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Protein

Transcription factor HES-4-B

Gene

hes4-b

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity8 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • floor plate development Source: UniProtKB
  • lens development in camera-type eye Source: UniProtKB
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of skeletal muscle tissue development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • neural crest formation Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB-KW
  • prechordal plate formation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Repressor
Biological processDifferentiation, Myogenesis, Neurogenesis, Notch signaling pathway, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor HES-4-B
Alternative name(s):
Hairy and enhancer of split 4-B
Protein hairy-2
Short name:
Xhairy21 Publication
Protein hairy-2a
Short name:
Xhairy2b1 Publication
Gene namesi
Name:hes4-b
Synonyms:hairy21 Publication, hairy2b1 Publication
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Organism-specific databases

XenbaseiXB-GENE-865740. hes4.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotationBy similarity

GO - Cellular componenti

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi43 – 47EKRRR → RELEE: 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. 2 Publications5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003712461 – 277Transcription factor HES-4-BAdd BLAST277

Expressioni

Tissue specificityi

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).9 Publications

Developmental stagei

Expressed zygotically. Shows higher zygotic expression than hes4-A/hairy2a.2 Publications

Inductioni

By Notch-signaling. Acts in a complex regulatory loop with other transcription factors and neural crest inducing signals at the neural plate border.4 Publications

Interactioni

Subunit structurei

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).By similarity3 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Structurei

3D structure databases

ProteinModelPortaliQ90VV1.
SMRiQ90VV1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 91bHLHPROSITE-ProRule annotationAdd BLAST58
Domaini110 – 143OrangePROSITE-ProRule annotationAdd BLAST34

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi274 – 277WRPW motifSequence analysis4

Domaini

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).By similarity
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.By similarity1 Publication

Phylogenomic databases

KOiK06054.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR003650. Orange_dom.
PfamiView protein in Pfam
PF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.

Sequencei

Sequence statusi: Complete.

Q90VV1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPADSMEKPT ASPIAGAPAN SAQTPDKPKS ASEHRKSSKP IMEKRRRARI
60 70 80 90 100
NESLGQLKTL ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRVQMTAAL
110 120 130 140 150
TADPSVLGKY RAGFNECMNE VTRFLSTCEG VNTEVRTRLL GHLSSCLGQI
160 170 180 190 200
VAMNYQQPPS SQQPVHVQLP SSTPVPMPCK VNPAEAISPK VFQGGFQLVP
210 220 230 240 250
ATDGQFAFLI PNPAYTSSPG PVIPLYANAT SPGGPPSQSP VQGLTSFAHK
260 270
MPHMAQAVSP LGGSTRADSA ESVWRPW
Length:277
Mass (Da):29,825
Last modified:December 1, 2001 - v1
Checksum:iF46C357B23484040
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF383160 mRNA. Translation: AAK63842.1.
BC070547 mRNA. Translation: AAH70547.1.
AF356000 mRNA. Translation: AAK39552.1.
RefSeqiNP_001082161.1. NM_001088692.1.
UniGeneiXl.86822.

Genome annotation databases

GeneIDi398258.
KEGGixla:398258.

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.

Entry informationi

Entry nameiHES4B_XENLA
AccessioniPrimary (citable) accession number: Q90VV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: December 1, 2001
Last modified: May 10, 2017
This is version 83 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

PubMed:17724611 reports that the probe used in PubMed:12774230 cross-hybridizes with hes4-A/hairy2a, so the maternal expression reported in PubMed:12774230 is in fact due to hes4-A/hairy2a and not hes4-B/hairy2b.Curated