ID GRP1_MOUSE Reviewed; 795 AA.
AC Q9Z1S3; Q3URH0; Q3V401; Q8BQP6;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 24-JAN-2024, entry version 185.
DE RecName: Full=RAS guanyl-releasing protein 1;
DE AltName: Full=Calcium and DAG-regulated guanine nucleotide exchange factor II;
DE Short=CalDAG-GEFII;
DE AltName: Full=Ras guanyl-releasing protein;
GN Name=Rasgrp1; Synonyms=Rasgrp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X C3H; TISSUE=Brain;
RX PubMed=10087292; DOI=10.1007/s003359901001;
RA Bottorff D.A., Ebinu J.O., Stone J.C.;
RT "RasGRP, a Ras activator: mouse and human cDNA sequences and chromosomal
RT positions.";
RL Mamm. Genome 10:358-361(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, Corpus striatum, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Fetal 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 [5]
RP FUNCTION, MUTAGENESIS OF ARG-271, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9819387; DOI=10.1128/mcb.18.12.6995;
RA Tognon C.E., Kirk H.E., Passmore L.A., Whitehead I.P., Der C.J., Kay R.J.;
RT "Regulation of RasGRP via a phorbol ester-responsive C1 domain.";
RL Mol. Cell. Biol. 18:6995-7008(1998).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION IN T-CELL ACTIVATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11017103; DOI=10.1038/79766;
RA Dower N.A., Stang S.L., Bottorff D.A., Ebinu J.O., Dickie P.,
RA Ostergaard H.L., Stone J.C.;
RT "RasGRP is essential for mouse thymocyte differentiation and TCR
RT signaling.";
RL Nat. Immunol. 1:317-321(2000).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12433368; DOI=10.1016/s1074-7613(02)00451-x;
RA Priatel J.J., Teh S.-J., Dower N.A., Stone J.C., Teh H.-S.;
RT "RasGRP1 transduces low-grade TCR signals which are critical for T cell
RT development, homeostasis, and differentiation.";
RL Immunity 17:617-627(2002).
RN [8]
RP RETRACTED PAPER.
RX PubMed=12932358; DOI=10.1016/s1074-7613(03)00209-7;
RA Layer K., Lin G., Nencioni A., Hu W., Schmucker A., Antov A.N., Li X.,
RA Takamatsu S., Chevassut T., Dower N.A., Stang S.L., Beier D., Buhlmann J.,
RA Bronson R.T., Elkon K.B., Stone J.C., Van Parijs L., Lim B.;
RT "Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1.";
RL Immunity 19:243-255(2003).
RN [9]
RP RETRACTION NOTICE OF PUBMED:12932358.
RX PubMed=22808526; DOI=10.1016/j.immuni.2012.05.007;
RA Layer K., Lin G., Nencioni A., Hu W., Schmucker A., Antov A.N., Li X.,
RA Takamatsu S., Chevassut T., Dower N.A., Stang S.L., Beier D., Buhlmann J.,
RA Bronson R.T., Elkon K.B., Stone J.C., Van Parijs L., Lim B.;
RL Immunity 36:886-886(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND INDUCTION
RP BY TPA.
RX PubMed=14532295; DOI=10.1074/jbc.m308240200;
RA Rambaratsingh R.A., Stone J.C., Blumberg P.M., Lorenzo P.S.;
RT "RasGRP1 represents a novel non-protein kinase C phorbol ester signaling
RT pathway in mouse epidermal keratinocytes.";
RL J. Biol. Chem. 278:52792-52801(2003).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=12538669; DOI=10.4049/jimmunol.170.3.1141;
RA Norment A.M., Bogatzki L.Y., Klinger M.B., Ojala E.W., Bevan M.J.,
RA Kay R.J.;
RT "Transgenic expression of RasGRP1 induces the maturation of double-negative
RT thymocytes and enhances the production of CD8 single-positive thymocytes.";
RL J. Immunol. 170:1141-1149(2003).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12845332; DOI=10.1038/nature01806;
RA Bivona T.G., Perez De Castro I., Ahearn I.M., Grana T.M., Chiu V.K.,
RA Lockyer P.J., Cullen P.J., Pellicer A., Cox A.D., Philips M.R.;
RT "Phospholipase Cgamma activates Ras on the Golgi apparatus by means of
RT RasGRP1.";
RL Nature 424:694-698(2003).
