LOCUS       NM_004448               4557 bp    mRNA    linear   PRI 11-MAR-2025
DEFINITION  Homo sapiens erb-b2 receptor tyrosine kinase 2 (ERBB2), transcript
            variant 1, mRNA.
ACCESSION   NM_004448
VERSION     NM_004448.4
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 4557)
  AUTHORS   Phillips,J.B., Park,S.S., Lin,C.H., Cho,J., Lim,S., Aurora,R.,
            Kim,J.H., Angajala,A., Park,B., Stone,J.K., Wang,B., Kahn,A.G.,
            Lim,S.S., Kim,J.H., Ahn,E.E. and Tan,M.
  TITLE     SON is an essential RNA splicing factor promoting ErbB2 and ErbB3
            expression in breast cancer
  JOURNAL   Br J Cancer 131 (9), 1437-1449 (2024)
   PUBMED   39313574
  REMARK    GeneRIF: SON is an essential RNA splicing factor promoting ErbB2
            and ErbB3 expression in breast cancer.
REFERENCE   2  (bases 1 to 4557)
  AUTHORS   Liu,X., Song,Y., Cheng,P., Liang,B. and Xing,D.
  TITLE     Targeting HER2 in solid tumors: Unveiling the structure and novel
            epitopes
  JOURNAL   Cancer Treat Rev 130, 102826 (2024)
   PUBMED   39270365
  REMARK    GeneRIF: Targeting HER2 in solid tumors: Unveiling the structure
            and novel epitopes.
            Review article
REFERENCE   3  (bases 1 to 4557)
  AUTHORS   Saravani,S., Nemati Rezvani,H., Shahraki,M. and Kadeh,H.
  TITLE     A Comparison of Immunohistochemical Expression of Epidermal Growth
            Factor Receptor and Human Epidermal Growth Factor Receptor 2 in
            Dental Follicles with Different Radiographic Sizes
  JOURNAL   Iran J Med Sci 49 (8), 508-514 (2024)
   PUBMED   39205824
  REMARK    GeneRIF: A Comparison of Immunohistochemical Expression of
            Epidermal Growth Factor Receptor and Human Epidermal Growth Factor
            Receptor 2 in Dental Follicles with Different Radiographic Sizes.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4557)
  AUTHORS   Yang,H., Wang,X., Blanco-Gomez,A., He,L., Garcia-Sancha,N.,
            Corchado-Cobos,R., Perez-Baena,M.J., Jimenez-Navas,A., Wang,P.,
            Inman,J.L., Snijders,A.M., Threadgill,D.W., Balmain,A., Chang,H.,
            Perez-Losada,J. and Mao,J.H.
  TITLE     A susceptibility gene signature for ERBB2-driven mammary tumour
            development and metastasis in collaborative cross mice
  JOURNAL   EBioMedicine 106, 105260 (2024)
   PUBMED   39067134
  REMARK    GeneRIF: A susceptibility gene signature for ERBB2-driven mammary
            tumour development and metastasis in collaborative cross mice.
REFERENCE   5  (bases 1 to 4557)
  AUTHORS   Oh,D.Y. and Bang,Y.J.
  TITLE     HER2-targeted therapies - a role beyond breast cancer
  JOURNAL   Nat Rev Clin Oncol 17 (1), 33-48 (2020)
   PUBMED   31548601
  REMARK    Review article
REFERENCE   6  (bases 1 to 4557)
  AUTHORS   Child,S.J., Miller,M.K. and Geballe,A.P.
  TITLE     Translational control by an upstream open reading frame in the
            HER-2/neu transcript
  JOURNAL   J Biol Chem 274 (34), 24335-24341 (1999)
   PUBMED   10446211
REFERENCE   7  (bases 1 to 4557)
  AUTHORS   Child,S.J., Miller,M.K. and Geballe,A.P.
  TITLE     Cell type-dependent and -independent control of HER-2/neu
            translation
  JOURNAL   Int J Biochem Cell Biol 31 (1), 201-213 (1999)
   PUBMED   10216954
  REMARK    Erratum:[Int J Biochem Cell Biol 1999 Aug;31(8):883-4]
REFERENCE   8  (bases 1 to 4557)
  AUTHORS   Gout,I., Dhand,R., Panayotou,G., Fry,M.J., Hiles,I., Otsu,M. and
            Waterfield,M.D.
  TITLE     Expression and characterization of the p85 subunit of the
            phosphatidylinositol 3-kinase complex and a related p85 beta
            protein by using the baculovirus expression system
  JOURNAL   Biochem J 288 (Pt 2) (Pt 2), 395-405 (1992)
   PUBMED   1334406
REFERENCE   9  (bases 1 to 4557)
  AUTHORS   Peles,E., Lamprecht,R., Ben-Levy,R., Tzahar,E. and Yarden,Y.
