GRHL3_MOUSE
ID GRHL3_MOUSE Reviewed; 603 AA.
AC Q5FWH3; A2ADI2;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Grainyhead-like protein 3 homolog {ECO:0000312|MGI:MGI:2655333};
DE AltName: Full=Transcription factor CP2-like 4;
GN Name=Grhl3 {ECO:0000312|MGI:MGI:2655333};
GN Synonyms=Get1, Som {ECO:0000303|PubMed:14608380}, Tfcp2l4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=14608380; DOI=10.1038/nm961;
RA Ting S.B., Wilanowski T., Auden A., Hall M., Voss A.K., Thomas T.,
RA Parekh V., Cunningham J.M., Jane S.M.;
RT "Inositol- and folate-resistant neural tube defects in mice lacking the
RT epithelial-specific factor Grhl-3.";
RL Nat. Med. 9:1513-1519(2003).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16949565; DOI=10.1016/j.ydbio.2006.07.015;
RA Yu Z., Lin K.K., Bhandari A., Spencer J.A., Xu X., Wang N., Lu Z.,
RA Gill G.N., Roop D.R., Wertz P., Andersen B.;
RT "The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates
RT epidermal terminal differentiation and interacts functionally with LMO4.";
RL Dev. Biol. 299:122-136(2006).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20654612; DOI=10.1016/j.ydbio.2010.07.017;
RA Rifat Y., Parekh V., Wilanowski T., Hislop N.R., Auden A., Ting S.B.,
RA Cunningham J.M., Jane S.M.;
RT "Regional neural tube closure defined by the Grainy head-like transcription
RT factors.";
RL Dev. Biol. 345:237-245(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPED, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=21081122; DOI=10.1016/j.ydbio.2010.11.011;
RA Boglev Y., Wilanowski T., Caddy J., Parekh V., Auden A., Darido C.,
RA Hislop N.R., Cangkrama M., Ting S.B., Jane S.M.;
RT "The unique and cooperative roles of the Grainy head-like transcription
RT factors in epidermal development reflect unexpected target gene
RT specificity.";
RL Dev. Biol. 349:512-522(2011).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24360809; DOI=10.1016/j.ajhg.2013.11.009;
RA Peyrard-Janvid M., Leslie E.J., Kousa Y.A., Smith T.L., Dunnwald M.,
RA Magnusson M., Lentz B.A., Unneberg P., Fransson I., Koillinen H.K.,
RA Rautio J., Pegelow M., Karsten A., Basel-Vanagaite L., Gordon W.,
RA Andersen B., Svensson T., Murray J.C., Cornell R.A., Kere J., Schutte B.C.;
RT "Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral
RT periderm development.";
RL Am. J. Hum. Genet. 94:23-32(2014).
RN [8]
RP FUNCTION.
RX PubMed=25347468; DOI=10.1172/jci77138;
RA Gordon W.M., Zeller M.D., Klein R.H., Swindell W.R., Ho H., Espetia F.,
RA Gudjonsson J.E., Baldi P.F., Andersen B.;
RT "A GRHL3-regulated repair pathway suppresses immune-mediated epidermal
RT hyperplasia.";
RL J. Clin. Invest. 124:5205-5218(2014).
CC -!- FUNCTION: Transcription factor playing important roles in primary
CC neurulation and in the differentiation of stratified epithelia of both
CC ectodermal and endodermal origin. Binds directly to the consensus DNA
CC sequence 5'-AACCGGTT-3' acting as an activator and repressor on
CC distinct target genes. Essential for epidermal differentiation and
CC barrier formation at the end of embryogenesis with TGM3 as critical
CC direct target (PubMed:21081122, PubMed:20654612, PubMed:25347468).
