {ECO:0000303|Ref.3};
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=1549351;
RA Kikuchi A., Kaibuchi K., Hori Y., Nonaka H., Sakoda T., Kawamura M.,
RA Mizuno T., Takai Y.;
RT "Molecular cloning of the human cDNA for a stimulatory GDP/GTP exchange
RT protein for c-Ki-ras p21 and smg p21.";
RL Oncogene 7:289-293(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=11948427; DOI=10.1038/sj.onc.1205306;
RA Vikis H.G., Stewart S., Guan K.L.;
RT "SmgGDS displays differential binding and exchange activity towards
RT different Ras isoforms.";
RL Oncogene 21:2425-2432(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Peripheral blood;
RA Hussey D.J., Albanese N.O., Dobrovic A.;
RT "The major isoform of RAP1GDS1 mRNA in peripheral blood mononuclear cells
RT encodes an isoform of smgGDS with 12 armadillo repeats.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 2; 3; 4 AND 5), AND
RP VARIANT THR-56.
RC TISSUE=Muscle;
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]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-230, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INTERACTION WITH RABL3.
RX PubMed=31406347; DOI=10.1038/s41588-019-0475-y;
RA Nissim S., Leshchiner I., Mancias J.D., Greenblatt M.B., Maertens O.,
RA Cassa C.A., Rosenfeld J.A., Cox A.G., Hedgepeth J., Wucherpfennig J.I.,
RA Kim A.J., Henderson J.E., Gonyo P., Brandt A., Lorimer E., Unger B.,
RA Prokop J.W., Heidel J.R., Wang X.X., Ukaegbu C.I., Jennings B.C.,
RA Paulo J.A., Gableske S., Fierke C.A., Getz G., Sunyaev S.R.,
RA Wade Harper J., Cichowski K., Kimmelman A.C., Houvras Y., Syngal S.,
RA Williams C., Goessling W.;
RT "Mutations in RABL3 alter KRAS prenylation and are associated with
RT hereditary pancreatic cancer.";
RL Nat. Genet. 51:1308-1314(2019).
RN [10]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=10477737;
RA Hussey D.J., Nicola M., Moore S., Peters G.B., Dobrovic A.;
RT "The (4;11)(q21;p15) translocation fuses the NUP98 and RAP1GDS1 genes and
RT is recurrent in T-cell acute lymphocytic leukemia.";
RL Blood 94:2072-2079(1999).
RN [11]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=10929031; DOI=10.1046/j.1365-2141.2000.02106.x;
RA Mecucci C., La Starza R., Negrini M., Sabbioni S., Crescenzi B., Leoni P.,
RA Di Raimondo F., Krampera M., Cimino G., Tafuri A., Cuneo A., Vitale A.,
RA Foa R.;
RT "t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes:
RT characterization of a new subset of T acute lymphoblastic leukaemia.";
RL Br. J. Haematol. 109:788-793(2000).
RN [12]
RP FUNCTION (ISOFORM 2), INTERACTION WITH RAC1 AND RHOA (ISOFORM 2),
RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL.
RX PubMed=12551911; DOI=10.1074/jbc.m211286200;
RA Lanning C.C., Ruiz-Velasco R., Williams C.L.;
RT "Novel mechanism of the co-regulation of nuclear transport of SmgGDS and
RT Rac1.";
RL J. Biol. Chem. 278:12495-12506(2003).
RN [13]
RP FUNCTION (ISOFORMS 1 AND 2), AND INTERACTION WITH RAP1A; KRAS; RHOA AND
RP RAC1 (ISOFORM 1 AND 2).
RX PubMed=20709748; DOI=10.1074/jbc.m110.129916;
RA Berg T.J., Gastonguay A.J., Lorimer E.L., Kuhnmuench J.R., Li R.,
RA Fields A.P., Williams C.L.;
RT "Splice variants of SmgGDS control small GTPase prenylation and membrane
RT localization.";
RL J. Biol. Chem. 285:35255-35266(2010).
RN [14]
RP FUNCTION (ISOFORM 2).
RX PubMed=21242305; DOI=10.1074/jbc.m110.191122;
RA Hamel B., Monaghan-Benson E., Rojas R.J., Temple B.R., Marston D.J.,
RA Burridge K., Sondek J.;
RT "SmgGDS is a guanine nucleotide exchange factor that specifically activates
RT RhoA and RhoC.";
RL J. Biol. Chem. 286:12141-12148(2011).
RN [15]
RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX PubMed=16419055; DOI=10.1002/gcc.20308;
RA van Zutven L.J., Onen E., Velthuizen S.C., van Drunen E., von Bergh A.R.,
RA van den Heuvel-Eibrink M.M., Veronese A., Mecucci C., Negrini M.,
RA de Greef G.E., Beverloo H.B.;
RT "Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13)
RT as a new partner gene.";
RL Genes Chromosomes Cancer 45:437-446(2006).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND TRANSGLUTAMINATION.
RX PubMed=24349085; DOI=10.1371/journal.pone.0081516;
RA Hsieh Y.F., Liu G.Y., Lee Y.J., Yang J.J., Sandor K., Sarang Z., Bononi A.,
RA Pinton P., Tretter L., Szondy Z., Tsay G.J.;
RT "Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by
RT modulating Ca2+ homeostasis via cross-linking RAP1GDS1.";
RL PLoS ONE 8:e81516-e81516(2013).
RN [17]
RP FUNCTION (ISOFORM 1 AND 2), AND INTERACTION WITH KRAS AND RAP1B (ISOFORM 1
RP AND 2).
RX PubMed=24415755; DOI=10.1074/jbc.m113.527192;
RA Schuld N.J., Vervacke J.S., Lorimer E.L., Simon N.C., Hauser A.D.,
RA Barbieri J.T., Distefano M.D., Williams C.L.;
RT "The chaperone protein SmgGDS interacts with small GTPases entering the
RT prenylation pathway by recognizing the last amino acid in the CAAX motif.";
RL J. Biol. Chem. 289:6862-6876(2014).
RN [18]
RP FUNCTION, AND INTERACTION WITH RHOT1.
RX PubMed=27716788; DOI=10.1371/journal.pgen.1006359;
RA Ding L., Lei Y., Han Y., Li Y., Ji X., Liu L.;
RT "Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.";
RL PLoS Genet. 12:e1006359-e1006359(2016).
RN [19] {ECO:0007744|PDB:5XGC}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 61-121 AND 171-607, FUNCTION
RP (ISOFORM 1 AND 2), AND INTERACTION WITH RHOA (ISOFORM 1 AND 2).
RX PubMed=28630045; DOI=10.1074/jbc.m117.792556;
RA Shimizu H., Toma-Fukai S., Saijo S., Shimizu N., Kontani K., Katada T.,
RA Shimizu T.;
RT "Structure-based analysis of the guanine nucleotide exchange factor SmgGDS
RT reveals armadillo-repeat motifs and key regions for activity and GTPase
RT binding.";
RL J. Biol. Chem. 292:13441-13448(2017).
RN [20] {ECO:0007744|PDB:5ZHX}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 61-121 AND 171-607 IN COMPLEX
RP WITH RHOA, FUNCTION (ISOFORM 1 AND 2), AND INTERACTION WITH RHOA (ISOFORM 1
RP AND 2).
RX PubMed=30190425; DOI=10.1073/pnas.1804740115;
RA Shimizu H., Toma-Fukai S., Kontani K., Katada T., Shimizu T.;
RT "GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated
RT RhoA complex and its implication for a chaperone mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:9563-9568(2018).
