LOCUS       NM_005475               5431 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens SH2B adaptor protein 3 (SH2B3), transcript variant 1,
            mRNA.
ACCESSION   NM_005475
VERSION     NM_005475.3
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 5431)
  AUTHORS   Wintering,A., Hecht,A., Meyer,J., Wong,E.B., Hubner,J., Abelson,S.,
            Feldman,K., Kennedy,V.E., Peretz,C.A.C., French,D.L., Maguire,J.A.,
            Jobaliya,C., Vasquez,M.R., Desai,S., Dulman,R., Nemecek,E.,
            Haines,H., Hammad,M., El Haddad,A., Kogan,S.C., Abdullaev,Z.,
            Chehab,F.F., Tasian,S.K., Smith,C.C., Loh,M.L. and Stieglitz,E.
  TITLE     LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia
  JOURNAL   Haematologica 109 (8), 2533-2541 (2024)
   PUBMED   38152053
  REMARK    GeneRIF: LNK/SH2B3 as a novel driver in juvenile myelomonocytic
            leukemia.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5431)
  AUTHORS   Arfeuille,C., Vial,Y., Cadenet,M., Caye-Eude,A., Fenneteau,O.,
            Neven,Q., Bonnard,A.A., Pizzi,S., Carpentieri,G., Capri,Y.,
            Girardi,K., Pedace,L., Macchiaiolo,M., Boudhar,K., Khaled,M.B.,
            Chahla,W.A., Lutun,A., Fahd,M., Drunat,S., Flex,E., Dalle,J.H.,
            Strullu,M., Locatelli,F., Tartaglia,M. and Cave,H.
  TITLE     Germline bi-allelic SH2B3/LNK alteration predisposes to a neonatal
            juvenile myelomonocytic leukemia-like disorder
  JOURNAL   Haematologica 109 (8), 2542-2554 (2024)
   PUBMED   37981895
  REMARK    GeneRIF: Germline bi-allelic SH2B3/LNK alteration predisposes to a
            neonatal juvenile myelomonocytic leukemia-like disorder.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5431)
  AUTHORS   Murphy,M.B., Yang,Z., Subati,T., Farber-Eger,E., Kim,K.,
            Blackwell,D.J., Fleming,M.R., Stark,J.M., Van Amburg,J.C.,
            Woodall,K.K., Van Beusecum,J.P., Agrawal,V., Smart,C.D., Pitzer,A.,
            Atkinson,J.B., Fogo,A.B., Bastarache,J.A., Kirabo,A., Wells,Q.S.,
            Madhur,M.S., Barnett,J.V. and Murray,K.T.
  TITLE     LNK/SH2B3 loss of function increases susceptibility to murine and
            human atrial fibrillation
  JOURNAL   Cardiovasc Res 120 (8), 899-913 (2024)
   PUBMED   38377486
  REMARK    GeneRIF: LNK/SH2B3 loss of function increases susceptibility to
            murine and human atrial fibrillation.
REFERENCE   4  (bases 1 to 5431)
  AUTHORS   Tae,I.H., Ryu,T.Y., Kang,Y., Lee,J., Kim,K., Lee,J.M., Kim,H.W.,
            Ko,J.H., Kim,D.S., Son,M.Y. and Cho,H.S.
  TITLE     Negative regulation of SH2B3 by SMYD5 controls
            epithelial-mesenchymal transition in lung cancer
  JOURNAL   Mol Cells 47 (5), 100067 (2024)
   PUBMED   38723947
  REMARK    GeneRIF: Negative regulation of SH2B3 by SMYD5 controls
            epithelial-mesenchymal transition in lung cancer.
REFERENCE   5  (bases 1 to 5431)
  AUTHORS   Zhang,Y., Morris,R., Brown,G.J., Lorenzo,A.M.D., Meng,X.,
            Kershaw,N.J., Kiridena,P., Burgio,G., Gross,S., Cappello,J.Y.,
            Shen,Q., Wang,H., Turnbull,C., Lea-Henry,T., Stanley,M., Yu,Z.,
            Ballard,F.D., Chuah,A., Lee,J.C., Hatch,A.M., Enders,A.,
            Masters,S.L., Headley,A.P., Trnka,P., Mallon,D., Fletcher,J.T.,
            Walters,G.D., Sestan,M., Jelusic,M., Cook,M.C., Athanasopoulos,V.,
            Fulcher,D.A., Babon,J.J., Vinuesa,C.G. and Ellyard,J.I.
