Q99453 (PHX2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 117.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Paired mesoderm homeobox protein 2B Alternative name(s): Neuroblastoma Phox Short name=NBPhox PHOX2B homeodomain protein Paired-like homeobox 2B | ||||
| Gene names |
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| 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 | 314 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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 | Defects in PHOX2B are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. Most mutations consist of 5-10 alanine expansions in the poly-Ala region from amino acids 241-260. CCHS is a 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. CCHS is frequently complicated with neurocristopathies such as Hirschsprung disease that occurs in about 16% of CCHS cases. Ref.5 Ref.6 Ref.8 Defects in PHOX2B are the cause of susceptibility to neuroblastoma type 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. |
| 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 | Triplet repeat expansion |
| Disease | Disease mutation |
| Domain | Homeobox |
| Ligand | DNA-binding |
| Molecular function | Activator Developmental protein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: BHF-UCL transcription, DNA-dependentInferred 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 activityTraceable author statement. Source: ProtInc transcription cofactor activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 314 | 314 | Paired mesoderm homeobox protein 2B | PRO_0000049262 | |||||
Regions | |||||||||
| DNA binding | 98 – 157 | 60 | Homeobox | ||||||
| Compositional bias | 159 – 167 | 9 | Poly-Ala | ||||||
| Compositional bias | 212 – 217 | 6 | Poly-Gly | ||||||
| Compositional bias | 241 – 260 | 20 | Poly-Ala | ||||||
Natural variations | |||||||||
| Natural variant | 100 | 1 | R → L Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma family. Ref.7 | VAR_026969 | |||||
| Natural variant | 141 | 1 | R → G. Ref.7 Corresponds to variant rs28939716 [ dbSNP | Ensembl ]. | VAR_026970 | |||||
| Natural variant | 141 | 1 | R → Q in CCHS. Ref.8 | VAR_046900 | |||||
| Natural variant | 143 | 1 | Q → R in CCHS. Ref.8 | VAR_046901 | |||||
| Natural variant | 197 | 1 | G → D Confers susceptibility to neuroblastoma. Ref.10 | VAR_046902 | |||||
| Natural variant | 241 | 1 | A → AAAAAAAAAAA in CCHS. Ref.5 | VAR_018257 | |||||
| Natural variant | 254 – 258 | 5 | Missing. | VAR_018258 | |||||
| Natural variant | 255 – 259 | 5 | Missing. | VAR_018259 | |||||
Experimental info | |||||||||
| Sequence conflict | 292 | 1 | A → G in BAA11555. Ref.1 | ||||||
| Sequence conflict | 292 | 1 | A → G in AAD26698. Ref.2 | ||||||
| Sequence conflict | 292 | 1 | A → G in BAA82670. Ref.3 | ||||||
Sequences
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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: 9039501] [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: 11034547] [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: 10395798] [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: 15489334] [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: 14566559] [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: 12640453] [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: 15024693] [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: 15657873] [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: 16691592] [Abstract] Cited for: VARIANT ASP-197, NEUROBLASTOMA SUCEPTIBILITY. |
| + | Additional computationally mapped references. |
Web resources
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. |
| IPI | IPI00293143. |
| PIR | JC5273. |
| RefSeq | NP_003915.2. NM_003924.3. |
| UniGene | Hs.87202. |
3D structure databases | |
| ProteinModelPortal | Q99453. |
| SMR | Q99453. Positions 100-157. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q99453. |
Polymorphism databases | |
| DMDM | 116242712. |
Proteomic databases | |
| PRIDE | Q99453. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000226382; ENSP00000226382; ENSG00000109132. |
| GeneID | 8929. |
| KEGG | hsa:8929. |
| UCSC | uc003gwf.2. human. |
Organism-specific databases | |
| CTD | 8929. |
| GeneCards | GC04M041746. |
| H-InvDB | HIX0004178. |
| HGNC | HGNC:9143. PHOX2B. |
| MIM | 209880. phenotype. 603851. gene. 613013. phenotype. |
| neXtProt | NX_Q99453. |
| Orphanet | 99803. Haddad syndrome. 635. Neuroblastoma. 661. Ondine syndrome. |
| PharmGKB | PA33467. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG09311. |
| GeneTree | ENSGT00600000084177. |
| HOGENOM | HBG444376. |
| HOVERGEN | HBG094678. |
| InParanoid | Q99453. |
| OMA | LVKTSMF. |
| PhylomeDB | Q99453. |
Gene expression databases | |
| ArrayExpress | Q99453. |
| Bgee | Q99453. |
| CleanEx | HS_PHOX2B. |
| Genevestigator | Q99453. |
| GermOnline | ENSG00000109132. 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 | 33574. |
| SOURCE | Search... |
Entry information
| Entry name | PHX2B_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99453 Secondary accession number(s): Q6PJD9 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 4 Human chromosome 4: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

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