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Aliases for GRHL2 Gene

Aliases for GRHL2 Gene

  • Grainyhead-Like 2 (Drosophila) 2 3
  • Transcription Factor CP2-Like 3 2 3 4
  • TFCP2L3 3 4 6
  • Brother Of Mammalian Grainyhead 3 4
  • DFNA28 3 6
  • BOM 3 4
  • Grainyhead-Like Protein 2 Homolog 3
  • Deafness, Autosomal Dominant 28 2
  • ECTDS 3

External Ids for GRHL2 Gene

Previous HGNC Symbols for GRHL2 Gene

  • DFNA28
  • TFCP2L3

Previous GeneCards Identifiers for GRHL2 Gene

  • GC08P102575
  • GC08P097702

Summaries for GRHL2 Gene

Entrez Gene Summary for GRHL2 Gene

  • The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]

GeneCards Summary for GRHL2 Gene

GRHL2 (Grainyhead-Like 2 (Drosophila)) is a Protein Coding gene. Diseases associated with GRHL2 include deafness, autosomal dominant 28 and ectodermal dysplasia/short stature syndrome. An important paralog of this gene is UBP1.

UniProtKB/Swiss-Prot for GRHL2 Gene

  • Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456). Binds directly to the consensus DNA sequence 5-AACCGGTT-3 acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GRHL2 Gene

Genomics for GRHL2 Gene

Regulatory Elements for GRHL2 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for GRHL2 Gene

Start:
101,492,432 bp from pter
End:
101,669,726 bp from pter
Size:
177,295 bases
Orientation:
Plus strand

Genomic View for GRHL2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GRHL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRHL2 Gene

Proteins for GRHL2 Gene

  • Protein details for GRHL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6ISB3-GRHL2_HUMAN
    Recommended name:
    Grainyhead-like protein 2 homolog
    Protein Accession:
    Q6ISB3
    Secondary Accessions:
    • A1L303
    • Q6NT03
    • Q9H8B8

    Protein attributes for GRHL2 Gene

    Size:
    625 amino acids
    Molecular mass:
    71105 Da
    Quaternary structure:
    • Homodimer, also forms heterodimers with GRHL1 or GRHL3.
    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.

    Alternative splice isoforms for GRHL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRHL2 Gene

Proteomics data for GRHL2 Gene at MOPED

Post-translational modifications for GRHL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GRHL2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for GRHL2 Gene

Domains for GRHL2 Gene

Protein Domains for GRHL2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GRHL2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q6ISB3

UniProtKB/Swiss-Prot:

GRHL2_HUMAN :
  • Q6ISB3
Family:
  • Belongs to the grh/CP2 family. Grainyhead subfamily.
genes like me logo Genes that share domains with GRHL2: view

No data available for Gene Families for GRHL2 Gene

Function for GRHL2 Gene

Molecular function for GRHL2 Gene

UniProtKB/Swiss-Prot Function: Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456). Binds directly to the consensus DNA sequence 5-AACCGGTT-3 acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).
UniProtKB/Swiss-Prot Induction: Expressed in proliferating cells, the expression decreases during senescence. In keratinocytes, expression levels decrease upon calcium exposure.

Gene Ontology (GO) - Molecular Function for GRHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001161 intronic transcription regulatory region sequence-specific DNA binding ISS --
GO:0003677 DNA binding --
GO:0003700 sequence-specific DNA binding transcription factor activity ISS --
GO:0005515 protein binding IPI 25416956
GO:0031490 chromatin DNA binding IDA 21081122
genes like me logo Genes that share ontologies with GRHL2: view
genes like me logo Genes that share phenotypes with GRHL2: view

Animal Model Products

CRISPR Products

miRNA for GRHL2 Gene

miRTarBase miRNAs that target GRHL2
Targeting motifs for GRHL2 Gene
HOMER Transcription Factor Regulatory Elements motif GRHL2
  • Consensus sequence: AAACYKGTTWDACMRGTTTB Submotif: canonical Cell Type: HBE GeoId: GSE46194

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for GRHL2

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Animal Models and Transcription Factor Targeting for GRHL2 Gene

Localization for GRHL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRHL2 Gene

Nucleus. Membrane. Note=detected at cell-cell contact areas. {ECO:0000269 PubMed:25152456}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for GRHL2 Gene COMPARTMENTS Subcellular localization image for GRHL2 gene
Compartment Confidence
nucleus 5
cytosol 3

Gene Ontology (GO) - Cellular Components for GRHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 20938050
GO:0005911 cell-cell junction IDA 25152456
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with GRHL2: view

Pathways for GRHL2 Gene

SuperPathways for GRHL2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for GRHL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001701 in utero embryonic development IEA --
GO:0001843 neural tube closure ISS --
GO:0003208 cardiac ventricle morphogenesis IEA --
GO:0003382 epithelial cell morphogenesis ISS --
GO:0006351 transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with GRHL2: view

No data available for Pathways by source for GRHL2 Gene

Transcripts for GRHL2 Gene

Unigene Clusters for GRHL2 Gene

Grainyhead-like 2 (Drosophila):
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for GRHL2

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for GRHL2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for GRHL2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16
SP1: -
SP2:

Relevant External Links for GRHL2 Gene

GeneLoc Exon Structure for
GRHL2
ECgene alternative splicing isoforms for
GRHL2

Expression for GRHL2 Gene

mRNA expression in normal human tissues for GRHL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GRHL2 Gene

This gene is overexpressed in Esophagus - Mucosa (7.0), Skin - Sun Exposed (Lower leg) (6.9), Skin - Not Sun Exposed (Suprapubic) (6.7), Prostate (5.0), and Minor Salivary Gland (4.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for GRHL2 Gene

SOURCE GeneReport for Unigene cluster for GRHL2 Gene Hs.661088

mRNA Expression by UniProt/SwissProt for GRHL2 Gene

Q6ISB3-GRHL2_HUMAN
Tissue specificity: Expressed in keratinocytes (at protein level). Highly expressed in placenta, prostate, brain and kidney. Lower-level expression in a variety of epithelial tissues such as thymus, lung, salivary gland, mammary gland and digestive tract. Expressed in the cochlear.
genes like me logo Genes that share expressions with GRHL2: view

In Situ Assay Products

Orthologs for GRHL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for GRHL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRHL2 35
  • 99.84 (n)
  • 100 (a)
GRHL2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GRHL2 35
  • 91.68 (n)
  • 96.64 (a)
GRHL2 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GRHL2 35
  • 92.48 (n)
  • 96.48 (a)
GRHL2 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Grhl2 35
  • 88.53 (n)
  • 94.72 (a)
Grhl2 16
Grhl2 36
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GRHL2 36
  • 92 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRHL2 36
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grhl2 35
  • 88.27 (n)
  • 94.72 (a)
chicken
(Gallus gallus)
Aves GRHL2 35
  • 80.85 (n)
  • 87.86 (a)
GRHL2 36
  • 88 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRHL2 36
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grhl2 35
  • 76 (n)
  • 82.85 (a)
zebrafish
(Danio rerio)
Actinopterygii grhl2a 36
  • 63 (a)
OneToMany
grhl2b 35
  • 71.56 (n)
  • 73.73 (a)
grhl2b 36
  • 73 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta grh 36
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea grh-1 36
  • 30 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 43 (a)
OneToMany
Species with no ortholog for GRHL2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GRHL2 Gene

ENSEMBL:
Gene Tree for GRHL2 (if available)
TreeFam:
Gene Tree for GRHL2 (if available)

Paralogs for GRHL2 Gene

Paralogs for GRHL2 Gene

Selected SIMAP similar genes for GRHL2 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with GRHL2: view

Variants for GRHL2 Gene

Sequence variations from dbSNP and Humsavar for GRHL2 Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type MAF
rs470801 -- 101,542,832(+) agggg(A/G)tgaag intron-variant
rs471757 -- 101,515,612(-) CCTCA(C/T)GGGAG intron-variant
rs475304 -- 101,504,276(-) TGTGG(A/C/G)GACAC intron-variant
rs476321 -- 101,497,571(-) AGTTT(A/G)AGATG intron-variant
rs479690 -- 101,583,039(+) ATCAG(C/T)CCTCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for GRHL2 Gene

Variant ID Type Subtype PubMed ID
nsv891229 CNV Loss 21882294
esv2252185 CNV Deletion 18987734
nsv396225 CNV Insertion 16902084
esv1282337 CNV Insertion 17803354
esv991268 CNV Insertion 20482838
nsv891230 CNV Gain 21882294
nsv396957 CNV Loss 16902084
dgv2248e1 CNV Complex 17122850
esv28138 CNV Loss 19812545
nsv8370 CNV Loss 18304495
nsv442525 CNV CNV 18776908
esv2421697 CNV Deletion 20811451
essv9539 CNV CNV 17122850
esv2677466 CNV Deletion 23128226
nsv515051 CNV Loss 21397061
esv2657338 CNV Deletion 23128226

Relevant External Links for GRHL2 Gene

HapMap Linkage Disequilibrium report
GRHL2
Human Gene Mutation Database (HGMD)
GRHL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRHL2 Gene

Disorders for GRHL2 Gene

(1) OMIM Diseases for GRHL2 Gene (608576)

UniProtKB/Swiss-Prot

GRHL2_HUMAN
  • Deafness, autosomal dominant, 28 (DFNA28) [MIM:608641]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA28 is characterized by mild to moderate hearing loss across most frequencies that progresses to severe loss in the higher frequencies by the fifth decade. {ECO:0000269 PubMed:12393799}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Ectodermal dysplasia/short stature syndrome (ECTDS) [MIM:616029]: An autosomal recessive ectodermal dysplasia syndrome characterized by nail dystrophy and/or loss, oral mucosa and/or tongue pigmentation, abnormal dentition, keratoderma affecting the margins of the palms and soles, focal hyperkeratosis of the dorsal aspects of the hands and feet, and short stature. {ECO:0000269 PubMed:25152456}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for GRHL2

Genetic Association Database (GAD)
GRHL2
Human Genome Epidemiology (HuGE) Navigator
GRHL2
genes like me logo Genes that share disorders with GRHL2: view

Publications for GRHL2 Gene

  1. The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. (PMID: 17921507) Van Laer L. … Van Camp G. (Hum. Mol. Genet. 2008) 3 23 48
  2. Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells. (PMID: 19015635) Kang X. … Park N.H. (Oncogene 2009) 3 4 23
  3. Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28. (PMID: 12393799) Peters L.M. … Morell R.J. (Hum. Mol. Genet. 2002) 2 3 4
  4. A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead. (PMID: 12175488) Wilanowski T. … Jane S.M. (Mech. Dev. 2002) 3 4
  5. The identification and characterization of human sister-of-mammalian grainyhead (SOM) expands the grainyhead-like family of developmental transcription factors. (PMID: 12549979) Ting S.B. … Jane S.M. (Biochem. J. 2003) 3 4

Products for GRHL2 Gene

Sources for GRHL2 Gene

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