GRHL2_MOUSE
ID GRHL2_MOUSE Reviewed; 625 AA.
AC Q8K5C0; Q80UZ5;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Grainyhead-like protein 2 homolog;
DE AltName: Full=Brother of mammalian grainyhead;
DE AltName: Full=Transcription factor CP2-like 3;
GN Name=Grhl2; Synonyms=Bom, Tcfcp2l3;
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 [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Teratocarcinoma;
RX PubMed=12175488; DOI=10.1016/s0925-4773(02)00046-1;
RA Wilanowski T., Tuckfield A., Cerruti L., O'Connell S., Saint R., Parekh V.,
RA Tao J., Cunningham J.M., Jane S.M.;
RT "A highly conserved novel family of mammalian developmental transcription
RT factors related to Drosophila grainyhead.";
RL Mech. Dev. 114:37-50(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor, and Olfactory epithelium;
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 DEVELOPMENTAL STAGE.
RX PubMed=12393799; DOI=10.1093/hmg/11.23.2877;
RA Peters L.M., Anderson D.W., Griffith A.J., Grundfast K.M.,
RA San Agustin T.B., Madeo A.C., Friedman T.B., Morell R.J.;
RT "Mutation of a transcription factor, TFCP2L3, causes progressive autosomal
RT dominant hearing loss, DFNA28.";
RL Hum. Mol. Genet. 11:2877-2885(2002).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20978075; DOI=10.1242/dev.055483;
RA Werth M., Walentin K., Aue A., Schonheit J., Wuebken A., Pode-Shakked N.,
RA Vilianovitch L., Erdmann B., Dekel B., Bader M., Barasch J., Rosenbauer F.,
RA Luft F.C., Schmidt-Ott K.M.;
RT "The transcription factor grainyhead-like 2 regulates the molecular
RT composition of the epithelial apical junctional complex.";
RL Development 137:3835-3845(2010).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
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.
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 DEVELOPMENTAL STAGE.
RX PubMed=22955271; DOI=10.1074/jbc.m112.408401;
RA Varma S., Cao Y., Tagne J.B., Lakshminarayanan M., Li J., Friedman T.B.,
RA Morell R.J., Warburton D., Kotton D.N., Ramirez M.I.;
RT "The transcription factors Grainyhead-like 2 and NK2-homeobox 1 form a
RT regulatory loop that coordinates lung epithelial cell morphogenesis and
RT differentiation.";
RL J. Biol. Chem. 287:37282-37295(2012).
RN [8]
RP FUNCTION, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=22696678; DOI=10.1091/mbc.e12-02-0097;
RA Senga K., Mostov K.E., Mitaka T., Miyajima A., Tanimizu N.;
RT "Grainyhead-like 2 regulates epithelial morphogenesis by establishing
RT functional tight junctions through the organization of a molecular network
RT among claudin3, claudin4, and Rab25.";
RL Mol. Biol. Cell 23:2845-2855(2012).
CC -!- FUNCTION: Transcription factor playing an important role in primary
CC neurulation and in epithelial development. Binds directly to the
CC consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and
CC repressor on distinct target genes (PubMed:22696678). During
CC embryogenesis, plays unique and cooperative roles with GRHL3 in
CC establishing distinct zones of primary neurulation. Essential for
CC closure 3 (rostral end of the forebrain), functions cooperatively with
CC GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior
CC neuropore closure (PubMed:20654612). Regulates epithelial morphogenesis
CC acting as a target gene-associated transcriptional activator of apical
CC junctional complex components. Up-regulates of CLDN3 and CLDN4, as well
CC as of RAB25, which increases the CLDN4 protein and its localization at
CC tight junctions (PubMed:22696678). Comprises an essential component of
CC the transcriptional machinery that establishes appropriate expression
CC levels of CLDN4 and CDH1 in different types of epithelia
CC (PubMed:20978075). Exhibits functional redundancy with GRHL3 in
CC epidermal morphogenetic events such as eyelid fusion and epidermal
CC wound repair (PubMed:21081122). In lung, forms a regulatory loop with
CC NKX2-1 that coordinates lung epithelial cell morphogenesis and
CC differentiation (PubMed:22955271). In keratinocytes, plays a role in
CC telomerase activation during cellular proliferation, regulates TERT
CC expression by binding to TERT promoter region and inhibiting DNA
CC methylation at the 5'-CpG island, possibly by interfering with DNMT1
CC enzyme activity. In addition, impairs keratinocyte differentiation and
CC epidermal function by inhibiting the expression of genes clustered at
CC the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3
CC through epigenetic mechanisms (By similarity).
