DegronMD - Q6ISB3(GRHL2)

FUNCTION: Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:29309642, 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). {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635, ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P195A	TCGA-23-1121	OV	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7503
p.P195A	DO28731	OV	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7503
p.A198V	TCGA-90-A4ED	LUSC	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.3056
p.A198V	DO45482	LUSC	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.3056
p.A198V	SIDM00251	Gastric Carcinoma	GDSC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.3056
p.A198V	ACH-000949	Gastric Cancer	CCLE	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.3056
p.A198V	TGBC11TKB	stomach	COSMIC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.3056
p.L204F	TCGA-A8-A06Z	BRCA	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1389
p.L204F	DO4092	BRCA	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1389
p.V194M	TCGA-AX-A1CE	UCEC	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7208
p.V194M	TCGA-FI-A2D5	UCEC	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7208
p.V194M	DO42280	UCEC	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7208
p.V194M	DO41331	UCEC	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7208
p.E181G	TCGA-FI-A2D0	UCEC	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1389
p.E181G	DO43891	UCEC	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1389
p.P195S	TCGA-GN-A8LK	SKCM	TCGA	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.6752
p.P195S	DO51259	SKCM	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.6752
p.Q191K	DO231618	LINC	ICGC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.5833
p.R183Q	SIDM00334	Endometrial Carcinoma	GDSC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1944
p.A202T	ACH-001610	Brain Cancer	CCLE	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1944
p.R193C	YT	haematopoietic and lymphoid tissue	COSMIC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.8301
p.A207T	RCH-ACV	haematopoietic and lymphoid tissue	COSMIC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.0556
p.A182V	TGBC11TKB	stomach	COSMIC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation rewiring degron network	0.1667
p.T195P	NCI-H2085	lung	COSMIC	EQTQYDVPSL	DEG_COP1_1	188:197	Mutation altering degron motif	0.7031

Kaplan plot for GRHL2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

GRHL2

UniProt ID: Q6ISB3

Entrez ID: 79977

Protein name: Grainyhead-like protein 2 homolog (Brother of mammalian grainyhead) (Transcription factor CP2-like 3)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for GRHL2 in