CC -!- FUNCTION: Acts as a GEF (guanine nucleotide exchange factor) for the
CC Rho family of small GTP-binding proteins (G proteins) that stimulates
CC the dissociation of GDP to enable subsequent binding of GTP
CC (PubMed:28630045, PubMed:30190425, PubMed:1549351, PubMed:11948427,
CC PubMed:20709748). Additionally, appears to chaperone the processing
CC and/or trafficking of small GTPases containing a C-terminal polybasic
CC region independently of GEF activity (PubMed:20709748,
CC PubMed:21242305). Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1
CC and KRAS (PubMed:1549351, PubMed:11948427, PubMed:20709748,
CC PubMed:24415755). Regulates mitochondrial dynamics by controlling RHOT
CC function to promote mitochondrial fission during high calcium
CC conditions (PubMed:27716788). Able to promote the Ca(2+) release from
CC the endoplasmic reticulum via both inositol trisphosphate (Ins3P) and
CC ryanodine sensitive receptors leading to a enhanced mitochondrial
CC Ca(2+) uptake (PubMed:24349085). {ECO:0000269|PubMed:11948427,
CC ECO:0000269|PubMed:1549351, ECO:0000269|PubMed:20709748,
CC ECO:0000269|PubMed:21242305, ECO:0000269|PubMed:24349085,
CC ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:27716788,
CC ECO:0000269|PubMed:28630045, ECO:0000269|PubMed:30190425,
CC ECO:0000305|PubMed:30190425}.
CC -!- FUNCTION: [Isoform 1]: Acts as a GEF (guanine nucleotide exchange
CC factor) for unprenylated RHOA (PubMed:30190425, PubMed:28630045,
CC PubMed:24415755). Chaperones the entry and passage of small GTPases
CC through the prenylation pathway (PubMed:20709748). Recognizes the last
CC amino acid in the GTPase C-terminal CAAX motif with a preference for
CC 'Leu' over 'Met', indicating involvement in the geranylgeranylation
CC pathway (PubMed:24415755). {ECO:0000269|PubMed:20709748,
CC ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:28630045,
CC ECO:0000269|PubMed:30190425}.
CC -!- FUNCTION: [Isoform 2]: Acts as a GEF (guanine nucleotide exchange
CC factor) for prenylated RHOA (PubMed:28630045, PubMed:30190425,
CC PubMed:21242305). Acts as a GEF for RHOC (PubMed:21242305). Chaperones
CC the downstream trafficking and/or processing of small newly prenylated
CC GTPases (PubMed:20709748). Escorts RAC1 to the nucleus
CC (PubMed:12551911). {ECO:0000269|PubMed:12551911,
CC ECO:0000269|PubMed:20709748, ECO:0000269|PubMed:21242305,
CC ECO:0000269|PubMed:28630045, ECO:0000269|PubMed:30190425}.
CC -!- SUBUNIT: Interacts with RABL3 (PubMed:31406347). Interacts with RHOT1
CC (PubMed:27716788). {ECO:0000269|PubMed:27716788,
CC ECO:0000269|PubMed:31406347}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with unprenylated RHOA; the interaction
CC is direct (PubMed:28630045, PubMed:30190425, PubMed:20709748).
CC Interacts with RAP1A (PubMed:20709748). Interacts with KRAS
CC (PubMed:20709748, PubMed:24415755). Interacts with RAC1
CC (PubMed:20709748). Interacts with RAP1B (PubMed:24415755).
CC Preferentially interacts with unprenylated GTPases that will become
CC geranylgeranylated (PubMed:24415755). May also interact with prenylated
CC GTPases (PubMed:24415755). {ECO:0000269|PubMed:20709748,
CC ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:28630045,
CC ECO:0000269|PubMed:30190425}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with prenylated RHOA; the interaction
CC is direct and in a 1:1 stoichiometry (PubMed:28630045, PubMed:30190425,
CC PubMed:20709748, PubMed:12551911). Interacts with RAP1A
CC (PubMed:20709748). Interacts with KRAS (PubMed:20709748,
CC PubMed:24415755). Interacts with RAC1 (PubMed:20709748,
CC PubMed:12551911). Interacts with RAP1B (PubMed:24415755).
CC Preferentially interacts with prenylated GTPases (PubMed:24415755).
