Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Grainyhead-like protein 3 homolog

Gene

Grhl3

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

Functioni

Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes. Essential for epidermal differentiation and barrier formation at the end of embryogenesis with TGM3 as critical direct target (PubMed:21081122, PubMed:20654612, PubMed:25347468). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events such as eyelid fusion and epidermal wound repair (PubMed:21081122). Despite being dispensable during normal epidermal homeostasis in the adulthood, is again required for barrier repair after immune-mediated epidermal damage, regulates distinct gene batteries in embryonic epidermal differentiation and adult epidermal barrier reformation after injury (PubMed:25347468). Plays unique and cooperative roles with GRHL2 in establishing distinct zones of primary neurulation. Essential for spinal closure, functions cooperatively with GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (PubMed:14608380, PubMed:20654612). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL1, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122).6 Publications

GO - Molecular functioni

GO - Biological processi

  • central nervous system development Source: MGI
  • cochlea morphogenesis Source: MGI
  • ectoderm development Source: MGI
  • epidermis development Source: UniProtKB
  • establishment of planar polarity Source: MGI
  • establishment of skin barrier Source: UniProtKB
  • eyelid development in camera-type eye Source: MGI
  • neural tube closure Source: UniProtKB
  • pattern specification process Source: MGI
  • planar cell polarity pathway involved in neural tube closure Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of GTPase activity Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of actin cytoskeleton organization Source: MGI
  • transcription from RNA polymerase II promoter Source: MGI
  • wound healing Source: MGI
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Grainyhead-like protein 3 homologImported
Alternative name(s):
Transcription factor CP2-like 4
Gene namesi
Name:Grhl3Imported
Synonyms:Get1, Som1 Publication, Tfcp2l4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2655333. Grhl3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant pups display neural tube defects and don't survive to weaning. During embryogenesis, fail to form the epidermal barrier and exhibit defective neural tube closure and embryonic wound repair. The epidermis show a severe barrier function defect associated with impaired differentiation of the epidermis, including defects of the stratum corneum, extracellular lipid composition and cell adhesion in the granular layer. Embryos have thoracolumbosacral spina bifida and curled tail, and 2% have coincident exencephaly. Embryos are smaller than their control littermates, exhibit failed eyelid fusion, the penetrance of which is influenced by genetic background, and shorter intestine with blood in the lumen (PubMed:14608380, PubMed:16949565, PubMed:21081122). Embryos have oral bilateral epithelial adhesions because of the loss of periderm and a cleft palate in some cases (PubMed:24360809). LMO4:GRHL3 double knockout embryos show significantly more frequent exencephaly than that found in single knockouts. Similarly, open-eye phenotype was more penetrant in double knockout mice. Double mutants show an enhancement of the epidermal terminal differentiation defect (PubMed:16949565).5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 603603Grainyhead-like protein 3 homologPRO_0000227998Add
BLAST

Proteomic databases

PaxDbiQ5FWH3.
PeptideAtlasiQ5FWH3.
PRIDEiQ5FWH3.

PTM databases

iPTMnetiQ5FWH3.
PhosphoSiteiQ5FWH3.

Expressioni

Developmental stagei

At E8.5, expression is confined to the non-neural ectoderm immediately adjacent to the neural plate, which was undergoing folding to form the neural tube. At later time points, more widespread expression is observed in the surface ectoderm, with a progressive increase until E15.5. Also expressed in other tissues lined by squamous epithelium, including the oral cavity, urogenital sinus and anal canal.1 Publication

Gene expression databases

BgeeiQ5FWH3.
CleanExiMM_GRHL3.
GenevisibleiQ5FWH3. MM.

Interactioni

Subunit structurei

Homodimer, also forms heterodimers with GRHL1 and GRHL2 (By similarity). Interacts with LMO4 (PubMed:16949565).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000101481.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 9566Transcription activationBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the grh/CP2 family. Grainyhead subfamily.Curated

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ5FWH3.
KOiK09275.
OMAiRTCSPFA.
OrthoDBiEOG744T8S.
PhylomeDBiQ5FWH3.
TreeFamiTF314132.

