Product Details

Purity

Greater than 85% as determined by SDS-PAGE.

Target Names

GRHL2

Uniprot No.

Q6ISB3

Research Area

Transcription

Alternative Names

Brother of mammalian grainyhead Transcription factor CP2-like 3

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

1-625aa

Target Protein Sequence

MSQESDNNKRLVALVPMPSDPPFNTRRAYTSEDEAWKSYLENPLTAATKAMMSINGDEDSAAALGLLYDYYKVPRDKRLLSVSKASDSQEDQEKRNCLGTSEAQSNLSGGENRVQVLKTVPVNLSLNQDHLENSKREQYSISFPESSAIIPVSGITVVKAEDFTPVFMAPPVHYPRGDGEEQRVVIFEQTQYDVPSLATHSAYLKDDQRSTPDSTYSESFKDAATEKFRSASVGAEEYMYDQTSSGTFQYTLEATKSLRQKQGEGPMTYLNKGQFYAITLSETGDNKCFRHPISKVRSVVMVVFSEDKNRDEQLKYWKYWHSRQHTAKQRVLDIADYKESFNTIGNIEEIAYNAVSFTWDVNEEAKIFITVNCLSTDFSSQKGVKGLPLMIQIDTYSYNNRSNKPIHRAYCQIKVFCDKGAERKIRDEERKQNRKKGKGQASQTQCNSSSDGKLAAIPLQKKSDITYFKTMPDLHSQPVLFIPDVHFANLQRTGQVYYNTDDEREGGSVLVKRMFRPMEEEFGPVPSKQMKEEGTKRVLLYVRKETDDVFDALMLKSPTVKGLMEAISEKYGLPVEKIAKLYKKSKKGILVNMDDNIIEHYSNEDTFILNMESMVEGFKVTLMEI
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

75.2 kDa

Protein Length

Full Length

Tag Info

N-terminal 6xHis-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

Producing recombinant human grainyhead-like protein 2 homolog (GRHL2) in E. coli involves several stages. Initially, the gene encoding the full-length GRHL2 protein (1-625aa) is co-cloned into an expression vector with an N-terminal 6xHis-tag gene and introduced into E. coli cells. The bacteria are grown to promote protein expression. After sufficient cell growth, cells are lysed to extract the recombinant GRHL2 protein. Purification is conducted using affinity chromatography. The protein's purity is assessed using SDS-PAGE, reaching up to 85%.

Human GRHL2 is a transcription factor particularly crucial for epithelial cells. GRHL2 has been identified as a key regulator of epithelial-mesenchymal transition (EMT) in both normal development and cancer progression [1][2][3]. Evidence has shown that GRHL2 suppresses EMT by inhibiting the expression of ZEB1 and TGF-β signaling, thereby restoring sensitivity to anoikis [2]. GRHL2 is essential for the expression of genes involved in the formation of adherens and tight junctions in different epithelial tissues [4][5]. Studies have highlighted its significance in maintaining epithelial barrier function during growth and injury [6].

Furthermore, GRHL2 has been associated with various conditions, including cancer and developmental abnormalities. It has been implicated in reducing invasion and migration in gastric cancer by inhibiting TGFβ-induced EMT [7]. Mutations in the GRHL2 gene are linked to an autosomal-recessive ectodermal dysplasia syndrome [8]. GRHL2 has been found to regulate renal epithelial barrier function and lumen expansion in the kidney [9].