CC {ECO:0000269|PubMed:12551911, ECO:0000269|PubMed:20709748,
CC ECO:0000269|PubMed:24415755, ECO:0000269|PubMed:28630045,
CC ECO:0000269|PubMed:30190425}.
CC -!- INTERACTION:
CC P52306; Q9NS73-5: MBIP; NbExp=3; IntAct=EBI-746389, EBI-10182361;
CC P52306; Q9UF11: PLEKHB1; NbExp=3; IntAct=EBI-746389, EBI-6447271;
CC P52306; PRO_0000449620 [P0DTD1]: rep; Xeno; NbExp=5; IntAct=EBI-746389, EBI-25475859;
CC P52306-4; Q96CV9: OPTN; NbExp=3; IntAct=EBI-25910540, EBI-748974;
CC P52306-5; O95057: DIRAS1; NbExp=5; IntAct=EBI-12832744, EBI-11993172;
CC P52306-5; Q96HU8: DIRAS2; NbExp=3; IntAct=EBI-12832744, EBI-911391;
CC P52306-5; P01112-2: HRAS; NbExp=5; IntAct=EBI-12832744, EBI-13290525;
CC P52306-5; P01111: NRAS; NbExp=6; IntAct=EBI-12832744, EBI-721993;
CC P52306-5; Q9UF11-2: PLEKHB1; NbExp=5; IntAct=EBI-12832744, EBI-12832742;
CC P52306-5; Q9NRW1: RAB6B; NbExp=5; IntAct=EBI-12832744, EBI-1760079;
CC P52306-5; P61225: RAP2B; NbExp=3; IntAct=EBI-12832744, EBI-750871;
CC P52306-5; Q9Y3L5: RAP2C; NbExp=3; IntAct=EBI-12832744, EBI-2856617;
CC P52306-5; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-12832744, EBI-2466594;
CC P52306-5; P10301: RRAS; NbExp=3; IntAct=EBI-12832744, EBI-968703;
CC P52306-5; P62070: RRAS2; NbExp=3; IntAct=EBI-12832744, EBI-491037;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:24349085}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:24349085}. Mitochondrion
CC {ECO:0000269|PubMed:24349085}. Nucleus {ECO:0000269|PubMed:12551911}.
CC Note=Nuclear import is dependent on complexing with a GTPase containing
CC a C-terminal polybasic region. {ECO:0000269|PubMed:12551911}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=SmgGDS-607 {ECO:0000303|PubMed:20709748};
CC IsoId=P52306-1; Sequence=Displayed;
CC Name=2; Synonyms=SmgGDS-558 {ECO:0000303|PubMed:20709748};
CC IsoId=P52306-2; Sequence=VSP_001658;
CC Name=3;
CC IsoId=P52306-3; Sequence=VSP_043660, VSP_001658;
CC Name=4;
CC IsoId=P52306-4; Sequence=VSP_043660, VSP_046214;
CC Name=5;
CC IsoId=P52306-5; Sequence=VSP_043660;
CC Name=6;
CC IsoId=P52306-6; Sequence=VSP_043660, VSP_047041;
CC -!- PTM: Forms covalent cross-links mediated by transglutaminase TGM2,
CC between a glutamine and the epsilon-amino group of a lysine residue,
CC forming homopolymers and heteropolymers. {ECO:0000269|PubMed:24349085}.
CC -!- DISEASE: Note=A chromosomal aberration involving RAP1GDS1 has been
CC found in M0 type acute myeloid leukemia. Translocation (t4;11)(q23;p15)
CC with NUP98. {ECO:0000269|PubMed:16419055}.
CC -!- DISEASE: Note=A chromosomal aberration involving RAP1GDS1 has been
CC found in T-cell acute lymphocytic leukemia. Translocation
CC t(4;11)(q23;p15) with NUP98. {ECO:0000269|PubMed:10477737,
CC ECO:0000269|PubMed:10929031}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RAP1GDS1ID400.html";
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DR EMBL; X63465; CAA45067.1; -; mRNA.
DR EMBL; AF215923; AAF32290.1; -; mRNA.
