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Protein

Grainyhead-like protein 2 homolog

Gene

Grhl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 (PubMed:22696678). 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 (PubMed:20654612). 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 (PubMed:22696678). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia (PubMed:20978075). Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events such as eyelid fusion and epidermal wound repair (PubMed:21081122). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (PubMed:22955271). 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 (By similarity).By similarity5 Publications

GO - Molecular functioni

  • chromatin binding Source: MGI
  • chromatin DNA binding Source: UniProtKB
  • DNA binding Source: MGI
  • intronic transcription regulatory region sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • bicellular tight junction assembly Source: UniProtKB
  • brain development Source: MGI
  • camera-type eye development Source: MGI
  • cardiac ventricle morphogenesis Source: MGI
  • cell adhesion Source: UniProtKB
  • cell junction assembly Source: UniProtKB
  • cell proliferation Source: MGI
  • embryonic cranial skeleton morphogenesis Source: MGI
  • embryonic digit morphogenesis Source: MGI
  • embryonic organ development Source: MGI
  • epidermis development Source: UniProtKB
  • epithelial cell morphogenesis Source: UniProtKB
  • epithelial cell morphogenesis involved in placental branching Source: MGI
  • epithelium migration Source: UniProtKB
  • face development Source: MGI
  • in utero embryonic development Source: MGI
  • lung epithelial cell differentiation Source: UniProtKB
  • lung lobe morphogenesis Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of keratinocyte differentiation Source: UniProtKB
  • neural tube closure Source: UniProtKB
  • neural tube development Source: MGI
  • positive regulation of telomerase activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: CACAO
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of DNA methylation Source: UniProtKB
  • regulation of gene expression Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • respiratory tube development Source: MGI
  • transcription from RNA polymerase II promoter Source: MGI
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Grainyhead-like protein 2 homolog
Alternative name(s):
Brother of mammalian grainyhead
Transcription factor CP2-like 3
Gene namesi
Name:Grhl2
Synonyms:Bom, Tcfcp2l3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2182543. Grhl2.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: UniProtKB
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant embryos show an epithelial and anterior and posterior neural tube defects leading to death at around day E11.5 (PubMed:20654612, PubMed:20978075). They exhibit a fully penetrant split-face malformation, associated with cranioschisis. Closure of the remainder of the neural tube ocrurred normally with the exception of the posterior neuropore. The dorso-lateral hinge points fail to form and closure do not proceed beyond this point (PubMed:20654612).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 625625Grainyhead-like protein 2 homologPRO_0000227995Add
BLAST

Proteomic databases

EPDiQ8K5C0.
PaxDbiQ8K5C0.
PeptideAtlasiQ8K5C0.
PRIDEiQ8K5C0.

PTM databases

iPTMnetiQ8K5C0.
PhosphoSiteiQ8K5C0.

Expressioni

Developmental stagei

At E14.5 expressed in lung, esophagus, skin and kidney. At E9.5 expressed in foregut and surface ectoderm but not in the neural tube. At E9.5 and E15.5, detected in the lung epithelium and in branchiolar and alveolar epithelial cells at E18.5 and adult. Expressed in otocyst at E11.5, prominent in epithelial derivatives of the otic placode in the vestibule and cochlear duct at E18.5. At postnatal day 5, epithelial cells of the cochlear duct, which surround the endolymph-containing scala media, continued to express low levels, while little or no expression was seen in the mesenchyme-derived cells lining the scala tympani and scala vestibuli. Detected in cholangiocytes in postnatal day 1 and postnatal day 8 livers.6 Publications

Gene expression databases

BgeeiQ8K5C0.
CleanExiMM_GRHL2.
ExpressionAtlasiQ8K5C0. baseline and differential.
GenevisibleiQ8K5C0. MM.

Interactioni

Subunit structurei

Homodimer, also forms heterodimers with GRHL1 or GRHL3.By similarity

Protein-protein interaction databases

BioGridi232985. 4 interactions.
IntActiQ8K5C0. 4 interactions.
MINTiMINT-4117994.
STRINGi10090.ENSMUSP00000022895.

Structurei

3D structure databases

ProteinModelPortaliQ8K5C0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9393Transcription activation1 PublicationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ8K5C0.
KOiK09275.
OMAiAPSKQMK.
OrthoDBiEOG7GBFWJ.
PhylomeDBiQ8K5C0.
TreeFamiTF314132.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q8K5C0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQESDNNKR LVALVPMPSD PPFNTRRAYT SEDEAWKSYL ENPLTAATKA
60 70 80 90 100
MMSINGDEDS AAALGLLYDY YKVPRDKRLL SVSKASDSQE DQDKRNCLGT
110 120 130 140 150
SEAQINLSGG ENRVQVLKTV PVNLCLSQDH MENSKREQYS VSITESSAVI
160 170 180 190 200
PVSGITVVKA EDFTPVFMAP PVHYPRADSE EQRVVIFEQT QYDLPSIASH
210 220 230 240 250
SSYLKDDQRS TPDSTYSESF KDGASEKFRS TSVGADEYTY DQTGSGTFQY
260 270 280 290 300
TLEATKSLRQ KQGEGPMTYL NKGQFYAITL SETGDNKCFR HPISKVRSVV
310 320 330 340 350
MVVFSEDKNR DEQLKYWKYW HSRQHTAKQR VLDIADYKES FNTIGNIEEI
360 370 380 390 400
AYNAVSFTWD VNEEAKIFIT VNCLSTDFSS QKGVKGLPLM IQIDTYSYNN
410 420 430 440 450
RSNKPIHRAY CQIKVFCDKG AERKIRDEER KQNRKKGKGQ ASQAQCNNSS
460 470 480 490 500
DGKMAAIPLQ KKSDITYFKT MPDLHSQPVL FIPDVHFANL QRTGQVYYNT
510 520 530 540 550
DDEREGSSVL VKRMFRPMEE EFGPTPSKQI KEENVKRVLL YVRKENDDVF
560 570 580 590 600
DALMLKSPTV KGLMEALSEK YGLPVEKITK LYKKSKKGIL VNMDDNIIEH
610 620
YSNEDTFILN MESMVEGFKI TLMEI
Length:625
Mass (Da):71,195
Last modified:October 1, 2002 - v1
Checksum:i879EE7689A5AA4E3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF411213 mRNA. Translation: AAM22619.1.
BC042575 mRNA. Translation: AAH42575.1.
BC055035 mRNA. Translation: AAH55035.1.
CCDSiCCDS27434.1.
RefSeqiNP_080772.2. NM_026496.4.
UniGeneiMm.244612.

Genome annotation databases

EnsembliENSMUST00000022895; ENSMUSP00000022895; ENSMUSG00000022286.
GeneIDi252973.
KEGGimmu:252973.
UCSCiuc007vne.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF411213 mRNA. Translation: AAM22619.1.
BC042575 mRNA. Translation: AAH42575.1.
BC055035 mRNA. Translation: AAH55035.1.
CCDSiCCDS27434.1.
RefSeqiNP_080772.2. NM_026496.4.
UniGeneiMm.244612.

3D structure databases

ProteinModelPortaliQ8K5C0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi232985. 4 interactions.
IntActiQ8K5C0. 4 interactions.
MINTiMINT-4117994.
STRINGi10090.ENSMUSP00000022895.

PTM databases

iPTMnetiQ8K5C0.
PhosphoSiteiQ8K5C0.

Proteomic databases

EPDiQ8K5C0.
PaxDbiQ8K5C0.
PeptideAtlasiQ8K5C0.
PRIDEiQ8K5C0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022895; ENSMUSP00000022895; ENSMUSG00000022286.
GeneIDi252973.
KEGGimmu:252973.
UCSCiuc007vne.2. mouse.

Organism-specific databases

CTDi79977.
MGIiMGI:2182543. Grhl2.

Phylogenomic databases

eggNOGiKOG4091. Eukaryota.
ENOG410XNZ6. LUCA.
GeneTreeiENSGT00760000119235.
HOGENOMiHOG000220859.
HOVERGENiHBG054154.
InParanoidiQ8K5C0.
KOiK09275.
OMAiAPSKQMK.
OrthoDBiEOG7GBFWJ.
PhylomeDBiQ8K5C0.
TreeFamiTF314132.

Miscellaneous databases

PROiQ8K5C0.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K5C0.
CleanExiMM_GRHL2.
ExpressionAtlasiQ8K5C0. baseline and differential.
GenevisibleiQ8K5C0. MM.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead."
    Wilanowski T., Tuckfield A., Cerruti L., O'Connell S., Saint R., Parekh V., Tao J., Cunningham J.M., Jane S.M.
    Mech. Dev. 114:37-50(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Tissue: Teratocarcinoma.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech II.
    Tissue: Mammary tumor and Olfactory epithelium.
  3. "Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28."
    Peters L.M., Anderson D.W., Griffith A.J., Grundfast K.M., San Agustin T.B., Madeo A.C., Friedman T.B., Morell R.J.
    Hum. Mol. Genet. 11:2877-2885(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  4. "The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex."
    Werth M., Walentin K., Aue A., Schonheit J., Wuebken A., Pode-Shakked N., Vilianovitch L., Erdmann B., Dekel B., Bader M., Barasch J., Rosenbauer F., Luft F.C., Schmidt-Ott K.M.
    Development 137:3835-3845(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
  5. "Regional neural tube closure defined by the Grainy head-like transcription factors."
    Rifat Y., Parekh V., Wilanowski T., Hislop N.R., Auden A., Ting S.B., Cunningham J.M., Jane S.M.
    Dev. Biol. 345:237-245(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
  6. "The unique and cooperative roles of the Grainy head-like transcription factors in epidermal development reflect unexpected target gene specificity."
    Boglev Y., Wilanowski T., Caddy J., Parekh V., Auden A., Darido C., Hislop N.R., Cangkrama M., Ting S.B., Jane S.M.
    Dev. Biol. 349:512-522(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation."
    Varma S., Cao Y., Tagne J.B., Lakshminarayanan M., Li J., Friedman T.B., Morell R.J., Warburton D., Kotton D.N., Ramirez M.I.
    J. Biol. Chem. 287:37282-37295(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  8. "Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25."
    Senga K., Mostov K.E., Mitaka T., Miyajima A., Tanimizu N.
    Mol. Biol. Cell 23:2845-2855(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiGRHL2_MOUSE
AccessioniPrimary (citable) accession number: Q8K5C0
Secondary accession number(s): Q80UZ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 1, 2002
Last modified: July 6, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.