LOCUS       NM_005982               2687 bp    mRNA    linear   PRI 16-JUN-2013
DEFINITION  Homo sapiens SIX homeobox 1 (SIX1), mRNA.
ACCESSION   NM_005982
VERSION     NM_005982.3  GI:186928837
KEYWORDS    RefSeq.
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 2687)
  AUTHORS   Patrick,A.N., Cabrera,J.H., Smith,A.L., Chen,X.S., Ford,H.L. and
            Zhao,R.
  TITLE     Structure-function analyses of the human SIX1-EYA2 complex reveal
            insights into metastasis and BOR syndrome
  JOURNAL   Nat. Struct. Mol. Biol. 20 (4), 447-453 (2013)
   PUBMED   23435380
  REMARK    GeneRIF: Given that SIX1 and EYA are overexpressed in many tumor
            types, our data indicate that targeting the SIX1-EYA complex may be
            a potent approach to inhibit tumor progression in multiple cancer
            types
REFERENCE   2  (bases 1 to 2687)
  AUTHORS   Dimasi,D.P., Burdon,K.P., Hewitt,A.W., Fitzgerald,J., Wang,J.J.,
            Healey,P.R., Mitchell,P., Mackey,D.A. and Craig,J.E.
  TITLE     Genetic investigation into the endophenotypic status of central
            corneal thickness and optic disc parameters in relation to
            open-angle glaucoma
  JOURNAL   Am. J. Ophthalmol. 154 (5), 833-842 (2012)
   PUBMED   22840486
  REMARK    GeneRIF: The identification of SIX1 and CDKN2B variant was found to
            be associated more strongly with advanced open-angle glaucoma.
REFERENCE   3  (bases 1 to 2687)
  AUTHORS   Wang,C.A., Jedlicka,P., Patrick,A.N., Micalizzi,D.S., Lemmer,K.C.,
            Deitsch,E., Casas-Selves,M., Harrell,J.C. and Ford,H.L.
  TITLE     SIX1 induces lymphangiogenesis and metastasis via upregulation of
            VEGF-C in mouse models of breast cancer
  JOURNAL   J. Clin. Invest. 122 (5), 1895-1906 (2012)
   PUBMED   22466647
  REMARK    GeneRIF: A critical role for SIX1 in lymphatic dissemination of
            breast cancer cells, providing a direct mechanistic explanation for
            how VEGF-C expression is upregulated in breast cancer.
REFERENCE   4  (bases 1 to 2687)
  AUTHORS   Wang,S.H., Wu,C.C., Lu,Y.C., Lin,Y.H., Su,Y.N., Hwu,W.L., Yu,I.S.
            and Hsu,C.J.
  TITLE     Mutation screening of the EYA1, SIX1, and SIX5 genes in an East
            Asian cohort with branchio-oto-renal syndrome
  JOURNAL   Laryngoscope 122 (5), 1130-1136 (2012)
   PUBMED   22447252
  REMARK    GeneRIF: In East Asian populations, a SIX1 mutation has been
            reported in a Japanese family with branchio-oto (BO) syndrome.
REFERENCE   5  (bases 1 to 2687)
  AUTHORS   Wiggs,J.L., Yaspan,B.L., Hauser,M.A., Kang,J.H., Allingham,R.R.,
            Olson,L.M., Abdrabou,W., Fan,B.J., Wang,D.Y., Brodeur,W.,
            Budenz,D.L., Caprioli,J., Crenshaw,A., Crooks,K., Delbono,E.,
            Doheny,K.F., Friedman,D.S., Gaasterland,D., Gaasterland,T.,
            Laurie,C., Lee,R.K., Lichter,P.R., Loomis,S., Liu,Y.,
            Medeiros,F.A., McCarty,C., Mirel,D., Moroi,S.E., Musch,D.C.,
            Realini,A., Rozsa,F.W., Schuman,J.S., Scott,K., Singh,K.,
            Stein,J.D., Trager,E.H., Vanveldhuisen,P., Vollrath,D.,
            Wollstein,G., Yoneyama,S., Zhang,K., Weinreb,R.N., Ernst,J.,
            Kellis,M., Masuda,T., Zack,D., Richards,J.E., Pericak-Vance,M.,
            Pasquale,L.R. and Haines,J.L.
