LOCUS       NM_005169               1716 bp    mRNA    linear   PRI 17-APR-2013
DEFINITION  Homo sapiens paired-like homeobox 2a (PHOX2A), mRNA.
ACCESSION   NM_005169
VERSION     NM_005169.3  GI:188536104
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 1716)
  AUTHORS   Dong,J.M., Shen,Q., Li,J., Du,W., Pang,H.L., Lin,S.F. and Bu,J.
  TITLE     [Identification of a novel PHOX2A gene mutation in a Chinese family
            with congenital fibrosis of extraocular muscles type 2]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 29 (1), 5-8 (2012)
   PUBMED   22311481
  REMARK    GeneRIF: Genetic linkage was found at 11q13 between D11S4151 and
            D11S1320 and the PHOX2A gene.
REFERENCE   2  (bases 1 to 1716)
  AUTHORS   Ohkubo,S.I., Matsuo,T., Hasebe,K., Shira,Y.H., Itoshima,E. and
            Ohtsuki,H.
  TITLE     Phenotype-phenotype and genotype-phenotype correlations in patients
            with idiopathic superior oblique muscle palsy
  JOURNAL   J. Hum. Genet. 57 (2), 122-129 (2012)
   PUBMED   22170461
  REMARK    GeneRIF: Patients with ARIX and/or PHOX2B polymorphisms had less
            hypoplastic superior oblique muscles.
REFERENCE   3  (bases 1 to 1716)
  AUTHORS   Khan,A.O., Khalil,D.S., Al-Sharif,L.J. and Al-Tassan,N.A.
  TITLE     Mutations in KIF21A and PHOX2A are absent in 16 patients with
            congenital vertical incomitant strabismus
  JOURNAL   Ophthalmic Genet. 30 (4), 206-207 (2009)
   PUBMED   19852579
  REMARK    GeneRIF: Our 16-patient sample suggests that KIF21A and PHOX2A
            sequence variation does not have a role in common forms of
            congenital incomitant vertical strabismus.
REFERENCE   4  (bases 1 to 1716)
  AUTHORS   Fan,Y., Huang,J., Kieran,N. and Zhu,M.Y.
  TITLE     Effects of transcription factors Phox2 on expression of
            norepinephrine transporter and dopamine beta-hydroxylase in
            SK-N-BE(2)C cells
  JOURNAL   J. Neurochem. 110 (5), 1502-1513 (2009)
   PUBMED   19573018
  REMARK    GeneRIF: Transfection of Phox2a cDNA significantly increases mRNA
            and protein levels of norepinephrine transporter and dopamine
            beta-hydroxylase.
REFERENCE   5  (bases 1 to 1716)
  AUTHORS   Wilzen,A., Nilsson,S., Sjoberg,R.M., Kogner,P., Martinsson,T. and
            Abel,F.
  TITLE     The Phox2 pathway is differentially expressed in neuroblastoma
            tumors, but no mutations were found in the candidate tumor
            suppressor gene PHOX2A
  JOURNAL   Int. J. Oncol. 34 (3), 697-705 (2009)
   PUBMED   19212675
  REMARK    GeneRIF: PHOX2A gene, localized in a tumor suppressor candidate
            region at 11q, weas screened for mutations by DNA sequencing in 47
            tumors of different stages.
REFERENCE   6  (bases 1 to 1716)
  AUTHORS   Swanson,D.J., Adachi,M. and Lewis,E.J.
  TITLE     The homeodomain protein Arix promotes protein kinase A-dependent
            activation of the dopamine beta-hydroxylase promoter through
            multiple elements and interaction with the coactivator
            cAMP-response element-binding protein-binding protein
  JOURNAL   J. Biol. Chem. 275 (4), 2911-2923 (2000)
   PUBMED   10644760
REFERENCE   7  (bases 1 to 1716)
  AUTHORS   Wang,S.M., Zwaan,J., Mullaney,P.B., Jabak,M.H., Al-Awad,A.,
            Beggs,A.H. and Engle,E.C.
  TITLE     Congenital fibrosis of the extraocular muscles type 2, an inherited
            exotropic strabismus fixus, maps to distal 11q13
  JOURNAL   Am. J. Hum. Genet. 63 (2), 517-525 (1998)
   PUBMED   9683611
REFERENCE   8  (bases 1 to 1716)
  AUTHORS   Swanson,D.J., Zellmer,E. and Lewis,E.J.
  TITLE     The homeodomain protein Arix interacts synergistically with cyclic
            AMP to regulate expression of neurotransmitter biosynthetic genes
  JOURNAL   J. Biol. Chem. 272 (43), 27382-27392 (1997)
   PUBMED   9341190
REFERENCE   9  (bases 1 to 1716)
  AUTHORS   Merscher,S., Bekri,S., de Leeuw,B., Pedeutour,F., Grosgeorge,J.,
            Shows,T.B., Mullenbach,R., Le Paslier,D., Nowak,N.J. and Gaudray,P.
  TITLE     A 5.5-Mb high-resolution integrated map of distal 11q13
  JOURNAL   Genomics 39 (3), 340-347 (1997)
   PUBMED   9119371
REFERENCE   10 (bases 1 to 1716)
  AUTHORS   Johnson,K.R., Smith,L., Johnson,D.K., Rhodes,J., Rinchik,E.M.,
            Thayer,M. and Lewis,E.J.
  TITLE     Mapping of the ARIX homeodomain gene to mouse chromosome 7 and
            human chromosome 11q13
  JOURNAL   Genomics 33 (3), 527-531 (1996)
   PUBMED   8661014
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK290645.1 and BC041564.1.
            This sequence is a reference standard in the RefSeqGene project.
            On May 20, 2008 this sequence version replaced gi:46249381.
            