  TITLE     Rare SH2B3 coding variants in lupus patients impair B cell
            tolerance and predispose to autoimmunity
  JOURNAL   J Exp Med 221 (4) (2024)
   PUBMED   38417019
  REMARK    GeneRIF: Rare SH2B3 coding variants in lupus patients impair B cell
            tolerance and predispose to autoimmunity.
REFERENCE   6  (bases 1 to 5431)
  AUTHORS   Takaki,S., Morita,H., Tezuka,Y. and Takatsu,K.
  TITLE     Enhanced hematopoiesis by hematopoietic progenitor cells lacking
            intracellular adaptor protein, Lnk
  JOURNAL   J Exp Med 195 (2), 151-160 (2002)
   PUBMED   11805142
  REMARK    Erratum:[J Exp Med 2002 May 6;195(9):1229]
REFERENCE   7  (bases 1 to 5431)
  AUTHORS   He,X., Li,Y., Schembri-King,J., Jakes,S. and Hayashi,J.
  TITLE     Identification of actin binding protein, ABP-280, as a binding
            partner of human Lnk adaptor protein
  JOURNAL   Mol Immunol 37 (10), 603-612 (2000)
   PUBMED   11163396
REFERENCE   8  (bases 1 to 5431)
  AUTHORS   Li,Y., He,X., Schembri-King,J., Jakes,S. and Hayashi,J.
  TITLE     Cloning and characterization of human Lnk, an adaptor protein with
            pleckstrin homology and Src homology 2 domains that can inhibit T
            cell activation
  JOURNAL   J Immunol 164 (10), 5199-5206 (2000)
   PUBMED   10799879
REFERENCE   9  (bases 1 to 5431)
  AUTHORS   Takaki,S., Watts,J.D., Forbush,K.A., Nguyen,N.T., Hayashi,J.,
            Alberola-Ila,J., Aebersold,R. and Perlmutter,R.M.
  TITLE     Characterization of Lnk. An adaptor protein expressed in
            lymphocytes
  JOURNAL   J Biol Chem 272 (23), 14562-14570 (1997)
   PUBMED   9169414
REFERENCE   10 (bases 1 to 5431)
  AUTHORS   Motto,D.G., Musci,M.A., Ross,S.E. and Koretzky,G.A.
  TITLE     Tyrosine phosphorylation of Grb2-associated proteins correlates
            with phospholipase C gamma 1 activation in T cells
  JOURNAL   Mol Cell Biol 16 (6), 2823-2829 (1996)
   PUBMED   8649391
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC005805.12, AF055581.1 and
            AB208911.1.
            
            On Aug 31, 2019 this sequence version replaced NM_005475.2.
            
            Summary: This gene encodes a member of the SH2B adaptor family of
            proteins, which are involved in a range of signaling activities by
            growth factor and cytokine receptors. The encoded protein is a key
            negative regulator of cytokine signaling and plays a critical role
            in hematopoiesis. Mutations in this gene have been associated with
            susceptibility to celiac disease type 13 and susceptibility to
            insulin-dependent diabetes mellitus. Alternatively spliced
            transcript variants encoding different isoforms have been found for
            this gene. [provided by RefSeq, Apr 2014].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer 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 :: AF055581.1, SRR14038193.1417449.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1970526
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000341259.7/ ENSP00000345492.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-25                AC005805.12        99107-99131
            26-2952             AF055581.1         1-2927
