GRP2_BOVIN
ID GRP2_BOVIN Reviewed; 608 AA.
AC A6N9I4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, 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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN SIMMENTAL THROMBOPATHIA, AND
RP VARIANTS LEU-218 AND PRO-234.
RX PubMed=18039909; DOI=10.1354/vp.44-6-932;
RA Boudreaux M.K., Schmutz S.M., French P.S. Jr.;
RT "Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI)
RT gene mutations in a thrombopathic Simmental calf.";
RL Vet. Pathol. 44:932-935(2007).
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 -!- SUBUNIT: Forms a signaling complex with RAP1 and BRAF. Interacts with
CC RAP1. Interacts with F-actin (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Synapse,
CC synaptosome {ECO:0000250}. Cell projection, ruffle membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Found
CC both in the cytosol and associated with membranes. Enriched at
CC juxtamembrane areas and membrane ruffles. Localizes to the cell bodies
CC and axons of striatal neurons. {ECO:0000250}.
CC -!- DOMAIN: The N-terminal Ras-GEF domain mediates association with F-
CC actin. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in RASGRP2 may be the cause of Simmental
CC thrombopathia. An inherited platelet disorder first described in
CC Simmental cattle and characterized by mild to severe bleeding episodes.
CC {ECO:0000305|PubMed:18039909}.
CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}.
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DR EMBL; EF633475; ABR27454.1; -; mRNA.
DR RefSeq; NP_001093416.1; NM_001099946.1.
DR RefSeq; XP_010819374.1; XM_010821072.2.
DR RefSeq; XP_010819376.1; XM_010821074.2.
DR RefSeq; XP_010819377.1; XM_010821075.2.
DR AlphaFoldDB; A6N9I4; -.
DR SMR; A6N9I4; -.
DR STRING; 9913.ENSBTAP00000001368; -.
DR PaxDb; A6N9I4; -.
DR PRIDE; A6N9I4; -.
DR Ensembl; ENSBTAT00000073104; ENSBTAP00000068916; ENSBTAG00000001029.
DR GeneID; 512056; -.
DR KEGG; bta:512056; -.
DR CTD; 10235; -.
DR VEuPathDB; HostDB:ENSBTAG00000001029; -.
DR VGNC; VGNC:33748; RASGRP2.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000160483; -.
DR InParanoid; A6N9I4; -.
DR OrthoDB; 355412at2759; -.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000001029; Expressed in retropharyngeal lymph node and 105 other tissues.
DR ExpressionAtlas; A6N9I4; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
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; PF13202; EF-hand_5; 2.
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 2: Evidence at transcript 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_0000315607"
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..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..591
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:0000250|UniProtKB:P0C643"
FT VARIANT 218
FT /note="P -> L"
FT /evidence="ECO:0000269|PubMed:18039909"
FT VARIANT 234
FT /note="L -> P (homozygous in a thrombopathic calf;
FT heterozygous in other calves)"
FT /evidence="ECO:0000269|PubMed:18039909"
SQ SEQUENCE 608 AA; 69180 MW; 176067A4A90F5625 CRC64;
MAGTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLAAKLLHIY
QQSRKDNSSS LQVKTCHLVR YWISAFPAEF DLNPELAEQI KELKALLDQE GNRRHSSLID
IENVPTYKWK RQVTQRNPVE QKKRKMSLLF DHLEPLELAA HLTYLEYRSF CKILFQDYHS
FVTHGCTVDN PVLERFISLF NSVSQWVQLM ILSKPTAPQR AGVITHFVHV AEELLHLQNF
NTLMAVVGGL SHSSISRLKE THSHVSPETI KLWEGLTELV TATGNYGNYR RRLAACVGFR
FPILGVHLKD LVALQLALPD WLDPARTRLN GAKMKQLFSI LEELAMVTSL RPPVQANPDL
LSLLMVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTTCTP PPRPPVLEEW TSAAKPKLDQ
AIMVEHIEKM VESVFRNFDV DGDGHISQEE FQIIRGNFPY LSAFGDLDQN QDGCISKEEM
VSYFLRSSSM LGGRMGFVHN FHESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC
KDRLSVECRR RAQSMSLEGS APSPSPTHTH HRAFSFSLPR PGRRGSRPPE IREEEVQTVE
DGVFDIHL
