LOCUS       NM_170604               3132 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens RAS guanyl releasing protein 4 (RASGRP4), transcript
            variant a, mRNA.
ACCESSION   NM_170604
VERSION     NM_170604.3
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  (bases 1 to 3132)
  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  (bases 1 to 3132)
  AUTHORS   Zhu,L., Xia,C., Wu,L., Zhang,Y., Liu,J., Chen,Y., Liu,J., Xiao,Y.,
            Nie,K., Huang,L., Qu,N. and Yu,H.
  TITLE     The critical role of RasGRP4 in the growth of diffuse large B cell
            lymphoma
  JOURNAL   Cell Commun Signal 17 (1), 92 (2019)
   PUBMED   31409422
  REMARK    GeneRIF: The findings indicate the oncogenic role of RasGRP4 in
            diffuse large B cell lymphoma (DLBCL), suggesting it as a
            prognostic biomarker and potential therapeutic target in DLBCL.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3132)
  AUTHORS   Kono,M., Yasuda,S., Stevens,R.L., Koide,H., Kurita,T., Shimizu,Y.,
            Kanetsuka,Y., Oku,K., Bohgaki,T., Amengual,O., Horita,T.,
            Shimizu,T., Majima,T., Koike,T. and Atsumi,T.
  TITLE     Ras guanine nucleotide-releasing protein 4 is aberrantly expressed
            in the fibroblast-like synoviocytes of patients with rheumatoid
            arthritis and controls their proliferation
  JOURNAL   Arthritis Rheumatol 67 (2), 396-407 (2015)
   PUBMED   25330932
  REMARK    GeneRIF: Ras guanine nucleotide-releasing protein 4 is aberrantly
            expressed in the fibroblast-like synoviocytes of patients with
            rheumatoid arthritis and controls their proliferation.
REFERENCE   4  (bases 1 to 3132)
  AUTHORS   Suire,S., Lecureuil,C., Anderson,K.E., Damoulakis,G., Niewczas,I.,
            Davidson,K., Guillou,H., Pan,D., Jonathan,Clark., Phillip,T.
            Hawkins and Stephens,L.
  TITLE     GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3
            and the RasGEF RasGRP4
  JOURNAL   EMBO J 31 (14), 3118-3129 (2012)
   PUBMED   22728827
  REMARK    GeneRIF: GPCR activation of Ras and PI3Kc in neutrophils depends on
            PLCb2/b3 and the RasGEF RasGRP4.
REFERENCE   5  (bases 1 to 3132)
  AUTHORS   Hashimoto,T., Yasuda,S., Koide,H., Kataoka,H., Horita,T., Atsumi,T.
            and Koike,T.
  TITLE     Aberrant splicing of the hRasGRP4 transcript and decreased levels
            of this signaling protein in the peripheral blood mononuclear cells
            in a subset of patients with rheumatoid arthritis
  JOURNAL   Arthritis Res Ther 13 (5), R154 (2011)
   PUBMED   21933395
  REMARK    GeneRIF: Identification of defective isoforms of hRasGRP4
            transcripts in rheumatoid arthritis(RA) patients raises the
            possibility that dysregulated expression of hRasGRP4 in developing
            monocytes plays a pathogenic role in this subset of RA patients.
REFERENCE   6  (bases 1 to 3132)
  AUTHORS   Watanabe-Okochi,N., Oki,T., Komeno,Y., Kato,N., Yuji,K., Ono,R.,
            Harada,Y., Harada,H., Hayashi,Y., Nakajima,H., Nosaka,T.,
            Kitaura,J. and Kitamura,T.
  TITLE     Possible involvement of RasGRP4 in leukemogenesis
  JOURNAL   Int J Hematol 89 (4), 470-481 (2009)
   PUBMED   19350351
  REMARK    GeneRIF: RasGRP4 cooperates with AML1 mutations in T cell
            leukemogenesis as a class I mutation
REFERENCE   7  (bases 1 to 3132)
  AUTHORS   Katsoulotos,G.P., Qi,M., Qi,J.C., Tanaka,K., Hughes,W.E.,
            Molloy,T.J., Adachi,R., Stevens,R.L. and Krilis,S.A.