Family and domain databases

InterProiIPR007604. CP2.
[Graphical view]
PfamiPF04516. CP2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5FWH3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSNELDFRSV RLLKNDPVSF QKFPYSNEDE AWKTYLENPL TAATKAMMRV
60 70 80 90 100
NGDEESVAAL SFLYDYYMGP KEKRILSSST GGRNDQGKKF YHSMDYEPDL
110 120 130 140 150
APLESPTHLM KFLTENVSGS PDYTDQLKKN NLLGLEGVLP TPGKTNTVPP
160 170 180 190 200
GPSKLEASSM DSYLLPASDI YDNGSLNSLF ESIHGVPPTQ RWQPDSTFKD
210 220 230 240 250
DPQESLLFPD ILKTSPDPPC PEDYPGLKSD FEYTLGSPKA IHIKAGESPM
260 270 280 290 300
AYLNKGQFYP VTLRTPAGGK GLALSSSKVK SVVMVVFDND KVPVEQLRFW
310 320 330 340 350
RHWHSRQPTA KQRVIDVADC KENFNTVQHI EEVAYNALSF VWNVNEEAKV
360 370 380 390 400
FIGVNCLSTD FSSQKGVKGV PLNLQIDTYD CGAGTERLVH RAVCQIKIFC
410 420 430 440 450
DKGAERKMRD DERKQFRRKV KCPDSSNNAG IKGCLLSGFR GNETTYLRPE
460 470 480 490 500
TDLETQPVLF IPNLHFSSLQ RPGGVVPSAG HSSSDRLPLK RTCSPFAEEF
510 520 530 540 550
EPLPSKQAKE DDLQRVLLYV RRETEEVFDA LMLKTPDLKG LRNAISEKYG
560 570 580 590 600
LPEENICKVY KKCKRGILVN MDNNIIQHYS NHVAFLLDMG ELDGKIQIIL

KEL
Length:603
Mass (Da):67,816
Last modified:March 1, 2005 - v1
Checksum:iB08AFA95155E05A9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL670720 Genomic DNA. Translation: CAM20773.1.
BC089372 mRNA. Translation: AAH89372.1.
CCDSiCCDS38920.1.
RefSeqiNP_001013778.1. NM_001013756.1.
UniGeneiMm.331972.

Genome annotation databases

EnsembliENSMUST00000105855; ENSMUSP00000101481; ENSMUSG00000037188.
GeneIDi230824.
KEGGimmu:230824.
UCSCiuc008vgr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL670720 Genomic DNA. Translation: CAM20773.1.
BC089372 mRNA. Translation: AAH89372.1.
CCDSiCCDS38920.1.
RefSeqiNP_001013778.1. NM_001013756.1.
UniGeneiMm.331972.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000101481.

PTM databases

iPTMnetiQ5FWH3.
PhosphoSiteiQ5FWH3.

Proteomic databases

PaxDbiQ5FWH3.
PeptideAtlasiQ5FWH3.
PRIDEiQ5FWH3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000105855; ENSMUSP00000101481; ENSMUSG00000037188.
GeneIDi230824.
KEGGimmu:230824.
UCSCiuc008vgr.1. mouse.

Organism-specific databases

CTDi57822.
MGIiMGI:2655333. Grhl3.

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ5FWH3.
KOiK09275.
OMAiRTCSPFA.
OrthoDBiEOG744T8S.
PhylomeDBiQ5FWH3.
TreeFamiTF314132.

Miscellaneous databases

PROiQ5FWH3.
SOURCEiSearch...

Gene expression databases

BgeeiQ5FWH3.
CleanExiMM_GRHL3.
GenevisibleiQ5FWH3. MM.

Family and domain databases

InterProiIPR007604. CP2.
[Graphical view]
PfamiPF04516. CP2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "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: Eye.
  3. "Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3."
    Ting S.B., Wilanowski T., Auden A., Hall M., Voss A.K., Thomas T., Parekh V., Cunningham J.M., Jane S.M.
    Nat. Med. 9:1513-1519(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  4. "The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4."
    Yu Z., Lin K.K., Bhandari A., Spencer J.A., Xu X., Wang N., Lu Z., Gill G.N., Roop D.R., Wertz P., Andersen B.
    Dev. Biol. 299:122-136(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "Regional neural tube closure defined by the Grainy head-like transcription factors."
    Rifat Y., Parekh V., Wilanowski T., Hislop N.R., Auden A., Ting S.B., Cunningham J.M., Jane S.M.
    Dev. Biol. 345:237-245(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  6. "The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity."
    Boglev Y., Wilanowski T., Caddy J., Parekh V., Auden A., Darido C., Hislop N.R., Cangkrama M., Ting S.B., Jane S.M.
    Dev. Biol. 349:512-522(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPED, SUBCELLULAR LOCATION, DNA-BINDING.
  7. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "A GRHL3-regulated repair pathway suppresses immune-mediated epidermal hyperplasia."
    Gordon W.M., Zeller M.D., Klein R.H., Swindell W.R., Ho H., Espetia F., Gudjonsson J.E., Baldi P.F., Andersen B.
    J. Clin. Invest. 124:5205-5218(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiGRHL3_MOUSE
AccessioniPrimary (citable) accession number: Q5FWH3
Secondary accession number(s): A2ADI2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2005
Last modified: July 6, 2016
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.1 Publication

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.