UniProtKB - Q8TE85 (GRHL3_HUMAN)
Protein
Grainyhead-like protein 3 homolog
Gene
GRHL3
Organism
Homo sapiens (Human)
Status
Functioni
Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin (By similarity). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (PubMed:21081122, PubMed:25347468). xhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair (By similarity). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events and epidermal wound repair but is essential to form the epidermal barrier with TGM3 as critical direct target gene among others. 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. 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 (By similarity). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122).By similarity4 Publications
Miscellaneous
GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxical 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.By similarity
GO - Molecular functioni
- chromatin DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: HGNC
- DNA-binding transcription factor activity Source: GO_Central
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- sequence-specific DNA binding Source: UniProtKB
GO - Biological processi
- central nervous system development Source: Ensembl
- cochlea morphogenesis Source: Ensembl
- ectoderm development Source: Ensembl
- epidermis development Source: UniProtKB
- establishment of planar polarity Source: Ensembl
- establishment of skin barrier Source: Ensembl
- eyelid development in camera-type eye Source: Ensembl
- neural tube closure Source: UniProtKB
- pattern specification process Source: Ensembl
- planar cell polarity pathway involved in neural tube closure Source: Ensembl
- positive regulation of GTPase activity Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: HGNC
- regulation of actin cytoskeleton organization Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
- wound healing Source: Ensembl
Keywordsi
Molecular function | DNA-binding |
Biological process | Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Grainyhead-like protein 3 homologImportedAlternative name(s): Sister of mammalian grainyhead Transcription factor CP2-like 4 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:25839 GRHL3 |
MIMi | 608317 gene |
neXtProti | NX_Q8TE85 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nuclear chromatin Source: NTNU_SB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Van der Woude syndrome 2 (VWS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant developmental disorder characterized by lower lip pits, cleft lip and/or cleft palate.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072616 | 298 | R → H in VWS2. 1 PublicationCorresponds to variant dbSNP:rs752673677EnsemblClinVar. | 1 | |
Natural variantiVAR_072617 | 391 | R → C in VWS2. 1 PublicationCorresponds to variant dbSNP:rs879255245EnsemblClinVar. | 1 | |
Natural variantiVAR_072618 | 520 | R → Q in VWS2. 1 PublicationCorresponds to variant dbSNP:rs946439477Ensembl. | 1 |
Organism-specific databases
DisGeNETi | 57822 |
MalaCardsi | GRHL3 |
MIMi | 606713 phenotype |
OpenTargetsi | ENSG00000158055 |
Orphaneti | 99771 Bifid uvula 101023 Cleft hard palate 99772 Cleft velum 155878 Submucosal cleft palate 888 Van der Woude syndrome |
PharmGKBi | PA134987320 |
Miscellaneous databases
Pharosi | Q8TE85 |
Polymorphism and mutation databases
BioMutai | GRHL3 |
DMDMi | 116242504 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000227997 | 1 – 626 | Grainyhead-like protein 3 homologAdd BLAST | 626 |
Proteomic databases
jPOSTi | Q8TE85 |
MassIVEi | Q8TE85 |
MaxQBi | Q8TE85 |
PaxDbi | Q8TE85 |
PeptideAtlasi | Q8TE85 |
PRIDEi | Q8TE85 |
ProteomicsDBi | 182 33731 74420 [Q8TE85-1] 74421 [Q8TE85-2] 74422 [Q8TE85-3] 74423 [Q8TE85-4] |
PTM databases
iPTMneti | Q8TE85 |
PhosphoSitePlusi | Q8TE85 |
Expressioni
Tissue specificityi
Expressed in brain, colon, pancreas, placenta and kidney. Isoform 1 is expressed in lung and tonsil. Isoform 2 is prostate-specific.1 Publication
Gene expression databases
Bgeei | ENSG00000158055 Expressed in 94 organ(s), highest expression level in ectocervix |
ExpressionAtlasi | Q8TE85 baseline and differential |
Genevisiblei | Q8TE85 HS |
Organism-specific databases
HPAi | HPA059960 |
Interactioni
Subunit structurei
Homodimer, also forms heterodimers with GRHL1 and GRHL2 (PubMed:12549979).
Interacts with LMO4 (By similarity).