RN [13]
RP FUNCTION IN B-CELLS, TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-271.
RX PubMed=14970203; DOI=10.1074/jbc.m314273200;
RA Guilbault B., Kay R.J.;
RT "RasGRP1 sensitizes an immature B cell line to antigen receptor-induced
RT apoptosis.";
RL J. Biol. Chem. 279:19523-19530(2004).
RN [14]
RP FUNCTION.
RX PubMed=16301621; DOI=10.4049/jimmunol.175.11.7179;
RA Coughlin J.J., Stang S.L., Dower N.A., Stone J.C.;
RT "RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell
RT receptor-Ras signaling.";
RL J. Immunol. 175:7179-7184(2005).
RN [15]
RP FUNCTION.
RX PubMed=15829980; DOI=10.1038/sj.onc.1208334;
RA Klinger M.B., Guilbault B., Goulding R.E., Kay R.J.;
RT "Deregulated expression of RasGRP1 initiates thymic lymphomagenesis
RT independently of T-cell receptors.";
RL Oncogene 24:2695-2704(2005).
RN [16]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16849453; DOI=10.4049/jimmunol.177.3.1470;
RA Priatel J.J., Chen X., Dhanji S., Abraham N., Teh H.-S.;
RT "RasGRP1 transmits prodifferentiation TCR signaling that is crucial for CD4
RT T cell development.";
RL J. Immunol. 177:1470-1480(2006).
RN [17]
RP DIACYLGLYCEROL-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=17523924; DOI=10.1042/bj20070294;
RA Johnson J.E., Goulding R.E., Ding Z., Partovi A., Anthony K.V.,
RA Beaulieu N., Tazmini G., Cornell R.B., Kay R.J.;
RT "Differential membrane binding and diacylglycerol recognition by C1 domains
RT of RasGRPs.";
RL Biochem. J. 406:223-236(2007).
RN [18]
RP FUNCTION.
RX PubMed=17210708; DOI=10.1158/0008-5472.can-06-3080;
RA Oki-Idouchi C.E., Lorenzo P.S.;
RT "Transgenic overexpression of RasGRP1 in mouse epidermis results in
RT spontaneous tumors of the skin.";
RL Cancer Res. 67:276-280(2007).
RN [19]
RP FUNCTION IN MAST CELL ACTIVATION, AND TISSUE SPECIFICITY.
RX PubMed=17190838; DOI=10.1084/jem.20061598;
RA Liu Y., Zhu M., Nishida K., Hirano T., Zhang W.;
RT "An essential role for RasGRP1 in mast cell function and IgE-mediated
RT allergic response.";
RL J. Exp. Med. 204:93-103(2007).
RN [20]
RP DISRUPTION PHENOTYPE.
RX PubMed=17675473; DOI=10.4049/jimmunol.179.4.2143;
RA Priatel J.J., Chen X., Zenewicz L.A., Shen H., Harder K.W., Horwitz M.S.,
RA Teh H.-S.;
RT "Chronic immunodeficiency in mice lacking RasGRP1 results in CD4 T cell
RT immune activation and exhaustion.";
RL J. Immunol. 179:2143-2152(2007).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=17567957; DOI=10.1091/mbc.e06-10-0932;
RA Beaulieu N., Zahedi B., Goulding R.E., Tazmini G., Anthony K.V.,
RA Omeis S.L., de Jong D.R., Kay R.J.;
RT "Regulation of RasGRP1 by B cell antigen receptor requires cooperativity
RT between three domains controlling translocation to the plasma membrane.";
RL Mol. Biol. Cell 18:3156-3168(2007).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Functions as a calcium- and diacylglycerol (DAG)-regulated
CC nucleotide exchange factor specifically activating Ras through the
CC exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade.
CC Regulates T-cell/B-cell development, homeostasis and differentiation by
CC coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. Regulates
CC NK cell cytotoxicity and ITAM-dependent cytokine production by
CC activation of Ras-mediated ERK and JNK pathways (By similarity).
CC Functions in mast cell degranulation and cytokine secretion, regulating
CC FcERI-evoked allergic responses (PubMed:17190838). May also function in
CC differentiation of other cell types. Proto-oncogene, which promotes T-
CC cell lymphomagenesis when its expression is deregulated
CC (PubMed:15829980, PubMed:17210708). {ECO:0000250|UniProtKB:O95267,
CC ECO:0000269|PubMed:11017103, ECO:0000269|PubMed:12433368,
CC ECO:0000269|PubMed:12538669, ECO:0000269|PubMed:12845332,
CC ECO:0000269|PubMed:14532295, ECO:0000269|PubMed:14970203,
CC ECO:0000269|PubMed:15829980, ECO:0000269|PubMed:16301621,
CC ECO:0000269|PubMed:16849453, ECO:0000269|PubMed:17190838,
CC ECO:0000269|PubMed:17210708, ECO:0000269|PubMed:9819387}.
CC -!- ACTIVITY REGULATION: Autoinhibited. Activated by diacylglycerol and
CC calcium binding, which induces a conformational change releasing the
CC autoinhibitory state. Regulated by DGKA. Regulated by DGKZ. Regulated
CC by PLC gamma and F-actin polymerization (By similarity).
CC {ECO:0000250|UniProtKB:O95267}.
CC -!- SUBUNIT: Homodimer. Forms a signaling complex with DGKZ and HRAS.
CC Interacts with F-actin. Interacts with SKAP1 (By similarity).
CC {ECO:0000250|UniProtKB:O95267}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Golgi
CC apparatus membrane; Peripheral membrane protein. Endoplasmic reticulum
CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Note=Found both in the cytosol and associated with membranes.
CC Relocalization to the cell membrane upon activation is F-actin-
CC dependent (By similarity). Translocates to the Golgi in response to
CC phorbol ester or nerve growth factor. Localizes to somata and dendrites
CC but not to axons of hippocampal pyramidal cells (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in spleen and thymus. Expressed by mature
CC thymocytes and to a lower extent by bone marrow-derived mast cells (at
CC protein level). Detected in B-cells and keratinocytes (at protein
CC level). {ECO:0000269|PubMed:11017103, ECO:0000269|PubMed:12433368,
CC ECO:0000269|PubMed:14532295, ECO:0000269|PubMed:14970203,
CC ECO:0000269|PubMed:17190838, ECO:0000269|PubMed:9819387}.
CC -!- INDUCTION: Up-regulated at the double-negative to double-positive
CC transition during thymocyte development. Down-regulated by 12-O-
CC tetradecanoylphorbol-13-acetate (TPA). {ECO:0000269|PubMed:12538669,
CC ECO:0000269|PubMed:14532295}.
CC -!- DOMAIN: The phorbol-ester/DAG-type zinc finger is the principal
CC mediator of the targeting to membranes and is required for functional
CC activation through DAG-binding.
CC -!- DOMAIN: Two EF-hand domains are present. However, only EF-hand 1 (and
CC not EF-hand 2) binds calcium. {ECO:0000250|UniProtKB:O95267}.
CC -!- DISRUPTION PHENOTYPE: Mice fail to mount anaphylactic allergic
CC reactions and display chronic T-cell immunodeficiencies. Lag
CC (lymphoproliferation-autoimmunity-glomerulonephritis) mice do not
CC express Rasgrp1 and display a systemic lupus erythematosus-like
CC phenotype. {ECO:0000269|PubMed:11017103, ECO:0000269|PubMed:16849453,
CC ECO:0000269|PubMed:17675473}.
CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}.