  TITLE     The Diacylglycerol-dependent translocation of ras guanine
            nucleotide-releasing protein 4 inside a human mast cell line
            results in substantial phenotypic changes, including expression of
            interleukin 13 receptor alpha2
  JOURNAL   J Biol Chem 283 (3), 1610-1621 (2008)
   PUBMED   18024961
  REMARK    GeneRIF: RasGRP4 translocates to varied intracellular compartments
            via its DAG/PMA-binding domain to regulate signaling pathways that
            control gene and protein expression in MCs, including the cell's
            ability to respond to IL-13.
REFERENCE   8  (bases 1 to 3132)
  AUTHORS   Li,L., Yang,Y. and Stevens,R.L.
  TITLE     RasGRP4 regulates the expression of prostaglandin D2 in human and
            rat mast cell lines
  JOURNAL   J Biol Chem 278 (7), 4725-4729 (2003)
   PUBMED   12493770
  REMARK    GeneRIF: RasGRP4 regulates the expression of prostaglandin D2 in
            mast cells
REFERENCE   9  (bases 1 to 3132)
  AUTHORS   Reuther,G.W., Lambert,Q.T., Rebhun,J.F., Caligiuri,M.A.,
            Quilliam,L.A. and Der,C.J.
  TITLE     RasGRP4 is a novel Ras activator isolated from acute myeloid
            leukemia
  JOURNAL   J Biol Chem 277 (34), 30508-30514 (2002)
   PUBMED   11880369
  REMARK    GeneRIF: RasGRP4 plays a role in myeloid cell signaling growth
            regulation pathways that are responsive to diacylglycerol levels
REFERENCE   10 (bases 1 to 3132)
  AUTHORS   Yang,Y., Li,L., Wong,G.W., Krilis,S.A., Madhusudhan,M.S., Sali,A.
            and Stevens,R.L.
  TITLE     RasGRP4, a new mast cell-restricted Ras guanine
            nucleotide-releasing protein with calcium- and
            diacylglycerol-binding motifs. Identification of defective variants
            of this signaling protein in asthma, mastocytosis, and mast cell
            leukemia patients and demonstration of the importance of RasGRP4 in
            mast cell development and function
  JOURNAL   J Biol Chem 277 (28), 25756-25774 (2002)
   PUBMED   11956218
  REMARK    GeneRIF: identification of defective variants of this signaling
            protein in asthma, mastocytosis, and mast cell leukemia patients
            and demonstration of the importance of RasGRP4 in mast cell
            development and function
            GeneRIF: RasGRP4 is a cation-dependent, guanine nucleotide exchange
            factor and diacylglycerol/phorbol ester receptor that is
            selectively expressed in mast cells and their progenitors.  RasGRP4
            regulates the final stages of mast cell development.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY048119.1, AF448437.1,
            AC011469.6, AC005789.1 and BQ028385.1.
            
            On Nov 22, 2018 this sequence version replaced NM_170604.2.
            
            Summary: The protein encoded by this gene is a member of the Ras
            guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine
            nucleotide exchange factors. It contains a Ras exchange motif, a
            diacylglycerol-binding domain, and two calcium-binding EF hands.
            This protein was shown to activate H-Ras in a cation-dependent
            manner in vitro. Expression of this protein in myeloid cell lines
            was found to be correlated with elevated level of activated RAS
            protein, and the RAS activation can be greatly enhanced by phorbol
            ester treatment, which suggested a role of this protein in
            diacylglycerol regulated cell signaling pathways. Studies of a mast
            cell leukemia cell line expressing substantial amounts of abnormal
            transcripts of this gene indicated that this gene may play an
            important role in the final stages of mast cell development.
            Multiple transcript variants encoding different isoforms have been
            found for this gene. [provided by RefSeq, Apr 2009].
            
            Transcript Variant: This variant (a) represents the longest
            transcript and encodes the longest isoform (a).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data because no single transcript was available
            for the full length of the gene. The extent of this transcript is
            supported by transcript alignments.
