Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Grainyhead-like protein 3 homolog

Gene

GRHL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000158055-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Grainyhead-like protein 3 homologImported
Alternative name(s):
Sister of mammalian grainyhead
Transcription factor CP2-like 4
Gene namesi
Name:GRHL3Imported
Synonyms:SOM, TFCP2L4Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:25839. GRHL3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & 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.
See also OMIM:606713
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072616298R → H in VWS2. 1 PublicationCorresponds to variant rs752673677dbSNPEnsembl.1
Natural variantiVAR_072617391R → C in VWS2. 1 Publication1
Natural variantiVAR_072618520R → Q in VWS2. 1 Publication1

Organism-specific databases

DisGeNETi57822.
MalaCardsiGRHL3.
MIMi606713. phenotype.
OpenTargetsiENSG00000158055.
Orphaneti888. Van der Woude syndrome.
PharmGKBiPA134987320.

Polymorphism and mutation databases

BioMutaiGRHL3.
DMDMi116242504.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002279971 – 626Grainyhead-like protein 3 homologAdd BLAST626

Proteomic databases

MaxQBiQ8TE85.
PaxDbiQ8TE85.
PeptideAtlasiQ8TE85.
PRIDEiQ8TE85.

PTM databases

iPTMnetiQ8TE85.
PhosphoSitePlusiQ8TE85.

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

BgeeiENSG00000158055.
CleanExiHS_GRHL3.
ExpressionAtlasiQ8TE85. baseline and differential.
GenevisibleiQ8TE85. HS.

Organism-specific databases

HPAiHPA051427.

Interactioni

Subunit structurei

Homodimer, also forms heterodimers with GRHL1 and GRHL2 (PubMed:12549979). Interacts with LMO4 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PRMT5O147442EBI-8469396,EBI-351098
PRMT6Q96LA82EBI-8469396,EBI-912440

Protein-protein interaction databases

BioGridi121781. 7 interactors.
IntActiQ8TE85. 3 interactors.
MINTiMINT-8417669.
STRINGi9606.ENSP00000288955.

Structurei

3D structure databases

ProteinModelPortaliQ8TE85.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 95Transcription activation1 PublicationAdd BLAST66

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ8TE85.
KOiK09275.
OMAiPTSDMYD.
OrthoDBiEOG091G03ME.
PhylomeDBiQ8TE85.
TreeFamiTF314132.

Family and domain databases

InterProiIPR007604. CP2.
[Graphical view]
PfamiPF04516. CP2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TE85-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:626
Mass (Da):70,345
Last modified:October 17, 2006 - v3
Checksum:i225C0E2049FF0CE6
GO
Isoform 2 (identifier: Q8TE85-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MSNELD → MWMNSILPIFL
     566-626: ETSLLHPRLS...NSLHFTVNSE → ILVNMDNNII...GKIQIILKEL

Show »
Length:607
Mass (Da):68,353
Checksum:iD750D50275F999B2
GO
Isoform 3 (identifier: Q8TE85-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: Missing.
     566-626: ETSLLHPRLS...NSLHFTVNSE → ILVNMDNNII...GKIQIILKEL

Note: No experimental confirmation available.
Show »
Length:556
Mass (Da):62,378
Checksum:i6D343D56FA89947C
GO
Isoform 4 (identifier: Q8TE85-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: Missing.
     566-626: ETSLLHPRLS...NSLHFTVNSE → ILVNMDNNII...GKIQIILKEL

Show »
Length:509
Mass (Da):57,045
Checksum:iECE5E4685D8B223D
GO
Isoform 5 (identifier: Q8TE85-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     566-626: ETSLLHPRLS...NSLHFTVNSE → ILVNMDNNII...GKIQIILKEL

Note: No experimental confirmation available.
Show »
Length:602
Mass (Da):67,696
Checksum:i036BE44B3F448A93
GO

Sequence cautioni

The sequence AAH36890 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG37608 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20L → S in BAB85067 (PubMed:14702039).Curated1
Sequence conflicti396I → V in BAG37608 (PubMed:14702039).Curated1
Sequence conflicti533K → R in BAB85067 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02790755D → E.Corresponds to variant rs2486668dbSNPEnsembl.1
Natural variantiVAR_055881160V → A.Corresponds to variant rs34637004dbSNPEnsembl.1
Natural variantiVAR_072616298R → H in VWS2. 1 PublicationCorresponds to variant rs752673677dbSNPEnsembl.1
Natural variantiVAR_072617391R → C in VWS2. 1 Publication1
Natural variantiVAR_072618520R → Q in VWS2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0176431 – 93Missing in isoform 4. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_0176441 – 46Missing in isoform 3. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_0176451 – 6MSNELD → MWMNSILPIFL in isoform 2. 1 Publication6
Alternative sequenceiVSP_017646566 – 626ETSLL…TVNSE → ILVNMDNNIIQHYSNHVAFL LDMGELDGKIQIILKEL in isoform 2, isoform 3, isoform 4 and isoform 5. 3 PublicationsAdd BLAST61