  TITLE     Common variants at 9p21 and 8q22 are associated with increased
            susceptibility to optic nerve degeneration in glaucoma
  JOURNAL   PLoS Genet. 8 (4), E1002654 (2012)
   PUBMED   22570617
REFERENCE   6  (bases 1 to 2687)
  AUTHORS   Ford,H.L., Landesman-Bollag,E., Dacwag,C.S., Stukenberg,P.T.,
            Pardee,A.B. and Seldin,D.C.
  TITLE     Cell cycle-regulated phosphorylation of the human SIX1 homeodomain
            protein
  JOURNAL   J. Biol. Chem. 275 (29), 22245-22254 (2000)
   PUBMED   10801845
REFERENCE   7  (bases 1 to 2687)
  AUTHORS   Salam,A.A., Hafner,F.M., Linder,T.E., Spillmann,T., Schinzel,A.A.
            and Leal,S.M.
  TITLE     A novel locus (DFNA23) for prelingual autosomal dominant
            nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German
            kindred
  JOURNAL   Am. J. Hum. Genet. 66 (6), 1984-1988 (2000)
   PUBMED   10777717
REFERENCE   8  (bases 1 to 2687)
  AUTHORS   Ford,H.L., Kabingu,E.N., Bump,E.A., Mutter,G.L. and Pardee,A.B.
  TITLE     Abrogation of the G2 cell cycle checkpoint associated with
            overexpression of HSIX1: a possible mechanism of breast
            carcinogenesis
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 95 (21), 12608-12613 (1998)
   PUBMED   9770533
REFERENCE   9  (bases 1 to 2687)
  AUTHORS   Boucher,C.A., Carey,N., Edwards,Y.H., Siciliano,M.J. and
            Johnson,K.J.
  TITLE     Cloning of the human SIX1 gene and its assignment to chromosome 14
  JOURNAL   Genomics 33 (1), 140-142 (1996)
   PUBMED   8617500
REFERENCE   10 (bases 1 to 2687)
  AUTHORS   Oliver,G., Wehr,R., Jenkins,N.A., Copeland,N.G., Cheyette,B.N.,
            Hartenstein,V., Zipursky,S.L. and Gruss,P.
  TITLE     Homeobox genes and connective tissue patterning
  JOURNAL   Development 121 (3), 693-705 (1995)
   PUBMED   7720577
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC008874.2, X91868.1 and
            AL049874.3.
            This sequence is a reference standard in the RefSeqGene project.
            On Apr 29, 2008 this sequence version replaced gi:142345106.
            
            Summary: The protein encoded by this gene is a homeobox protein
            that is similar to the Drosophila 'sine oculis' gene product. This
            gene is found in a cluster of related genes on chromosome 14 and is
            thought to be involved in limb development. Defects in this gene
            are a cause of autosomal dominant deafness type 23 (DFNA23) and
            branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul
            2008].