  TITLE     Regulated coupling of the Neu receptor to phosphatidylinositol
            3'-kinase and its release by oncogenic activation
  JOURNAL   J Biol Chem 267 (17), 12266-12274 (1992)
   PUBMED   1351056
REFERENCE   10 (bases 1 to 4557)
  AUTHORS   Hall,J.M. and King,M.C.
  TITLE     PCR detection of an MboI polymorphism in the ERBB2 (HER2; NEU) gene
            on chromosome 17q11.2-q12
  JOURNAL   Nucleic Acids Res 19 (9), 2515 (1991)
   PUBMED   1675005
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC087491.5, BC167147.1 and
            AC079199.9.
            
            On May 18, 2020 this sequence version replaced NM_004448.3.
            
            Summary: This gene encodes a member of the epidermal growth factor
            (EGF) receptor family of receptor tyrosine kinases. This protein
            has no ligand binding domain of its own and therefore cannot bind
            growth factors. However, it does bind tightly to other ligand-bound
            EGF receptor family members to form a heterodimer, stabilizing
            ligand binding and enhancing kinase-mediated activation of
            downstream signalling pathways, such as those involving
            mitogen-activated protein kinase and phosphatidylinositol-3 kinase.
            Allelic variations at amino acid positions 654 and 655 of isoform a
            (positions 624 and 625 of isoform b) have been reported, with the
            most common allele, Ile654/Ile655, shown here. Amplification and/or
            overexpression of this gene has been reported in numerous cancers,
            including breast and ovarian tumors. Alternative splicing results
            in several additional transcript variants, some encoding different
            isoforms and others that have not been fully characterized.
            [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (a).
            
            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 :: X03363.1, M11730.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000269571.10/ ENSP00000269571.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            regulatory uORF        :: PMID: 10446211
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-172               AC087491.5         130663-130834
            173-3943            BC167147.1         1-3771
            3944-4557           AC079199.9         72504-73117
FEATURES             Location/Qualifiers
     source          1..4557
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q12"
     gene            1..4557
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /note="erb-b2 receptor tyrosine kinase 2"
                     /db_xref="GeneID:2064"
                     /db_xref="HGNC:HGNC:3430"
                     /db_xref="MIM:164870"
     exon            1..248
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      150..170
                     /regulatory_class="uORF"
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:10446211]"
                     /note="this uORF is predicted to encode a 6 aa peptide
                     (PMID:10446211)"
     CDS             176..3943
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /EC_number="2.7.10.1"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; herstatin; receptor tyrosine-protein kinase
                     erbB-2; neuroblastoma/glioblastoma derived oncogene
                     homolog; c-erb B2/neu protein; proto-oncogene Neu;
                     proto-oncogene c-ErbB-2; metastatic lymph node gene 19
                     protein; tyrosine kinase-type cell surface receptor HER2;
                     v-erb-b2 avian erythroblastic leukemia viral oncogene
                     homolog 2; v-erb-b2 erythroblastic leukemia viral oncogene
                     homolog 2, neuro/glioblastoma derived oncogene homolog;
                     v-erb-b2 avian erythroblastic leukemia viral oncoprotein
                     2; human epidermal growth factor receptor 2"
                     /codon_start=1
                     /product="receptor tyrosine-protein kinase erbB-2 isoform
                     a precursor"
                     /protein_id="NP_004439.2"
                     /db_xref="CCDS:CCDS32642.1"
                     /db_xref="GeneID:2064"
                     /db_xref="HGNC:HGNC:3430"
                     /db_xref="MIM:164870"
                     /translation="MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLD
                     MLRHLYQGCQVVQGNLELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIV
                     RGTQLFEDNYALAVLDNGDPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQ
                     LCYQDTILWKDIFHKNNQLALTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRT
                     VCAGGCARCKGPLPTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNT
                     DTFESMPNPEGRYTFGASCVTACPYNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKC
                     SKPCARVCYGLGMEHLREVRAVTSANIQEFAGCKKIFGSLAFLPESFDGDPASNTAPL
                     QPEQLQVFETLEEITGYLYISAWPDSLPDLSVFQNLQVIRGRILHNGAYSLTLQGLGI
                     SWLGLRSLRELGSGLALIHHNTHLCFVHTVPWDQLFRNPHQALLHTANRPEDECVGEG
                     LACHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPE
                     CQPQNGSVTCFGPEADQCVACAHYKDPPFCVARCPSGVKPDLSYMPIWKFPDEEGACQ
                     PCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKI
                     RKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWI
                     PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT
                     QLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSP
                     NHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWE
                     LMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL
                     VSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGF
                     FCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDG
                     DLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVR
                     PQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQGGAA
                     PQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV"
     exon            249..400
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            401..614
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            615..749
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            750..818
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            819..934
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            935..1076
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1077..1196
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1197..1323
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1324..1397
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1398..1488
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1489..1688
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1689..1821
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1822..1912
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            1913..2073
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2074..2121
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2122..2260
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2261..2383
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2384..2482
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2483..2668
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2669..2824
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2825..2900
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            2901..3047
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            3048..3145
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            3146..3334
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            3335..3587
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     exon            3588..4557
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4456..4461
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /note="hexamer: AATAAA"
     polyA_site      4476
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /note="major polyA site"
     regulatory      4540..4545
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
                     /note="hexamer: AATATA"
     polyA_site      4557
                     /gene="ERBB2"
                     /gene_synonym="c-ERB-2; c-ERB2; CD340; HER-2; HER-2/neu;
                     HER2; MLN 19; MLN-19; NEU; NGL; p185(erbB2); TKR1; VSCN2"
ORIGIN      
        1 cccctccatt gggaccggag aaaccagggg agccccccgg gcagccgcgc gccccttccc
       61 acggggccct ttactgcgcc gcgcgcccgg cccccacccc tcgcagcacc ccgcgccccg
      121 cgccctccca gccgggtcca gccggagcca tggggccgga gccgcagtga gcaccatgga
      181 gctggcggcc ttgtgccgct gggggctcct cctcgccctc ttgccccccg gagccgcgag
      241 cacccaagtg tgcaccggca cagacatgaa gctgcggctc cctgccagtc ccgagaccca
      301 cctggacatg ctccgccacc tctaccaggg ctgccaggtg gtgcagggaa acctggaact
      361 cacctacctg cccaccaatg ccagcctgtc cttcctgcag gatatccagg aggtgcaggg
      421 ctacgtgctc atcgctcaca accaagtgag gcaggtccca ctgcagaggc tgcggattgt
      481 gcgaggcacc cagctctttg aggacaacta tgccctggcc gtgctagaca atggagaccc
      541 gctgaacaat accacccctg tcacaggggc ctccccagga ggcctgcggg agctgcagct
      601 tcgaagcctc acagagatct tgaaaggagg ggtcttgatc cagcggaacc cccagctctg
      661 ctaccaggac acgattttgt ggaaggacat cttccacaag aacaaccagc tggctctcac
      721 actgatagac accaaccgct ctcgggcctg ccacccctgt tctccgatgt gtaagggctc
