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Protein

Class E basic helix-loop-helix protein 22

Gene

Bhlhe22

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 chord 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).By similarity4 Publications

GO - Molecular functioni

  • chromatin binding Source: MGI
  • protein homodimerization activity Source: MGI
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: MGI

GO - Biological processi

  • anterior commissure morphogenesis Source: MGI
  • central nervous system projection neuron axonogenesis Source: MGI
  • cerebral cortex regionalization Source: MGI
  • corpus callosum morphogenesis Source: MGI
  • corticospinal tract morphogenesis Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • neuron differentiation Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: GOC
  • retinal bipolar neuron differentiation Source: MGI
  • retina morphogenesis in camera-type eye Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Neurogenesis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Class E basic helix-loop-helix protein 22
Short name:
bHLHe22
Alternative name(s):
Class B basic helix-loop-helix protein 5
Short name:
bHLHb5
Protein BETA3
Gene namesi
Name:Bhlhe22
Synonyms:Bhlhb5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1930001. Bhlhe22.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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 chord inhibitory interneurons.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 355355Class E basic helix-loop-helix protein 22PRO_0000274286Add
BLAST

Proteomic databases

MaxQBiQ8C6A8.
PaxDbiQ8C6A8.
PRIDEiQ8C6A8.

PTM databases

PhosphoSiteiQ8C6A8.

Expressioni

Tissue specificityi

Brain-specific, with the highest expression in the cerebellum.1 Publication

Developmental stagei

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.4 Publications

Gene expression databases

BgeeiQ8C6A8.

Interactioni

Subunit structurei

Interacts with PRDM8.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026120.

Chemistry

BindingDBiQ8C6A8.

Structurei

3D structure databases

ProteinModelPortaliQ8C6A8.
SMRiQ8C6A8. Positions 218-279.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini216 – 27055bHLHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi56 – 594Poly-Ser
Compositional biasi71 – 206136Gly-richAdd
BLAST
Compositional biasi289 – 33143Ala-richAdd
BLAST

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3898. Eukaryota.
ENOG410ZDH5. LUCA.
HOGENOMiHOG000060094.
InParanoidiQ8C6A8.
KOiK09086.
OrthoDBiEOG7GQXWR.
PhylomeDBiQ8C6A8.
TreeFamiTF322733.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR032654. Bhlhe22.
[Graphical view]
PANTHERiPTHR19290:SF52. PTHR19290:SF52. 2 hits.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8C6A8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERGLHLGAA AASEDDLFLH KSLGTSAAKR LEAAFRSTPP GMDLSLAPPT
60 70 80 90 100
RERPASSSSP LGCFEPADPE GAGLRLPPPG GGGGASGGGG GVSVPGLLVG
110 120 130 140 150
SAGVGGEPSL SSLPAGAALC LKYGESAGRG SVAESSGGEQ SPDDDSDGLC
160 170 180 190 200
ELVLRAGGPD PRASPRAGGG SAKVAEGCSN AHLHGGSGLP PGGPTSGGGS
210 220 230 240 250
GGGGGGSSKK SKEQKALRLN INARERRRMH DLNDALDELR AVIPYAHSPS
260 270 280 290 300
VRKLSKIATL LLAKNYILMQ AQALEEMRRL VAYLNQGQAI SAASLPSSAA
310 320 330 340 350
AAAAAAALHP ALGAYEQAAG YPFSAGLPPA ASCPEKCALF NSVSSSLCKQ

CTEKP
Length:355
Mass (Da):35,217
Last modified:March 1, 2003 - v1
Checksum:iCA221A9169FCB897
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti75 – 751R → L in AAF32324 (PubMed:12213201).Curated
Sequence conflicti149 – 1491L → R in AAF32324 (PubMed:12213201).Curated
Sequence conflicti166 – 1661R → G in AAF32324 (PubMed:12213201).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF218865 mRNA. Translation: AAF32324.1.
AK076228 mRNA. Translation: BAC36262.1.
BC053007 mRNA. Translation: AAH53007.1.
CCDSiCCDS17253.1.
RefSeqiNP_067535.3. NM_021560.4.
UniGeneiMm.149938.

Genome annotation databases

GeneIDi59058.
KEGGimmu:59058.
UCSCiuc008orl.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF218865 mRNA. Translation: AAF32324.1.
AK076228 mRNA. Translation: BAC36262.1.
BC053007 mRNA. Translation: AAH53007.1.
CCDSiCCDS17253.1.
RefSeqiNP_067535.3. NM_021560.4.
UniGeneiMm.149938.

3D structure databases

ProteinModelPortaliQ8C6A8.
SMRiQ8C6A8. Positions 218-279.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000026120.

Chemistry

BindingDBiQ8C6A8.

PTM databases

PhosphoSiteiQ8C6A8.

Proteomic databases

MaxQBiQ8C6A8.
PaxDbiQ8C6A8.
PRIDEiQ8C6A8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59058.
KEGGimmu:59058.
UCSCiuc008orl.2. mouse.

Organism-specific databases

CTDi27319.
MGIiMGI:1930001. Bhlhe22.

Phylogenomic databases

eggNOGiKOG3898. Eukaryota.
ENOG410ZDH5. LUCA.
HOGENOMiHOG000060094.
InParanoidiQ8C6A8.
KOiK09086.
OrthoDBiEOG7GQXWR.
PhylomeDBiQ8C6A8.
TreeFamiTF322733.

Miscellaneous databases

NextBioi314710.
PROiQ8C6A8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8C6A8.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR032654. Bhlhe22.
[Graphical view]
PANTHERiPTHR19290:SF52. PTHR19290:SF52. 2 hits.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor."
    Xu Z.-P., Dutra A., Stellrecht C.M., Wu C., Piatigorsky J., Saunders G.F.
    Genomics 80:311-318(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Head.
  3. "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].
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "Bhlhb5 is expressed in the CNS and sensory organs during mouse embryonic development."
    Brunelli S., Innocenzi A., Cossu G.
    Gene Expr. Patterns 3:755-759(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  5. "Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina."
    Feng L., Xie X., Joshi P.S., Yang Z., Shibasaki K., Chow R.L., Gan L.
    Development 133:4815-4825(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  6. "Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex."
    Joshi P.S., Molyneaux B.J., Feng L., Xie X., Macklis J.D., Gan L.
    Neuron 60:258-272(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  7. Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  8. "Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly."
    Ross S.E., McCord A.E., Jung C., Atan D., Mok S.I., Hemberg M., Kim T.K., Salogiannis J., Hu L., Cohen S., Lin Y., Harrar D., McInnes R.R., Greenberg M.E.
    Neuron 73:292-303(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PRDM8.

Entry informationi

Entry nameiBHE22_MOUSE
AccessioniPrimary (citable) accession number: Q8C6A8
Secondary accession number(s): Q9JL05
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: March 1, 2003
Last modified: February 17, 2016
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.