CC -!- CAUTION: Was reported that thymocytes isolated from a RasGRP1 mutant
CC mouse strain show a defect in Ras activation following T-cell-receptor
CC (TCR) engagement (PubMed:12932358). However, this paper has been
CC retracted because the data in one figure was falsified by one of the
CC authors (PubMed:22808526). The authors stand by the validity of the
CC other figures, results and interpretation in this paper
CC (PubMed:22808526). Furthermore, evidence supporting function is derived
CC by similarity with the human ortholog, so may be true.
CC {ECO:0000269|PubMed:12932358, ECO:0000269|PubMed:22808526,
CC ECO:0000305}.
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DR EMBL; AF106070; AAC97348.1; -; mRNA.
DR EMBL; AK028308; BAE20439.1; -; mRNA.
DR EMBL; AK047613; BAC33100.1; -; mRNA.
DR EMBL; AK141524; BAE24718.1; -; mRNA.
DR EMBL; AL844579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057120; AAH57120.1; -; mRNA.
DR EMBL; BC057341; AAH57341.1; -; mRNA.
DR CCDS; CCDS16572.1; -.
DR RefSeq; NP_035376.1; NM_011246.2.
DR AlphaFoldDB; Q9Z1S3; -.
DR SMR; Q9Z1S3; -.
DR IntAct; Q9Z1S3; 4.
DR MINT; Q9Z1S3; -.
DR STRING; 10090.ENSMUSP00000099593; -.
DR iPTMnet; Q9Z1S3; -.
DR PhosphoSitePlus; Q9Z1S3; -.
DR EPD; Q9Z1S3; -.
DR jPOST; Q9Z1S3; -.
DR MaxQB; Q9Z1S3; -.
DR PaxDb; 10090-ENSMUSP00000099593; -.
DR ProteomicsDB; 271099; -.
DR Antibodypedia; 53148; 177 antibodies from 22 providers.
DR DNASU; 19419; -.
DR Ensembl; ENSMUST00000102534.11; ENSMUSP00000099593.5; ENSMUSG00000027347.20.
DR GeneID; 19419; -.
DR KEGG; mmu:19419; -.
DR UCSC; uc033hpk.1; mouse.
DR AGR; MGI:1314635; -.
DR CTD; 10125; -.
DR MGI; MGI:1314635; Rasgrp1.
DR VEuPathDB; HostDB:ENSMUSG00000027347; -.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000158910; -.
DR InParanoid; Q9Z1S3; -.
DR OMA; CAKWENG; -.
DR OrthoDB; 4260488at2759; -.
DR PhylomeDB; Q9Z1S3; -.
DR TreeFam; TF312918; -.
DR Reactome; R-MMU-1169092; Activation of RAS in B cells.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-392517; Rap1 signalling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 19419; 5 hits in 76 CRISPR screens.
DR PRO; PR:Q9Z1S3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9Z1S3; Protein.
DR Bgee; ENSMUSG00000027347; Expressed in olfactory tubercle and 154 other cell types or tissues.
DR ExpressionAtlas; Q9Z1S3; baseline and differential.
DR Genevisible; Q9Z1S3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0019992; F:diacylglycerol binding; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:CACAO.
DR GO; GO:0042113; P:B cell activation; ISO:MGI.
DR GO; GO:0042100; P:B cell proliferation; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IMP:MGI.
DR GO; GO:0043303; P:mast cell degranulation; IMP:MGI.
DR GO; GO:0030101; P:natural killer cell activation; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IMP:CACAO.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IMP:CACAO.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; IMP:CACAO.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0032729; P:positive regulation of type II interferon production; ISO:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI.
DR GO; GO:0032252; P:secretory granule localization; IMP:MGI.
DR GO; GO:0042110; P:T cell activation; ISO:MGI.
DR GO; GO:0042098; P:T cell proliferation; ISO:MGI.
DR GO; GO:0047496; P:vesicle transport along microtubule; IMP:MGI.
DR CDD; cd20860; C1_RASGRP1; 1.
DR CDD; cd22290; cc_RasGRP1_C; 1.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 3.30.60.20; -; 1.