By similarity1 PublicationBinary interactionsi
Protein-protein interaction databases
BioGridi | 121781, 7 interactors |
IntActi | Q8TE85, 7 interactors |
MINTi | Q8TE85 |
STRINGi | 9606.ENSP00000288955 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 30 – 95 | Transcription activation1 PublicationAdd BLAST | 66 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG4091 Eukaryota ENOG410XNZ6 LUCA |
GeneTreei | ENSGT00940000157970 |
HOGENOMi | HOG000220859 |
InParanoidi | Q8TE85 |
KOi | K09275 |
OMAi | MAVFEND |
OrthoDBi | 286319at2759 |
PhylomeDBi | Q8TE85 |
TreeFami | TF314132 |
Family and domain databases
InterProi | View protein in InterPro IPR007604 CP2 IPR040167 TF_CP2-like |
PANTHERi | PTHR11037 PTHR11037, 1 hit |
Pfami | View protein in Pfam PF04516 CP2, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8TE85-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSNELDFRSV RLLKNDPVNL QKFSYTSEDE AWKTYLENPL TAATKAMMRV
60 70 80 90 100
NGDDDSVAAL SFLYDYYMGP KEKRILSSST GGRNDQGKRY YHGMEYETDL
110 120 130 140 150
TPLESPTHLM KFLTENVSGT PEYPDLLKKN NLMSLEGALP TPGKAAPLPA
160 170 180 190 200
GPSKLEAGSV DSYLLPTTDM YDNGSLNSLF ESIHGVPPTQ RWQPDSTFKD
210 220 230 240 250
DPQESMLFPD ILKTSPEPPC PEDYPSLKSD FEYTLGSPKA IHIKSGESPM
260 270 280 290 300
AYLNKGQFYP VTLRTPAGGK GLALSSNKVK SVVMVVFDNE KVPVEQLRFW
310 320 330 340 350
KHWHSRQPTA KQRVIDVADC KENFNTVEHI EEVAYNALSF VWNVNEEAKV
360 370 380 390 400
FIGVNCLSTD FSSQKGVKGV PLNLQIDTYD CGLGTERLVH RAVCQIKIFC
410 420 430 440 450
DKGAERKMRD DERKQFRRKV KCPDSSNSGV KGCLLSGFRG NETTYLRPET
460 470 480 490 500
DLETPPVLFI PNVHFSSLQR SGGAAPSAGP SSSNRLPLKR TCSPFTEEFE
510 520 530 540 550
PLPSKQAKEG DLQRVLLYVR RETEEVFDAL MLKTPDLKGL RNAISEKYGF
560 570 580 590 600
PEENIYKVYK KCKRGETSLL HPRLSRHPPP DCLECSHPVT QVRNMGFGDG
610 620
FWRQRDLDSN PSPTTVNSLH FTVNSE
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PLT6 | E9PLT6_HUMAN | Grainyhead-like protein 3 homolog | GRHL3 | 81 | Annotation score: | ||
E9PLG9 | E9PLG9_HUMAN | Grainyhead-like protein 3 homolog | GRHL3 | 52 | Annotation score: |
Sequence cautioni
The sequence AAH36890 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAG37608 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 20 | L → S in BAB85067 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 396 | I → V in BAG37608 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 533 | K → R in BAB85067 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_027907 | 55 | D → E. Corresponds to variant dbSNP:rs2486668Ensembl. | 1 | |
Natural variantiVAR_055881 | 160 | V → A. Corresponds to variant dbSNP:rs34637004EnsemblClinVar. | 1 | |
Natural variantiVAR_072616 | 298 | R → H in VWS2. 1 PublicationCorresponds to variant dbSNP:rs752673677EnsemblClinVar. | 1 | |
Natural variantiVAR_072617 | 391 | R → C in VWS2. 1 PublicationCorresponds to variant dbSNP:rs879255245EnsemblClinVar. | 1 | |
Natural variantiVAR_072618 | 520 | R → Q in VWS2. 1 PublicationCorresponds to variant dbSNP:rs946439477Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_017643 | 1 – 93 | Missing in isoform 4. 1 PublicationAdd BLAST | 93 | |
Alternative sequenceiVSP_017644 | 1 – 46 | Missing in isoform 3. 1 PublicationAdd BLAST | 46 | |
Alternative sequenceiVSP_017645 | 1 – 6 | MSNELD → MWMNSILPIFL in isoform 2. 1 Publication | 6 | |
Alternative sequenceiVSP_017646 | 566 – 626 | ETSLL…TVNSE → ILVNMDNNIIQHYSNHVAFL LDMGELDGKIQIILKEL in isoform 2, isoform 3, isoform 4 and isoform 5. 3 PublicationsAdd BLAST | 61 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY231160 mRNA Translation: AAO67370.1 AY231161 mRNA No translation available. AK074386 mRNA Translation: BAB85067.1 AK315164 mRNA Translation: BAG37608.1 Different initiation. AL031431 Genomic DNA No translation available. AL138902 Genomic DNA No translation available. CH471134 Genomic DNA Translation: EAW95121.1 BC036890 mRNA Translation: AAH36890.1 Different initiation. |
CCDSi | CCDS251.1 [Q8TE85-2] CCDS252.2 [Q8TE85-1] CCDS44088.1 [Q8TE85-5] CCDS53284.1 [Q8TE85-3] |