      781 ccgctgctgg ggagagagtt ctgaggattg tcagagcctg acgcgcactg tctgtgccgg
      841 tggctgtgcc cgctgcaagg ggccactgcc cactgactgc tgccatgagc agtgtgctgc
      901 cggctgcacg ggccccaagc actctgactg cctggcctgc ctccacttca accacagtgg
      961 catctgtgag ctgcactgcc cagccctggt cacctacaac acagacacgt ttgagtccat
     1021 gcccaatccc gagggccggt atacattcgg cgccagctgt gtgactgcct gtccctacaa
     1081 ctacctttct acggacgtgg gatcctgcac cctcgtctgc cccctgcaca accaagaggt
     1141 gacagcagag gatggaacac agcggtgtga gaagtgcagc aagccctgtg cccgagtgtg
     1201 ctatggtctg ggcatggagc acttgcgaga ggtgagggca gttaccagtg ccaatatcca
     1261 ggagtttgct ggctgcaaga agatctttgg gagcctggca tttctgccgg agagctttga
     1321 tggggaccca gcctccaaca ctgccccgct ccagccagag cagctccaag tgtttgagac
     1381 tctggaagag atcacaggtt acctatacat ctcagcatgg ccggacagcc tgcctgacct
     1441 cagcgtcttc cagaacctgc aagtaatccg gggacgaatt ctgcacaatg gcgcctactc
     1501 gctgaccctg caagggctgg gcatcagctg gctggggctg cgctcactga gggaactggg
     1561 cagtggactg gccctcatcc accataacac ccacctctgc ttcgtgcaca cggtgccctg
     1621 ggaccagctc tttcggaacc cgcaccaagc tctgctccac actgccaacc ggccagagga
     1681 cgagtgtgtg ggcgagggcc tggcctgcca ccagctgtgc gcccgagggc actgctgggg
     1741 tccagggccc acccagtgtg tcaactgcag ccagttcctt cggggccagg agtgcgtgga
     1801 ggaatgccga gtactgcagg ggctccccag ggagtatgtg aatgccaggc actgtttgcc
     1861 gtgccaccct gagtgtcagc cccagaatgg ctcagtgacc tgttttggac cggaggctga
     1921 ccagtgtgtg gcctgtgccc actataagga ccctcccttc tgcgtggccc gctgccccag
     1981 cggtgtgaaa cctgacctct cctacatgcc catctggaag tttccagatg aggagggcgc
     2041 atgccagcct tgccccatca actgcaccca ctcctgtgtg gacctggatg acaagggctg
     2101 ccccgccgag cagagagcca gccctctgac gtccatcatc tctgcggtgg ttggcattct
     2161 gctggtcgtg gtcttggggg tggtctttgg gatcctcatc aagcgacggc agcagaagat
     2221 ccggaagtac acgatgcgga gactgctgca ggaaacggag ctggtggagc cgctgacacc
     2281 tagcggagcg atgcccaacc aggcgcagat gcggatcctg aaagagacgg agctgaggaa
     2341 ggtgaaggtg cttggatctg gcgcttttgg cacagtctac aagggcatct ggatccctga
     2401 tggggagaat gtgaaaattc cagtggccat caaagtgttg agggaaaaca catcccccaa
     2461 agccaacaaa gaaatcttag acgaagcata cgtgatggct ggtgtgggct ccccatatgt
     2521 ctcccgcctt ctgggcatct gcctgacatc cacggtgcag ctggtgacac agcttatgcc
     2581 ctatggctgc ctcttagacc atgtccggga aaaccgcgga cgcctgggct cccaggacct
     2641 gctgaactgg tgtatgcaga ttgccaaggg gatgagctac ctggaggatg tgcggctcgt
     2701 acacagggac ttggccgctc ggaacgtgct ggtcaagagt cccaaccatg tcaaaattac
     2761 agacttcggg ctggctcggc tgctggacat tgacgagaca gagtaccatg cagatggggg
     2821 caaggtgccc atcaagtgga tggcgctgga gtccattctc cgccggcggt tcacccacca
     2881 gagtgatgtg tggagttatg gtgtgactgt gtgggagctg atgacttttg gggccaaacc
     2941 ttacgatggg atcccagccc gggagatccc tgacctgctg gaaaaggggg agcggctgcc
     3001 ccagcccccc atctgcacca ttgatgtcta catgatcatg gtcaaatgtt ggatgattga
     3061 ctctgaatgt cggccaagat tccgggagtt ggtgtctgaa ttctcccgca tggccaggga
     3121 cccccagcgc tttgtggtca tccagaatga ggacttgggc ccagccagtc ccttggacag
     3181 caccttctac cgctcactgc tggaggacga tgacatgggg gacctggtgg atgctgagga
     3241 gtatctggta ccccagcagg gcttcttctg tccagaccct gccccgggcg ctgggggcat
     3301 ggtccaccac aggcaccgca gctcatctac caggagtggc ggtggggacc tgacactagg
     3361 gctggagccc tctgaagagg aggcccccag gtctccactg gcaccctccg aaggggctgg
     3421 ctccgatgta tttgatggtg acctgggaat gggggcagcc aaggggctgc aaagcctccc
     3481 cacacatgac cccagccctc tacagcggta cagtgaggac cccacagtac ccctgccctc
     3541 tgagactgat ggctacgttg cccccctgac ctgcagcccc cagcctgaat atgtgaacca
     3601 gccagatgtt cggccccagc ccccttcgcc ccgagagggc cctctgcctg ctgcccgacc
     3661 tgctggtgcc actctggaaa ggcccaagac tctctcccca gggaagaatg gggtcgtcaa
     3721 agacgttttt gcctttgggg gtgccgtgga gaaccccgag tacttgacac cccagggagg
     3781 agctgcccct cagccccacc ctcctcctgc cttcagccca gccttcgaca acctctatta
     3841 ctgggaccag gacccaccag agcggggggc tccacccagc accttcaaag ggacacctac
     3901 ggcagagaac ccagagtacc tgggtctgga cgtgccagtg tgaaccagaa ggccaagtcc
     3961 gcagaagccc tgatgtgtcc tcagggagca gggaaggcct gacttctgct ggcatcaaga
     4021 ggtgggaggg ccctccgacc acttccaggg gaacctgcca tgccaggaac ctgtcctaag
     4081 gaaccttcct tcctgcttga gttcccagat ggctggaagg ggtccagcct cgttggaaga
     4141 ggaacagcac tggggagtct ttgtggattc tgaggccctg cccaatgaga ctctagggtc
     4201 cagtggatgc cacagcccag cttggccctt tccttccaga tcctgggtac tgaaagcctt
     4261 agggaagctg gcctgagagg ggaagcggcc ctaagggagt gtctaagaac aaaagcgacc
     4321 cattcagaga ctgtccctga aacctagtac tgccccccat gaggaaggaa cagcaatggt
     4381 gtcagtatcc aggctttgta cagagtgctt ttctgtttag tttttacttt ttttgttttg
     4441 tttttttaaa gatgaaataa agacccaggg ggagaatggg tgttgtatgg ggaggcaagt
     4501 gtggggggtc cttctccaca cccactttgt ccatttgcaa atatattttg gaaaaca
//
