GRP2_RAT
ID GRP2_RAT Reviewed; 608 AA.
AC P0C643;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=RAS guanyl-releasing protein 2;
DE AltName: Full=Calcium and DAG-regulated guanine nucleotide exchange factor I;
DE Short=CalDAG-GEFI;
GN Name=Rasgrp2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9789079; DOI=10.1073/pnas.95.22.13278;
RA Kawasaki H., Springett G.M., Toki S., Canales J.J., Harlan P.,
RA Blumenstiel J.P., Chen E.J., Bany I.A., Mochizuki N., Ashbacher A.,
RA Matsuda M., Housman D.E., Graybiel A.M.;
RT "A Rap guanine nucleotide exchange factor enriched highly in the basal
RT ganglia.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13278-13283(1998).
RN [3]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAP1 AND BRAF.
RX PubMed=11292831; DOI=10.1074/jbc.m101277200;
RA Guo F.-F., Kumahara E., Saffen D.;
RT "A CalDAG-GEFI/Rap1/B-Raf cassette couples M(1) muscarinic acetylcholine
RT receptors to the activation of ERK1/2.";
RL J. Biol. Chem. 276:25568-25581(2001).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11503142; DOI=10.1002/cne.1291;
RA Toki S., Kawasaki H., Tashiro N., Housman D.E., Graybiel A.M.;
RT "Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are
RT colocalized in striatal projection neurons.";
RL J. Comp. Neurol. 437:398-407(2001).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-575, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Functions as a calcium- and DAG-regulated nucleotide exchange
CC factor specifically activating Rap through the exchange of bound GDP
CC for GTP. May also activate other GTPases such as RRAS, RRAS2, NRAS,
CC KRAS but not HRAS. Functions in aggregation of platelets and adhesion
CC of T-lymphocytes and neutrophils probably through inside-out integrin
CC activation. May function in the muscarinic acetylcholine receptor
CC M1/CHRM1 signaling pathway. {ECO:0000250|UniProtKB:Q7LDG7,
CC ECO:0000269|PubMed:11292831}.
CC -!- SUBUNIT: Forms a signaling complex with RAP1 and BRAF. Interacts with
CC F-actin (By similarity). Interacts with RAP1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Synapse,
CC synaptosome {ECO:0000269|PubMed:11503142, ECO:0000269|PubMed:9789079}.
CC Cell projection, ruffle membrane {ECO:0000305}; Peripheral membrane
CC protein {ECO:0000305}. Note=Found both in the cytosol and associated
CC with membranes (By similarity). Enriched at juxtamembrane areas and
CC membrane ruffles (By similarity). Localizes to the cell bodies and
CC axons of striatal neurons. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in striatal neurons (at protein level).
CC Expressed in the hematopoietic system. Detected in olfactory structures
CC and deep cortical layers of brain. {ECO:0000269|PubMed:11503142,
CC ECO:0000269|PubMed:9789079}.
CC -!- DOMAIN: The N-terminal Ras-GEF domain mediates association with F-
CC actin. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}.
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DR EMBL; AABR03006336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03008223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03009977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03011305; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001076446.1; NM_001082977.1.
DR AlphaFoldDB; P0C643; -.
DR BMRB; P0C643; -.
DR SMR; P0C643; -.
DR STRING; 10116.ENSRNOP00000028646; -.
DR iPTMnet; P0C643; -.
DR PhosphoSitePlus; P0C643; -.
DR SwissPalm; P0C643; -.
DR PaxDb; P0C643; -.
DR PRIDE; P0C643; -.
DR GeneID; 361714; -.
DR KEGG; rno:361714; -.
DR UCSC; RGD:1311630; rat.
DR CTD; 10235; -.
DR RGD; 1311630; Rasgrp2.
DR eggNOG; KOG3417; Eukaryota.
DR InParanoid; P0C643; -.
DR OrthoDB; 355412at2759; -.
DR PhylomeDB; P0C643; -.
DR TreeFam; TF312918; -.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-392517; Rap1 signalling.
DR PRO; PR:P0C643; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR InterPro; IPR046349; C1-like_sf.
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; PTHR23113; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
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; Cell projection; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Synaptosome; Zinc;
KW Zinc-finger.
FT CHAIN 1..608
FT /note="RAS guanyl-releasing protein 2"
FT /id="PRO_0000315610"
FT DOMAIN 4..126
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 154..387
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 426..461
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 463..490
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT ZN_FING 498..548
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 382..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 441
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 443
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 445
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 450
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 468
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 470
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 472
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 474
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 479
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUG9"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUG9"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUG9"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUG9"
FT MOD_RES 575
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 608 AA; 69291 MW; 0AA7ACFCEE989112 CRC64;
MASTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLASKLLHFY
QQSRKDNSNS LQVKTCHLVR YWVSAFPAEF DLNPELAEQI KELKALLDQE GNRRHSSLID
IESVPTYKWK RQVTQRNPVE QKKRKMSLLF DHLEPMELAE HLTYLEYRSF CKILFQDYHS
FVTHGCTVDN PVLERFISLF NSVSQWVQLM ILSKPTATQR ALVITHFVHV AEKLLQLQNF
NTLMAVVGGL SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR
FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFSI LEELAMVTSL RPPVQANPDL
LSLLTVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTSCTP PPRPPVLEEW TSVAKPKLDQ
ALVAEHIEKM VESVFRNFDV DGDGHISQEE FQIIRGNFPY LSAFGDLDQN QDGCISREEM
ISYFLRSSSV LGGRMGFVHN LQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC
KDRLSVECRR RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQTVE
DGVFDIHL
