GRP4_MOUSE
ID GRP4_MOUSE Reviewed; 673 AA.
AC Q8BTM9; Q3TNQ1; Q3TRL5; Q3U3I4; Q811P7; Q8BKV7; Q91ZC8; Q920A2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=RAS guanyl-releasing protein 4;
GN Name=Rasgrp4;
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] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Mast cell;
RX PubMed=11956218; DOI=10.1074/jbc.m202575200;
RA Yang Y., Li L., Wong G.W., Krilis S.A., Madhusudhan M.S., Sali A.,
RA Stevens R.L.;
RT "RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing
RT protein with calcium- and diacylglycerol-binding motifs. Identification of
RT defective variants of this signaling protein in asthma, mastocytosis, and
RT mast cell leukemia patients and demonstration of the importance of RasGRP4
RT in mast cell development and function.";
RL J. Biol. Chem. 277:25756-25774(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION,
RP ACTIVITY REGULATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C3H/HeJ;
RX PubMed=12817022; DOI=10.4049/jimmunol.171.1.390;
RA Li L., Yang Y., Wong G.W., Stevens R.L.;
RT "Mast cells in airway hyporesponsive C3H/HeJ mice express a unique isoform
RT of the signaling protein Ras guanine nucleotide releasing protein 4 that is
RT unresponsive to diacylglycerol and phorbol esters.";
RL J. Immunol. 171:390-397(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone, Dendritic cell, Embryo, and Ovary;
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 [4]
RP 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).
CC -!- FUNCTION: Functions as a cation- and diacylglycerol (DAG)-regulated
CC nucleotide exchange factor activating Ras through the exchange of bound
CC GDP for GTP. May function in mast cells differentiation.
CC {ECO:0000269|PubMed:12817022}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Recruited to
CC membranes upon activation by DAG.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=RASGRP4alpha;
CC IsoId=Q8BTM9-1; Sequence=Displayed;
CC Name=2; Synonyms=RASGRP4beta;
CC IsoId=Q8BTM9-2; Sequence=VSP_030483;
CC Name=3;
CC IsoId=Q8BTM9-3; Sequence=VSP_030484, VSP_030487;
CC Name=4;
CC IsoId=Q8BTM9-4; Sequence=VSP_030485, VSP_030486;
CC -!- TISSUE SPECIFICITY: Expressed by mast cells and their progenitors (at
CC protein level). {ECO:0000269|PubMed:11956218,
CC ECO:0000269|PubMed:12817022}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages in the development of mast
CC cells. {ECO:0000269|PubMed:12817022}.
CC -!- DOMAIN: The phorbol-ester/DAG-type zinc finger mediates the binding and
CC the functional activation by DAG.
CC -!- MISCELLANEOUS: [Isoform 3]: Due to an intron retention. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Minor isoform which is not activated by DAG
CC and probably not functional. Preferentially expressed in the C3H/HeJ
CC strain. May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE32802.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF331457; AAK84299.1; -; mRNA.
DR EMBL; AY040628; AAK81694.1; -; mRNA.
DR EMBL; AY196476; AAO20841.1; -; mRNA.
DR EMBL; AK049562; BAC33811.1; -; mRNA.
DR EMBL; AK089282; BAC40827.1; -; mRNA.
DR EMBL; AK154746; BAE32802.1; ALT_FRAME; mRNA.
DR EMBL; AK162667; BAE37013.1; -; mRNA.
DR EMBL; AK165106; BAE38037.1; -; mRNA.
DR CCDS; CCDS85257.1; -. [Q8BTM9-1]
DR CCDS; CCDS85258.1; -. [Q8BTM9-2]
DR RefSeq; NP_001167626.1; NM_001174155.1. [Q8BTM9-2]
DR RefSeq; NP_660131.2; NM_145149.4. [Q8BTM9-1]
DR AlphaFoldDB; Q8BTM9; -.
DR SMR; Q8BTM9; -.
DR BioGRID; 231357; 1.
DR IntAct; Q8BTM9; 2.
DR STRING; 10090.ENSMUSP00000092200; -.
DR iPTMnet; Q8BTM9; -.
DR PhosphoSitePlus; Q8BTM9; -.
DR MaxQB; Q8BTM9; -.
DR PaxDb; Q8BTM9; -.
DR PRIDE; Q8BTM9; -.
DR ProteomicsDB; 271308; -. [Q8BTM9-1]
DR ProteomicsDB; 271309; -. [Q8BTM9-2]
DR ProteomicsDB; 271310; -. [Q8BTM9-3]
DR ProteomicsDB; 271311; -. [Q8BTM9-4]
DR Antibodypedia; 30068; 81 antibodies from 20 providers.
DR DNASU; 233046; -.