            2953-3753           AB208911.1         2164-2964
            3754-5430           AB208911.1         2966-4642
            5431-5431           AF055581.1         5404-5404
FEATURES             Location/Qualifiers
     source          1..5431
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.12"
     gene            1..5431
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /note="SH2B adaptor protein 3"
                     /db_xref="GeneID:10019"
                     /db_xref="HGNC:HGNC:29605"
                     /db_xref="MIM:605093"
     exon            1..355
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            356..1114
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     CDS             383..2110
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /note="isoform 1 is encoded by transcript variant 1;
                     signal transduction protein Lnk; lymphocyte-specific
                     adapter protein Lnk"
                     /codon_start=1
                     /product="SH2B adapter protein 3 isoform 1"
                     /protein_id="NP_005466.1"
                     /db_xref="CCDS:CCDS9153.1"
                     /db_xref="GeneID:10019"
                     /db_xref="HGNC:HGNC:29605"
                     /db_xref="MIM:605093"
                     /translation="MNGPALQPSSPSSAPSASPAAAPRGWSEFCELHAVAAARELARQ
                     YWLFAREHPQHAPLRAELVSLQFTDLFQRYFCREVRDGRAPGRDYRDTGRGPPAKAEA
                     SPEPGPGPAAPGLPKARSSEELAPPRPPGPCSFQHFRRSLRHIFRRRSAGELPAAHTA
                     AAPGTPGEAAETPARPGLAKKFLPWSLAREPPPEALKEAVLRYSLADEASMDSGARWQ
                     RGRLALRRAPGPDGPDRVLELFDPPKSSRPKLQAACSSIQEVRWCTRLEMPDNLYTFV
                     LKVKDRTDIIFEVGDEQQLNSWMAELSECTGRGLESTEAEMHIPSALEPSTSSSPRGS
                     TDSLNQGASPGGLLDPACQKTDHFLSCYPWFHGPISRVKAAQLVQLQGPDAHGVFLVR
                     QSETRRGEYVLTFNFQGIAKHLRLSLTERGQCRVQHLHFPSVVDMLHHFQRSPIPLEC
                     GAACDVRLSSYVVVVSQPPGSCNTVLFPFSLPHWDSESLPHWGSELGLPHLSSSGCPR
                     GLSPEGLPGRSSPPEQIFHLVPSPEELANSLQHLEHEPVNRARDSDYEMDSSSRSHLR
                     AIDNQYTPL"
     exon            1115..1216
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1217..1308
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1309..1403
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1404..1618
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1619..1790
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     exon            1791..5431
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5408..5413
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /note="hexamer: ATTAAA"
     polyA_site      5431
                     /gene="SH2B3"
                     /gene_synonym="IDDM20; LNK"
                     /note="major polyA site"
ORIGIN      
        1 acataacggc gcggggcggc atgggcccgg gccaccgcct ccgcccggct gcccgcccgg
       61 actgtcgcgg cccgcggtgg cgacggcggc cgctgcaaag tttccccggc ggcggcggcc
      121 cgggggcgca tcctcccgca actgtcaagc gctggcggcg gaaatgatga ggcgctggcc
      181 attttccgag cccgggtttc ctgcctgagc cccgctcgag cgagccgcga gcgaggagcc
      241 ggcgggcggg agaggacgcg cccagggcgg gggcccgccc gccccctcgg gatttcgagg