            
            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 :: BC008874.2, X91868.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           ERS025081, ERS025084 [ECO:0000348]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-542               BC008874.2         1-542
            543-1351            X91868.1           570-1378
            1352-2687           AL049874.3         135862-137197       c
FEATURES             Location/Qualifiers
     source          1..2687
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q23.1"
     gene            1..2687
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="SIX homeobox 1"
                     /db_xref="GeneID:6495"
                     /db_xref="HGNC:10887"
                     /db_xref="HPRD:03125"
                     /db_xref="MIM:601205"
     exon            1..808
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /inference="alignment:Splign:1.39.8"
     misc_feature    147..149
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="upstream in-frame stop codon"
     CDS             249..1103
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="sine oculis homeobox homolog 1"
                     /codon_start=1
                     /product="homeobox protein SIX1"
                     /protein_id="NP_005973.1"
                     /db_xref="GI:5174681"
                     /db_xref="CCDS:CCDS9748.1"
                     /db_xref="GeneID:6495"
                     /db_xref="HGNC:10887"
                     /db_xref="HPRD:03125"
                     /db_xref="MIM:601205"
                     /translation="

MSMLPSFGFTQEQVACVCEVLQQGGNLERLGRFLWSLPACDHLHKNESVLKAKAVVAFHRGNFRELYKILESHQFSPHNHPKLQQLWLKAHYVEAEKLRGRPLGAVGKYRVRRKFPLPRTIWDGEETSYCFKEKSRGVLREWYAHNPYPSPREKRELAEATGLTTTQVSNWFKNRRQRDRAAEAKERENTENNNSSSNKQNQLSPLEGGKPLMSSSEEEFSPPQSPDQNSVLLLQGNMGHARSSNYSLPGLTASQPSHGLQTHQHQLQDSLLGPLTSSLVDLGS

"
     misc_feature    639..788
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="Homeodomain;  DNA binding domains involved in the
                     transcriptional regulation of key eukaryotic developmental
                     processes; may bind to DNA as monomers or as homo- and/or
                     heterodimers, in a sequence-specific manner; Region:
                     homeodomain; cd00086"
                     /db_xref="CDD:28970"
     misc_feature    order(639..641,690..692,708..710,747..749,753..758,
                     765..770,774..782,786..788)
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="DNA binding site [nucleotide binding]"
                     /db_xref="CDD:28970"
     misc_feature    order(756..758,765..770,777..779)
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /note="specific DNA base contacts [nucleotide binding];
                     other site"
                     /db_xref="CDD:28970"
     exon            809..2687
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /inference="alignment:Splign:1.39.8"
     STS             1096..1337
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /standard_name="RH106538"
                     /db_xref="UniSTS:100611"
     STS             1155..1287
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /standard_name="RH70939"
                     /db_xref="UniSTS:49314"
     STS             1727..1845
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /standard_name="RH78873"
                     /db_xref="UniSTS:2398"
     polyA_signal    2095..2100
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
     polyA_site      2116
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
     variation       2147
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /replace="g"
                     /replace="t"
                     /db_xref="dbSNP:3742637"
     variation       2223
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:3742638"
     variation       2373..2374
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
                     /replace=""
                     /replace="at"
                     /db_xref="dbSNP:3832952"
     polyA_signal    2664..2669
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
     polyA_site      2687
                     /gene="SIX1"