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, AL138902 Genomic DNA. Translation: CAI21406.2.
AL031431, AL138902 Genomic DNA. Translation: CAI21407.2.
AL138902, AL031431 Genomic DNA. Translation: CAI22857.2.
AL138902, AL031431 Genomic DNA. Translation: CAI22858.2.
CH471134 Genomic DNA. Translation: EAW95121.1.
BC036890 mRNA. Translation: AAH36890.1. Different initiation.
CCDSiCCDS251.1. [Q8TE85-2]
CCDS252.2. [Q8TE85-1]
CCDS44088.1. [Q8TE85-5]
CCDS53284.1. [Q8TE85-3]
RefSeqiNP_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]
UniGeneiHs.657920.

Genome annotation databases

EnsembliENST00000236255; ENSP00000236255; ENSG00000158055. [Q8TE85-2]
ENST00000350501; ENSP00000288955; ENSG00000158055. [Q8TE85-1]
ENST00000356046; ENSP00000348333; ENSG00000158055. [Q8TE85-3]
ENST00000361548; ENSP00000354943; ENSG00000158055. [Q8TE85-5]
GeneIDi57822.
KEGGihsa:57822.
UCSCiuc001bix.3. human. [Q8TE85-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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, AL138902 Genomic DNA. Translation: CAI21406.2.
AL031431, AL138902 Genomic DNA. Translation: CAI21407.2.
AL138902, AL031431 Genomic DNA. Translation: CAI22857.2.
AL138902, AL031431 Genomic DNA. Translation: CAI22858.2.
CH471134 Genomic DNA. Translation: EAW95121.1.
BC036890 mRNA. Translation: AAH36890.1. Different initiation.
CCDSiCCDS251.1. [Q8TE85-2]
CCDS252.2. [Q8TE85-1]
CCDS44088.1. [Q8TE85-5]
CCDS53284.1. [Q8TE85-3]
RefSeqiNP_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]
UniGeneiHs.657920.

3D structure databases

ProteinModelPortaliQ8TE85.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121781. 7 interactors.
IntActiQ8TE85. 3 interactors.
MINTiMINT-8417669.
STRINGi9606.ENSP00000288955.

PTM databases

iPTMnetiQ8TE85.
PhosphoSitePlusiQ8TE85.

Polymorphism and mutation databases

BioMutaiGRHL3.
DMDMi116242504.

Proteomic databases

MaxQBiQ8TE85.
PaxDbiQ8TE85.
PeptideAtlasiQ8TE85.
PRIDEiQ8TE85.

Protocols and materials databases

DNASUi57822.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236255; ENSP00000236255; ENSG00000158055. [Q8TE85-2]
ENST00000350501; ENSP00000288955; ENSG00000158055. [Q8TE85-1]
ENST00000356046; ENSP00000348333; ENSG00000158055. [Q8TE85-3]
ENST00000361548; ENSP00000354943; ENSG00000158055. [Q8TE85-5]
GeneIDi57822.
KEGGihsa:57822.
UCSCiuc001bix.3. human. [Q8TE85-1]

Organism-specific databases

CTDi57822.
DisGeNETi57822.
GeneCardsiGRHL3.
HGNCiHGNC:25839. GRHL3.
HPAiHPA051427.
MalaCardsiGRHL3.
MIMi606713. phenotype.
608317. gene.
neXtProtiNX_Q8TE85.
OpenTargetsiENSG00000158055.
Orphaneti888. Van der Woude syndrome.
PharmGKBiPA134987320.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ8TE85.
KOiK09275.
OMAiPTSDMYD.
OrthoDBiEOG091G03ME.
PhylomeDBiQ8TE85.
TreeFamiTF314132.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000158055-MONOMER.

Miscellaneous databases

GenomeRNAii57822.
PROiQ8TE85.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158055.
CleanExiHS_GRHL3.
ExpressionAtlasiQ8TE85. baseline and differential.
GenevisibleiQ8TE85. HS.

Family and domain databases

InterProiIPR007604. CP2.
[Graphical view]
PfamiPF04516. CP2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRHL3_HUMAN
AccessioniPrimary (citable) accession number: Q8TE85
Secondary accession number(s): A2A297
, B2RCL1, G3XAF0, Q5TH78, Q86Y06, Q8N407
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.