Q99453 (PHX2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:	PHOX2B
Synonyms:	PMX2B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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 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	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 proliferation Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara 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 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 neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16144830PubMed 16280598. Source: BHF-UCL 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 sympathetic nervous system development Inferred from sequence or structural similarity. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 16280598. Source: BHF-UCL
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from direct assay PubMed 16144830. Source: BHF-UCL sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
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

	Sequence		Length	Mass (Da)
	Q99453 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 40737F71948B595A	FASTA	314	31,621
	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

References

	« Hide 'large scale' referencesShow '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.

Web resources

GeneReviews

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.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000226382.
PTM databases
PhosphoSite	Q99453.
Polymorphism databases
DMDM	116242712.
Proteomic databases
PaxDb	Q99453.
PRIDE	Q99453.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000226382; ENSP00000226382; ENSG00000109132.
GeneID	8929.
KEGG	hsa:8929.
UCSC	uc003gwf.4. human.
Organism-specific databases
CTD	8929.
GeneCards	GC04M041746.
H-InvDB	HIX0120072.
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	NOG301263.
HOGENOM	HOG000013060.
HOVERGEN	HBG094678.
InParanoid	Q99453.
KO	K09330.
OMA	LVKTSMF.
PhylomeDB	Q99453.
Gene expression databases
Bgee	Q99453.
CleanEx	HS_PHOX2B.
Genevestigator	Q99453.
GermOnline	ENSG00000109132. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. [Graphical view]
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
GenomeRNAi	8929.
NextBio	33574.
SOURCE	Search...

Entry information

Entry name

PHX2B_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 131 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.