O14813 (PHX2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Paired mesoderm homeobox protein 2A

Alternative name(s):
ARIX1 homeodomain protein
Aristaless homeobox protein homolog
Paired-like homeobox 2A

Gene names

Name:	PHOX2A
Synonyms:	ARIX, PMX2A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	284 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes. Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype.
Subcellular location	Nucleus By similarity.
Involvement in disease	Defects in PHOX2A are the cause of congenital fibrosis of extraocular muscles type 2 (CFEOM2) [MIM:602078]. CFEOM encompasses several different inherited strabismus syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. CFEOM is characterized clinically by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. CFEOM2 may result from the aberrant development of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. Ref.5
Sequence similarities	Belongs to the paired homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	noradrenergic neuron differentiation Non-traceable author statement. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nuclear chromatin Inferred from direct assay. Source: BHF-UCL
Molecular function	RNA polymerase II regulatory region sequence-specific DNA binding Inferred from direct assay. Source: BHF-UCL sequence-specific DNA binding transcription factor activity Non-traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 284	284	Paired mesoderm homeobox protein 2A		PRO_0000049259
Regions
	DNA binding	90 – 149	60	Homeobox
	Compositional bias	193 – 198	6	Poly-Pro
	Compositional bias	237 – 246	10	Poly-Gly
Natural variations
	Natural variant	72	1	A → V in CFEOM2. Ref.5		VAR_019014
	Natural variant	256	1	P → Q May be involved in congenital central hypoventilation syndrome. Ref.6		VAR_019016
Experimental info
	Sequence conflict	76	1	K → N in AAB82744. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O14813 [UniParc]. Last modified October 11, 2005. Version 2. Checksum: F123D5695FB45A99	FASTA	284	29,653
	10 20 30 40 50 60 MDYSYLNSYD SCVAAMEASA YGDFGACSQP GGFQYSPLRP AFPAAGPPCP ALGSSNCALG 70 80 90 100 110 120 ALRDHQPAPY SAVPYKFFPE PSGLHEKRKQ RRIRTTFTSA QLKELERVFA ETHYPDIYTR 130 140 150 160 170 180 EELALKIDLT EARVQVWFQN RRAKFRKQER AASAKGAAGA AGAKKGEARC SSEDDDSKES 190 200 210 220 230 240 TCSPTPDSTA SLPPPPAPGL ASPRLSPSPL PVALGSGPGP GPGPQPLKGA LWAGVAGGGG 250 260 270 280 GGPGAGAAEL LKAWQPAESG PGPFSGVLSS FHRKPGPALK TNLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human chromosome 11q13." Johnson K.R., Smith L., Johnson D.K., Rhodes J., Rinchik E.M., Thayer M., Lewis E.J. Genomics 33:527-531(1996) [PubMed: 8661014] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryo.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2." Nakano M., Yamada K., Fain J., Sener E.C., Selleck C.J., Awad A.H., Zwaan J., Mullaney P.B., Bosley T.M., Engle E.C. Nat. Genet. 29:315-320(2001) [PubMed: 11600883] [Abstract] Cited for: VARIANT CFEOM2 VAL-72.
[6]	"Molecular analysis of congenital central hypoventilation syndrome." Sasaki A., Kanai M., Kijima K., Akaba K., Hashimoto M., Hasegawa H., Otaki S., Koizumi T., Kusuda S., Ogawa Y., Tuchiya K., Yamamoto W., Nakamura T., Hayasaka K. Hum. Genet. 114:22-26(2003) [PubMed: 14566559] [Abstract] Cited for: VARIANT GLN-256.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF022724, AF022722, AF022723 Genomic DNA. Translation: AAB82744.1. AK290645 mRNA. Translation: BAF83334.1. CH471076 Genomic DNA. Translation: EAW74856.1. BC041564 mRNA. Translation: AAH41564.1.
IPI	IPI00024171.
RefSeq	NP_005160.2. NM_005169.3.
UniGene	Hs.729726.
3D structure databases
ProteinModelPortal	O14813.
SMR	O14813. Positions 92-149.
ModBase	Search...
Protein-protein interaction databases
STRING	O14813.
PTM databases
PhosphoSite	O14813.
Proteomic databases
PRIDE	O14813.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298231; ENSP00000298231; ENSG00000165462.
GeneID	401.
KEGG	hsa:401.
UCSC	uc001osh.2. human.
Organism-specific databases
CTD	401.
GeneCards	GC11M071950.
H-InvDB	HIX0026290.
HGNC	HGNC:691. PHOX2A.
MIM	602078. phenotype. 602753. gene.
neXtProt	NX_O14813.
Orphanet	45358. Congenital fibrosis of extraocular muscles.
PharmGKB	PA28093.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09311.
GeneTree	ENSGT00600000084177.
HOGENOM	HBG444376.
HOVERGEN	HBG053590.
InParanoid	O14813.
OMA	WAGVTGG.
OrthoDB	EOG4N30PS.
PhylomeDB	O14813.
Gene expression databases
ArrayExpress	O14813.
Bgee	O14813.
CleanEx	HS_PHOX2A.
Genevestigator	O14813.
GermOnline	ENSG00000165462. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KO	K09330.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	1681.
SOURCE	Search...

Entry information

Entry name

PHX2A_HUMAN

Accession

Primary (citable) accession number: O14813
Secondary accession number(s): A8K3N0, Q8IVZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	October 11, 2005
Last modified:	January 25, 2012
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.