CC Exhibits functional redundancy with GRHL2 in epidermal morphogenetic
CC events such as eyelid fusion and epidermal wound repair
CC (PubMed:21081122). Despite being dispensable during normal epidermal
CC homeostasis in the adulthood, is again required for barrier repair
CC after immune-mediated epidermal damage, regulates distinct gene
CC batteries in embryonic epidermal differentiation and adult epidermal
CC barrier reformation after injury (PubMed:25347468). Plays unique and
CC cooperative roles with GRHL2 in establishing distinct zones of primary
CC neurulation. Essential for spinal closure, functions cooperatively with
CC GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior
CC neuropore closure (PubMed:14608380, PubMed:20654612). Also required for
CC proper development of the oral periderm (PubMed:24360809). No genetic
CC interaction with GRHL1, no functional cooperativity due to diverse
CC target gene selectivity (PubMed:21081122).
CC {ECO:0000269|PubMed:14608380, ECO:0000269|PubMed:16949565,
CC ECO:0000269|PubMed:20654612, ECO:0000269|PubMed:21081122,
CC ECO:0000269|PubMed:24360809, ECO:0000269|PubMed:25347468}.
CC -!- SUBUNIT: Homodimer, also forms heterodimers with GRHL1 and GRHL2 (By
CC similarity). Interacts with LMO4 (PubMed:16949565).
CC {ECO:0000250|UniProtKB:Q8TE85, ECO:0000269|PubMed:16949565}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21081122}.
CC -!- DEVELOPMENTAL STAGE: At 8.5 dpc, expression is confined to the non-
CC neural ectoderm immediately adjacent to the neural plate, which was
CC undergoing folding to form the neural tube. At later time points, more
CC widespread expression is observed in the surface ectoderm, with a
CC progressive increase until 15.5 dpc. Also expressed in other tissues
CC lined by squamous epithelium, including the oral cavity, urogenital
CC sinus and anal canal. {ECO:0000269|PubMed:14608380}.
CC -!- DISRUPTION PHENOTYPE: Mutant pups display neural tube defects and don't
CC survive to weaning. During embryogenesis, fail to form the epidermal
CC barrier and exhibit defective neural tube closure and embryonic wound
CC repair. The epidermis show a severe barrier function defect associated
CC with impaired differentiation of the epidermis, including defects of
CC the stratum corneum, extracellular lipid composition and cell adhesion
CC in the granular layer. Embryos have thoracolumbosacral spina bifida and
CC curled tail, and 2% have coincident exencephaly. Embryos are smaller
CC than their control littermates, exhibit failed eyelid fusion, the
CC penetrance of which is influenced by genetic background, and shorter
CC intestine with blood in the lumen (PubMed:14608380, PubMed:16949565,
CC PubMed:21081122). Embryos have oral bilateral epithelial adhesions
CC because of the loss of periderm and a cleft palate in some cases
CC (PubMed:24360809). LMO4:GRHL3 double knockout embryos show
CC significantly more frequent exencephaly than that found in single
CC knockouts. Similarly, open-eye phenotype was more penetrant in double
CC knockout mice. Double mutants show an enhancement of the epidermal
CC terminal differentiation defect (PubMed:16949565).
CC {ECO:0000269|PubMed:14608380, ECO:0000269|PubMed:16949565,
CC ECO:0000269|PubMed:20654612, ECO:0000269|PubMed:21081122,
CC ECO:0000269|PubMed:24360809}.
CC -!- MISCELLANEOUS: GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal
CC lack of redundancy despite their extensive sequence identity in the
CC DNA-binding and protein dimerization domains and the fact that the core
CC consensus DNA binding sites are identical. They have related but
CC remarkably different functions during embryogenesis because of their
CC differential spatiotemporal expression patterns during development.
CC {ECO:0000305|PubMed:21081122}.
CC -!- SIMILARITY: Belongs to the grh/CP2 family. Grainyhead subfamily.
CC {ECO:0000305}.
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DR EMBL; AL670720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC089372; AAH89372.1; -; mRNA.
DR CCDS; CCDS38920.1; -.
DR RefSeq; NP_001013778.1; NM_001013756.1.
DR AlphaFoldDB; Q5FWH3; -.
DR SMR; Q5FWH3; -.
