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Q99453

- PHX2B_HUMAN

UniProt

Q99453 - PHX2B_HUMAN

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Protein
Paired mesoderm homeobox protein 2B
Gene
PHOX2B, PMX2B
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi98 – 15760Homeobox
Add
BLAST

GO - Molecular functioni

  1. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  2. RNA polymerase II regulatory region sequence-specific DNA binding Source: BHF-UCL
  3. sequence-specific DNA binding transcription factor activity Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. autonomic nervous system development Source: BHF-UCL
  2. brainstem development Source: BHF-UCL
  3. cell differentiation in hindbrain Source: BHF-UCL
  4. cellular response to BMP stimulus Source: BHF-UCL
  5. dopaminergic neuron differentiation Source: BHF-UCL
  6. efferent axon development in a lateral line nerve Source: BHF-UCL
  7. enteric nervous system development Source: BHF-UCL
  8. glial cell differentiation Source: BHF-UCL
  9. hindbrain tangential cell migration Source: BHF-UCL
  10. inner ear development Source: BHF-UCL
  11. medullary reticular formation development Source: BHF-UCL
  12. negative regulation of cell cycle arrest Source: UniProtKB
  13. negative regulation of cell proliferation Source: Ensembl
  14. negative regulation of neuron differentiation Source: Ensembl
  15. neural crest cell migration involved in autonomic nervous system development Source: BHF-UCL
  16. neuron migration Source: BHF-UCL
  17. noradrenergic neuron development Source: UniProtKB
  18. noradrenergic neuron differentiation Source: BHF-UCL
  19. parasympathetic nervous system development Source: BHF-UCL
  20. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  21. positive regulation of neuron differentiation Source: Ensembl
  22. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  23. regulation of gene expression Source: UniProtKB
  24. regulation of respiratory gaseous exchange by neurological system process Source: BHF-UCL
  25. respiratory system development Source: BHF-UCL
  26. retrotrapezoid nucleus neuron differentiation Source: BHF-UCL
  27. skeletal muscle cell differentiation Source: Ensembl
  28. sympathetic ganglion development Source: UniProtKB
  29. sympathetic nervous system development Source: BHF-UCL
  30. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

SignaLinkiQ99453.

Names & Taxonomyi

Protein namesi
Recommended name:
Paired mesoderm homeobox protein 2B
Alternative name(s):
Neuroblastoma Phox
Short name:
NBPhox
PHOX2B homeodomain protein
Paired-like homeobox 2B
Gene namesi
Name:PHOX2B
Synonyms:PMX2B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:9143. PHOX2B.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. nuclear chromatin Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.3 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti141 – 1411R → Q in CCHS. 1 Publication
VAR_046900
Natural varianti143 – 1431Q → R in CCHS. 1 Publication
VAR_046901
Natural varianti241 – 2411A → AAAAAAAAAAA in CCHS. 1 Publication
VAR_018257
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.

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi209880. phenotype.
613013. phenotype.
Orphaneti99803. Haddad syndrome.
635. Neuroblastoma.
661. Ondine syndrome.
PharmGKBiPA33467.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 314314Paired mesoderm homeobox protein 2B
PRO_0000049262Add
BLAST

Proteomic databases

PaxDbiQ99453.
PRIDEiQ99453.

PTM databases

PhosphoSiteiQ99453.

Expressioni

Tissue specificityi

Expressed in neuroblastoma, brain and adrenal gland.

Gene expression databases

BgeeiQ99453.
CleanExiHS_PHOX2B.
GenevestigatoriQ99453.

Interactioni

Subunit structurei

Interacts with TRIM11 By similarity.

Protein-protein interaction databases

BioGridi114443. 1 interaction.
STRINGi9606.ENSP00000226382.

Structurei

3D structure databases

ProteinModelPortaliQ99453.
SMRiQ99453. Positions 100-157.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi159 – 1679Poly-Ala
Compositional biasi212 – 2176Poly-Gly
Compositional biasi241 – 26020Poly-Ala
Add
BLAST

Sequence similaritiesi

Belongs to the paired homeobox family.

