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FLASH GENE

Symbol

PHOX2B

contributors: mct - updated : 14-01-2011

HGNC name	paired-like homeobox 2b
HGNC id	9143

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CCHS3 congenital central hypoventilation syndrome 3 NBL4 neuroblastoma
Location	4p13      Physical location : 41.746.099 - 41.750.987
Synonym name	paired mesoderm homeobox 2b
	neuroblastoma paired-type homeobox protein
	neuroblastoma Phox
	PHOX2B homeodomain protein
Synonym symbol(s)	NBPHOX, PMXB, PMX2B, NBLST2

DNA

TYPE	functioning gene
STRUCTURE	4.89 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003924 3 - 3033 NP_003915 31.5 314 - 2008 18438890

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland         Nervous brain       moderately Reproductive male system prostate     moderately Respiratory lung       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol nervous neuron

cell lineage
cell lines	neuroblastoma cell lines
fluid/secretion

at STAGE

physiological period

embryo

Text	expressed during neural development in central autonomic circuits and perpheral neural crest deerivatives

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a paired-like homeodomain protein
	two short and stable polyalanine repeats of 9 and 20n residues, respectively
	five putative DNA sites that potentially bind homeodomain proteins, including PHOX2B itself

HOMOLOGY

intraspecies

homolog to ARIX

Homologene

FAMILY

paired homeobox family

CATEGORY

transcription factor , signaling neurotransmitter

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome
text	mutants carrying alanine expansion retained in the cytoplasm, both in widespread diffuse and in aggregated forms

basic FUNCTION	involved in the signal-mediated expression in developing and mature catecholaminergic cells and neuradrenergic neurons and regulating ARIX during nervous system development
	playing a major role in the patterning of the autonomous ventilation system and in the autonomic nervous system
	transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages
	regulates its own expression by a transcriptional auto-regulatory mechanism
	master regulator genes for peripheral SNS differentiation
	drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target)

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

nervous system

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with PHOX2A (for its transcriptional regulation) and with DBH (role in the catecholamine biosynthesis)
	needed for RET expression
	able to bind the cell-specific element in the 5 prime regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells (involved in the cascade leading to TLX2 transactivation and presumably in the intestinal neuronal differentiation)
	interacting with MSX1 (downstream target of PHOX2B that activates the Delta-Notch pathway in neuroblastoma
	HAND2 interacted with TCF3, and bound to the PHOX2B promoter region in sympathetic nervous system (SNS) differentiation
	HAND2 can activate the SNS differentiation program by induction of SNS-related genes, including PHOX2B, ASCL1, DBH and TH
	SOX10 regulation by PHOX2B is pivotal for the development and pathogenesis of the autonomic ganglia

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CCHS3 , NBL4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in familiar and sporadic neuroblastomas constitutional         schizophrenia with strabismus

Susceptibility

to neuroblastoma to Parkinson disease (in association with ASCL1)

Variant & Polymorphism other	variation in the 20-alanine homopolymer

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

murine b-/- death in utero