CC {ECO:0000250|UniProtKB:Q6ISB3, ECO:0000269|PubMed:20654612,
CC ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:21081122,
CC ECO:0000269|PubMed:22696678, ECO:0000269|PubMed:22955271}.
CC -!- SUBUNIT: Homodimer, also forms heterodimers with GRHL1 or GRHL3.
CC {ECO:0000250|UniProtKB:Q6ISB3}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20978075,
CC ECO:0000269|PubMed:22696678}. Membrane {ECO:0000250|UniProtKB:Q6ISB3}.
CC Note=detected at cell-cell contact areas.
CC {ECO:0000250|UniProtKB:Q6ISB3}.
CC -!- DEVELOPMENTAL STAGE: At 14.5 dpc expressed in lung, esophagus, skin and
CC kidney. At 9.5 dpc expressed in foregut and surface ectoderm but not in
CC the neural tube. At 9.5 dpc and 15.5 dpc, detected in the lung
CC epithelium and in branchiolar and alveolar epithelial cells at 18.5 dpc
CC and adult. Expressed in otocyst at 11.5 dpc, prominent in epithelial
CC derivatives of the otic placode in the vestibule and cochlear duct at
CC 18.5 dpc. At postnatal day 5, epithelial cells of the cochlear duct,
CC which surround the endolymph-containing scala media, continued to
CC express low levels, while little or no expression was seen in the
CC mesenchyme-derived cells lining the scala tympani and scala vestibuli.
CC Detected in cholangiocytes in postnatal day 1 and postnatal day 8
CC livers. {ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:12393799,
CC ECO:0000269|PubMed:20654612, ECO:0000269|PubMed:20978075,
CC ECO:0000269|PubMed:22696678, ECO:0000269|PubMed:22955271}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos show an epithelial and anterior
CC and posterior neural tube defects leading to death at around 11.5 dpc
CC (PubMed:20654612, PubMed:20978075). They exhibit a fully penetrant
CC split-face malformation, associated with cranioschisis. Closure of the
CC remainder of the neural tube ocrurred normally with the exception of
CC the posterior neuropore. The dorso-lateral hinge points fail to form
CC and closure do not proceed beyond this point (PubMed:20654612).
CC {ECO:0000269|PubMed:20654612, ECO:0000269|PubMed:20978075}.
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; AF411213; AAM22619.1; -; mRNA.
DR EMBL; BC042575; AAH42575.1; -; mRNA.
DR EMBL; BC055035; AAH55035.1; -; mRNA.
DR CCDS; CCDS27434.1; -.
DR RefSeq; NP_080772.2; NM_026496.4.
DR AlphaFoldDB; Q8K5C0; -.
DR SMR; Q8K5C0; -.
DR BioGRID; 232985; 5.
DR IntAct; Q8K5C0; 3.
DR MINT; Q8K5C0; -.
DR STRING; 10090.ENSMUSP00000022895; -.
DR iPTMnet; Q8K5C0; -.
DR PhosphoSitePlus; Q8K5C0; -.
DR MaxQB; Q8K5C0; -.
DR PaxDb; Q8K5C0; -.
DR PeptideAtlas; Q8K5C0; -.
DR PRIDE; Q8K5C0; -.
DR ProteomicsDB; 271297; -.
DR Antibodypedia; 1306; 162 antibodies from 21 providers.
DR DNASU; 252973; -.
