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Q99453 (PHX2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Paired mesoderm homeobox protein 2B
Alternative name(s):
Neuroblastoma Phox
Short name=NBPhox
PHOX2B homeodomain protein
Paired-like homeobox 2B
Gene names
Name:PHOX2B
Synonyms:PMX2B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the development of several major noradrenergic neuron populations, including the locus coeruleus. Transcription factor which could determine a neurotransmitter phenotype in vertebrates. Enhances second-messenger-mediated activation of the dopamine beta-hydrolase and c-fos promoters, and of several enhancers including cAMP-response element and serum-response element.

Subunit structure

Interacts with TRIM11 By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed in neuroblastoma, brain and adrenal gland.

Involvement in disease

Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6 Ref.8

Neuroblastoma 2 (NBLST2) [MIM:613013]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the paired homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityTriplet repeat expansion
   DiseaseDisease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processautonomic nervous system development

Inferred from mutant phenotype Ref.6. Source: BHF-UCL

brainstem development

Inferred from expression pattern Ref.6. Source: BHF-UCL

cell differentiation in hindbrain

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to BMP stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

dopaminergic neuron differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

efferent axon development in a lateral line nerve

Inferred from sequence or structural similarity. Source: BHF-UCL

enteric nervous system development

Inferred from expression pattern Ref.6. Source: BHF-UCL

glial cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

hindbrain tangential cell migration

Inferred from sequence or structural similarity. Source: BHF-UCL

inner ear development

Inferred from sequence or structural similarity. Source: BHF-UCL

medullary reticular formation development

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

neural crest cell migration involved in autonomic nervous system development

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron migration

Inferred from sequence or structural similarity. Source: BHF-UCL

noradrenergic neuron development

Inferred from sequence or structural similarity. Source: UniProtKB

noradrenergic neuron differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

parasympathetic nervous system development

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of G2/M transition of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16144830PubMed 16280598. Source: BHF-UCL

regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of respiratory gaseous exchange by neurological system process

Inferred from sequence or structural similarity. Source: BHF-UCL

respiratory system development

Inferred from sequence or structural similarity. Source: BHF-UCL

retrotrapezoid nucleus neuron differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

sympathetic ganglion development

Inferred from sequence or structural similarity. Source: UniProtKB

sympathetic nervous system development

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnuclear chromatin

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

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 16144830. Source: BHF-UCL

RNA polymerase II regulatory region sequence-specific DNA binding

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

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 314314Paired mesoderm homeobox protein 2B
PRO_0000049262

Regions

DNA binding98 – 15760Homeobox
Compositional bias159 – 1679Poly-Ala
Compositional bias212 – 2176Poly-Gly
Compositional bias241 – 26020Poly-Ala

Natural variations

Natural variant1001R → L Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma family. Ref.7
VAR_026969
Natural variant1411R → G. Ref.7
Corresponds to variant rs28939716 [ dbSNP | Ensembl ].
VAR_026970
Natural variant1411R → Q in CCHS. Ref.8
VAR_046900
Natural variant1431Q → R in CCHS. Ref.8
VAR_046901
Natural variant1971G → D Confers susceptibility to neuroblastoma. Ref.10
VAR_046902
Natural variant2411A → AAAAAAAAAAA in CCHS. Ref.5
VAR_018257
Natural variant254 – 2585Missing.
VAR_018258
Natural variant255 – 2595Missing.
VAR_018259

Experimental info

Sequence conflict2921A → G in BAA11555. Ref.1
Sequence conflict2921A → G in AAD26698. Ref.2
Sequence conflict2921A → G in BAA82670. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q99453 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 40737F71948B595A

FASTA31431,621
        10         20         30         40         50         60 
MYKMEYSYLN SSAYESCMAG MDTSSLASAY ADFSSCSQAS GFQYNPIRTT FGATSGCPSL 

        70         80         90        100        110        120 
TPGSCSLGTL RDHQSSPYAA VPYKLFTDHG GLNEKRKQRR IRTTFTSAQL KELERVFAET 

       130        140        150        160        170        180 
HYPDIYTREE LALKIDLTEA RVQVWFQNRR AKFRKQERAA AAAAAAAKNG SSGKKSDSSR 

       190        200        210        220        230        240 
DDESKEAKST DPDSTGGPGP NPNPTPSCGA NGGGGGGPSP AGAPGAAGPG GPGGEPGKGG 

       250        260        270        280        290        300 
AAAAAAAAAA AAAAAAAAAA GGLAAAGGPG QGWAPGPGPI TSIPDSLGGP FASVLSSLQR 