            Summary: The protein encoded by this gene contains a paired-like
            homeodomain most similar to that of the Drosophila aristaless gene
            product. The encoded protein plays a central role in development of
            the autonomic nervous system. It regulates the expression of
            tyrosine hydroxylase and dopamine beta-hydroxylase, two
            catecholaminergic biosynthetic enzymes essential for the
            differentiation and maintenance of the noradrenergic
            neurotransmitter phenotype. The encoded protein has also been shown
            to regulate transcription of the alpha3 nicotinic acetylcholine
            receptor gene. Mutations in this gene have been associated with
            autosomal recessive congenital fibrosis of the extraocular muscles.
            [provided by RefSeq, Jul 2008].
            
            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 :: BC041564.1, BX376662.2 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           ERS025084, ERS025085 [ECO:0000350]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1294              AK290645.1         1-1294
            1295-1716           BC041564.1         1277-1698
FEATURES             Location/Qualifiers
     source          1..1716
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.2"
     gene            1..1716
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /note="paired-like homeobox 2a"
                     /db_xref="GeneID:401"
                     /db_xref="HGNC:691"
                     /db_xref="MIM:602753"
     exon            1..389
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /inference="alignment:Splign:1.39.8"
     misc_feature    20..22
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /note="upstream in-frame stop codon"
     variation       complement(123)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:200284055"
     variation       complement(154)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:140850664"
     CDS             173..1027
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /note="arix homeodomain protein; aristaless homeobox
                     homolog; ARIX1 homeodomain protein; aristaless homeobox
                     protein homolog"
                     /codon_start=1
                     /product="paired mesoderm homeobox protein 2A"
                     /protein_id="NP_005160.2"
                     /db_xref="GI:46249382"
                     /db_xref="CCDS:CCDS8214.1"
                     /db_xref="GeneID:401"
                     /db_xref="HGNC:691"
                     /db_xref="MIM:602753"
                     /translation="

MDYSYLNSYDSCVAAMEASAYGDFGACSQPGGFQYSPLRPAFPAAGPPCPALGSSNCALGALRDHQPAPYSAVPYKFFPEPSGLHEKRKQRRIRTTFTSAQLKELERVFAETHYPDIYTREELALKIDLTEARVQVWFQNRRAKFRKQERAASAKGAAGAAGAKKGEARCSSEDDDSKESTCSPTPDSTASLPPPPAPGLASPRLSPSPLPVALGSGPGPGPGPQPLKGALWAGVAGGGGGGPGAGAAELLKAWQPAESGPGPFSGVLSSFHRKPGPALKTNLF

"
     misc_feature    443..619
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /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(443..457,461..463,512..514,530..532,569..571,
                     575..580,587..592,596..604,608..613)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /note="DNA binding site [nucleotide binding]"
                     /db_xref="CDD:28970"
     misc_feature    order(449..451,458..460,578..580,587..592,599..601)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /note="specific DNA base contacts [nucleotide binding];
                     other site"
                     /db_xref="CDD:28970"
     variation       complement(328)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:182932220"
     variation       complement(356)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:12787525"
     variation       complement(373)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:374332283"
     variation       387
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:104894269"
     exon            390..577
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /inference="alignment:Splign:1.39.8"
     variation       complement(425)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:148937033"
     variation       complement(428)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:145702565"
     variation       complement(434)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:370435269"
     variation       complement(445)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:145380401"
     variation       complement(520)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:376482990"
     exon            578..1699
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /inference="alignment:Splign:1.39.8"
     variation       complement(652..660)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace=""
                     /replace="ggcgggcgc"
                     /db_xref="dbSNP:200556921"
     STS             1009..1677
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /standard_name="PHOX2A_8209"
                     /db_xref="UniSTS:467830"
     variation       complement(1021)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="g"
                     /db_xref="dbSNP:374198327"
     variation       complement(1055)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:369751238"
     variation       complement(1199)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="c"
                     /replace="t"
                     /db_xref="dbSNP:375530553"
     variation       complement(1400)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="a"
                     /replace="c"
                     /db_xref="dbSNP:372904530"
     variation       complement(1410)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="g"
                     /replace="t"
                     /db_xref="dbSNP:56787483"
     variation       complement(1430)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace="a"
                     /replace="g"
                     /db_xref="dbSNP:80340347"
     polyA_signal    1675..1680
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
     variation       complement(1681..1684)
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
                     /replace=""
                     /replace="actt"
                     /db_xref="dbSNP:70940830"
     polyA_site      1699
                     /gene="PHOX2A"
                     /gene_synonym="ARIX; CFEOM2; FEOM2; NCAM2; PMX2A"
ORIGIN      

