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Q99453

- PHX2B_HUMAN

UniProt

Q99453 - PHX2B_HUMAN

Protein

Paired mesoderm homeobox protein 2B

Gene

PHOX2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 2 (17 Oct 2006)
      Previous versions | rss
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    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 – 15760HomeoboxPROSITE-ProRule annotationAdd
    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

    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

    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 PROSITE-ProRule annotation

    GO - Cellular componenti

    1. nuclear chromatin Source: BHF-UCL

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 2BPRO_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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

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

    Sequence similaritiesi

    Belongs to the paired homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti292 – 2921A → G in BAA11555. (PubMed:9039501)Curated
    Sequence conflicti292 – 2921A → G in AAD26698. (PubMed:11034547)Curated
    Sequence conflicti292 – 2921A → G in BAA82670. (PubMed:10395798)Curated

    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.1 Publication
    VAR_018258
    Natural varianti255 – 2595Missing.1 Publication
    VAR_018259

    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...
    MobiDBi 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-InvDB 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

    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: October 1, 2014
    This is version 142 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