GRHL2_HUMAN
ID GRHL2_HUMAN Reviewed; 625 AA.
AC Q6ISB3; A1L303; Q6NT03; Q9H8B8;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
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, TFCP2L3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [4]
RP INVOLVEMENT IN DFNA28, AND TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH GRHL1.
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 [6]
RP INTERACTION WITH GRHL3.
RX PubMed=12549979; DOI=10.1042/bj20021476;
RA Ting S.B., Wilanowski T., Cerruti L., Zhao L.L., Cunningham J.M.,
RA Jane S.M.;
RT "The identification and characterization of human sister-of-mammalian
RT grainyhead (SOM) expands the grainyhead-like family of developmental
RT transcription factors.";
RL Biochem. J. 370:953-962(2003).
RN [7]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=19015635; DOI=10.1038/onc.2008.404;
RA Kang X., Chen W., Kim R.H., Kang M.K., Park N.H.;
RT "Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and
RT GRHL2 in human oral squamous cell carcinoma cells.";
RL Oncogene 28:565-574(2009).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY SENESCENCE.
RX PubMed=20938050; DOI=10.1074/jbc.m110.103812;
RA Chen W., Dong Q., Shin K.H., Kim R.H., Oh J.E., Park N.H., Kang M.K.;
RT "Grainyhead-like 2 enhances the human telomerase reverse transcriptase gene
RT expression by inhibiting DNA methylation at the 5'-CpG island in normal
RT human keratinocytes.";
RL J. Biol. Chem. 285:40852-40863(2010).
RN [10]
RP FUNCTION, AND INDUCTION BY CALCIUM.
RX PubMed=23254293; DOI=10.1038/cddis.2012.190;
RA Chen W., Xiao Liu Z., Oh J.E., Shin K.H., Kim R.H., Jiang M., Park N.H.,
RA Kang M.K.;
RT "Grainyhead-like 2 (GRHL2) inhibits keratinocyte differentiation through
RT epigenetic mechanism.";
RL Cell Death Dis. 3:E450-E450(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 217-492, FUNCTION, AND
RP MUTAGENESIS OF ARG-423.
RX PubMed=29309642; DOI=10.1093/nar/gkx1299;
RA Ming Q., Roske Y., Schuetz A., Walentin K., Ibraimi I., Schmidt-Ott K.M.,
RA Heinemann U.;
RT "Structural basis of gene regulation by the Grainyhead/CP2 transcription
RT factor family.";
RL Nucleic Acids Res. 46:2082-2095(2018).
RN [12]
RP INVOLVEMENT IN ECTDS, VARIANTS ECTDS HIS-398 AND LYS-482, CHARACTERIZATION
RP OF VARIANT ECTDS LYS-482, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=25152456; DOI=10.1016/j.ajhg.2014.08.001;
RA Petrof G., Nanda A., Howden J., Takeichi T., McMillan J.R., Aristodemou S.,
RA Ozoemena L., Liu L., South A.P., Pourreyron C., Dafou D., Proudfoot L.E.,
RA Al-Ajmi H., Akiyama M., McLean W.H., Simpson M.A., Parsons M.,
RA McGrath J.A.;
RT "Mutations in GRHL2 result in an autosomal-recessive ectodermal Dysplasia
RT syndrome.";
RL Am. J. Hum. Genet. 95:308-314(2014).
RN [13]
RP INVOLVEMENT IN PPCD4, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=29499165; DOI=10.1016/j.ajhg.2018.02.002;
RA Liskova P., Dudakova L., Evans C.J., Rojas Lopez K.E., Pontikos N.,
RA Athanasiou D., Jama H., Sach J., Skalicka P., Stranecky V., Kmoch S.,
RA Thaung C., Filipec M., Cheetham M.E., Davidson A.E., Tuft S.J.,
RA Hardcastle A.J.;
RT "Ectopic GRHL2 expression due to non-coding mutations promotes cell state
RT transition and causes posterior polymorphous corneal dystrophy 4.";
RL Am. J. Hum. Genet. 102:447-459(2018).
CC -!- FUNCTION: Transcription factor playing an important role in primary
CC neurulation and in epithelial development (PubMed:29309642,
CC PubMed:25152456). Binds directly to the consensus DNA sequence 5'-
CC AACCGGTT-3' acting as an activator and repressor on distinct target
CC genes (By similarity). During embryogenesis, plays unique and
CC cooperative roles with GRHL3 in establishing distinct zones of primary
CC neurulation. Essential for closure 3 (rostral end of the forebrain),
CC functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain
CC boundary) and posterior neuropore closure (By similarity). Regulates
CC epithelial morphogenesis acting as a target gene-associated
CC transcriptional activator of apical junctional complex components. Up-
CC regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the
CC CLDN4 protein and its localization at tight junctions (By similarity).