       310 
PNGAKAALVK SSMF 

« Hide

References

« Hide 'large scale' references
[1]"Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles."
Yokoyama M., Nishi Y., Yoshii J., Okubo K., Matsubara K.
DNA Res. 3:311-320(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Neuroblastoma.
[2]"Paired-like homeodomain proteins Phox2a/Arix and Phox2b/NBPhox have similar genetic organization and independently regulate dopamine beta-hydroxylase gene transcription."
Adachi M., Browne D., Lewis E.J.
DNA Cell Biol. 19:539-554(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Genomic structure and functional characterization of NBPhox (PMX2B), a homeodomain protein specific to catecholaminergic cells that is involved in second messenger-mediated transcriptional activation."
Yokoyama M., Watanabe H., Nakamura M.
Genomics 59:40-50(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [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]"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 CCHS ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-241 INS, VARIANTS 254-ALA--ALA-258 DEL AND 255-ALA--ALA-259 DEL.
[6]"Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome."
Amiel J., Laudier B., Attie-Bitach T., Trang H., de Pontual L., Gener B., Trochet D., Etchevers H., Ray P., Simonneau M., Vekemans M., Munnich A., Gaultier C., Lyonnet S.
Nat. Genet. 33:459-461(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CCHS, TRIPLET REPEAT EXPANSION.
[7]"Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma."
Trochet D., Bourdeaut F., Janoueix-Lerosey I., Deville A., de Pontual L., Schleiermacher G., Coze C., Philip N., Frebourg T., Munnich A., Lyonnet S., Delattre O., Amiel J.
Am. J. Hum. Genet. 74:761-764(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-100 AND GLY-141.
[8]"PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome."
Trochet D., O'Brien L.M., Gozal D., Trang H., Nordenskjoeld A., Laudier B., Svensson P.-J., Uhrig S., Cole T., Niemann S., Munnich A., Gaultier C., Lyonnet S., Amiel J.
Am. J. Hum. Genet. 76:421-426(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CCHS GLN-141 AND ARG-143, TRIPLET REPEAT EXPANSION.
[9]Erratum
Trochet D., O'Brien L.M., Gozal D., Trang H., Nordenskjoeld A., Laudier B., Svensson P.-J., Uhrig S., Cole T., Niemann S., Munnich A., Gaultier C., Lyonnet S., Amiel J.
Am. J. Hum. Genet. 76:715-715(2002)
[10]"PHOX2B analysis in non-syndromic neuroblastoma cases shows novel mutations and genotype-phenotype associations."
McConville C., Reid S., Baskcomb L., Douglas J., Rahman N.
Am. J. Med. Genet. A 140:1297-1301(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-197, NEUROBLASTOMA SUSCEPTIBILITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D82344 mRNA. Translation: BAA11555.1.
AF117979 Genomic DNA. Translation: AAD26698.1.
AB015671 Genomic DNA. Translation: BAA82670.1.
BC017199 mRNA. Translation: AAH17199.1.
CCDSCCDS3463.1.
PIRJC5273.
RefSeqNP_003915.2. NM_003924.3.
UniGeneHs.87202.

3D structure databases

ProteinModelPortalQ99453.
SMRQ99453. Positions 100-157.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114443. 1 interaction.
STRING9606.ENSP00000226382.

PTM databases

PhosphoSiteQ99453.

Polymorphism databases

DMDM116242712.

Proteomic databases

PaxDbQ99453.
PRIDEQ99453.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000226382; ENSP00000226382; ENSG00000109132.
GeneID8929.
KEGGhsa:8929.
UCSCuc003gwf.4. human.

Organism-specific databases

CTD8929.
GeneCardsGC04M041746.
GeneReviewsPHOX2B.
H-InvDBHIX0120072.
HGNCHGNC:9143. PHOX2B.
MIM209880. phenotype.
603851. gene.
613013. phenotype.
neXtProtNX_Q99453.
Orphanet99803. Haddad syndrome.
635. Neuroblastoma.
661. Ondine syndrome.
PharmGKBPA33467.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG301263.
HOGENOMHOG000013060.
HOVERGENHBG094678.
InParanoidQ99453.
KOK09330.
OMALVKTSMF.
OrthoDBEOG7C2R1F.
PhylomeDBQ99453.
TreeFamTF351612.

Enzyme and pathway databases

SignaLinkQ99453.

Gene expression databases

BgeeQ99453.
CleanExHS_PHOX2B.
GenevestigatorQ99453.

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

GeneWikiPHOX2B.
GenomeRNAi8929.
NextBio33574.
PROQ99453.
SOURCESearch...

Entry information

Entry namePHX2B_HUMAN
AccessionPrimary (citable) accession number: Q99453
Secondary accession number(s): Q6PJD9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 141 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 4

Human chromosome 4: entries, gene names and cross-references to MIM