DR Ensembl; ENSMUST00000022895; ENSMUSP00000022895; ENSMUSG00000022286.
DR GeneID; 252973; -.
DR KEGG; mmu:252973; -.
DR UCSC; uc007vne.2; mouse.
DR CTD; 79977; -.
DR MGI; MGI:2182543; Grhl2.
DR VEuPathDB; HostDB:ENSMUSG00000022286; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000155788; -.
DR HOGENOM; CLU_021156_1_1_1; -.
DR InParanoid; Q8K5C0; -.
DR OMA; XGTFQYT; -.
DR OrthoDB; 286319at2759; -.
DR PhylomeDB; Q8K5C0; -.
DR TreeFam; TF314132; -.
DR BioGRID-ORCS; 252973; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Grhl2; mouse.
DR PRO; PR:Q8K5C0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K5C0; protein.
DR Bgee; ENSMUSG00000022286; Expressed in lacrimal gland and 203 other tissues.
DR ExpressionAtlas; Q8K5C0; baseline and differential.
DR Genevisible; Q8K5C0; MM.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0061713; P:anterior neural tube closure; IMP:MGI.
DR GO; GO:0070830; P:bicellular tight junction assembly; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:MGI.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0034329; P:cell junction assembly; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0048568; P:embryonic organ development; IMP:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0003382; P:epithelial cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0060672; P:epithelial cell morphogenesis involved in placental branching; IMP:MGI.
DR GO; GO:0090132; P:epithelium migration; IMP:UniProtKB.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0060487; P:lung epithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0060463; P:lung lobe morphogenesis; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CACAO.
DR GO; GO:0044030; P:regulation of DNA methylation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0030323; P:respiratory tube development; IMP:MGI.
DR InterPro; IPR007604; CP2.
DR Pfam; PF04516; CP2; 1.
DR PROSITE; PS51968; GRH_CP2_DB; 1.
PE 2: Evidence at transcript level;
KW Activator; DNA-binding; Membrane; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..625
FT /note="Grainyhead-like protein 2 homolog"
FT /id="PRO_0000227995"
FT DOMAIN 244..482
FT /note="Grh/CP2 DB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01313"
FT REGION 1..93
FT /note="Transcription activation"
FT /evidence="ECO:0000269|PubMed:20978075"
FT REGION 198..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 423
FT /note="Important for activation of transcription"
FT /evidence="ECO:0000250|UniProtKB:Q6ISB3"
SQ SEQUENCE 625 AA; 71195 MW; 879EE7689A5AA4E3 CRC64;
MSQESDNNKR LVALVPMPSD PPFNTRRAYT SEDEAWKSYL ENPLTAATKA MMSINGDEDS
AAALGLLYDY YKVPRDKRLL SVSKASDSQE DQDKRNCLGT SEAQINLSGG ENRVQVLKTV
PVNLCLSQDH MENSKREQYS VSITESSAVI PVSGITVVKA EDFTPVFMAP PVHYPRADSE
EQRVVIFEQT QYDLPSIASH SSYLKDDQRS TPDSTYSESF KDGASEKFRS TSVGADEYTY
DQTGSGTFQY TLEATKSLRQ KQGEGPMTYL NKGQFYAITL SETGDNKCFR HPISKVRSVV
MVVFSEDKNR DEQLKYWKYW HSRQHTAKQR VLDIADYKES FNTIGNIEEI AYNAVSFTWD
VNEEAKIFIT VNCLSTDFSS QKGVKGLPLM IQIDTYSYNN RSNKPIHRAY CQIKVFCDKG
AERKIRDEER KQNRKKGKGQ ASQAQCNNSS DGKMAAIPLQ KKSDITYFKT MPDLHSQPVL
FIPDVHFANL QRTGQVYYNT DDEREGSSVL VKRMFRPMEE EFGPTPSKQI KEENVKRVLL
YVRKENDDVF DALMLKSPTV KGLMEALSEK YGLPVEKITK LYKKSKKGIL VNMDDNIIEH
YSNEDTFILN MESMVEGFKI TLMEI