CC Comprises an essential component of the transcriptional machinery that
CC establishes appropriate expression levels of CLDN4 and CDH1 in
CC different types of epithelia. Exhibits functional redundancy with GRHL3
CC in epidermal morphogenetic events and epidermal wound repair (By
CC similarity). In lung, forms a regulatory loop with NKX2-1 that
CC coordinates lung epithelial cell morphogenesis and differentiation (By
CC similarity). In keratinocytes, plays a role in telomerase activation
CC during cellular proliferation, regulates TERT expression by binding to
CC TERT promoter region and inhibiting DNA methylation at the 5'-CpG
CC island, possibly by interfering with DNMT1 enzyme activity
CC (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte
CC differentiation and epidermal function by inhibiting the expression of
CC genes clustered at the epidermal differentiation complex (EDC) as well
CC as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293).
CC {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635,
CC ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075,
CC ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456,
CC ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}.
CC -!- SUBUNIT: Homodimer, also forms heterodimers with GRHL1 or GRHL3.
CC {ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:12549979}.
CC -!- INTERACTION:
CC Q6ISB3; P61968: LMO4; NbExp=7; IntAct=EBI-10219092, EBI-2798728;
CC Q6ISB3; Q02548: PAX5; NbExp=3; IntAct=EBI-10219092, EBI-296331;
CC Q6ISB3; P26367: PAX6; NbExp=3; IntAct=EBI-10219092, EBI-747278;
CC Q6ISB3; O75928-2: PIAS2; NbExp=3; IntAct=EBI-10219092, EBI-348567;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20938050,
CC ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29499165}. Membrane
CC {ECO:0000269|PubMed:25152456}. Note=detected at cell-cell contact
CC areas. {ECO:0000269|PubMed:25152456}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6ISB3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ISB3-2; Sequence=VSP_017642;
CC -!- TISSUE SPECIFICITY: Expressed in keratinocytes (at protein level).
CC Highly expressed in placenta, prostate, brain and kidney. Lower-level
CC expression in a variety of epithelial tissues such as thymus, lung,
CC salivary gland, mammary gland and digestive tract. Expressed in the
CC cochlear. Expressed in corneal epithelial cells, but not in the
CC endothelium or stroma (PubMed:29499165). {ECO:0000269|PubMed:12175488,
CC ECO:0000269|PubMed:12393799, ECO:0000269|PubMed:20978075,
CC ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29499165}.
CC -!- INDUCTION: Expressed in proliferating cells, the expression decreases
CC during senescence. In keratinocytes, expression levels decrease upon
CC calcium exposure. {ECO:0000269|PubMed:20938050,
CC ECO:0000269|PubMed:23254293}.
CC -!- DISEASE: Deafness, autosomal dominant, 28 (DFNA28) [MIM:608641]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. DFNA28 is characterized by mild to moderate hearing loss
CC across most frequencies that progresses to severe loss in the higher
CC frequencies by the fifth decade. {ECO:0000269|PubMed:12393799}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Ectodermal dysplasia/short stature syndrome (ECTDS)
CC [MIM:616029]: An autosomal recessive ectodermal dysplasia syndrome
CC characterized by nail dystrophy and/or loss, oral mucosa and/or tongue
CC pigmentation, abnormal dentition, keratoderma affecting the margins of
CC the palms and soles, focal hyperkeratosis of the dorsal aspects of the
CC hands and feet, and short stature. {ECO:0000269|PubMed:25152456}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Corneal dystrophy, posterior polymorphous, 4 (PPCD4)
CC [MIM:618031]: A subtype of posterior corneal dystrophy, a disease
CC characterized by alterations of Descemet membrane presenting as
CC vesicles, opacities or band-like lesions on slit-lamp examination and
CC specular microscopy. In severe cases, corneal endothelial failure may
CC occur and corneal transplantation is required to restore vision.
CC Secondary complications are common and include corneal edema, glaucoma,
CC iris adherence to the cornea, and corectopia. PPCD4 transmission
CC pattern is consistent with autosomal dominant inheritance.
CC {ECO:0000269|PubMed:29499165}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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:0000250|UniProtKB:Q8K5C0}.
CC -!- SIMILARITY: Belongs to the grh/CP2 family. Grainyhead subfamily.