            
            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 :: AF448437.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000615439.5/ ENSP00000479844.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-57                AY048119.1         87-143
            58-180              AF448437.1         1-123
            181-181             AC011469.6         8360-8360           c
            182-1162            AF448437.1         125-1105
            1163-1163           AC011469.6         1279-1279           c
            1164-2350           AF448437.1         1107-2293
            2351-3002           AC005789.1         43679-44330         c
            3003-3132           BQ028385.1         18-147              c
FEATURES             Location/Qualifiers
     source          1..3132
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.2"
     gene            1..3132
                     /gene="RASGRP4"
                     /note="RAS guanyl releasing protein 4"
                     /db_xref="GeneID:115727"
                     /db_xref="HGNC:HGNC:18958"
                     /db_xref="MIM:607320"
     exon            1..151
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     CDS             129..2150
                     /gene="RASGRP4"
                     /note="isoform a is encoded by transcript variant a;
                     guanyl nucleotide releasing protein 4"
                     /codon_start=1
                     /product="RAS guanyl-releasing protein 4 isoform a"
                     /protein_id="NP_733749.1"
                     /db_xref="CCDS:CCDS46068.1"
                     /db_xref="GeneID:115727"
                     /db_xref="HGNC:HGNC:18958"
                     /db_xref="MIM:607320"
                     /translation="MNRKDSKRKSHQECTGKIGGRGRPRQVRRHKTCPSPREISKVMA
                     SMNLGLLSEGGCSEDELLEKCIQSFDSAGSLCHEDHMLNMVLAMHSWVLPSADLAARL
                     LTSYQKATGDTQELRRLQICHLVRYWLMRHPEVMHQDPQLEEVIGRFWATVAREGNSA
                     QRRLGDSSDLLSPGGPGPPLPMSSPGLGKKRKVSLLFDHLETGELAQHLTYLEFRSFQ
                     AITPQDLRSYVLQGSVRGCPALEGSVGLSNSVSRWVQVMVLSRPGPLQRAQVLDKFIH
                     VAQRLHQLQNFNTLMAVTGGLCHSAISRLKDSHAHLSPDSTKALLELTELLASHNNYA
                     RYRRTWAGCAGFRLPVLGVHLKDLVSLHEAQPDRLPDGRLHLPKLNNLYLRLQELVAL
                     QGQHPPCSANEDLLHLLTLSLDLFYTEDEIYELSYAREPRCPKSLPPSPFNAPLVVEW
                     APGVTPKPDRVTLGRHVEQLVESVFKNYDPEGRGTISQEDFERLSGNFPFACHGLHPP
                     PRQGRGSFSREELTGYLLRASAICSKLGLAFLHTFHEVTFRKPTFCDSCSGFLWGVTK
                     QGYRCRECGLCCHKHCRDQVKVECKKRPGAKGDAGPPGAPVPSTPAPHASCGSEENHS
                     YTLSLEPETGCQLRHAWTQTESPHPSWETDTVPCPVMDPPSTASSKLDS"
     exon            152..336
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            337..442
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            443..505
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            506..637
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            638..791
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            792..965
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            966..1082
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1083..1358
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1359..1439
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1440..1544
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1545..1663
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1664..1808
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1809..1845
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1846..1980
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            1981..2093
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     exon            2094..3132
                     /gene="RASGRP4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3114..3119
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RASGRP4"
                     /note="hexamer: ATTAAA"
     polyA_site      3132
                     /gene="RASGRP4"
