GRP3_HUMAN
ID GRP3_HUMAN Reviewed; 690 AA.
AC Q8IV61; D6W583; O94931; Q53SD7;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Ras guanyl-releasing protein 3;
DE AltName: Full=Calcium and DAG-regulated guanine nucleotide exchange factor III;
DE AltName: Full=Guanine nucleotide exchange factor for Rap1;
GN Name=RASGRP3; Synonyms=GRP3, KIAA0846;
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 {ECO:0000312|EMBL:AAH27849.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain {ECO:0000269|PubMed:10048485};
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=10934204; DOI=10.1074/jbc.m005327200;
RA Rebhun J.F., Castro A.F., Quilliam L.A.;
RT "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1
RT GTPase. Regulation of MR-GEF by M-Ras-GTP interaction.";
RL J. Biol. Chem. 275:34901-34908(2000).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for Ras and Rap1.
CC {ECO:0000269|PubMed:10934204}.
CC -!- INTERACTION:
CC Q8IV61; Q96FJ2: DYNLL2; NbExp=3; IntAct=EBI-1047876, EBI-742371;
CC Q8IV61; O00258: GET1; NbExp=3; IntAct=EBI-1047876, EBI-18908258;
CC Q8IV61; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-1047876, EBI-1052304;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IV61-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IV61-2; Sequence=VSP_047371;
CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74869.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB020653; BAA74869.2; ALT_INIT; mRNA.
DR EMBL; BX647990; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC020594; AAY15037.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00432.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00433.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00434.1; -; Genomic_DNA.
DR EMBL; BC027849; AAH27849.1; -; mRNA.
DR CCDS; CCDS46256.1; -. [Q8IV61-1]
DR CCDS; CCDS54346.1; -. [Q8IV61-2]
DR RefSeq; NP_001132960.1; NM_001139488.1. [Q8IV61-1]
DR RefSeq; NP_056191.1; NM_015376.2. [Q8IV61-2]
DR RefSeq; NP_733772.1; NM_170672.2. [Q8IV61-1]
DR RefSeq; XP_005264303.1; XM_005264246.3.
DR RefSeq; XP_011531048.1; XM_011532746.2. [Q8IV61-1]
DR RefSeq; XP_011531049.1; XM_011532747.2.
DR RefSeq; XP_011531050.2; XM_011532748.2. [Q8IV61-1]
DR RefSeq; XP_016859248.1; XM_017003759.1. [Q8IV61-1]
DR RefSeq; XP_016859249.1; XM_017003760.1.
DR RefSeq; XP_016859250.1; XM_017003761.1. [Q8IV61-1]
DR RefSeq; XP_016859251.1; XM_017003762.1.
DR RefSeq; XP_016859252.1; XM_017003763.1.
DR AlphaFoldDB; Q8IV61; -.
DR SMR; Q8IV61; -.
DR BioGRID; 117315; 15.
DR IntAct; Q8IV61; 6.
DR STRING; 9606.ENSP00000384192; -.
DR BindingDB; Q8IV61; -.
DR ChEMBL; CHEMBL3638; -.
DR iPTMnet; Q8IV61; -.
DR PhosphoSitePlus; Q8IV61; -.
DR BioMuta; RASGRP3; -.
DR DMDM; 34395670; -.
DR MassIVE; Q8IV61; -.
DR MaxQB; Q8IV61; -.
DR PaxDb; Q8IV61; -.
DR PeptideAtlas; Q8IV61; -.
DR PRIDE; Q8IV61; -.
DR ProteomicsDB; 15160; -.
DR ProteomicsDB; 70665; -. [Q8IV61-1]
DR Antibodypedia; 29256; 317 antibodies from 26 providers.
DR DNASU; 25780; -.
DR Ensembl; ENST00000402538.7; ENSP00000385886.3; ENSG00000152689.18. [Q8IV61-1]
DR Ensembl; ENST00000403687.8; ENSP00000384192.3; ENSG00000152689.18. [Q8IV61-1]
DR Ensembl; ENST00000407811.5; ENSP00000383917.1; ENSG00000152689.18. [Q8IV61-2]
DR GeneID; 25780; -.
DR KEGG; hsa:25780; -.
DR MANE-Select; ENST00000403687.8; ENSP00000384192.3; NM_001139488.2; NP_001132960.1.