DR EMBL; AF237413; AAF43211.1; -; mRNA.
DR EMBL; AC019077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC058823; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06069.1; -; Genomic_DNA.
DR EMBL; CH471057; EAX06071.1; -; Genomic_DNA.
DR EMBL; BC001816; AAH01816.1; -; mRNA.
DR EMBL; BC001851; AAH01851.2; -; mRNA.
DR EMBL; BT006837; AAP35483.1; -; mRNA.
DR EMBL; BC098269; AAH98269.1; -; mRNA.
DR EMBL; BC098334; AAH98334.1; -; mRNA.
DR EMBL; BC099708; AAH99708.1; -; mRNA.
DR EMBL; BC099845; AAH99845.1; -; mRNA.
DR CCDS; CCDS43253.1; -. [P52306-1]
DR CCDS; CCDS43254.1; -. [P52306-2]
DR CCDS; CCDS47105.1; -. [P52306-5]
DR CCDS; CCDS47106.1; -. [P52306-4]
DR CCDS; CCDS47107.1; -. [P52306-3]
DR CCDS; CCDS47108.1; -. [P52306-6]
DR PIR; I37456; I37456.
DR RefSeq; NP_001093896.1; NM_001100426.1. [P52306-5]
DR RefSeq; NP_001093897.1; NM_001100427.1. [P52306-1]
DR RefSeq; NP_001093898.1; NM_001100428.1. [P52306-3]
DR RefSeq; NP_001093899.1; NM_001100429.1. [P52306-2]
DR RefSeq; NP_001093900.1; NM_001100430.1. [P52306-6]
DR RefSeq; NP_066982.3; NM_021159.4. [P52306-4]
DR PDB; 5XGC; X-ray; 2.10 A; A=61-607.
DR PDB; 5ZHX; X-ray; 3.50 A; A/B/C/D=77-607.
DR PDBsum; 5XGC; -.
DR PDBsum; 5ZHX; -.
DR AlphaFoldDB; P52306; -.
DR SMR; P52306; -.
DR BioGRID; 111845; 147.
DR DIP; DIP-61080N; -.
DR IntAct; P52306; 54.
DR MINT; P52306; -.
DR STRING; 9606.ENSP00000340454; -.
DR GlyGen; P52306; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P52306; -.
DR MetOSite; P52306; -.
DR PhosphoSitePlus; P52306; -.
DR SwissPalm; P52306; -.
DR BioMuta; RAP1GDS1; -.
DR DMDM; 212276504; -.
DR EPD; P52306; -.
DR jPOST; P52306; -.
DR MassIVE; P52306; -.
DR MaxQB; P52306; -.
DR PaxDb; P52306; -.
DR PeptideAtlas; P52306; -.
DR PRIDE; P52306; -.
DR ProteomicsDB; 20432; -.
DR ProteomicsDB; 34006; -.
DR ProteomicsDB; 56479; -. [P52306-1]
DR ProteomicsDB; 56480; -. [P52306-2]
DR ProteomicsDB; 56481; -. [P52306-3]
DR Antibodypedia; 6907; 152 antibodies from 29 providers.
DR DNASU; 5910; -.
DR Ensembl; ENST00000264572.11; ENSP00000264572.7; ENSG00000138698.15. [P52306-6]
DR Ensembl; ENST00000339360.9; ENSP00000340454.5; ENSG00000138698.15. [P52306-5]
DR Ensembl; ENST00000380158.8; ENSP00000369503.4; ENSG00000138698.15. [P52306-3]
DR Ensembl; ENST00000408900.7; ENSP00000386223.3; ENSG00000138698.15. [P52306-2]
DR Ensembl; ENST00000408927.8; ENSP00000386153.4; ENSG00000138698.15. [P52306-1]
DR Ensembl; ENST00000453712.6; ENSP00000407157.2; ENSG00000138698.15. [P52306-4]
DR GeneID; 5910; -.
DR KEGG; hsa:5910; -.
DR MANE-Select; ENST00000408927.8; ENSP00000386153.4; NM_001100427.2; NP_001093897.1.
