PHX2A_HUMAN
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-AUG-2022, entry version 194.
DE RecName: Full=Paired mesoderm homeobox protein 2A;
DE AltName: Full=ARIX1 homeodomain protein;
DE AltName: Full=Aristaless homeobox protein homolog;
DE AltName: Full=Paired-like homeobox 2A;
GN Name=PHOX2A; Synonyms=ARIX, PMX2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8661014; DOI=10.1006/geno.1996.0230;
RA Johnson K.R., Smith L., Johnson D.K., Rhodes J., Rinchik E.M., Thayer M.,
RA 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP VARIANT CFEOM2 VAL-72.
RX 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 the
RT extraocular muscles type 2.";
RL Nat. Genet. 29:315-320(2001).
RN [6]
RP VARIANT GLN-256.
RX 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 expression
CC of the catecholamine biosynthetic genes. Acts as a transcription
CC activator/factor. Could maintain the noradrenergic phenotype.
CC -!- INTERACTION:
CC O14813; P50570-2: DNM2; NbExp=3; IntAct=EBI-25844430, EBI-10968534;
CC O14813; O43464: HTRA2; NbExp=3; IntAct=EBI-25844430, EBI-517086;
CC O14813; P41219: PRPH; NbExp=3; IntAct=EBI-25844430, EBI-752074;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DISEASE: Fibrosis of extraocular muscles, congenital, 2 (CFEOM2)
CC [MIM:602078]: A congenital ocular motility disorder marked by
CC restrictive ophthalmoplegia affecting extraocular muscles innervated by
CC the oculomotor and/or trochlear nerves. It is clinically characterized
CC by anchoring of the eyes in downward gaze, ptosis, and backward tilt of
CC the head. Congenital fibrosis of extraocular muscles type 2 may result
CC from the defective development of the oculomotor (nIII), trochlear
CC (nIV) and abducens (nVI) cranial nerve nuclei.
CC {ECO:0000269|PubMed:11600883}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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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 CCDS; CCDS8214.1; -.
DR RefSeq; NP_005160.2; NM_005169.3.
DR AlphaFoldDB; O14813; -.
DR SMR; O14813; -.
DR BioGRID; 106894; 6.
DR IntAct; O14813; 3.
DR STRING; 9606.ENSP00000298231; -.
DR iPTMnet; O14813; -.
DR PhosphoSitePlus; O14813; -.
DR BioMuta; PHOX2A; -.
DR MassIVE; O14813; -.
DR PaxDb; O14813; -.
DR PeptideAtlas; O14813; -.
DR PRIDE; O14813; -.
DR ProteomicsDB; 48252; -.
DR Antibodypedia; 16943; 212 antibodies from 35 providers.
DR DNASU; 401; -.
DR Ensembl; ENST00000298231.5; ENSP00000298231.5; ENSG00000165462.5.
DR GeneID; 401; -.
DR KEGG; hsa:401; -.
DR MANE-Select; ENST00000298231.5; ENSP00000298231.5; NM_005169.4; NP_005160.2.
DR UCSC; uc001osh.4; human.
DR CTD; 401; -.
DR DisGeNET; 401; -.
DR GeneCards; PHOX2A; -.
DR GeneReviews; PHOX2A; -.
DR HGNC; HGNC:691; PHOX2A.
DR HPA; ENSG00000165462; Group enriched (adrenal gland, brain).
DR MalaCards; PHOX2A; -.
DR MIM; 602078; phenotype.
DR MIM; 602753; gene.
DR neXtProt; NX_O14813; -.
DR OpenTargets; ENSG00000165462; -.
DR Orphanet; 45358; Congenital fibrosis of extraocular muscles.
DR PharmGKB; PA28093; -.
DR VEuPathDB; HostDB:ENSG00000165462; -.
DR eggNOG; KOG0484; Eukaryota.
DR GeneTree; ENSGT00940000161147; -.
DR HOGENOM; CLU_081152_0_0_1; -.
DR InParanoid; O14813; -.
DR OMA; GPACPGL; -.
DR OrthoDB; 1505098at2759; -.
DR PhylomeDB; O14813; -.
DR TreeFam; TF351612; -.
DR PathwayCommons; O14813; -.
DR SignaLink; O14813; -.
DR SIGNOR; O14813; -.
DR BioGRID-ORCS; 401; 26 hits in 1091 CRISPR screens.
DR ChiTaRS; PHOX2A; human.
DR GeneWiki; PHOX2A; -.
DR GenomeRNAi; 401; -.
DR Pharos; O14813; Tbio.
DR PRO; PR:O14813; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O14813; protein.
DR Bgee; ENSG00000165462; Expressed in muscle layer of sigmoid colon and 57 other tissues.
DR ExpressionAtlas; O14813; baseline and differential.
DR Genevisible; O14813; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IC:BHF-UCL.
DR GO; GO:0048484; P:enteric nervous system development; IBA:GO_Central.
DR GO; GO:0021703; P:locus ceruleus development; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0003357; P:noradrenergic neuron differentiation; NAS:BHF-UCL.
DR GO; GO:0021623; P:oculomotor nerve formation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0021523; P:somatic motor neuron differentiation; IEA:Ensembl.
DR GO; GO:0048485; P:sympathetic nervous system development; IEA:Ensembl.
DR GO; GO:0021642; P:trochlear nerve formation; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Disease variant; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..284
FT /note="Paired mesoderm homeobox protein 2A"
FT /id="PRO_0000049259"
FT DNA_BIND 90..149
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 145..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..205
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 72
FT /note="A -> V (in CFEOM2; dbSNP:rs104894269)"
FT /evidence="ECO:0000269|PubMed:11600883"
FT /id="VAR_019014"
FT VARIANT 256
FT /note="P -> Q (may be involved in congenital central
FT hypoventilation syndrome; dbSNP:rs1041507260)"
FT /evidence="ECO:0000269|PubMed:14566559"
FT /id="VAR_019016"
FT CONFLICT 76
FT /note="K -> N (in Ref. 1; AAB82744)"
FT /evidence="ECO:0000305"
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