DR UCSC; uc002rox.4; human. [Q8IV61-1]
DR CTD; 25780; -.
DR DisGeNET; 25780; -.
DR GeneCards; RASGRP3; -.
DR HGNC; HGNC:14545; RASGRP3.
DR HPA; ENSG00000152689; Tissue enhanced (brain, skeletal muscle).
DR MIM; 609531; gene.
DR neXtProt; NX_Q8IV61; -.
DR OpenTargets; ENSG00000152689; -.
DR PharmGKB; PA134937092; -.
DR VEuPathDB; HostDB:ENSG00000152689; -.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000158843; -.
DR InParanoid; Q8IV61; -.
DR OMA; WIQCMIL; -.
DR OrthoDB; 355412at2759; -.
DR PhylomeDB; Q8IV61; -.
DR TreeFam; TF312918; -.
DR PathwayCommons; Q8IV61; -.
DR Reactome; R-HSA-1169092; Activation of RAS in B cells.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR SignaLink; Q8IV61; -.
DR SIGNOR; Q8IV61; -.
DR BioGRID-ORCS; 25780; 12 hits in 1072 CRISPR screens.
DR ChiTaRS; RASGRP3; human.
DR GeneWiki; RASGRP3; -.
DR GenomeRNAi; 25780; -.
DR Pharos; Q8IV61; Tchem.
DR PRO; PR:Q8IV61; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8IV61; protein.
DR Bgee; ENSG00000152689; Expressed in corpus callosum and 173 other tissues.
DR ExpressionAtlas; Q8IV61; baseline and differential.
DR Genevisible; Q8IV61; HS.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; NAS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB.
DR GO; GO:0019992; F:diacylglycerol binding; NAS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0019900; F:kinase binding; IEA:Ensembl.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; NAS:UniProtKB.
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 GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:UniProtKB.
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; 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 InterPro; IPR029645; RASGRP3.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF178; PTHR23113:SF178; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF13202; EF-hand_5; 2.
DR Pfam; PF00617; RasGEF; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
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 Alternative splicing; Calcium; Guanine-nucleotide releasing factor;
KW Metal-binding; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..690
FT /note="Ras guanyl-releasing protein 3"
FT /id="PRO_0000068883"
FT DOMAIN 3..125
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 152..383
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 420..455
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 458..484
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT ZN_FING 494..544
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 667..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..690
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 462
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 464
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 473
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 388
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485"
FT /id="VSP_047371"
FT VARIANT 393
FT /note="T -> A (in dbSNP:rs13388394)"
FT /id="VAR_051901"
SQ SEQUENCE 690 AA; 78332 MW; 747BBAA2CCAC2D12 CRC64;
MGSSGLGKAA TLDELLCTCI EMFDDNGELD NSYLPRIVLL MHRWYLSSTE LAEKLLCMYR
NATGESCNEF RLKICYFMRY WILKFPAEFN LDLGLIRMTE EFREVASQLG YEKHVSLIDI
SSIPSYDWMR RVTQRKKVSK KGKACLLFDH LEPIELAEHL TFLEHKSFRR ISFTDYQSYV
IHGCLENNPT LERSIALFNG ISKWVQLMVL SKPTPQQRAE VITKFINVAK KLLQLKNFNT
LMAVVGGLSH SSISRLKETH SHLSSEVTKN WNEMTELVSS NGNYCNYRKA FADCDGFKIP
ILGVHLKDLI AVHVIFPDWT EENKVNIVKM HQLSVTLSEL VSLQNASHHL EPNMDLINLL
TLSLDLYHTE DDIYKLSLVL EPRNSKSQPT SPTTPNKPVV PLEWALGVMP KPDPTVINKH
IRKLVESVFR NYDHDHDGYI SQEDFESIAA NFPFLDSFCV LDKDQDGLIS KDEMMAYFLR
AKSQLHCKMG PGFIHNFQEM TYLKPTFCEH CAGFLWGIIK QGYKCKDCGA NCHKQCKDLL
VLACRRFARA PSLSSGHGSL PGSPSLPPAQ DEVFEFPGVT AGHRDLDSRA ITLVTGSSRK
ISVRLQRATT SQATQTEPVW SEAGWGDSGS HTFPKMKSKF HDKAAKDKGF AKWENEKPRV
HAGVDVVDRG TEFELDQDEG EETRQDGEDG
