Q90VV1 · HES4B_XENLA
- ProteinTranscription factor HES-4-B
- Genehes4-b
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids277 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3'. Promotes floor plate development and prechordal plate development. Required for lens development as early as the stage of lens field formation, partly through regulation of gene expression of the cell cycle inhibitor cdknx/p27(xic1). Required for formation of the neural crest downstream of multiple signaling pathways, and acts at the neural plate border via both DNA-binding dependent and independent mechanisms; acts in a DNA-binding dependent manner to repress pro-apoptotic and neural crest differentiation genes, including id3, delta1, and cdknx/p27(xic1), and thus promote the cell survival of neural plate border cells and maintain them in an undifferentiated state. Represses transcription of id3, at least in part through the repression of bmp4. On the other hand, acts in a DNA-independent manner separate from the transcriptional repressor function, to stimulate cell proliferation and promote neural crest formation. Via this DNA-independent route, acts in neurulae upstream of stat3 to transiently up-regulate the notch ligand dll1/delta1, which in turn up-regulates id3 expression. Then interacts directly with id3, which blocks the transcriptional repressor function of hes4-B/hairy2b to allow the progression of neural crest progenitors through specification and differentiation. Also acts via repressor-dependent and repressor-independent mechanisms in early gastrulae to establish the prospective anterior prechordal mesoderm identity in the Spemann organizer; induces specific genes independently from direct transcriptional regulation, and represses the genes specific for neighboring tissues through direct transcriptional repression. Modulates lateral inhibition during notch signaling and regulates the cell context dependent effects of notch (which can have inhibitory, permissive or enhancing roles in muscle or neural differentiation). Inhibits myogenesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | nucleus | |
Molecular Function | protein heterodimerization activity | |
Molecular Function | sequence-specific DNA binding | |
Biological Process | floor plate development | |
Biological Process | lens development in camera-type eye | |
Biological Process | muscle organ development | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | negative regulation of DNA-templated transcription | |
Biological Process | negative regulation of skeletal muscle tissue development | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | neural crest formation | |
Biological Process | Notch signaling pathway | |
Biological Process | prechordal plate formation |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameTranscription factor HES-4-B
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus
Accessions
- Primary accessionQ90VV1
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 43-47 | Disrupts DNA-binding. Unable to repress id3 transcription. Disrupts the ability to promote cell survival and up-regulate neural border genes. Does not disrupt the ability to promote cell proliferation and neural crest cell formation. | ||||
Sequence: EKRRR → RELEE |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000371246 | 1-277 | Transcription factor HES-4-B | |||
Sequence: MPADSMEKPTASPIAGAPANSAQTPDKPKSASEHRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNLQRVQMTAALTADPSVLGKYRAGFNECMNEVTRFLSTCEGVNTEVRTRLLGHLSSCLGQIVAMNYQQPPSSQQPVHVQLPSSTPVPMPCKVNPAEAISPKVFQGGFQLVPATDGQFAFLIPNPAYTSSPGPVIPLYANATSPGGPPSQSPVQGLTSFAHKMPHMAQAVSPLGGSTRADSAESVWRPW |
Expression
Tissue specificity
Dynamically expressed in the borders of several tissue territories. Expressed in the pre-placodal ectoderm (PPE) from gastrula stage. During gastrulation, expressed in the deep layer of the dorsal lip, the Spemann organizer and three distinct regions in the prospective neuroectoderm: neural plate border, presumptive floor plate/notoplate and anterior neural plate. At later stages, expression is localized to the anterior of the prechordal plate, the presomitic mesoderm, neural tube, neural crest derivatives and several tissues of the central nervous system, with expression in the developing floor plate continues to at least the tadpole stage. From the early tailbud stage, expressed in the dorsoanterior region of the developing pronephros. During early tailbud stages, broadly expressed within the pronephric mesoderm. and in the sensorial layer of the ectoderm covering the pronephros anlagen. During late tailbud to early tadpole stages, expressed in the ventral region of the pronephros. Expression remains in the proximal and distal tubules at late tadpole stages (stage 35).
Induction
By Notch-signaling. Acts in a complex regulatory loop with other transcription factors and neural crest inducing signals at the neural plate border.
Developmental stage
Expressed zygotically. Shows higher zygotic expression than hes4-A/hairy2a.
Gene expression databases
Interaction
Subunit
Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with the bHLH protein hes6; this interaction may inhibit the transcriptional repressor activity (By similarity).
Binds DNA in the form of a heterodimer with the bHLH protein hey1/hrt1. Interacts (via Orange domain) with id3 (via HLH domain)
Binds DNA in the form of a heterodimer with the bHLH protein hey1/hrt1. Interacts (via Orange domain) with id3 (via HLH domain)
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-44 | Disordered | ||||
Sequence: MPADSMEKPTASPIAGAPANSAQTPDKPKSASEHRKSSKPIMEK | ||||||
Compositional bias | 28-44 | Basic and acidic residues | ||||
Sequence: PKSASEHRKSSKPIMEK | ||||||
Domain | 34-91 | bHLH | ||||
Sequence: HRKSSKPIMEKRRRARINESLGQLKTLILDALKKDSSRHSKLEKADILEMTVKHLRNL | ||||||
Domain | 110-143 | Orange | ||||
Sequence: YRAGFNECMNEVTRFLSTCEGVNTEVRTRLLGHL | ||||||
Region | 258-277 | Disordered | ||||
Sequence: VSPLGGSTRADSAESVWRPW | ||||||
Motif | 274-277 | WRPW motif | ||||
Sequence: WRPW |
Domain
Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins (By similarity).
The WPRW motif is also required for the inductive function, independent of a transcription regulation activity
The WPRW motif is also required for the inductive function, independent of a transcription regulation activity
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length277
- Mass (Da)29,825
- Last updated2001-12-01 v1
- ChecksumF46C357B23484040
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 28-44 | Basic and acidic residues | ||||
Sequence: PKSASEHRKSSKPIMEK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF383160 EMBL· GenBank· DDBJ | AAK63842.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070547 EMBL· GenBank· DDBJ | AAH70547.1 EMBL· GenBank· DDBJ | mRNA | ||
AF356000 EMBL· GenBank· DDBJ | AAK39552.1 EMBL· GenBank· DDBJ | mRNA |