References:
[1] B. Cieply, P. Riley, P. Pifer, J. Widmeyer, J. Addison, A. Ivanovet al., Suppression of the epithelial–mesenchymal transition by grainyhead-like-2, Cancer Research, vol. 72, no. 9, p. 2440-2453, 2012. https://doi.org/10.1158/0008-5472.can-11-4038
[2] B. Cieply, J. Farris, J. Denvir, H. Ford, & S. Frisch, Epithelial–mesenchymal transition and tumor suppression are controlled by a reciprocal feedback loop between zeb1 and grainyhead-like-2, Cancer Research, vol. 73, no. 20, p. 6299-6309, 2013. https://doi.org/10.1158/0008-5472.can-12-4082
[3] L. Ma, H. Yan, H. Zhao, & J. Sun, Grainyhead-like 2 in development and cancer, Tumor Biology, vol. 39, no. 5, p. 101042831769837, 2017. https://doi.org/10.1177/1010428317698375
[4] M. Werth, K. Walentin, A. Aue, J. Schönheit, A. Wuebken, N. Pode‐Shakkedet al., The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex, Development, vol. 137, no. 22, p. 3835-3845, 2010. https://doi.org/10.1242/dev.055483
[5] K. Senga, K. Mostov, T. Mitaka, A. Miyajima, & N. Tanimizu, Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and rab25, Molecular Biology of the Cell, vol. 23, no. 15, p. 2845-2855, 2012. https://doi.org/10.1091/mbc.e12-02-0097
[6] N. Mathiyalagan, L. Miles, P. Anderson, T. Wilanowski, B. Grills, S. McDonaldet al., Meta-analysis of grainyhead-like dependent transcriptional networks: a roadmap for identifying novel conserved genetic pathways, Genes, vol. 10, no. 11, p. 876, 2019. https://doi.org/10.3390/genes10110876
[7] J. Xiang, X. Fu, W. Ran, & Z. Wang, Grhl2 reduces invasion and migration through inhibition of tgfβ-induced emt in gastric cancer, Oncogenesis, vol. 6, no. 1, p. e284-e284, 2017. https://doi.org/10.1038/oncsis.2016.83
[8] G. Petrof, A. Nanda, J. Howden, T. Takeichi, J. McMillan, S. Aristodemouet al., Mutations in grhl2 result in an autosomal-recessive ectodermal dysplasia syndrome, The American Journal of Human Genetics, vol. 95, no. 3, p. 308-314, 2014. https://doi.org/10.1016/j.ajhg.2014.08.001
[9] A. Aue, C. Hinze, K. Walentin, J. Ruffert, Y. Yurtdas, M. Werthet al., A grainyhead-like 2/ovo-like 2 pathway regulates renal epithelial barrier function and lumen expansion, Journal of the American Society of Nephrology, vol. 26, no. 11, p. 2704-2715, 2015. https://doi.org/10.1681/asn.2014080759

Target Background

Function

Transcription factor playing an important role in primary neurulation and in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes. 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. 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. 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. In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation. 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. 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.

