LOCUS       NP_001132960             690 aa            linear   PRI 04-APR-2024
DEFINITION  ras guanyl-releasing protein 3 isoform 1 [Homo sapiens].
ACCESSION   NP_001132960
VERSION     NP_001132960.1
DBSOURCE    REFSEQ: accession NM_001139488.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 690)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   2  (residues 1 to 690)
  AUTHORS   Zhang,Z., Ma,M., Hu,R., Xu,B., Zong,L., Wei,H. and Meng,Y.
  TITLE     RasGRP3, a Ras guanyl releasing protein 3 that contributes to
            malignant proliferation and aggressiveness in human esophageal
            squamous cell carcinoma
  JOURNAL   Clin Exp Pharmacol Physiol 45 (7), 720-728 (2018)
   PUBMED   29461644
  REMARK    GeneRIF: RasGRP3, a Ras guanyl releasing protein 3 that contributes
            to malignant proliferation and aggressiveness in human esophageal
            squamous cell carcinoma
REFERENCE   3  (residues 1 to 690)
  AUTHORS   Czikora,A., Kedei,N., Kalish,H. and Blumberg,P.M.
  TITLE     Importance of the REM (Ras exchange) domain for membrane
            interactions by RasGRP3
  JOURNAL   Biochim Biophys Acta Biomembr 1859 (12), 2350-2360 (2017)
   PUBMED   28912101
  REMARK    GeneRIF: The marked differences between RasGRP3 and RasGRP1 in
            membrane interaction necessarily will contribute to their different
            behavior in cells.
REFERENCE   4  (residues 1 to 690)
  AUTHORS   Hu,G., Zhou,Y., Zhu,Y., Zhou,L., Ling,R., Wu,D., Mi,L., Wang,X.,
            Dai,D., Mao,C. and Chen,D.
  TITLE     Novel transduction of nutrient stress to Notch pathway by RasGRP3
            promotes malignant aggressiveness in human esophageal squamous cell
            carcinoma
  JOURNAL   Oncol Rep 38 (5), 2975-2984 (2017)
   PUBMED   29048643
  REMARK    GeneRIF: In conclusion, these findings provide a new insight into
            the upregulation of RasGRP3 involved in Notch pathway activation in
            the development of esophageal squamous cell carcinoma , especially
            under nutrient deprivation.
REFERENCE   5  (residues 1 to 690)
  AUTHORS   Qiu,W., Xia,X., Qiu,Z., Guo,M. and Yang,Z.
  TITLE     RasGRP3 controls cell proliferation and migration in papillary
            thyroid cancer by regulating the Akt-MDM2 pathway
  JOURNAL   Gene 633, 35-41 (2017)
   PUBMED   28864115
  REMARK    GeneRIF: these data show that RasGRP3 exerts its oncogenic effect
            in papillary thyroid cancer through Akt-mediated MDM2 activation.
REFERENCE   6  (residues 1 to 690)
  AUTHORS   Brodie,C., Steinhart,R., Kazimirsky,G., Rubinfeld,H., Hyman,T.,
            Ayres,J.N., Hur,G.M., Toth,A., Yang,D., Garfield,S.H., Stone,J.C.
            and Blumberg,P.M.
  TITLE     PKCdelta associates with and is involved in the phosphorylation of
            RasGRP3 in response to phorbol esters
  JOURNAL   Mol Pharmacol 66 (1), 76-84 (2004)
   PUBMED   15213298
REFERENCE   7  (residues 1 to 690)
  AUTHORS   Teixeira,C., Stang,S.L., Zheng,Y., Beswick,N.S. and Stone,J.C.
  TITLE     Integration of DAG signaling systems mediated by PKC-dependent
            phosphorylation of RasGRP3
  JOURNAL   Blood 102 (4), 1414-1420 (2003)
   PUBMED   12730099
REFERENCE   8  (residues 1 to 690)
  AUTHORS   Lorenzo,P.S., Kung,J.W., Bottorff,D.A., Garfield,S.H., Stone,J.C.
            and Blumberg,P.M.
  TITLE     Phorbol esters modulate the Ras exchange factor RasGRP3
  JOURNAL   Cancer Res 61 (3), 943-949 (2001)
   PUBMED   11221888
REFERENCE   9  (residues 1 to 690)
  AUTHORS   Rebhun,J.F., Castro,A.F. and Quilliam,L.A.
  TITLE     Identification of guanine nucleotide exchange factors (GEFs) for
            the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction
  JOURNAL   J Biol Chem 275 (45), 34901-34908 (2000)
   PUBMED   10934204
REFERENCE   10 (residues 1 to 690)
  AUTHORS   Adams,M.D., Soares,M.B., Kerlavage,A.R., Fields,C. and Venter,J.C.
  TITLE     Rapid cDNA sequencing (expressed sequence tags) from a
            directionally cloned human infant brain cDNA library
  JOURNAL   Nat Genet 4 (4), 373-380 (1993)
   PUBMED   8401585
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA336406.1, DA439087.1,
            BC027849.1, AA351079.1 and BX647990.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: The protein encoded by this gene is a guanine nucleotide
            exchange factor that activates the oncogenes HRAS and RAP1A.
            Defects in this gene have been associated with systemic lupus
            erythematosus and several cancers. [provided by RefSeq, Mar 2017].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1). Variants 1, 2, and 4-6 all encode the same isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BX647990.1, SRR1803611.264331.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000403687.8/ ENSP00000384192.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..690
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p22.3"
     Protein         1..690
                     /product="ras guanyl-releasing protein 3 isoform 1"
                     /note="guanine nucleotide exchange factor for Rap1; ras
                     guanyl-releasing protein 3; RAS guanyl releasing protein 3
                     (calcium and DAG-regulated); CalDAG-GEFIII; calcium- and
                     diacylglycerol-regulated guanine nucleotide exchange
                     factor III; calcium and DAG-regulated guanine nucleotide
                     exchange factor III"
                     /calculated_mol_wt=78201
     Region          11..126
                     /region_name="REM"
                     /note="Guanine nucleotide exchange factor for Ras-like
                     GTPases; N-terminal domain (RasGef_N), also called REM
                     domain (Ras exchanger motif). This domain is common in
                     nucleotide exchange factors for Ras-like small GTPases and
                     is typically found immediately...; cd06224"
                     /db_xref="CDD:100121"
     Site            order(22,68,72..73,76,79..80,115..116,119,126)
                     /site_type="other"
                     /note="GTPase interaction site [polypeptide binding]"
                     /db_xref="CDD:100121"
     Region          148..384
                     /region_name="RasGEF"
                     /note="Guanine nucleotide exchange factor for Ras-like
                     small GTPases; smart00147"
                     /db_xref="CDD:214539"
     Site            order(181..183,191..192,194..196,198..199,202..203,206,
                     239,242..243,245..247,249..252,254..255,275,278,283..285,
                     288,301..303,306..308,310..312,314..317,332,336,371,
                     374..375)
                     /site_type="other"
                     /note="Ras interaction site [polypeptide binding]"
                     /db_xref="CDD:238087"
     Region          <421..478
                     /region_name="FRQ1"
                     /note="Ca2+-binding protein, EF-hand superfamily [Signal
                     transduction mechanisms]; COG5126"
                     /db_xref="CDD:444056"
     Region          488..546
                     /region_name="C1_RASGRP3"
                     /note="protein kinase C conserved region 1 (C1 domain)
                     found in RAS guanyl-releasing protein 3 (RASGRP3) and
                     similar proteins; cd20862"
                     /db_xref="CDD:410412"
     Site            order(500..506,514..518,521)
                     /site_type="other"
                     /note="putative DAG/PE binding site [chemical binding]"
                     /db_xref="CDD:410412"
     Region          667..690
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IV61.1)"
     CDS             1..690
                     /gene="RASGRP3"
                     /gene_synonym="GRP3"
                     /coded_by="NM_001139488.2:320..2392"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS46256.1"
                     /db_xref="GeneID:25780"
                     /db_xref="HGNC:HGNC:14545"
                     /db_xref="MIM:609531"
ORIGIN      
        1 mgssglgkaa tldellctci emfddngeld nsylprivll mhrwylsste laekllcmyr
       61 natgescnef rlkicyfmry wilkfpaefn ldlglirmte efrevasqlg yekhvslidi
      121 ssipsydwmr rvtqrkkvsk kgkacllfdh lepielaehl tflehksfrr isftdyqsyv
      181 ihgclennpt lersialfng iskwvqlmvl skptpqqrae vitkfinvak kllqlknfnt
      241 lmavvgglsh ssisrlketh shlssevtkn wnemtelvss ngnycnyrka fadcdgfkip
      301 ilgvhlkdli avhvifpdwt eenkvnivkm hqlsvtlsel vslqnashhl epnmdlinll
      361 tlsldlyhte ddiyklslvl eprnsksqpt spttpnkpvv plewalgvmp kpdptvinkh
      421 irklvesvfr nydhdhdgyi sqedfesiaa nfpfldsfcv ldkdqdglis kdemmayflr
      481 aksqlhckmg pgfihnfqem tylkptfceh cagflwgiik qgykckdcga nchkqckdll
      541 vlacrrfara pslssghgsl pgspslppaq devfefpgvt aghrdldsra itlvtgssrk
      601 isvrlqratt sqatqtepvw seagwgdsgs htfpkmkskf hdkaakdkgf akwenekprv
      661 hagvdvvdrg tefeldqdeg eetrqdgedg
//