                     /gene_synonym="BOS3; DFNA23; TIP39"
ORIGIN      

cggaggcagcaaggccttaaaggctactgagtgcgccggccgttccgtgtccagaacctcccctactcctccgccttctcttccttggccgcccaccgccaagttccgactccggttttcgcctttgcaaagcctaaggaggaggttaggaacagccgcgcccccctccctgcggccgccgccccctgcctctcggctctgctccctgccgcgtgcgcctgggccgtgcgccccggcaggccccagccatgtcgatgctgccgtcgtttggctttacgcaggagcaagtggcgtgcgtgtgcgaggttctgcagcaaggcggaaacctggagcgcctgggcaggttcctgtggtcactgcccgcctgcgaccacctgcacaagaacgagagcgtactcaaggccaaggcggtggtcgccttccaccgcggcaacttccgtgagctctacaagatcctggagagccaccagttctcgcctcacaaccaccccaaactgcagcaactgtggctgaaggcgcattacgtggaggccgagaagctgcgcggccgacccctgggcgccgtgggcaaatatcgggtgcgccgaaaatttccactgccgcgcaccatctgggacggcgaggagaccagctactgcttcaaggagaagtcgaggggtgtcctgcgggagtggtacgcgcacaatccctacccatcgccgcgtgagaagcgggagctggccgaggccaccggcctcaccaccacccaggtcagcaactggtttaagaaccggaggcaaagagaccgggccgcggaggccaaggaaagggagaacaccgaaaacaataactcctcctccaacaagcagaaccaactctctcctctggaagggggcaagccgctcatgtccagctcagaagaggaattctcacctccccaaagtccagaccagaactcggtccttctgctgcagggcaatatgggccacgccaggagctcaaactattctctcccgggcttaacagcctcgcagcccagtcacggcctgcagacccaccagcatcagctccaagactctctgctcggccccctcacctccagtctggtggacttggggtcctaagtggggagggactggggcctcgaagggattcctggagcagcaaccactgcagcgactagggacacttgtaaatagaaatcaggaacatttttgcagcttgtttctggagttgtttgcgcataaaggaatggtggactttcacaaatatctttttaaaaatcaaaaccaacagcgatctcaagcttaatctcctcttctctccaactctttccacttttgcattttccttcccaatgcagagatcagggaaaaaaaaaaaaaaaaacccaaacaaacaaaagcacccaggcacccagtctgagttctgggcaactgatacgcctgtttcagcagcctttcttttttttcaatgaatgggaattgcaaatcaactggattttcattatttccttttaatttatatatggagaaatgtgaagagggaaaggaaatggaaagagaaagagaaagggagataaaaatagtgaaaataagagcctccaggctcagaagaactgattacattcttaaggtgaacaggaaaaatacaatctataactttctttgatgaggaaaaattaagtttacatttttcatatttagtgttaaacaatttaatgtagattaaaataaaagaccagtattaggaggaaaaaacaagtgcctaaatgtcttaatgctctctatgtgagacagaaatagacgtgaccattagtaatgcaactatttttgtcaaatttagtgggattttttggttgttgtttgttttcttgggttttttttttttaaatgacaaactctaaaaatgtaccaatgtgaaaaaacactttcctgaatgccattactcatgccctcaaagctttcatatctgtagcctactcctgtaaagggtttctcctgtttctagtttctagtttgcaaaggtatgccaacgaatctggcaacctggtatttgttactaaaacagcatgtgttttcaggtttcttttctattgtacctaaagcagtctaaattaaaacttagtagaacaccaggagtatgattctgtttctgaaaggtgagtggtgtattgctgtcattgggccctatttttttttttaaatatatttttctttcttacttaatggtggctgtgaattgcagggtactttgaaggccatcatctgaaccaagagtagtaactagattaattatatgacagaaagagtgaatttagccttggggtatttattaacttctattatttagatatgcaattttgtttaccactatctcttcacagcattcatatgttaactaagctcttttgtgttaacaagtttatgacaagactgtgaaagtaaaaataatttatctgcttgaagacaaaaaagggaaggagaacaaggatagaaacattgtgaattaatttgtacaaatagaaagcagaccagcaggacaggagctcttttgcagtgctgccggatggtgtctagaaaaatcccagtaatcatgtaggctccatattatttttgcctggggcaaaatgatgtatcttctgtatttagcttttaaaattagtgaaacaaatggcattatttattaaaattctactcaggataaca

//

ANNOTATIONS from NCBI Entrez Gene (20130726):
            GeneID:6495 -> Molecular function: GO:0003677 [DNA binding] evidence: IDA
            GeneID:6495 -> Molecular function: GO:0003682 [chromatin binding] evidence: IEA
            GeneID:6495 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: IDA
            GeneID:6495 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: ISS
            GeneID:6495 -> Molecular function: GO:0005515 [protein binding] evidence: IPI
            GeneID:6495 -> Molecular function: GO:0043565 [sequence-specific DNA binding] evidence: IDA
            GeneID:6495 -> Molecular function: GO:0044212 [transcription regulatory region DNA binding] evidence: IDA
            GeneID:6495 -> Biological process: GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] evidence: IEA
            GeneID:6495 -> Biological process: GO:0001657 [ureteric bud development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0001658 [branching involved in ureteric bud morphogenesis] evidence: ISS
            GeneID:6495 -> Biological process: GO:0001759 [organ induction] evidence: ISS
            GeneID:6495 -> Biological process: GO:0001822 [kidney development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0003151 [outflow tract morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:0006351 [transcription, DNA-dependent] evidence: IEA
            GeneID:6495 -> Biological process: GO:0006355 [regulation of transcription, DNA-dependent] evidence: ISS