DR UCSC; uc003htv.5; human. [P52306-1]
DR CTD; 5910; -.
DR DisGeNET; 5910; -.
DR GeneCards; RAP1GDS1; -.
DR HGNC; HGNC:9859; RAP1GDS1.
DR HPA; ENSG00000138698; Tissue enhanced (brain).
DR MIM; 179502; gene.
DR MIM; 613065; phenotype.
DR neXtProt; NX_P52306; -.
DR OpenTargets; ENSG00000138698; -.
DR PharmGKB; PA34221; -.
DR VEuPathDB; HostDB:ENSG00000138698; -.
DR eggNOG; KOG4500; Eukaryota.
DR GeneTree; ENSGT00390000014293; -.
DR HOGENOM; CLU_021124_1_0_1; -.
DR InParanoid; P52306; -.
DR OMA; IAWLINN; -.
DR OrthoDB; 561489at2759; -.
DR PhylomeDB; P52306; -.
DR PathwayCommons; P52306; -.
DR Reactome; R-HSA-9013419; RHOT2 GTPase cycle.
DR Reactome; R-HSA-9013425; RHOT1 GTPase cycle.
DR SignaLink; P52306; -.
DR SIGNOR; P52306; -.
DR BioGRID-ORCS; 5910; 17 hits in 1087 CRISPR screens.
DR ChiTaRS; RAP1GDS1; human.
DR GeneWiki; RAP1GDS1; -.
DR GenomeRNAi; 5910; -.
DR Pharos; P52306; Tbio.
DR PRO; PR:P52306; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P52306; protein.
DR Bgee; ENSG00000138698; Expressed in lateral nuclear group of thalamus and 207 other tissues.
DR ExpressionAtlas; P52306; baseline and differential.
DR Genevisible; P52306; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0086098; P:angiotensin-activated signaling pathway involved in heart process; IEA:Ensembl.
DR GO; GO:0080120; P:CAAX-box protein maturation; IMP:UniProtKB.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; IEA:Ensembl.
DR GO; GO:0031034; P:myosin filament assembly; IEA:Ensembl.
DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0070376; P:regulation of ERK5 cascade; IEA:Ensembl.
DR GO; GO:1904464; P:regulation of matrix metallopeptidase secretion; IEA:Ensembl.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0014829; P:vascular associated smooth muscle contraction; IEA:Ensembl.
DR Gene3D; 1.25.10.10; -; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR040144; RAP1GDS1.
DR PANTHER; PTHR10957; PTHR10957; 1.
DR Pfam; PF00514; Arm; 4.
DR SMART; SM00185; ARM; 5.
DR SUPFAM; SSF48371; SSF48371; 2.
DR PROSITE; PS50176; ARM_REPEAT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosomal rearrangement;
KW Cytoplasm; Endoplasmic reticulum; Guanine-nucleotide releasing factor;
KW Mitochondrion; Nucleus; Reference proteome; Repeat.
