ID   PHX2A_HUMAN             Reviewed;         284 AA.
AC   O14813; A8K3N0; Q8IVZ2;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   03-NOV-2009, entry version 97.
DE   RecName: Full=Paired mesoderm homeobox protein 2A;
DE   AltName: Full=Paired-like homeobox 2A;
DE   AltName: Full=Aristaless homeobox protein homolog;
DE   AltName: Full=ARIX1 homeodomain protein;
GN   Name=PHOX2A; Synonyms=ARIX, PMX2A;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=96299650; PubMed=8661014; DOI=10.1006/geno.1996.0230;
RA   Johnson K.R., Smith L., Johnson D.K., Rhodes J., Rinchik E.M.,
RA   Thayer M., Lewis E.J.;
RT   "Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human
RT   chromosome 11q13.";
RL   Genomics 33:527-531(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   VARIANT CFEOM2 VAL-72.
RX   MEDLINE=21547502; PubMed=11600883; DOI=10.1038/ng744;
RA   Nakano M., Yamada K., Fain J., Sener E.C., Selleck C.J., Awad A.H.,
RA   Zwaan J., Mullaney P.B., Bosley T.M., Engle E.C.;
RT   "Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of
RT   the extraocular muscles type 2.";
RL   Nat. Genet. 29:315-320(2001).
RN   [6]
RP   VARIANT GLN-256.
RX   MEDLINE=22982299; PubMed=14566559; DOI=10.1007/s00439-003-1036-z;
RA   Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H.,
RA   Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W.,
RA   Nakamura T., Hayasaka K.;
RT   "Molecular analysis of congenital central hypoventilation syndrome.";
RL   Hum. Genet. 114:22-26(2003).
CC   -!- FUNCTION: May be involved in regulating the specificity of
CC       expression of the catecholamine biosynthetic genes. Acts as a
CC       transcription activator/factor. Could maintain the noradrenergic
CC       phenotype.
CC   -!- SUBCELLULAR LOCATION: Nucleus (By similarity).
CC   -!- DISEASE: Defects in PHOX2A are the cause of congenital fibrosis of
CC       extraocular muscles type 2 (CFEOM2) [MIM:602078]. CFEOM
CC       encompasses several different inherited strabismus syndromes
CC       characterized by congenital restrictive ophthalmoplegia affecting
CC       extraocular muscles innervated by the oculomotor and/or trochlear
CC       nerves. CFEOM is characterized clinically by anchoring of the eyes
CC       in downward gaze, ptosis, and backward tilt of the head. CFEOM2
CC       may result from the aberrant development of the oculomotor (nIII),
CC       trochlear (nIV) and abducens (nVI) cranial nerve nuclei.
CC   -!- SIMILARITY: Belongs to the paired homeobox family.
CC   -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PHOX2A";
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DR   EMBL; AF022724; AAB82744.1; -; Genomic_DNA.
DR   EMBL; AF022722; AAB82744.1; JOINED; Genomic_DNA.
DR   EMBL; AF022723; AAB82744.1; JOINED; Genomic_DNA.
DR   EMBL; AK290645; BAF83334.1; -; mRNA.
DR   EMBL; CH471076; EAW74856.1; -; Genomic_DNA.
DR   EMBL; BC041564; AAH41564.1; -; mRNA.
DR   IPI; IPI00024171; -.
DR   RefSeq; NP_005160.2; -.
DR   UniGene; Hs.707879; -.
DR   HSSP; P06601; 1FJL.
DR   STRING; O14813; -.
DR   PhosphoSite; O14813; -.
DR   PRIDE; O14813; -.
DR   Ensembl; ENST00000298231; ENSP00000298231; ENSG00000165462; Homo sapiens.
DR   GeneID; 401; -.
DR   KEGG; hsa:401; -.
DR   UCSC; uc001osh.2; human.
DR   CTD; 401; -.
DR   GeneCards; GC11M071627; -.
DR   H-InvDB; HIX0026290; -.
DR   HGNC; HGNC:691; PHOX2A.
DR   MIM; 602078; phenotype.
DR   MIM; 602753; gene.
DR   Orphanet; 45358; Congenital fibrosis of extraocular muscles.
DR   PharmGKB; PA28093; -.
DR   HOGENOM; O14813; -.
DR   HOVERGEN; O14813; -.
DR   OMA; PAPYSAX; -.
DR   NextBio; 1681; -.
DR   ArrayExpress; O14813; -.
DR   Bgee; O14813; -.
DR   CleanEx; HS_PHOX2A; -.
DR   Genevestigator; O14813; -.
DR   GermOnline; ENSG00000165462; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR   GO; GO:0003700; F:transcription factor activity; NAS:ProtInc.
DR   GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:InterPro.
DR   GO; GO:0006350; P:transcription; IEA:UniProtKB-KW.
DR   InterPro; IPR001356; Homeobox.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR012287; Homeodomain-rel.
DR   Gene3D; G3DSA:1.10.10.60; Homeodomain-rel; 1.
DR   Pfam; PF00046; Homeobox; 1.
DR   ProDom; PD000010; Homeobox; 1.
DR   SMART; SM00389; HOX; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   Activator; Complete proteome; Disease mutation; DNA-binding; Homeobox;
KW   Nucleus; Polymorphism; Transcription; Transcription regulation.
FT   CHAIN         1    284       Paired mesoderm homeobox protein 2A.
FT                                /FTId=PRO_0000049259.
FT   DNA_BIND     90    149       Homeobox.
FT   COMPBIAS    193    198       Poly-Pro.
FT   COMPBIAS    237    246       Poly-Gly.
FT   VARIANT      72     72       A -> V (in CFEOM2).
FT                                /FTId=VAR_019014.
FT   VARIANT     256    256       P -> Q (may be involved in congenital
FT                                central hypoventilation syndrome).
FT                                /FTId=VAR_019016.
FT   CONFLICT     76     76       K -> N (in Ref. 1; AAB82744).
SQ   SEQUENCE   284 AA;  29653 MW;  F123D5695FB45A99 CRC64;
     MDYSYLNSYD SCVAAMEASA YGDFGACSQP GGFQYSPLRP AFPAAGPPCP ALGSSNCALG
     ALRDHQPAPY SAVPYKFFPE PSGLHEKRKQ RRIRTTFTSA QLKELERVFA ETHYPDIYTR
     EELALKIDLT EARVQVWFQN RRAKFRKQER AASAKGAAGA AGAKKGEARC SSEDDDSKES
     TCSPTPDSTA SLPPPPAPGL ASPRLSPSPL PVALGSGPGP GPGPQPLKGA LWAGVAGGGG
     GGPGAGAAEL LKAWQPAESG PGPFSGVLSS FHRKPGPALK TNLF
//