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   17-JUN-2020, entry version 134.
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};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   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; 34 antibodies.
DR   Ensembl; ENST00000393423; ENSP00000377075; ENSG00000205517.
DR   GeneID; 57139; -.
DR   KEGG; hsa:57139; -.
DR   UCSC; uc002mro.3; human. [Q3MIN7-1]
DR   CTD; 57139; -.
DR   DisGeNET; 57139; -.
DR   EuPathDB; HostDB:ENSG00000205517.12; -.
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   eggNOG; KOG3629; Eukaryota.
DR   eggNOG; ENOG410ZUT5; LUCA.
DR   InParanoid; Q3MIN7; -.
DR   KO; K17639; -.
DR   OrthoDB; 940219at2759; -.
DR   PhylomeDB; Q3MIN7; -.
DR   TreeFam; TF315204; -.
DR   BioGRID-ORCS; 57139; 3 hits in 786 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 left lobe of thyroid gland and 130 other tissues.
DR   ExpressionAtlas; Q3MIN7; baseline and differential.
DR   Genevisible; Q3MIN7; HS.
DR   GO; GO:0008321; F:Ral guanyl-nucleotide exchange factor activity; IEA:Ensembl.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
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   Polymorphism; 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          612..707
FT                   /note="Interaction with HRAS, MRAS and RIT1"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        231..234
FT                   /note="Poly-Glu"
FT   COMPBIAS        537..607
FT                   /note="Pro-rich"
FT   MOD_RES         52
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|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:0000244|PubMed:18669648,
FT                   ECO:0000244|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:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569"
FT   MOD_RES         573
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         591
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:20068231"
FT   MOD_RES         601
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|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
//