      301 gcccgggggc gcgcgacgcc atgggccggc cgggcccaga gctcctgtct ctcagcccgg
      361 ccgcaccacc tgggtctccg ccatgaacgg gcctgccctg cagccctcct cgccctcttc
      421 cgcgccctca gcctccccgg cggcggcccc gcggggctgg agcgagttct gtgagttgca
      481 cgccgtagcg gcggcccggg agctggcccg ccagtactgg ctgttcgccc gggagcatcc
      541 gcagcacgcg ccgctgcgcg ccgagctggt gtcgctgcag ttcaccgacc tcttccagcg
      601 ctacttctgc cgcgaggtgc gcgacggacg ggcgccgggc cgcgactacc gggacacagg
      661 ccgtgggccc ccagccaagg ccgaggcgtc cccggagcca ggccccggcc ccgccgcccc
      721 tggcctgccc aaggcccgca gctctgagga gctggccccg ccgcggccgc ccgggccctg
      781 ctccttccag cactttcgcc gcagcctccg ccacatcttc cgccgccgct cggccgggga
      841 gctgccagcg gcccacaccg ctgccgcccc cgggaccccc ggagaggctg ctgagacccc
      901 cgcccggcct ggcctggcca agaagttcct gccctggagc ctggcccggg agccgccacc
      961 cgaggcgctg aaggaggcgg tgctgcgcta cagcctggcc gacgaggcct ccatggacag
     1021 cggggcacgc tggcagcgcg ggaggctggc gctgcgccgg gccccgggcc ccgatggccc
     1081 cgaccgcgtg ctggagctct tcgacccacc caagagttca aggcccaagc tacaagcagc
     1141 ttgctccagc atccaggagg tccggtggtg cacacggctt gagatgcctg acaaccttta
     1201 cacctttgtg ctgaaggtga aggaccggac agacatcatc tttgaggtgg gagacgagca
     1261 gcagctgaat tcatggatgg ctgagctctc ggagtgcaca ggccgagggc tggagagcac
     1321 agaagcagag atgcatattc cctcagccct agagcctagc acgtccagct ccccaagggg
     1381 cagcacagat tcccttaacc aaggtgcttc tcctgggggg ctgctggacc cggcctgcca
     1441 gaagacggac catttcctgt cctgctaccc ctggttccac ggccccatct ccagagtgaa
     1501 agcagctcag ctggttcagc tgcagggccc tgatgctcat ggagtgttcc tggtgcggca
     1561 gagcgagacg cggcgtgggg aatacgtgct cactttcaac tttcagggga tagccaagca
     1621 cctgcgcctg tcgctgacag agcggggcca gtgccgtgtg cagcacctcc actttccctc
     1681 ggtcgtggac atgctccacc acttccagcg ctcgcccatc ccactcgagt gcggcgccgc
     1741 ctgtgatgtc cggctctcca gctacgtggt agtcgtctcc caaccaccag gttcctgcaa
     1801 cacggtcctc ttccctttct cccttcctca ctgggattca gagtcccttc ctcactgggg
     1861 ttcagagttg ggccttcccc accttagttc ttctggctgt ccccgggggc tcagcccaga
     1921 gggtctccca gggcgatcct caccccccga gcagatcttc cacctggtgc cttcgcccga
     1981 agaactggcc aacagcctgc agcacctgga gcatgagcct gtgaatcgag cccgggactc
     2041 ggactacgaa atggactcat cctcccggag ccacctgcgg gccatagaca atcagtacac
     2101 acctctctga ccagtgagga attccaggcc tcaacagctg cccttgagga gcacaggcag
     2161 aagtgtgaac ttgtgaatgt aattgatctt tccttccttc cagagaaaga tttaagggac
     2221 actgttaact gctcgtgcca gtttggaagt gacccttcta ttaggcctgt tgaagggccc
     2281 tcctgtaggt ttcatctatc cacctggctt tctccttatt gtttacagat gtagttcttg
     2341 ttagaggatg ccgctagctc ctgcccgggg tccctatgcc cagtccccgt tactcttaga
     2401 gaaaggagtt ggggtgaggg ccagagctgg cagtggaaac ttgttctctt tttcactgac
     2461 actgtcacag cggatgacag actttctacg gggaggaggg ggggatcatc aggaagccca
     2521 gaacactaac aagcggttct cccatctacc gtcagtccac atggcaggtc tgctgtgtcc
     2581 acaccacaga tgaccacatc taatcctgct tctactctca gctttaggac aaaagctctg
     2641 tcagaggcac aagctgaagg tcaaaaatga tttaaaacat tttacctcag actaatttct
     2701 ttaaaggatt caggttcaaa acttaaccac tgcttatttc agtgcactgt ttcaactaac
     2761 acccatgcta tttttgtagt cagaaacagc tatgcaaacc ctacctaatt tacagtctga
     2821 gccagcatgc tggcttgtct actgcatcct cgggacagtc acctgccact gagtggccac