acttgcgttgcacccgggctgagtgcggccgcgacggggcgggcggactctcgggcgctcagagctggcctcgggtcctcggagcctggcgctcgaacctcccttccgacctccacccggaccccgaccccgacccggcctggcccggcccccgcccccgccccccgggccgatggactactcctacctcaattcgtacgactcgtgcgtggcggccatggaggcgtccgcctacggcgactttggcgcctgcagccagcccggcggcttccaatacagccccctgcggcccgctttccccgcggcagggccgccctgccccgcgctcggctcctccaactgcgcacttggcgccctacgcgaccaccagcccgcgccctactcggcagtgccctacaagttcttcccagagccatccggcctgcacgagaagcgcaagcagcggcgcatccgcaccacgttcaccagcgcgcagctcaaggagctggagcgcgttttcgctgagacccactaccccgacatttacacgcgtgaggagctggcgctcaagatcgacctcactgaggctcgcgtgcaggtctggttccagaaccgccgggccaagttccgcaaacaggagcgcgcggccagcgccaagggcgcggcgggcgcggcgggcgccaaaaagggcgaggcgcgctgctcctccgaggacgacgattccaaggagtccacgtgcagccccacgcccgatagcaccgcctcgctgccgccgccgcctgcgcccggcctggccagcccgcgcctgagccccagcccgctgcccgtcgcactgggctccgggccgggacctgggccggggccacagccgctcaagggcgcactgtgggccggtgtggcgggcggtgggggcggcgggcctggcgcgggagcggccgaactacttaaggcttggcagccggcggagtccggccccgggcccttctccggggttctgtcctcctttcaccggaagcccggccccgccctgaagaccaatctcttctagctgccggcctctggaggctccgagcctgcccccagagacgtccctgcccctccaggacctgacagcccctcccatcctggccacccgcctggaagtccccatccgtctccactccctactgtctcacccctcggtgtgtcctccccaactttggagaccaagtcagggccactctcgtcctcacccaccctctaccagcagagcggagttctttataccgggacctcctccaggagaaccccggagctccttctagcttggccttctttggatgcggtatcacatgaggcctgtccctaacagtgccctcaaagtgaaggtcctcaaggaggatcggcacagcccccttccctggctctgcagcggctgggtcaccccttacgctggtgatcaggaaagcccgctgccccacccctcgggcccacccgtacagaggctggtggtcgccgggataattaatgaccaccgccaattcatccctcacgtgtctcctctcttccctagcccgtctggcacagagggtggacctgttagaggagtggaggggctgcctggggaatgggacagagggattctctttccctaatttttttggttgtcctttttctttgaaaaacttgtaatttattgaagttttactcaatccaaataaaacttaatttattgaagacaaaaaaaaaaaaaaaaaa

//

ANNOTATIONS from NCBI Entrez Gene (20130726):
            GeneID:401 -> Molecular function: GO:0000977 [RNA polymerase II regulatory region sequence-specific DNA binding] evidence: IDA
            GeneID:401 -> Molecular function: GO:0003700 [sequence-specific DNA binding transcription factor activity] evidence: IEA
            GeneID:401 -> Biological process: GO:0003357 [noradrenergic neuron differentiation] evidence: IC
            GeneID:401 -> Biological process: GO:0003357 [noradrenergic neuron differentiation] evidence: NAS
            GeneID:401 -> Biological process: GO:0006351 [transcription, DNA-dependent] evidence: IEA
            GeneID:401 -> Biological process: GO:0021523 [somatic motor neuron differentiation] evidence: IEA
            GeneID:401 -> Biological process: GO:0021623 [oculomotor nerve formation] evidence: IEA
            GeneID:401 -> Biological process: GO:0021642 [trochlear nerve formation] evidence: IEA
            GeneID:401 -> Biological process: GO:0021703 [locus ceruleus development] evidence: IEA
            GeneID:401 -> Biological process: GO:0030901 [midbrain development] evidence: IEA
            GeneID:401 -> Biological process: GO:0043576 [regulation of respiratory gaseous exchange] evidence: IEA
            GeneID:401 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IDA
            GeneID:401 -> Biological process: GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] evidence: IMP
            GeneID:401 -> Biological process: GO:0048485 [sympathetic nervous system development] evidence: IEA
            GeneID:401 -> Biological process: GO:0071542 [dopaminergic neuron differentiation] evidence: IC
            GeneID:401 -> Cellular component: GO:0000790 [nuclear chromatin] evidence: IDA