DR Gene3D; 6.10.250.2730; -; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR Gene3D; 1.10.840.10; Ras guanine-nucleotide exchange factors catalytic domain; 1.
DR Gene3D; 1.20.870.10; Son of sevenless (SoS) protein Chain: S domain 1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR PANTHER; PTHR23113; GUANINE NUCLEOTIDE EXCHANGE FACTOR; 1.
DR PANTHER; PTHR23113:SF174; RAS GUANYL-RELEASING PROTEIN 1; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00054; EFh; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF57889; Cysteine-rich domain; 1.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF48366; Ras GEF; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Coiled coil; Cytoplasm; Differentiation;
KW Endoplasmic reticulum; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT CHAIN 1..795
FT /note="RAS guanyl-releasing protein 1"
FT /id="PRO_0000316979"
FT DOMAIN 53..176
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 205..436
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 470..505
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 506..532
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT ZN_FING 541..591
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..110
FT /note="Ras exchanger motif region; required for
FT transforming activity"
FT REGION 686..694
FT /note="Suppress the PT region-mediated translocation to
FT plasma membrane"
FT REGION 717..795
FT /note="PT region; mediates the BCR-dependent translocation
FT to plasma membrane"
FT COILED 738..779
FT /evidence="ECO:0000255"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 485
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 487
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 489
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 184
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:O95267"
FT MOD_RES 597
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1K8"
FT MUTAGEN 271
FT /note="R->E: Loss of function and transforming activity."
FT /evidence="ECO:0000269|PubMed:14970203,
FT ECO:0000269|PubMed:9819387"
FT CONFLICT 171
FT /note="T -> R (in Ref. 2; BAE24718)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="Q -> K (in Ref. 2; BAE20439)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="D -> E (in Ref. 2; BAE20439)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="S -> T (in Ref. 2; BAE20439)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="D -> H (in Ref. 2; BAE20439)"
FT /evidence="ECO:0000305"
FT CONFLICT 768
FT /note="K -> R (in Ref. 2; BAC33100)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 90304 MW; E2096D985DFB79A0 CRC64;
MGTLGKAREA PRKPCHGSRA GPKARLEAKS TNSPLPAQPS LAQITQFRMM VSLGHLAKGA
SLDDLIDSCI QSFDADGNLC RNNQLLQVML TMHRIIISSA ELLQKVMNLY KDALEKNSPG
VCLKICYFVR YWITEFWIMF KMDASLTSTM EEFQDLVKAN GEETHCHLID TTQINSRDWS
RKLTQRIKSN TSKKRKVSLL FDHLEPEELS EHLTYLEFKS FRRISFSDYQ NYLVNSCVKE
NPTMERSIAL CNGISQWVQL MVLSRPTPQL RAEVFIKFIH VAQKLHQLQN FNTLMAVIGG
LCHSSISRLK ETSSHVPHEI NKVLGEMTEL LSSCRNYDNY RRAYGECTHF KIPILGVHLK
DLISLYEAMP DYLEDGKVNV QKLLALYNHI NELVQLQEMA PPLDANKDLV HLLTLSLDLY
YTEDEIYELS YAREPRNHRA PPLTPSKPPV VVDWASGVSP KPDPKTISKH VQRMVDSVFK
NYDLDQDGYI SQEEFEKIAA SFPFSFCVMD KDREGLISRD EITAYFMRAS SIYSKLGLGF
PHNFQETTYL KPTFCDNCAG FLWGVIKQGY RCKDCGMNCH KQCKDLVVFE CKKRIKSPAI
STENISSVVP MSTLCPLGTK DLLHAPEEGS FIFQNGEIVD HSEESKDRTI MLLGVSSQKI
SVRLKRTVAH KSTQTESFPW VGGETTPGHF VLSSPRKSAQ GALYVHSPAS PCPSPALVRK
RAFVKWENKE SLIKPKPELH LRLRTYQELE QEINTLKADN DALKIQLKYA QKKIESLQLG
KSNHVLAQMD HGDSA
//