CC {ECO:0000305}.
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DR EMBL; AK023844; BAB14699.1; -; mRNA.
DR EMBL; CH471060; EAW91834.1; -; Genomic_DNA.
DR EMBL; BC069618; AAH69618.1; -; mRNA.
DR EMBL; BC069633; AAH69633.1; -; mRNA.
DR EMBL; BC069638; AAH69638.1; -; mRNA.
DR EMBL; BC129822; AAI29823.1; -; mRNA.
DR EMBL; BC129823; AAI29824.1; -; mRNA.
DR CCDS; CCDS34931.1; -. [Q6ISB3-1]
DR CCDS; CCDS83312.1; -. [Q6ISB3-2]
DR RefSeq; NP_001317522.1; NM_001330593.1. [Q6ISB3-2]
DR RefSeq; NP_079191.2; NM_024915.3. [Q6ISB3-1]
DR RefSeq; XP_011515608.1; XM_011517306.2. [Q6ISB3-2]
DR PDB; 5MR7; X-ray; 2.50 A; A/B=217-492.
DR PDBsum; 5MR7; -.
DR AlphaFoldDB; Q6ISB3; -.
DR SMR; Q6ISB3; -.
DR BioGRID; 123042; 18.
DR IntAct; Q6ISB3; 9.
DR MINT; Q6ISB3; -.
DR STRING; 9606.ENSP00000251808; -.
DR GlyGen; Q6ISB3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ISB3; -.
DR PhosphoSitePlus; Q6ISB3; -.
DR BioMuta; GRHL2; -.
DR DMDM; 74736618; -.
DR EPD; Q6ISB3; -.
DR jPOST; Q6ISB3; -.
DR MassIVE; Q6ISB3; -.
DR MaxQB; Q6ISB3; -.
DR PaxDb; Q6ISB3; -.
DR PeptideAtlas; Q6ISB3; -.
DR PRIDE; Q6ISB3; -.
DR ProteomicsDB; 66492; -. [Q6ISB3-1]
DR ProteomicsDB; 66493; -. [Q6ISB3-2]
DR Antibodypedia; 1306; 162 antibodies from 21 providers.
DR DNASU; 79977; -.
DR Ensembl; ENST00000395927.1; ENSP00000379260.1; ENSG00000083307.12. [Q6ISB3-2]
DR Ensembl; ENST00000646743.1; ENSP00000495564.1; ENSG00000083307.12. [Q6ISB3-1]
DR GeneID; 79977; -.
DR KEGG; hsa:79977; -.
DR MANE-Select; ENST00000646743.1; ENSP00000495564.1; NM_024915.4; NP_079191.2.
DR UCSC; uc010mbu.4; human. [Q6ISB3-1]
DR CTD; 79977; -.
DR DisGeNET; 79977; -.
DR GeneCards; GRHL2; -.
DR GeneReviews; GRHL2; -.
DR HGNC; HGNC:2799; GRHL2.
DR HPA; ENSG00000083307; Tissue enhanced (skin).
DR MalaCards; GRHL2; -.
DR MIM; 608576; gene.
DR MIM; 608641; phenotype.
DR MIM; 616029; phenotype.
DR MIM; 618031; phenotype.
DR neXtProt; NX_Q6ISB3; -.
DR OpenTargets; ENSG00000083307; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 423454; Nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome.
DR Orphanet; 98973; Posterior polymorphous corneal dystrophy.
DR PharmGKB; PA27270; -.
DR VEuPathDB; HostDB:ENSG00000083307; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000155788; -.
DR HOGENOM; CLU_021156_1_1_1; -.
DR InParanoid; Q6ISB3; -.
DR OMA; XGTFQYT; -.
DR OrthoDB; 286319at2759; -.
DR PhylomeDB; Q6ISB3; -.
DR TreeFam; TF314132; -.
DR PathwayCommons; Q6ISB3; -.
DR SignaLink; Q6ISB3; -.
DR SIGNOR; Q6ISB3; -.
DR BioGRID-ORCS; 79977; 81 hits in 1095 CRISPR screens.
DR ChiTaRS; GRHL2; human.
DR GenomeRNAi; 79977; -.
DR Pharos; Q6ISB3; Tbio.
DR PRO; PR:Q6ISB3; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6ISB3; protein.
DR Bgee; ENSG00000083307; Expressed in buccal mucosa cell and 139 other tissues.
DR Genevisible; Q6ISB3; HS.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:HGNC.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; ISS: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; IEA:Ensembl.