DR Ensembl; ENSMUST00000032811; ENSMUSP00000032811; ENSMUSG00000030589. [Q8BTM9-1]
DR Ensembl; ENSMUST00000159351; ENSMUSP00000124183; ENSMUSG00000030589. [Q8BTM9-4]
DR Ensembl; ENSMUST00000159975; ENSMUSP00000125137; ENSMUSG00000030589. [Q8BTM9-2]
DR GeneID; 233046; -.
DR KEGG; mmu:233046; -.
DR UCSC; uc009gas.2; mouse. [Q8BTM9-1]
DR UCSC; uc009gat.1; mouse. [Q8BTM9-3]
DR UCSC; uc012fha.1; mouse. [Q8BTM9-2]
DR CTD; 115727; -.
DR MGI; MGI:2386851; Rasgrp4.
DR VEuPathDB; HostDB:ENSMUSG00000030589; -.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000159883; -.
DR HOGENOM; CLU_019261_2_1_1; -.
DR InParanoid; Q8BTM9; -.
DR OMA; LHHAWTQ; -.
DR OrthoDB; 355412at2759; -.
DR PhylomeDB; Q8BTM9; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 233046; 1 hit in 33 CRISPR screens.
DR PRO; PR:Q8BTM9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BTM9; protein.
DR Bgee; ENSMUSG00000030589; Expressed in granulocyte and 50 other tissues.
DR ExpressionAtlas; Q8BTM9; baseline and differential.
DR Genevisible; Q8BTM9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0009991; P:response to extracellular stimulus; ISS:UniProtKB.
DR CDD; cd00029; C1; 1.
DR CDD; cd00155; RasGEF; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
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; PTHR23113; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00617; RasGEF; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00147; RasGEF; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
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 Alternative splicing; Calcium; Cell membrane; Cytoplasm; Differentiation;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..673
FT /note="RAS guanyl-releasing protein 4"
FT /id="PRO_0000315214"
FT DOMAIN 49..175
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 201..432
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 466..501
FT /note="EF-hand"
FT ZN_FING 540..590
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 592..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 560
FT /note="F -> FVSTGP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11956218"
FT /id="VSP_030483"
FT VAR_SEQ 561..611
FT /note="LWGVTKQGYRCRDCGLCCHRHCRDQVRVECKKRPETKGDPGPPGAPVPATS
FT -> VSTGPVSTLGSHLPWIVSAPHTLTWDSVGTGFWWWWGLQKCPHLRYSTEFI (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030484"
FT VAR_SEQ 574..578
FT /note="CGLCC -> TAGIK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12817022"
FT /id="VSP_030485"
FT VAR_SEQ 579..673
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12817022"
FT /id="VSP_030486"
FT VAR_SEQ 612..673
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030487"
FT CONFLICT 182
FT /note="M -> I (in Ref. 1; AAK81694/AAK84299)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="K -> R (in Ref. 1; AAK81694/AAK84299)"
FT /evidence="ECO:0000305"
FT CONFLICT 468
FT /note="E -> G (in Ref. 1; AAK81694/AAK84299)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 673 AA; 74907 MW; 418DACEF8064AD18 CRC64;
MNRKDIKRKS HQECSGKAGG RGRSRQARRH KTCPTPREIS KVMASMNLGV LSESSCSEDE
LLEECIRCFD SAGSLRRGDH ILKMVLTMHS WVLPSSELAA RLLTSYQKAA KDAQELRQLQ
ICYLVRYWLT HHHEAVHQEP QLEAVISRFW TTVAQEGNMA QRSLGDASSL LSPGGPGPPP
PMSSPGLGKK RKVSLLFDHL ETEELAQHLT YLEFRSFQAI TPQDLRGYVL QGSVRGCPAL
EGSVGLSNSV SRWVQVMVLS RPGPAQRAQV LDKFIRVAQR LHQLQNFNTL MAVTGGLCHS
AISRLKDSHV HLSPDSTKAL LELTELLSSH NNYAHYRRTW AGCTGFRLPV LGVHLKDLVS
LYEAHPDRLP DGRLHLPKLN SLYLRLQELM ALQGQHPPCS ANEDLLHLLT LSLDLFYTED
EIYELSYARE PRCPKSLPPS PFKAPVVVEW AQGVTPKPDS VTLGQHVEQL VESVFKNYDP
EGRGSISLED FERLSGNFPF ACHGLHPPPR HGSGSFSREE LTKYLLHASA ICSKLGLAFL
HAFQEVTFRK PTFCHSCSGF LWGVTKQGYR CRDCGLCCHR HCRDQVRVEC KKRPETKGDP
GPPGAPVPAT SLPPANCGSE ESLSYTLSPD PESGCHLRHA WTQTESSHSS WEPEVVPCPA
RVLPSRASSK PSV