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG301263.
HOGENOMiHOG000013060.
HOVERGENiHBG094678.
InParanoidiQ99453.
KOiK09330.
OMAiLVKTSMF.
OrthoDBiEOG7C2R1F.
PhylomeDBiQ99453.
TreeFamiTF351612.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99453-1 [UniParc]FASTAAdd to Basket

« Hide

MYKMEYSYLN SSAYESCMAG MDTSSLASAY ADFSSCSQAS GFQYNPIRTT    50
FGATSGCPSL TPGSCSLGTL RDHQSSPYAA VPYKLFTDHG GLNEKRKQRR 100
IRTTFTSAQL KELERVFAET HYPDIYTREE LALKIDLTEA RVQVWFQNRR 150
AKFRKQERAA AAAAAAAKNG SSGKKSDSSR DDESKEAKST DPDSTGGPGP 200
NPNPTPSCGA NGGGGGGPSP AGAPGAAGPG GPGGEPGKGG AAAAAAAAAA 250
AAAAAAAAAA GGLAAAGGPG QGWAPGPGPI TSIPDSLGGP FASVLSSLQR 300
PNGAKAALVK SSMF 314
Length:314
Mass (Da):31,621
Last modified:October 17, 2006 - v2
Checksum:i40737F71948B595A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti100 – 1001R → L Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma family. 1 Publication
VAR_026969
Natural varianti141 – 1411R → G.1 Publication
Corresponds to variant rs28939716 [ dbSNP | Ensembl ].
VAR_026970
Natural varianti141 – 1411R → Q in CCHS. 1 Publication
VAR_046900
Natural varianti143 – 1431Q → R in CCHS. 1 Publication
VAR_046901
Natural varianti197 – 1971G → D Confers susceptibility to neuroblastoma. 1 Publication
VAR_046902
Natural varianti241 – 2411A → AAAAAAAAAAA in CCHS. 1 Publication
VAR_018257
Natural varianti254 – 2585Missing.
VAR_018258
Natural varianti255 – 2595Missing.
VAR_018259

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti292 – 2921A → G in BAA11555. 1 Publication
Sequence conflicti292 – 2921A → G in AAD26698. 1 Publication
Sequence conflicti292 – 2921A → G in BAA82670. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D82344 mRNA. Translation: BAA11555.1.
AF117979 Genomic DNA. Translation: AAD26698.1.
AB015671 Genomic DNA. Translation: BAA82670.1.
BC017199 mRNA. Translation: AAH17199.1.
CCDSiCCDS3463.1.
PIRiJC5273.
RefSeqiNP_003915.2. NM_003924.3.
UniGeneiHs.87202.

Genome annotation databases

EnsembliENST00000226382; ENSP00000226382; ENSG00000109132.
GeneIDi8929.
KEGGihsa:8929.
UCSCiuc003gwf.4. human.

Polymorphism databases

DMDMi116242712.

Keywords - Coding sequence diversityi

Triplet repeat expansion

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D82344 mRNA. Translation: BAA11555.1 .
AF117979 Genomic DNA. Translation: AAD26698.1 .
AB015671 Genomic DNA. Translation: BAA82670.1 .
BC017199 mRNA. Translation: AAH17199.1 .
CCDSi CCDS3463.1.
PIRi JC5273.
RefSeqi NP_003915.2. NM_003924.3.
UniGenei Hs.87202.

3D structure databases

ProteinModelPortali Q99453.
SMRi Q99453. Positions 100-157.
ModBasei Search...

Protein-protein interaction databases

BioGridi 114443. 1 interaction.
STRINGi 9606.ENSP00000226382.

PTM databases

PhosphoSitei Q99453.

Polymorphism databases

DMDMi 116242712.

Proteomic databases

PaxDbi Q99453.
PRIDEi Q99453.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000226382 ; ENSP00000226382 ; ENSG00000109132 .
GeneIDi 8929.
KEGGi hsa:8929.
UCSCi uc003gwf.4. human.

Organism-specific databases

CTDi 8929.
GeneCardsi GC04M041746.
GeneReviewsi PHOX2B.
H-InvDBi HIX0120072.
HGNCi HGNC:9143. PHOX2B.
MIMi 209880. phenotype.
603851. gene.
613013. phenotype.
neXtProti NX_Q99453.
Orphaneti 99803. Haddad syndrome.
635. Neuroblastoma.
661. Ondine syndrome.
PharmGKBi PA33467.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG301263.
HOGENOMi HOG000013060.
HOVERGENi HBG094678.
InParanoidi Q99453.
KOi K09330.
OMAi LVKTSMF.
OrthoDBi EOG7C2R1F.
PhylomeDBi Q99453.
TreeFami TF351612.

Enzyme and pathway databases

SignaLinki Q99453.

Miscellaneous databases

GeneWikii PHOX2B.
GenomeRNAii 8929.
NextBioi 33574.
PROi Q99453.
SOURCEi Search...

Gene expression databases

Bgeei Q99453.
CleanExi HS_PHOX2B.
Genevestigatori Q99453.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view ]
Pfami PF00046. Homeobox. 1 hit.
[Graphical view ]
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. "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.

Entry informationi

Entry nameiPHX2B_HUMAN
AccessioniPrimary (citable) accession number: Q99453
Secondary accession number(s): Q6PJD9
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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