            GeneID:6495 -> Biological process: GO:0006915 [apoptotic process] evidence: IEA
            GeneID:6495 -> Biological process: GO:0007389 [pattern specification process] evidence: ISS
            GeneID:6495 -> Biological process: GO:0007519 [skeletal muscle tissue development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0007605 [sensory perception of sound] evidence: IEA
            GeneID:6495 -> Biological process: GO:0008582 [regulation of synaptic growth at neuromuscular junction] evidence: IEA
            GeneID:6495 -> Biological process: GO:0021610 [facial nerve morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:0030855 [epithelial cell differentiation] evidence: ISS
            GeneID:6495 -> Biological process: GO:0030878 [thyroid gland development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0032880 [regulation of protein localization] evidence: IEA
            GeneID:6495 -> Biological process: GO:0034504 [protein localization to nucleus] evidence: IDA
            GeneID:6495 -> Biological process: GO:0035909 [aorta morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:0042472 [inner ear morphogenesis] evidence: ISS
            GeneID:6495 -> Biological process: GO:0042474 [middle ear morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:0043524 [negative regulation of neuron apoptotic process] evidence: ISS
            GeneID:6495 -> Biological process: GO:0045664 [regulation of neuron differentiation] evidence: ISS
            GeneID:6495 -> Biological process: GO:0045893 [positive regulation of transcription, DNA-dependent] evidence: ISS
            GeneID:6495 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IDA
            GeneID:6495 -> Biological process: GO:0048538 [thymus development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0048665 [neuron fate specification] evidence: IEA
            GeneID:6495 -> Biological process: GO:0048699 [generation of neurons] evidence: ISS
            GeneID:6495 -> Biological process: GO:0048701 [embryonic cranial skeleton morphogenesis] evidence: ISS
            GeneID:6495 -> Biological process: GO:0048704 [embryonic skeletal system morphogenesis] evidence: ISS
            GeneID:6495 -> Biological process: GO:0048839 [inner ear development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0051451 [myoblast migration] evidence: ISS
            GeneID:6495 -> Biological process: GO:0060037 [pharyngeal system development] evidence: IEA
            GeneID:6495 -> Biological process: GO:0071599 [otic vesicle development] evidence: IEA
            GeneID:6495 -> Biological process: GO:0072075 [metanephric mesenchyme development] evidence: ISS
            GeneID:6495 -> Biological process: GO:0072095 [regulation of branch elongation involved in ureteric bud branching] evidence: ISS
            GeneID:6495 -> Biological process: GO:0072107 [positive regulation of ureteric bud formation] evidence: ISS
            GeneID:6495 -> Biological process: GO:0072172 [mesonephric tubule formation] evidence: ISS
            GeneID:6495 -> Biological process: GO:0072193 [ureter smooth muscle cell differentiation] evidence: IEA
            GeneID:6495 -> Biological process: GO:0072513 [positive regulation of secondary heart field cardioblast proliferation] evidence: IEA
            GeneID:6495 -> Biological process: GO:0090103 [cochlea morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:0090190 [positive regulation of branching involved in ureteric bud morphogenesis] evidence: ISS
            GeneID:6495 -> Biological process: GO:0090191 [negative regulation of branching involved in ureteric bud morphogenesis] evidence: IEA
            GeneID:6495 -> Biological process: GO:2000729 [positive regulation of mesenchymal cell proliferation involved in ureter development] evidence: IEA
            GeneID:6495 -> Cellular component: GO:0005634 [nucleus] evidence: IDA
            GeneID:6495 -> Cellular component: GO:0005667 [transcription factor complex] evidence: ISS
            GeneID:6495 -> Cellular component: GO:0005730 [nucleolus] evidence: IDA
            GeneID:6495 -> Cellular component: GO:0005737 [cytoplasm] evidence: IEA