RefSeqi | NP_001181939.1, NM_001195010.1 [Q8TE85-3] NP_067003.2, NM_021180.3 [Q8TE85-2] NP_937816.1, NM_198173.2 [Q8TE85-5] NP_937817.3, NM_198174.2 [Q8TE85-1] XP_011540171.1, XM_011541869.1 [Q8TE85-3] XP_011540172.1, XM_011541870.2 [Q8TE85-4] |
Genome annotation databases
Ensembli | ENST00000236255; ENSP00000236255; ENSG00000158055 [Q8TE85-2] ENST00000350501; ENSP00000288955; ENSG00000158055 [Q8TE85-1] ENST00000356046; ENSP00000348333; ENSG00000158055 [Q8TE85-3] ENST00000361548; ENSP00000354943; ENSG00000158055 [Q8TE85-5] |
GeneIDi | 57822 |
KEGGi | hsa:57822 |
UCSCi | uc001bix.3 human [Q8TE85-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY231160 mRNA Translation: AAO67370.1 AY231161 mRNA No translation available. AK074386 mRNA Translation: BAB85067.1 AK315164 mRNA Translation: BAG37608.1 Different initiation. AL031431 Genomic DNA No translation available. AL138902 Genomic DNA No translation available. CH471134 Genomic DNA Translation: EAW95121.1 BC036890 mRNA Translation: AAH36890.1 Different initiation. |
CCDSi | CCDS251.1 [Q8TE85-2] CCDS252.2 [Q8TE85-1] CCDS44088.1 [Q8TE85-5] CCDS53284.1 [Q8TE85-3] |
RefSeqi | NP_001181939.1, NM_001195010.1 [Q8TE85-3] NP_067003.2, NM_021180.3 [Q8TE85-2] NP_937816.1, NM_198173.2 [Q8TE85-5] NP_937817.3, NM_198174.2 [Q8TE85-1] XP_011540171.1, XM_011541869.1 [Q8TE85-3] XP_011540172.1, XM_011541870.2 [Q8TE85-4] |
3D structure databases
SMRi | Q8TE85 |
ModBasei | Search... |
Protein-protein interaction databases
BioGridi | 121781, 7 interactors |
IntActi | Q8TE85, 7 interactors |
MINTi | Q8TE85 |
STRINGi | 9606.ENSP00000288955 |
PTM databases
iPTMneti | Q8TE85 |
PhosphoSitePlusi | Q8TE85 |
Polymorphism and mutation databases
BioMutai | GRHL3 |
DMDMi | 116242504 |
Proteomic databases
jPOSTi | Q8TE85 |
MassIVEi | Q8TE85 |
MaxQBi | Q8TE85 |
PaxDbi | Q8TE85 |
PeptideAtlasi | Q8TE85 |
PRIDEi | Q8TE85 |
ProteomicsDBi | 182 33731 74420 [Q8TE85-1] 74421 [Q8TE85-2] 74422 [Q8TE85-3] 74423 [Q8TE85-4] |
Protocols and materials databases
DNASUi | 57822 |
Genome annotation databases
Ensembli | ENST00000236255; ENSP00000236255; ENSG00000158055 [Q8TE85-2] ENST00000350501; ENSP00000288955; ENSG00000158055 [Q8TE85-1] ENST00000356046; ENSP00000348333; ENSG00000158055 [Q8TE85-3] ENST00000361548; ENSP00000354943; ENSG00000158055 [Q8TE85-5] |
GeneIDi | 57822 |
KEGGi | hsa:57822 |
UCSCi | uc001bix.3 human [Q8TE85-1] |
Organism-specific databases
CTDi | 57822 |
DisGeNETi | 57822 |
GeneCardsi | GRHL3 |
HGNCi | HGNC:25839 GRHL3 |
HPAi | HPA059960 |
MalaCardsi | GRHL3 |
MIMi | 606713 phenotype 608317 gene |
neXtProti | NX_Q8TE85 |
OpenTargetsi | ENSG00000158055 |
Orphaneti | 99771 Bifid uvula 101023 Cleft hard palate 99772 Cleft velum 155878 Submucosal cleft palate 888 Van der Woude syndrome |
PharmGKBi | PA134987320 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4091 Eukaryota ENOG410XNZ6 LUCA |
GeneTreei | ENSGT00940000157970 |
HOGENOMi | HOG000220859 |
InParanoidi | Q8TE85 |
KOi | K09275 |
OMAi | MAVFEND |
OrthoDBi | 286319at2759 |
PhylomeDBi | Q8TE85 |
TreeFami | TF314132 |
Miscellaneous databases
ChiTaRSi | GRHL3 human |
GenomeRNAii | 57822 |
Pharosi | Q8TE85 |
PROi | PR:Q8TE85 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000158055 Expressed in 94 organ(s), highest expression level in ectocervix |
ExpressionAtlasi | Q8TE85 baseline and differential |
Genevisiblei | Q8TE85 HS |
Family and domain databases
InterProi | View protein in InterPro IPR007604 CP2 IPR040167 TF_CP2-like |
PANTHERi | PTHR11037 PTHR11037, 1 hit |
Pfami | View protein in Pfam PF04516 CP2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GRHL3_HUMAN | |
Accessioni | Q8TE85Primary (citable) accession number: Q8TE85 Secondary accession number(s): A2A297 Q8N407 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 21, 2006 |
Last sequence update: | October 17, 2006 | |
Last modified: | October 16, 2019 | |
This is version 137 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot