PHOX2B

Protein identityUniProt · HPA

UniProt accession

Q99453

Gene

PHOX2B

Ensembl

ENSG00000109132

Chromosome

4

Canonical length

314 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription factor involved in the development of several major noradrenergic neuron populations and the determination of neurotransmitter phenotype. The gene product is linked to enhancement of second messenger-mediated activation of the dopamine beta-hydroylase, c-fos promoters and several enhancers, including cyclic amp-response element and serum-response element. Expansion of a 20 amino acid polyalanine tract in this protein by 5-13 aa has been associated with congenital central hypoventilation syndrome. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

314 residues, UniProt reviewed canonical sequence.

>Q99453|PHOX2B
     1  MYKMEYSYLN SSAYESCMAG MDTSSLASAY ADFSSCSQAS GFQYNPIRTT FGATSGCPSL
    61  TPGSCSLGTL RDHQSSPYAA VPYKLFTDHG GLNEKRKQRR IRTTFTSAQL KELERVFAET
   121  HYPDIYTREE LALKIDLTEA RVQVWFQNRR AKFRKQERAA AAAAAAAKNG SSGKKSDSSR
   181  DDESKEAKST DPDSTGGPGP NPNPTPSCGA NGGGGGGPSP AGAPGAAGPG GPGGEPGKGG
   241  AAAAAAAAAA AAAAAAAAAA GGLAAAGGPG QGWAPGPGPI TSIPDSLGGP FASVLSSLQR
   301  PNGAKAALVK SSMF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PHOX2B can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.64

Highest tissue expression

8.1 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PHOX2B.

Disease | AllUniProt

Conditions PHOX2B is implicated in, by any mechanism.

• Central hypoventilation syndrome, congenital, 1 (CCHS1) MIM:209880
• Neuroblastoma 2 (NBLST2) MIM:613013

Disease | GeneticClinVar

82 pathogenic / likely-pathogenic of 1,269 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary cancer-predisposing syndrome
• PHOX2B-related disorder
• Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
• Congenital central hypoventilation
• Haddad syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.34

gnomAD pLI

0.94

gnomAD missense Z

2.08

DepMap mean gene effect

0.16

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autonomic nervous system development
• brainstem development
• cell differentiation in hindbrain
• cellular response to BMP stimulus
• cellular response to carbon dioxide
• dopaminergic neuron differentiation
• enteric nervous system development
• glial cell differentiation
• hindbrain tangential cell migration
• inner ear development
• membrane depolarization
• motor neuron migration
• negative regulation of neuron differentiation
• negative regulation of type B pancreatic cell proliferation
• neural crest cell migration involved in autonomic nervous system development
• neuron development
• neuron migration
• noradrenergic neuron development
• noradrenergic neuron differentiation
• positive regulation of cold-induced thermogenesis
• positive regulation of G2/M transition of mitotic cell cycle
• positive regulation of neuron differentiation
• positive regulation of transcription by RNA polymerase II
• regulation of gene expression
• regulation of respiratory gaseous exchange by nervous system process
• regulation of transcription by RNA polymerase II
• respiratory system development
• response to activity
• skeletal muscle cell differentiation
• sympathetic ganglion development
• sympathetic nervous system development
• type B pancreatic cell proliferation
• efferent axon development in a lateral line nerve
• medullary reticular formation development
• parasympathetic nervous system development
• retrotrapezoid nucleus neuron differentiation

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox, conserved site
• Paired Homeobox Transcription Factors
• Homeodomain

KeywordsUniProt

• Activator
• Developmental protein
• DNA-binding
• Homeobox
• Nucleus
• Transcription
• Transcription regulation
• Triplet repeat expansion

InteractionsUniProt · HPA

Protein binding partners of PHOX2B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TRIM11