     2881 tgtccttcct aaatgtcaag aagtgaagta tgtcaccctt tcagggaaat tcaggcaatt
     2941 actgaaatag gagggtggca agaacagttc tatcctggtg ccttacgaat aaaaaactgg
     3001 attctggttt acagcagctt tacagtgata gttaaattaa ctggggctag gggaagagca
     3061 agcaaaaagg gaagaaggac tcctaggccc tttctagtaa atccttcagc aacaaggctg
     3121 gcttggtgcc ctccaagcat ctaatggctt attaaattat cccacaagtg ggttttaggc
     3181 tccttttttg agccaaaatg gaagctggga atctggtgcc ataactaatg agaaactcct
     3241 ttaatagccc acaatcagtg ttctgttcta gctggctact gcttcactgg attgagaatc
     3301 tatctatctc cttgcacaca tgggcacaca caatctccac catccaggga ggtcctgaag
     3361 tcaaatctct atctatacaa gtgatacaat tcataggggg ctggctcctc ccagaacctg
     3421 tctggaggct cagaaacggg ggcagtgaca gtggagtcag ctgctcttgg gtgccagcag
     3481 agccattcag tacaaccccc aggctcacag cagtggcttc taggaaactg ggagtttaga
     3541 tcagctttac agatacatcg atcagaggct aaaatgaaac ctcagcctaa aactcatagg
     3601 actgactgcc tgggaggagg gttaggtctg cttcttccac ttatacttag tctctgtgct
     3661 ccaagaggtc aaatttttgc ttctagaatt tccttggggt ctttcagagg gtgggggaac
     3721 aaacccctat gcacttttct tttttttttt tttgagatgg agtttctctt gtcaaccggg
     3781 ctggagtgca gtggtgcaat cttggctcac tgcaacctcc accttcctgg ttcaagcgat
     3841 tctgcctcga cctctcaagt agctgggatt acaagcacca gccaccatgc ctggctaatt
     3901 ttgtattttt agtagagaca gggtttcacc atgttggcca ggctggtctc gaatgtctga
     3961 cctcaggtga tccacccgcc ttggcctccc aaagtgctgg gattacaggc gcgagccacc
     4021 gcgcccagcc tacaccactt ttagtaccaa cactcttggg tgatttcatg gaccctaaag
     4081 cagacctgac actgatccag atttgcagtc catttttaag gacacctgtc tttatttcct
     4141 caaagtcaag cagctttctc tggaaaatga atgctaatta gtgtgaacca aaagagtaag
     4201 taagagtctg aagttttttt aaaggagaaa gcttattatg gaaagtcact ggtcctcccc
     4261 tccgcacagg aaaggtaccc agtagataat gaaccaaatt aagttccctc cctccagcca
     4321 gaagttaaac atctgggata tgacgtcttc atgccagggg cactcatttc ttagcagcct
     4381 ctctacatac atctctcagg tggtgccaag aggcacacca ggtagagcaa acttagcagc
     4441 tctgactaac aggctgcaaa gtgcaagttc agattctgtg gcagagattt ggaaggcacc
     4501 cacctccaga ctgcttcccg tccaagttac caggacagct caaaaacatg ctgacagaaa
     4561 actcccatgg ctctaggaag aagtgacact aagccaacac ctttctttat gtgggagcag
     4621 aatcagctga tgaaggggtg ggcagcagtg tggggcaggc accccactgg ctgcagctag
     4681 cccaccatag gcacagcaca tcccaccact ctccttccag tcctgaccag gccccagccg
     4741 gcaacttcta ccgagagcca tggctcaaca ccaaactgga cagtagacat catgatccct
     4801 ccagttagct ctaattacag accccaccag tacagcttga cagctcccgg caccatccct
     4861 tccttcatct gacttattga acttttacaa actaacagtc accagcacca aagaattaag
     4921 tcaactaacc tgccttgaat tttagaccag caatccatat ggctttatct ggtataaatc
     4981 ttctgccttt gatcatttct ggaccgtagg aaaaaggaat agcaatcatt aaaatcttgg
     5041 gccagagaac actattttta cataacagtt tcttaaccta aagtcaaggc cttggactct
     5101 tccctgaggg ttgcctgaga ttccttcatg ctttctattc aggactaagt cccttactgc
     5161 aaatgtgtta gctctaacat ctcccacaag ctagaggaac ttgcgagtat attaacaagg
     5221 acacatctga catcctgtgt ttggttagaa tatacagcac attgtgataa cataaagtgg
     5281 attcatcttg tatcattata ggcagaaggt atttggcaaa tttttatgta ttgttttatg
     5341 tactgtacaa gtaacttatt cttgaataat gcaaattttg ctataatgta caaattgcta
     5401 tatgtgaatt aaaaagtttt cagaatcttg a
//