FT CHAIN 1..607
FT /note="Rap1 GTPase-GDP dissociation stimulator 1"
FT /id="PRO_0000056759"
FT REPEAT 89..131
FT /note="ARM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00259"
FT REPEAT 170..211
FT /note="ARM 2"
FT /evidence="ECO:0000255"
FT REPEAT 347..390
FT /note="ARM 3"
FT /evidence="ECO:0000255"
FT REPEAT 391..431
FT /note="ARM 4"
FT /evidence="ECO:0000255"
FT REPEAT 479..519
FT /note="ARM 5"
FT /evidence="ECO:0000255"
FT REGION 122..170
FT /note="Prevents binding to prenylated RHOA"
FT /evidence="ECO:0000269|PubMed:30190425"
FT REGION 239..255
FT /note="Interacts with polybasic regions in GTPases"
FT /evidence="ECO:0000269|PubMed:21242305,
FT ECO:0000269|PubMed:28630045"
FT REGION 379..428
FT /note="Critical for catalytic activity"
FT /evidence="ECO:0000269|PubMed:21242305,
FT ECO:0000269|PubMed:28630045"
FT MOTIF 4..13
FT /note="Nuclear export signal (NES)"
FT /evidence="ECO:0000269|PubMed:12551911"
FT SITE 1..2
FT /note="Breakpoint for translocation to form the NUP98-
FT RAP1GDS1 fusion protein"
FT /evidence="ECO:0000269|PubMed:10477737,
FT ECO:0000269|PubMed:16419055"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1
FT /note="M -> MA (in isoform 3, isoform 4, isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043660"
FT VAR_SEQ 121..213
FT /note="HEGRSAVDQAGGAQIVIDHLRSLCSITDPANEKLLTVFCGMLMNYSNENDSL
FT QAQLINMGVIPTLVKLLGIHCQNAALTEMCLVAFGNLAELE -> Q (in isoform
FT 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_047041"
FT VAR_SEQ 122..170
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1549351"
FT /id="VSP_001658"
FT VAR_SEQ 434
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046214"
FT VARIANT 56
FT /note="S -> T (in dbSNP:rs17849535)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_069149"
FT VARIANT 314
FT /note="K -> E (in dbSNP:rs34392334)"
FT /id="VAR_049158"
FT CONFLICT 237
FT /note="E -> G (in Ref. 6; AAH98269)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="T -> P (in Ref. 3; AAF43211)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="N -> D (in Ref. 1; CAA45067 and 2; AAF32290)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="A -> R (in Ref. 1; CAA45067 and 2; AAF32290)"
FT /evidence="ECO:0000305"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 103..115
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 196..209
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 224..234
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 255..263
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 266..277
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 283..299
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 303..310
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 316..324
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 330..343
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 347..355
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 358..367
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 368..372
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 375..388
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 392..401
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 403..408
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 409..412
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 416..429
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 434..441
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 444..454
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 460..477
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 480..489
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 491..498
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 504..531
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 534..540
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 550..553
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 554..562
FT /evidence="ECO:0007829|PDB:5XGC"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:5ZHX"
FT HELIX 572..574
FT /evidence="ECO:0007829|PDB:5XGC"
FT HELIX 576..580
FT /evidence="ECO:0007829|PDB:5XGC"
FT TURN 582..584
FT /evidence="ECO:0007829|PDB:5ZHX"
FT HELIX 590..605
FT /evidence="ECO:0007829|PDB:5XGC"
SQ SEQUENCE 607 AA; 66317 MW; ED0F359DFA3F0510 CRC64;
MDNLSDTLKK LKITAVDKTE DSLEGCLDCL LQALAQNNTE TSEKIQASGI LQLFASLLTP
QSSCKAKVAN IIAEVAKNEF MRIPCVDAGL ISPLVQLLNS KDQEVLLQTG RALGNICYDS
HEGRSAVDQA GGAQIVIDHL RSLCSITDPA NEKLLTVFCG MLMNYSNEND SLQAQLINMG
VIPTLVKLLG IHCQNAALTE MCLVAFGNLA ELESSKEQFA STNIAEELVK LFKKQIEHDK
REMIFEVLAP LAENDAIKLQ LVEAGLVECL LEIVQQKVDS DKEDDITELK TGSDLMVLLL
LGDESMQKLF EGGKGSVFQR VLSWIPSNNH QLQLAGALAI ANFARNDANC IHMVDNGIVE
KLMDLLDRHV EDGNVTVQHA ALSALRNLAI PVINKAKMLS AGVTEAVLKF LKSEMPPVQF
KLLGTLRMLI DAQAEAAEQL GKNVKLVERL VEWCEAKDHA GVMGESNRLL SALIRHSKSK
DVIKTIVQSG GIKHLVTMAT SEHVIMQNEA LVALALIAAL ELGTAEKDLE SAKLVQILHR
LLADERSAPE IKYNSMVLIC ALMGSECLHK EVQDLAFLDV VSKLRSHENK SVAQQASLTE
QRLTVES
