RGL3_HUMAN
ID RGL3_HUMAN Reviewed; 710 AA.
AC Q3MIN7; B5ME84; B7ZL22; Q0P6G0;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Ral guanine nucleotide dissociation stimulator-like 3;
DE Short=RalGDS-like 3;
GN Name=RGL3;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP HIS-162 AND VAL-164.
RC TISSUE=Heart, Kidney, and Lung;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-512, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-591 AND SER-601, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512; SER-569 AND SER-573, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for Ral-A. Potential
CC effector of GTPase HRas and Ras-related protein M-Ras. Negatively
CC regulates Elk-1-dependent gene induction downstream of HRas and MEKK1
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with GTP-bound forms of RIT1, HRAS and MRAS.
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q3MIN7; Q8TCP9: FAM200A; NbExp=3; IntAct=EBI-2856274, EBI-2799179;
CC Q3MIN7; Q53G59: KLHL12; NbExp=3; IntAct=EBI-2856274, EBI-740929;
CC Q3MIN7; P01111: NRAS; NbExp=3; IntAct=EBI-2856274, EBI-721993;
CC Q3MIN7; Q92963: RIT1; NbExp=3; IntAct=EBI-2856274, EBI-365845;
CC Q3MIN7; Q99578: RIT2; NbExp=3; IntAct=EBI-2856274, EBI-365914;
CC Q3MIN7; P62070: RRAS2; NbExp=3; IntAct=EBI-2856274, EBI-491037;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3MIN7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3MIN7-2; Sequence=VSP_045369;
CC -!- DOMAIN: The Ras-associating domain plays a central role in the
CC activation of Ral-A GDP/GTP exchange activity. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14426.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AC024575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014426; AAH14426.1; ALT_FRAME; mRNA.
DR EMBL; BC101756; AAI01757.1; -; mRNA.
DR EMBL; BC111958; AAI11959.1; -; mRNA.
DR EMBL; BC143530; AAI43531.1; -; mRNA.
DR CCDS; CCDS32910.1; -. [Q3MIN7-1]
DR CCDS; CCDS54221.1; -. [Q3MIN7-2]
DR RefSeq; NP_001030300.3; NM_001035223.3.
DR RefSeq; NP_001155088.2; NM_001161616.2.
DR AlphaFoldDB; Q3MIN7; -.
DR SMR; Q3MIN7; -.
DR BioGRID; 121398; 72.
DR IntAct; Q3MIN7; 8.
DR STRING; 9606.ENSP00000377075; -.
DR iPTMnet; Q3MIN7; -.
DR PhosphoSitePlus; Q3MIN7; -.
DR BioMuta; RGL3; -.
DR DMDM; 296452877; -.
DR EPD; Q3MIN7; -.
DR jPOST; Q3MIN7; -.
DR MassIVE; Q3MIN7; -.
DR MaxQB; Q3MIN7; -.
DR PaxDb; Q3MIN7; -.
DR PeptideAtlas; Q3MIN7; -.
DR PRIDE; Q3MIN7; -.
DR ProteomicsDB; 61789; -. [Q3MIN7-1]
DR ProteomicsDB; 6217; -.
DR Antibodypedia; 52109; 33 antibodies from 12 providers.
DR DNASU; 57139; -.
DR Ensembl; ENST00000393423.7; ENSP00000377075.3; ENSG00000205517.13.
DR GeneID; 57139; -.
DR KEGG; hsa:57139; -.
DR UCSC; uc002mro.3; human. [Q3MIN7-1]
DR CTD; 57139; -.
DR DisGeNET; 57139; -.
DR GeneCards; RGL3; -.
DR HGNC; HGNC:30282; RGL3.
DR HPA; ENSG00000205517; Tissue enhanced (parathyroid gland, thyroid gland).
DR MIM; 616743; gene.
DR neXtProt; NX_Q3MIN7; -.
DR PharmGKB; PA134979213; -.
DR VEuPathDB; HostDB:ENSG00000205517; -.
DR eggNOG; KOG3629; Eukaryota.
DR InParanoid; Q3MIN7; -.
DR OrthoDB; 940219at2759; -.
DR PhylomeDB; Q3MIN7; -.
DR TreeFam; TF315204; -.
DR PathwayCommons; Q3MIN7; -.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR SignaLink; Q3MIN7; -.
DR BioGRID-ORCS; 57139; 6 hits in 1070 CRISPR screens.
DR ChiTaRS; RGL3; human.
DR GenomeRNAi; 57139; -.
DR Pharos; Q3MIN7; Tdark.
DR PRO; PR:Q3MIN7; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q3MIN7; protein.
DR Bgee; ENSG00000205517; Expressed in right lobe of thyroid gland and 109 other tissues.
DR ExpressionAtlas; Q3MIN7; baseline and differential.
DR Genevisible; Q3MIN7; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR030750; RGL3.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF220; PTHR23113:SF220; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS00720; RASGEF; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Guanine-nucleotide releasing factor; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..710
FT /note="Ral guanine nucleotide dissociation stimulator-like
FT 3"
FT /id="PRO_0000306799"
FT DOMAIN 65..200
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 247..505
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 613..700
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT REGION 28..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 526..609
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 612..707
FT /note="Interaction with HRAS, MRAS and RIT1"
FT /evidence="ECO:0000250"
FT COMPBIAS 531..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..578
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UYI5"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UYI5"
FT MOD_RES 569
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 549
FT /note="S -> SSLCISP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045369"
FT VARIANT 162
FT /note="P -> H (in dbSNP:rs167479)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_035298"
FT VARIANT 164
FT /note="A -> V (in dbSNP:rs160838)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_035299"
FT VARIANT 615
FT /note="R -> C (in dbSNP:rs2291516)"
FT /id="VAR_035300"
SQ SEQUENCE 710 AA; 78079 MW; E36E9E66201D7F47 CRC64;
MERTAGKELA LAPLQDWGEE TEDGAVYSVS LRRQRSQRRS PAEGPGGSQA PSPIANTFLH
YRTSKVRVLR AARLERLVGE LVFGDREQDP SFMPAFLATY RTFVPTACLL GFLLPPMPPP
PPPGVEIKKT AVQDLSFNKN LRAVVSVLGS WLQDHPQDFR DPPAHSDLGS VRTFLGWAAP
GSAEAQKAEK LLEDFLEEAE REQEEEPPQV WTGPPRVAQT SDPDSSEACA EEEEGLMPQG
PQLLDFSVDE VAEQLTLIDL ELFSKVRLYE CLGSVWSQRD RPGAAGASPT VRATVAQFNT
VTGCVLGSVL GAPGLAAPQR AQRLEKWIRI AQRCRELRNF SSLRAILSAL QSNPIYRLKR
SWGAVSREPL STFRKLSQIF SDENNHLSSR EILFQEEATE GSQEEDNTPG SLPSKPPPGP
VPYLGTFLTD LVMLDTALPD MLEGDLINFE KRRKEWEILA RIQQLQRRCQ SYTLSPHPPI
LAALHAQNQL TEEQSYRLSR VIEPPAASCP SSPRIRRRIS LTKRLSAKLA REKSSSPSGS
PGDPSSPTSS VSPGSPPSSP RSRDAPAGSP PASPGPQGPS TKLPLSLDLP SPRPFALPLG
SPRIPLPAQQ SSEARVIRVS IDNDHGNLYR SILLTSQDKA PSVVRRALQK HNVPQPWACD
YQLFQVLPGD RVLLIPDNAN VFYAMSPVAP RDFMLRRKEG TRNTLSVSPS