Gene References into Functions

Whole-genome sequencing identified a unique variant (c.20+544G>T) within an intronic regulatory region of GRHL2. PMID: 29499165
GRHL2 gene may have a role in orbital innervations and the defect in this gene (deletion) may be related to the Congenital fibrosis of the extraocular muscles type 1 phenotype. PMID: 29110737
In this study, we demonstrated for the first time that GRHL2 has a functional role in the regulation of epithelial plasticity of PDAC cells. PMID: 28960866
data analysis and modeling results highlight the relationships among multiple crucial Epithelial-to-Mesenchymal Transition /Mesenchymal-to-Epithelial Transition drivers including ZEB1, GRHL2, CD24, and ESRP1, particularly in basal-like breast cancers, which are most similar to triple-negative breast cancer (TNBC) and are considered the most dangerous subtype PMID: 28266048
Data indicate a 'phenotypic stability factors' (PSFs) such as GRHL2 that couple to the core epithelial-to-mesenchymal transition (EMT) decision-making circuit (miR-200/ZEB) and stabilize hybrid epithelial/mesenchymal (hybrid E/M) E/M phenotype. PMID: 27008704
Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of clear cell renal cell carcinoma (ccRCC). These changes support the potential role for GRHL2 as a suppressor of ccRCC. PMID: 28543713
Results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations. PMID: 27084311
GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and colocated with AR at specific sites on chromatin to regulate genes relevant to disease progression. PMID: 28473532
Studies indicate that Grainyhead-like transcription factor 2 (GRHL2) controls the expression of E-cadherin (CDH1) required for adherens junctions and possibly regulates the expression of claudin-4 (CLDN4) in tight junctions. PMID: 28636799
results indicated GRHL2 might be a noise-induced hearing loss (NIHL) susceptibility gene, but the effect of POU4F3 on NIHL could only be detected when taking noise exposure into account and their effects were enhanced by higher levels of noise exposure PMID: 27271650
These data are indicative for a strong oncogenic potential of the GRHL2 gene in epithelial ovarian cancer cells displaying either epithelial (A2780s) or mesenchymal (SKOV3) phenotypes. PMID: 28278050
In this review, we summarized recent progress on grainyhead-like 2 in development and cancer in order to get an insight into the regulation network of grainyhead-like 2 and understand the roles of grainyhead-like 2 in various cancers. PMID: 28459369
A loss or strong reduction in GRHL2 expression appears to be a characteristic of cervical cancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. PMID: 25550776
In skin from psoriasis patients, the effect of miR-194 on cell proliferation and differentiation was significantly reversed by overexpression of GRHL2. Moreover, the expression of miR-194 and GRHL2 was inversely correlated in psoriasis lesional skin. Taken together, our results suggest that miR-194 inhibits the proliferation and promotes the differentiation of keratinocytes through targeting GRHL2. PMID: 28040329
A novel connection between GRHL2 and miR-200 in oral cancer.Grainyhead-like 2 regulates epithelial plasticity and stemness in oral cancer cells. PMID: 26933170
GRHL2 genetic polymorphisms, rs611419 and rs10955255, have a protective role against sudden sensorineural hearing loss (SSHL) and reduce the risk of SSHL. However, rs6989650 is not associated with SSHL. PMID: 26847018
This study showed that Mendelian sensorineural hearing loss exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. PMID: 27083884
study demonstrates that loss of GRHL2 increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding sites at miR-200b/a and E-cadherin genes. These findings support GRHL2 as a pivotal gatekeeper of EMT in EOC via miR-200-ZEB1. PMID: 26887977
Taken together, our results demonstrate a role for miR-217 in the regulation of keratinocyte differentiation, partially through the regulation of GRHL2. PMID: 26826389
Genetic variations in the EYA4, GRHL2 and DFNA5 genes and their interactions with occupational noise exposure may play an important role in the incidence of noise-induced hearing loss (NIHL). PMID: 26400775
The p63 gene is regulated by GRHL2 through reciprocal feedback and determines the epithelial phenotype in human keratinocytes. PMID: 26085095
A Grhl2-dependent gene network controls trophoblast branching morphogenesis. PMID: 25758223
has identified ZEB1 as a target of GRHL2 and suggested a reciprocal GRHL2-ZEB1 repressive relationship, providing a novel mechanism through which proliferation may be modulated in colorectal cancer cells. PMID: 24756066
Mutations in GRHL2 result in an autosomal-recessive ectodermal Dysplasia syndrome. PMID: 25152456
Over-expression of Grhl2 decreased c-Myc and Bcl-2 protein expression level. PMID: 24068586
These findings indicate that GRHL2 may be a noise-induced hearing loss susceptibility gene and that polymorphisms of GRLH2 may contribute to the etiology of noise-induced hearing loss. PMID: 24131873
expression of GRHL2 is directly suppressed by the ZEB1, which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop PMID: 23814079
Frameshift mutation in GRHL2 is associated with autosomal-dominant deafness. PMID: 23813623
GRHL2 plays a key role in regulating many physiological functions of human airway epithelium, including those involving cell morphogenesis, adhesion, and motility. PMID: 23690579
Grhl2 plays an essential role in the determination of epithelial phenotype of breast cancers, EMT and tumor progression PMID: 23284647
GRHL2 impairs keratinocyte differentiation through transcriptional inhibition of the genes clustered at the epidermal differentiation complex. PMID: 23254293
Findings define a major role for GRHL2 in the suppression of oncogenic EMT in breast cancer cells. PMID: 22379025
GRHL2 suppresses death-receptor expression. PMID: 21949371
No positive association was found between GRHL2 polymorphisms and age-related hearing impairment in Han Chinese individuals. PMID: 21557239
GRHL2 regulates the hTERT expression through an epigenetic mechanism and controls the cellular life span. PMID: 20938050
Grhl2 expression in human tissue samples, including adult kidney, embryonic kidney, renal cell carcinomas and Wilms tumors was highly correlated with E-cadherin expression PMID: 20978075
Fine mapping demonstrated that the majority of the associated SNPs reside in intron 1 of GRHL2 gene; the causative variant may change the expression levels of a GRHL2 isoform. PMID: 17921507
a gain of GRHL2 in 8q22.3 was associated with early recurrence of hepatocellular carcinoma, controlling for clinical parameters PMID: 18752864
Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells. PMID: 19015635

Hide All

Involvement in disease

Deafness, autosomal dominant, 28 (DFNA28); Ectodermal dysplasia/short stature syndrome (ECTDS)

Subcellular Location

Nucleus. Membrane.

Protein Families

Grh/CP2 family, Grainyhead subfamily

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 co

Database Links

HGNC: 2799

OMIM: 608576

KEGG: hsa:79977

STRING: 9606.ENSP00000251808

UniGene: Hs.661088

Code	CSB-EP750350HU
Abbreviation	Recombinant Human GRHL2 protein
MSDS	MSDS Datasheet
Size	$306
	Order now
Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
Have Questions?	Leave a Message or Start an on-line Chat

Recombinant Human Grainyhead-like protein 2 homolog (GRHL2)

Product Details

Related Products

Customer Reviews and Q&A

Target Background

×CloseMessage