DR GO; GO:0070830; P:bicellular tight junction assembly; IMP:UniProtKB.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0034329; P:cell junction assembly; IMP:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0008544; P:epidermis development; IDA:UniProtKB.
DR GO; GO:0003382; P:epithelial cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0060672; P:epithelial cell morphogenesis involved in placental branching; IEA:Ensembl.
DR GO; GO:0090132; P:epithelium migration; ISS:UniProtKB.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0060487; P:lung epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0060463; P:lung lobe morphogenesis; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IBA:GO_Central.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:HGNC.
DR GO; GO:0044030; P:regulation of DNA methylation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR007604; CP2.
DR Pfam; PF04516; CP2; 1.
DR PROSITE; PS51968; GRH_CP2_DB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Corneal dystrophy; Deafness;
KW Disease variant; DNA-binding; Dwarfism; Ectodermal dysplasia; Membrane;
KW Non-syndromic deafness; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..625
FT /note="Grainyhead-like protein 2 homolog"
FT /id="PRO_0000227994"
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:0000250|UniProtKB:Q8K5C0"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..97
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 423
FT /note="Important for activation of transcription"
FT /evidence="ECO:0000269|PubMed:29309642"
FT VAR_SEQ 1..16
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017642"
FT VARIANT 398
FT /note="Y -> H (in ECTDS; dbSNP:rs587777737)"
FT /evidence="ECO:0000269|PubMed:25152456"
FT /id="VAR_071989"
FT VARIANT 415
FT /note="V -> I (in dbSNP:rs3779617)"
FT /id="VAR_049293"
FT VARIANT 482
FT /note="I -> K (in ECTDS; reduced expression; altered cell
FT morphology; impaired tight junctions; adhesion defects;
FT cytoplasmic translocation; dbSNP:rs587777738)"
FT /evidence="ECO:0000269|PubMed:25152456"
FT /id="VAR_071990"
FT MUTAGEN 423
FT /note="R->A,Q: Loss of activity as transcriptional
FT activator."
FT /evidence="ECO:0000269|PubMed:29309642"
FT CONFLICT 53
FT /note="S -> I (in Ref. 1; BAB14699)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="R -> Q (in Ref. 1; BAB14699)"
FT /evidence="ECO:0000305"
FT CONFLICT 436
FT /note="K -> N (in Ref. 1; BAB14699)"
FT /evidence="ECO:0000305"
FT CONFLICT 561
FT /note="K -> M (in Ref. 1; BAB14699)"
FT /evidence="ECO:0000305"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 295..306
FT /evidence="ECO:0007829|PDB:5MR7"
FT HELIX 310..322
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:5MR7"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 354..360
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 365..371
FT /evidence="ECO:0007829|PDB:5MR7"
FT TURN 375..378
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 389..400
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 406..417
FT /evidence="ECO:0007829|PDB:5MR7"
FT HELIX 420..429
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:5MR7"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:5MR7"
SQ SEQUENCE 625 AA; 71105 MW; 147CF33798248BB6 CRC64;
MSQESDNNKR LVALVPMPSD PPFNTRRAYT SEDEAWKSYL ENPLTAATKA MMSINGDEDS
AAALGLLYDY YKVPRDKRLL SVSKASDSQE DQEKRNCLGT SEAQSNLSGG ENRVQVLKTV
PVNLSLNQDH LENSKREQYS ISFPESSAII PVSGITVVKA EDFTPVFMAP PVHYPRGDGE
EQRVVIFEQT QYDVPSLATH SAYLKDDQRS TPDSTYSESF KDAATEKFRS ASVGAEEYMY
DQTSSGTFQY TLEATKSLRQ KQGEGPMTYL NKGQFYAITL SETGDNKCFR HPISKVRSVV
MVVFSEDKNR DEQLKYWKYW HSRQHTAKQR VLDIADYKES FNTIGNIEEI AYNAVSFTWD
VNEEAKIFIT VNCLSTDFSS QKGVKGLPLM IQIDTYSYNN RSNKPIHRAY CQIKVFCDKG
AERKIRDEER KQNRKKGKGQ ASQTQCNSSS DGKLAAIPLQ KKSDITYFKT MPDLHSQPVL
FIPDVHFANL QRTGQVYYNT DDEREGGSVL VKRMFRPMEE EFGPVPSKQM KEEGTKRVLL
YVRKETDDVF DALMLKSPTV KGLMEAISEK YGLPVEKIAK LYKKSKKGIL VNMDDNIIEH
YSNEDTFILN MESMVEGFKV TLMEI
