Q8C6A8 · BHE22_MOUSE

  • Protein
    Class E basic helix-loop-helix protein 22
  • Gene
    Bhlhe22
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix factors. Despite the presence of an intact basic domain, does not bind to DNA (By similarity).
In the brain, may function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization. May be required for the survival of a specific population of inhibitory neurons in the superficial laminae of the spinal cord dorsal horn that may regulate pruritis. Seems to play a crucial role in the retinogenesis, in the specification of amacrine and bipolar subtypes. Forms with PRDM8 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation (PubMed:22284184).

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular Functionchromatin binding
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular FunctionE-box binding
Molecular Functionidentical protein binding
Molecular Functionprotein dimerization activity
Biological Processamacrine cell differentiation
Biological Processanterior commissure morphogenesis
Biological Processaxon development
Biological Processcentral nervous system projection neuron axonogenesis
Biological Processcerebral cortex regionalization
Biological Processcorpus callosum morphogenesis
Biological Processcorticospinal tract morphogenesis
Biological ProcessGABAergic neuron differentiation
Biological Processnegative regulation of DNA-templated transcription
Biological Processneuron fate commitment
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processretina morphogenesis in camera-type eye
Biological Processretinal bipolar neuron differentiation
Biological Processsensory organ development

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Class E basic helix-loop-helix protein 22
  • Short names
    bHLHe22
  • Alternative names
    • Class B basic helix-loop-helix protein 5 (bHLHb5)
    • Protein BETA3

Gene names

    • Name
      Bhlhe22
    • Synonyms
      Bhlhb5

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8C6A8
  • Secondary accessions
    • Q9JL05

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Null mice exhibits aberrant expression of brain area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, vibrissal barrels display postsynaptic disorganization. In caudal motor cortex, anomalous differentiation of corticospinal motor neurons is observed, accompanied by failure of corticospinal tract formation. Mice also develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents, due to the selective loss of a subset of spinal cord inhibitory interneurons.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00002742861-355Class E basic helix-loop-helix protein 22

Proteomic databases

PTM databases

Expression

Tissue specificity

Brain-specific, with the highest expression in the cerebellum.

Developmental stage

Expressed at 11.5 dpc within the neuroblast layer (NBL) of the central retina. As retinogenesis progressed from central to peripheral retina from 12 dpc to 15.5 dpc, expression expanded to the entire retina with the majority of Bhlhb5+ cells being detected in the proliferating NBL. From 17.5 dpc to birth (P0), expression became restricted to the ganglion cell layer (GCL) and to the inner boundary of the NBL (INL; inner nuclear layer), presumably the newly formed ACL (amacrine cells). Predominantly expressed in post-mitotic cells in the developing retina. Expressed from 9.5 dpc in the neural tube, restricted to longitudinal ventral columns of neurons, extending from the hindbrain to the caudal spinal cord. In the developing cortex, at 12.5 dpc, expressed in the nascent cortical plate of the dorsal telencephalon (at protein level). During peak production of deep layer neurons between 12.5 and 13.5 dpc, restricted to postmigrational neurons, with no expression in the proliferative ventricular zone (VZ) or in migrating neurons. Between 15.5 and 17.5 dpc, when superficial layer neurons are generated, strongly expressed in the cortical plate and weakly in presumptive migrating neurons and in the subventricular zone (SVZ). Does not colocalize with proliferating progenitors in S or M phase in either the VZ or the SVZ; restricted to postmitotic glutamatergic projection neurons during neurogenesis. Not detected in cortical GABAergic interneurons or their extracortical sites of genesis, the medial and caudal ganglionic eminences (at protein level). Postnatally, down-regulation begins at the junction of the cingulate cortex and neocortex; by postnatal day 4 (P4), down-regulation well into the neocortex is observed anteriorly, with the exception of the most superficial layer. At P4, expressed in neocortical layers II, III, IV, and V. Within layer VI, expressed in only very rare scattered TBR1 negative neurons. Down-regulation continues from medial to lateral, exhibiting a markedly reduced expression by P14. Expression varies strikingly along the A-P axis with a precipitous decrease in the rostral cortical plate. At 12.5 dpc, highly expressed medially in the cingulate cortex with weak expression in the rest of the cortex. At 15.5 dpc, expressed in a high caudomedial to a low rostrolateral gradient. Between 15.5dpc and P0, expression increases laterally and the gradient gradually transforms into a sharp border between the presumptive rostral motor and sensory domains. During the first postnatal week, there is a further transformation from homogeneous expression across sensory cortex into discrete areas of high expression coincident with the primary sensory areas. At P4 and P7, expressed in primary visual cortex, primary auditory cortex and distinct primary somatosensory representations, including the vibrissal barrel field. In the spinal chord, transiently expressed in V1, V2, and dI6 interneurons at 10.5 dpc. Also observed in a subpopulation of late-born neurons that migrate to the superficial layers of the dorsal horn. Expression starts shortly after the neurons exit mitosis at 13.5 dpc and persisting for up to 2 weeks postnatally. At birth, about one-third of dorsal horn neurons expressing the protein are excitatory and two-thirds inhibitory. Also expressed in the developing eye and hair follicles, in the epithelial layer of the cochlea in the developing inner, and in the nasal epithelium. At 16.5 dpc, expressed outside the CNS, in particular in all sensory organs; in the nasal pits, transcripts can be detected in the olfactory epithelium. In the developing eye it can be found in the inner and outer retinal layer, and it is also detectable in the sensory layer of the cochlea in the developing inner ear. In addition, expression is found in the developing hair follicles, both in the epithelial component and in the dermal papilla, and in the skin.

Interaction

Subunit

Interacts with PRDM8.

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region34-90Disordered
Region128-215Disordered
Domain216-270bHLH

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    355
  • Mass (Da)
    35,217
  • Last updated
    2003-03-01 v1
  • Checksum
    CA221A9169FCB897
MERGLHLGAAAASEDDLFLHKSLGTSAAKRLEAAFRSTPPGMDLSLAPPTRERPASSSSPLGCFEPADPEGAGLRLPPPGGGGGASGGGGGVSVPGLLVGSAGVGGEPSLSSLPAGAALCLKYGESAGRGSVAESSGGEQSPDDDSDGLCELVLRAGGPDPRASPRAGGGSAKVAEGCSNAHLHGGSGLPPGGPTSGGGSGGGGGGSSKKSKEQKALRLNINARERRRMHDLNDALDELRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQALEEMRRLVAYLNQGQAISAASLPSSAAAAAAAAALHPALGAYEQAAGYPFSAGLPPAASCPEKCALFNSVSSSLCKQCTEKP

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0R4J056A0A0R4J056_MOUSEBhlhe22355

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict75in Ref. 1; AAF32324
Sequence conflict149in Ref. 1; AAF32324
Sequence conflict166in Ref. 1; AAF32324

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF218865
EMBL· GenBank· DDBJ
AAF32324.1
EMBL· GenBank· DDBJ
mRNA
AK076228
EMBL· GenBank· DDBJ
BAC36262.1
EMBL· GenBank· DDBJ
mRNA
BC053007
EMBL· GenBank· DDBJ
AAH53007.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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