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Protein

Grainyhead-like protein 3 homolog

Gene

Grhl3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:2655333 Grhl3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00002279981 – 603Grainyhead-like protein 3 homologAdd BLAST603

Proteomic databases

PaxDbiQ5FWH3
PeptideAtlasiQ5FWH3
PRIDEiQ5FWH3

PTM databases

iPTMnetiQ5FWH3
PhosphoSitePlusiQ5FWH3

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

BgeeiENSMUSG00000037188 Expressed in 94 organ(s), highest expression level in urinary bladder urothelium
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

Structurei

3D structure databases

SMRiQ5FWH3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 95Transcription activationBy similarityAdd BLAST66

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG4091 Eukaryota
ENOG410XNZ6 LUCA
GeneTreeiENSGT00760000119235
HOGENOMiHOG000220859
HOVERGENiHBG054154
InParanoidiQ5FWH3
KOiK09275
OMAiKRTCSPF
OrthoDBiEOG091G03ME
PhylomeDBiQ5FWH3
TreeFamiTF314132

Family and domain databases

InterProiView protein in InterPro
IPR007604 CP2
PfamiView protein in Pfam
PF04516 CP2, 1 hit

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 No translation available.
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL670720 Genomic DNA No translation available.
BC089372 mRNA Translation: AAH89372.1
CCDSiCCDS38920.1
RefSeqiNP_001013778.1, NM_001013756.1
UniGeneiMm.331972

3D structure databases

SMRiQ5FWH3
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiQ5FWH3
PhosphoSitePlusiQ5FWH3

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
OMAiKRTCSPF
OrthoDBiEOG091G03ME
PhylomeDBiQ5FWH3
TreeFamiTF314132

Miscellaneous databases

PROiPR:Q5FWH3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037188 Expressed in 94 organ(s), highest expression level in urinary bladder urothelium
CleanExiMM_GRHL3
GenevisibleiQ5FWH3 MM

Family and domain databases

InterProiView protein in InterPro
IPR007604 CP2
PfamiView protein in Pfam
PF04516 CP2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGRHL3_MOUSE
AccessioniPrimary (citable) accession number: Q5FWH3
Secondary accession number(s): A2ADI2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2005
Last modified: September 12, 2018
This is version 95 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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