Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14813 (PHX2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Congenital fibrosis of extraocular muscles 2 (CFEOM2) [MIM:602078]: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 2 may result from the defective development of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the paired homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdopaminergic neuron differentiation

Inferred by curator PubMed 19573018. Source: BHF-UCL

locus ceruleus development

Inferred from electronic annotation. Source: Ensembl

midbrain development

Inferred from electronic annotation. Source: Ensembl

noradrenergic neuron differentiation

Non-traceable author statement PubMed 16280598. Source: BHF-UCL

oculomotor nerve formation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

regulation of respiratory gaseous exchange

Inferred from electronic annotation. Source: Ensembl

somatic motor neuron differentiation

Inferred from electronic annotation. Source: Ensembl

sympathetic nervous system development

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

trochlear nerve formation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

   Molecular_functionRNA polymerase II regulatory region sequence-specific DNA binding

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Non-traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Paired mesoderm homeobox protein 2A
PRO_0000049259

Regions

DNA binding90 – 14960Homeobox
Compositional bias193 – 1986Poly-Pro
Compositional bias237 – 24610Poly-Gly

Natural variations

Natural variant721A → V in CFEOM2. Ref.5
VAR_019014
Natural variant2561P → Q May be involved in congenital central hypoventilation syndrome. Ref.6
VAR_019016

Experimental info

Sequence conflict761K → N in AAB82744. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O14813 [UniParc].

Last modified October 11, 2005. Version 2.
Checksum: F123D5695FB45A99

FASTA28429,653
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-256.
+Additional computationally mapped references.

Web resources

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.
RefSeqNP_005160.2. NM_005169.3.
UniGeneHs.731115.

3D structure databases

ProteinModelPortalO14813.
SMRO14813. Positions 92-149.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106894. 5 interactions.
STRING9606.ENSP00000298231.

PTM databases

PhosphoSiteO14813.

Proteomic databases

PaxDbO14813.
PRIDEO14813.

Protocols and materials databases

DNASU401.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298231; ENSP00000298231; ENSG00000165462.
GeneID401.
KEGGhsa:401.
UCSCuc001osh.4. human.

Organism-specific databases

CTD401.
GeneCardsGC11M071950.
HGNCHGNC:691. PHOX2A.
MIM602078. phenotype.
602753. gene.
neXtProtNX_O14813.
Orphanet45358. Congenital fibrosis of extraocular muscles.
PharmGKBPA28093.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301263.
HOGENOMHOG000013060.
HOVERGENHBG053590.
InParanoidO14813.
KOK09330.
OMAKGPLWAG.
PhylomeDBO14813.
TreeFamTF351612.

Enzyme and pathway databases

SignaLinkO14813.

Gene expression databases

BgeeO14813.
CleanExHS_PHOX2A.
GenevestigatorO14813.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPHOX2A.
GenomeRNAi401.
NextBio1681.
PROO14813.
SOURCESearch...

Entry information

Entry namePHX2A_HUMAN
AccessionPrimary (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: March 19, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM