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Entry version 112 (02 Jun 2021)
Sequence version 1 (01 Mar 2005)
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Protein

Grainyhead-like protein 3 homolog

Gene

Grhl3

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

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Grainyhead-like protein 3 homologImported
Alternative name(s):
Transcription factor CP2-like 4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Grhl3Imported
Synonyms:Get1, Som1 Publication, Tfcp2l4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:2655333, Grhl3

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>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

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002279981 – 603Grainyhead-like protein 3 homologAdd BLAST603

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q5FWH3

PeptideAtlas

More...
PeptideAtlasi
Q5FWH3

PRoteomics IDEntifications database

More...
PRIDEi
Q5FWH3

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
271016

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q5FWH3

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q5FWH3

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

At 8.5 dpc, 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 15.5 dpc. Also expressed in other tissues lined by squamous epithelium, including the oral cavity, urogenital sinus and anal canal.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000037188, Expressed in urinary bladder urothelium and 137 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q5FWH3, MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer, also forms heterodimers with GRHL1 and GRHL2 (By similarity).

Interacts with LMO4 (PubMed:16949565).

By similarity1 Publication

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000101481

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
Q5FWH3, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
Q5FWH3

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini226 – 461Grh/CP2 DBPROSITE-ProRule annotationAdd BLAST236

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni30 – 95Transcription activationBy similarityAdd BLAST66

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4091, Eukaryota

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000157970

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_021156_1_1_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q5FWH3

Identification of Orthologs from Complete Genome Data

More...
OMAi
PEENICK

Database of Orthologous Groups

More...
OrthoDBi
286319at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q5FWH3

TreeFam database of animal gene trees

More...
TreeFami
TF314132

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR007604, CP2

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF04516, CP2, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS51968, GRH_CP2_DB, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB08AFA95155E05A9
GO

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AL670720 Genomic DNA No translation available.
BC089372 mRNA Translation: AAH89372.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS38920.1

NCBI Reference Sequences

More...
RefSeqi
NP_001013778.1, NM_001013756.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000105855; ENSMUSP00000101481; ENSMUSG00000037188

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
230824

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:230824

UCSC genome browser

More...
UCSCi
uc008vgr.1, mouse

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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

3D structure databases

SMRiQ5FWH3
ModBaseiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000101481

PTM databases

iPTMnetiQ5FWH3
PhosphoSitePlusiQ5FWH3

Proteomic databases

PaxDbiQ5FWH3
PeptideAtlasiQ5FWH3
PRIDEiQ5FWH3
ProteomicsDBi271016

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
15710, 177 antibodies

The DNASU plasmid repository

More...
DNASUi
230824

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
57822
MGIiMGI:2655333, Grhl3

Phylogenomic databases

eggNOGiKOG4091, Eukaryota
GeneTreeiENSGT00940000157970
HOGENOMiCLU_021156_1_1_1
InParanoidiQ5FWH3
OMAiPEENICK
OrthoDBi286319at2759
PhylomeDBiQ5FWH3
TreeFamiTF314132

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
230824, 1 hit in 52 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
Grhl3, mouse

Protein Ontology

More...
PROi
PR:Q5FWH3
RNActiQ5FWH3, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000037188, Expressed in urinary bladder urothelium and 137 other tissues
GenevisibleiQ5FWH3, MM

Family and domain databases

InterProiView protein in InterPro
IPR007604, CP2
PfamiView protein in Pfam
PF04516, CP2, 1 hit
PROSITEiView protein in PROSITE
PS51968, GRH_CP2_DB, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiGRHL3_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q5FWH3
Secondary accession number(s): A2ADI2
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 1, 2005
Last modified: June 2, 2021
This is version 112 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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
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