                     /note="major polyA site"
ORIGIN      
        1 ctctttcctt cccaagcacc gaggaggccc cagctcccta ggggctgaga agctggagtc
       61 ctgggcaagg ggaggagctg agccctactc ttgcaagacc cccggcctcc tcaccccacg
      121 cgggaagcat gaacagaaaa gacagtaaga ggaagtccca ccaggaatgc accggaaaaa
      181 taggagggcg aggccggccc cgccaagtgc gccgccacaa gacatgcccc agccctcggg
      241 aaatcagcaa ggtcatggct tccatgaacc tgggcctgct gagtgagggc ggctgcagcg
      301 aagatgagct gctggagaaa tgcatccagt ccttcgattc agctggcagc ctgtgccacg
      361 aggaccacat gctcaacatg gtgctggcca tgcacagctg ggtgctgccg tccgccgacc
      421 tggctgcccg cctgctgacc tcataccaga aggccacagg ggacacccag gagctgagac
      481 ggctgcagat ctgtcacctg gtcaggtact ggctgatgcg acaccctgag gtgatgcacc
      541 aggatcccca gctagaagaa gtcataggtc gtttctgggc caccgtggcc cgggagggca
      601 actcagccca gagaagactg ggagactctt ctgacctcct gagccctggt ggccctggcc
      661 ccccactccc aatgagcagc ccaggcctgg gcaaaaagcg caaagtgtcc ttgcttttcg
      721 accacttgga gacgggggag ctggctcagc acctcaccta cctggagttc cggtccttcc
      781 aggctatcac gccccaggac ctgcggagct acgttttgca gggctcagta cgaggctgcc
      841 cggccctgga gggctccgta ggtctcagca acagcgtgtc ccgctgggtg caggtgatgg
      901 tgctgagccg tcccgggccc ctacagcgtg cacaggtgct ggacaagttc attcacgtgg
      961 cacagaggct ccaccagctg cagaatttca acacgctgat ggcagtcaca gggggcctgt
     1021 gtcacagtgc catctccaga ctcaaggact cccatgccca cctgagccct gacagcacca
     1081 aggccctcct ggagctcact gagctccttg cctcccacaa caactacgcc cgctaccgcc
     1141 gcacctgggc tggctgcgcg ggtttccggc tgcctgtact gggcgtgcac ctcaaggacc
     1201 tggtgtccct gcatgaggca cagcccgaca ggttgcctga cggccgcctg cacctaccca
     1261 agctgaacaa cctctacctg cggctgcagg agctggtggc cctccaaggg cagcatccac
     1321 cctgcagcgc caatgaggat ctgctgcacc tgctcacgct ctccctggac ctcttctaca
     1381 cggaagacga gatctatgag ctttcttatg cccgggagcc gcgttgtccc aagagcctgc
     1441 caccctcccc cttcaatgca cctctggtgg tggagtgggc ccctggtgtg acacccaagc
     1501 cggacagggt cacactgggt cggcatgtgg agcagctggt ggagtctgtg ttcaagaatt
     1561 atgaccctga aggccgagga acaatctctc aggaggactt tgagcgactc tcgggcaatt
     1621 ttcccttcgc ctgccatggg cttcacccac ccccacgcca ggggagagga tccttcagca
     1681 gagaggagct gacagggtac ctgctccggg ccagcgccat ctgctccaag ttgggcctgg
     1741 ccttcctgca caccttccat gaggtcacct tccgaaagcc taccttctgc gacagctgca
     1801 gtggcttcct ctggggtgtc accaagcaag gctaccgctg tcgggagtgc gggctgtgtt
     1861 gccacaaaca ctgcagagac caggtgaagg tagaatgtaa gaagaggcca ggggccaagg
     1921 gcgatgcagg accccccgga gctcctgtcc catccacacc agctccccat gccagctgtg
     1981 gctccgagga aaatcactcc tacacgctat ccctggagcc tgagactggg tgccagcttc
     2041 gccatgcctg gacccagact gaatccccac acccttcctg ggaaacagat acggtcccct
     2101 gcccggtgat ggacccacca tcaactgcat cctccaagct ggattcctag acatctcttg
     2161 gtctcctctc ttcctcactc ccttccccca gtcagtcctg agtcctgccg tcagactctg
     2221 gcagggctcc cagaggtagg cctccagagg catccgcctt cccatccaca ctgcctttag
     2281 tggtacgtcc gtcatctttt tccctggaag tgactttcct cttttgcatc ctggtggatg
     2341 ctaatcctgc tccctttccc tgcacttagt atctgtgcgg ctgtgtgttg gatacattta
     2401 gactcaggcc tcattctacc aactccctac atctccattt cttttttttt ttgagacaga
     2461 gtcttgctct gtcacccagg ctggagtgca atgatgcaat ctcagctcac tgcaacttcc
     2521 gcctcctggg ttcaagtgat tcttctgcct cagcctccca agtagctggg attacaggca
     2581 cgcgccacca tgcccggcta atttttgtat ttttagtaga gacggggttt ccccatgttg
     2641 gccaagatgg tctcaaactc ctgacctcat gatccaccag cctcagcctc ccaaagtgct
     2701 gggaatacag gcgtgagcca ccacgcccag ctcctgtttt tctgcataga atgtgctccc
     2761 tctgacagcc tatacttttt ccctctttat ctcgttgaac gtctgtcttt cctcaacagg
     2821 agcatcaact ccaggagaac agggatttct atcaatgtca ttcactgctg catccccagt
     2881 gcctagaaca gggctggcag gtggtaggcg cctgacagat gcttgtctga tgcctgaatg
     2941 tctccttacc catgcccacg gcacaggata gatgtgctat agggcaaaga actttgaggg
     3001 tcgagcagca ggggcccatt cagtcccagg gagcagagac ccccccaacc ccttcacaaa
     3061 ccccaacacc cctgacttgg cccccacaga gagaggtcct acagctgtca taaattaaat
     3121 ttattctctg ga
//