DR STRING; 10090.ENSMUSP00000101481; -.
DR iPTMnet; Q5FWH3; -.
DR PhosphoSitePlus; Q5FWH3; -.
DR PaxDb; Q5FWH3; -.
DR PeptideAtlas; Q5FWH3; -.
DR PRIDE; Q5FWH3; -.
DR ProteomicsDB; 271016; -.
DR Antibodypedia; 15710; 184 antibodies from 22 providers.
DR DNASU; 230824; -.
DR Ensembl; ENSMUST00000105855; ENSMUSP00000101481; ENSMUSG00000037188.
DR GeneID; 230824; -.
DR KEGG; mmu:230824; -.
DR UCSC; uc008vgr.1; mouse.
DR CTD; 57822; -.
DR MGI; MGI:2655333; Grhl3.
DR VEuPathDB; HostDB:ENSMUSG00000037188; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000157970; -.
DR HOGENOM; CLU_021156_1_1_1; -.
DR InParanoid; Q5FWH3; -.
DR OMA; PEENICK; -.
DR OrthoDB; 286319at2759; -.
DR PhylomeDB; Q5FWH3; -.
DR TreeFam; TF314132; -.
DR BioGRID-ORCS; 230824; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Grhl3; mouse.
DR PRO; PR:Q5FWH3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q5FWH3; protein.
DR Bgee; ENSMUSG00000037188; Expressed in mucosa of urinary bladder and 108 other tissues.
DR Genevisible; Q5FWH3; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IMP:MGI.
DR GO; GO:0090103; P:cochlea morphogenesis; IGI:MGI.
DR GO; GO:0007398; P:ectoderm development; IMP:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0001736; P:establishment of planar polarity; IGI:MGI.
DR GO; GO:0061436; P:establishment of skin barrier; IMP:UniProtKB.
DR GO; GO:0061029; P:eyelid development in camera-type eye; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IGI:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0042060; P:wound healing; IMP:MGI.
DR InterPro; IPR007604; CP2.
DR Pfam; PF04516; CP2; 1.
DR PROSITE; PS51968; GRH_CP2_DB; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..603
FT /note="Grainyhead-like protein 3 homolog"
FT /id="PRO_0000227998"
FT DOMAIN 226..461
FT /note="Grh/CP2 DB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01313"
FT REGION 30..95
FT /note="Transcription activation"
FT /evidence="ECO:0000250|UniProtKB:Q8TE85"
SQ SEQUENCE 603 AA; 67816 MW; B08AFA95155E05A9 CRC64;
MSNELDFRSV RLLKNDPVSF QKFPYSNEDE AWKTYLENPL TAATKAMMRV NGDEESVAAL
SFLYDYYMGP KEKRILSSST GGRNDQGKKF YHSMDYEPDL APLESPTHLM KFLTENVSGS
PDYTDQLKKN NLLGLEGVLP TPGKTNTVPP GPSKLEASSM DSYLLPASDI YDNGSLNSLF
ESIHGVPPTQ RWQPDSTFKD DPQESLLFPD ILKTSPDPPC PEDYPGLKSD FEYTLGSPKA
IHIKAGESPM AYLNKGQFYP VTLRTPAGGK GLALSSSKVK SVVMVVFDND KVPVEQLRFW
RHWHSRQPTA KQRVIDVADC KENFNTVQHI EEVAYNALSF VWNVNEEAKV FIGVNCLSTD
FSSQKGVKGV PLNLQIDTYD CGAGTERLVH RAVCQIKIFC DKGAERKMRD DERKQFRRKV
KCPDSSNNAG IKGCLLSGFR GNETTYLRPE TDLETQPVLF IPNLHFSSLQ RPGGVVPSAG
HSSSDRLPLK RTCSPFAEEF EPLPSKQAKE DDLQRVLLYV RRETEEVFDA LMLKTPDLKG
LRNAISEKYG LPEENICKVY KKCKRGILVN MDNNIIQHYS NHVAFLLDMG ELDGKIQIIL
KEL
