GRHL1_MOUSE
ID GRHL1_MOUSE Reviewed; 618 AA.
AC Q921D9; Q8K5C1;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Grainyhead-like protein 1 homolog {ECO:0000312|MGI:MGI:2182540};
DE AltName: Full=Transcription factor CP2-like 2;
DE AltName: Full=Transcription factor LBP-32;
GN Name=Grhl1 {ECO:0000312|MGI:MGI:2182540}; Synonyms=Mgr, Tcfcp2l2;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, DNA-BINDING, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18288204; DOI=10.1038/emboj.2008.24;
RA Wilanowski T., Caddy J., Ting S.B., Hislop N.R., Cerruti L., Auden A.,
RA Zhao L.L., Asquith S., Ellis S., Sinclair R., Cunningham J.M., Jane S.M.;
RT "Perturbed desmosomal cadherin expression in grainy head-like 1-null
RT mice.";
RL EMBO J. 27:886-897(2008).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24586629; DOI=10.1371/journal.pone.0089247;
RA Mlacki M., Darido C., Jane S.M., Wilanowski T.;
RT "Loss of Grainy head-like 1 is associated with disruption of the epidermal
RT barrier and squamous cell carcinoma of the skin.";
RL PLoS ONE 9:E89247-E89247(2014).
CC -!- FUNCTION: Transcription factor involved in epithelial development.
CC Binds directly to the consensus DNA sequence 5'-AACCGGTT-3'
CC (PubMed:18288204, PubMed:21081122). Important regulator of DSG1 in the
CC context of hair anchorage and epidermal differentiation, participates
CC in the maintenance of the skin barrier (PubMed:18288204,
CC PubMed:24586629). There is no genetic interaction with GRHL3 no genetic
CC interaction with GRHL3, no functional cooperativity due to diverse
CC target gene selectivity during epithelia development (PubMed:21081122).
CC {ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:21081122,
CC ECO:0000269|PubMed:24586629}.
CC -!- SUBUNIT: Binds DNA as homodimer. Homodimer, also forms heterodimers
CC with GRHL2 or GRHL3. {ECO:0000250|UniProtKB:Q9NZI5}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18288204}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p70 Mgr;
CC IsoId=Q921D9-1; Sequence=Displayed;
CC Name=2; Synonyms=p61 Mgr;
CC IsoId=Q921D9-2; Sequence=VSP_017641, VSP_017640;
CC -!- TISSUE SPECIFICITY: Isoform 1 is highly expressed in brain, pancreas,
CC tonsil, placenta and kidney. Isoform 2 is highly expressed in brain and
CC liver. Expression in the skin is confined to the suprabasal layers of
CC the epidermis and to the hair follicles. {ECO:0000269|PubMed:12175488,
CC ECO:0000269|PubMed:18288204}.
CC -!- DEVELOPMENTAL STAGE: At 15.5 dpc isoform 1 is expressed predominantly
CC in the skin and in the developing hair germ, isoform 2 is expressed
CC predominantly in the epidermis. {ECO:0000269|PubMed:12175488,
CC ECO:0000269|PubMed:18288204}.
CC -!- DISRUPTION PHENOTYPE: Mutants are healthy and fertile, but display an
CC initial delay in coat growth, with older mice exhibiting hair loss as a
CC result of poor anchoring or the hair shaft in the follicle. They show
CC reduced numbers of abnormal desmosomes in the interfollicular
CC epidermis. Develop palmoplantar keratoderma (PubMed:21081122). They
CC also exhibit mild chronic skin barrier defects with altered
CC keratinocyte terminal differentiation, increased expression of
CC inflammatory markers and infiltration of the skin by immune cells.
CC {ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:21081122,
CC ECO:0000269|PubMed:24586629}.
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; AF411211; AAM22617.1; -; mRNA.
DR EMBL; AF411212; AAM22618.1; -; mRNA.
DR EMBL; AK161048; BAE36170.1; -; mRNA.
DR EMBL; BC013080; AAH13080.1; -; mRNA.
DR EMBL; BC037233; AAH37233.1; -; mRNA.
DR CCDS; CCDS36420.1; -. [Q921D9-2]
DR CCDS; CCDS49038.1; -. [Q921D9-1]
DR RefSeq; NP_001154878.1; NM_001161406.1. [Q921D9-1]
DR AlphaFoldDB; Q921D9; -.
DR SMR; Q921D9; -.
DR STRING; 10090.ENSMUSP00000082689; -.
DR iPTMnet; Q921D9; -.
DR PhosphoSitePlus; Q921D9; -.
DR PaxDb; Q921D9; -.
DR PRIDE; Q921D9; -.
DR ProteomicsDB; 271160; -. [Q921D9-1]
DR ProteomicsDB; 271161; -. [Q921D9-2]
DR Antibodypedia; 1788; 127 antibodies from 24 providers.
DR DNASU; 195733; -.
DR Ensembl; ENSMUST00000085553; ENSMUSP00000082689; ENSMUSG00000020656. [Q921D9-1]
DR GeneID; 195733; -.
DR KEGG; mmu:195733; -.
DR UCSC; uc007nem.2; mouse. [Q921D9-1]
DR CTD; 29841; -.
DR MGI; MGI:2182540; Grhl1.
DR VEuPathDB; HostDB:ENSMUSG00000020656; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000157612; -.
DR HOGENOM; CLU_021156_1_1_1; -.
DR InParanoid; Q921D9; -.
DR OMA; VHHPISK; -.
DR OrthoDB; 286319at2759; -.
DR PhylomeDB; Q921D9; -.
DR TreeFam; TF314132; -.
DR BioGRID-ORCS; 195733; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Grhl1; mouse.
DR PRO; PR:Q921D9; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q921D9; protein.
DR Bgee; ENSMUSG00000020656; Expressed in hair follicle and 164 other tissues.
DR ExpressionAtlas; Q921D9; baseline and differential.
DR Genevisible; Q921D9; MM.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0002934; P:desmosome organization; IMP:MGI.
DR GO; GO:0008544; P:epidermis development; IDA:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; 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; ISA:MGI.
DR InterPro; IPR007604; CP2.
DR Pfam; PF04516; CP2; 1.
DR PROSITE; PS51968; GRH_CP2_DB; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Developmental protein; DNA-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..618
FT /note="Grainyhead-like protein 1 homolog"
FT /id="PRO_0000227991"
FT DOMAIN 248..474
FT /note="Grh/CP2 DB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01313"
FT REGION 1..91
FT /note="Transcription activation"
FT /evidence="ECO:0000250|UniProtKB:Q8K5C0"
FT REGION 76..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..389
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI5"
FT REGION 427..430
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI5"
FT COMPBIAS 76..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI5"
FT VAR_SEQ 1..82
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12175488"
FT /id="VSP_017641"
FT VAR_SEQ 83..93
FT /note="GEHPEPEHSKR -> MASLDDELCDL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12175488"
FT /id="VSP_017640"
SQ SEQUENCE 618 AA; 70176 MW; 7AC6F5CE8081E453 CRC64;
MTQEYDNKRP VLVLQNEALY PQRRSYTSED EAWKSFLENP LTAATKAMMS INGDEDSAAA
LGLLYDYYKV PRERRSSAVK PEGEHPEPEH SKRNSIPNVT EQPLISAGEN RVQVLKNVPF
NIVLPHSNQL GIDKRGHLTA PDTTVTVSIA TMPTHSIKTE IQPHGFAVGI PPAVYHSEPT
ERVVVFDRSL STDQFSSGTQ PPNAQRRTPD STFSETFKEG VQEVFFPSEL SLRMPGMNSE
DYVFDNVSGN NFEYTLEASK SLRQKQGDST MTYLNKGQFY PVTLKEGSSN EGIHHPISKV
RSVIMVVFAE DKSREDQLRH WKYWHSRQHT AKQRCIDIAD YKESFNTISN IEEIAYNAIS
FTWDINDEAK VFISVNCLST DFSSQKGVKG LPLNIQIDTY SYNNRSNKPV HRAYCQIKVF
CDKGAERKIR DEERKQSKRK VSDVKVQLLP SHKRTDITVF KPFLDLDTQP VLFIPDVHFT
NLQRGSHVLS LPSEELEGEG SVLKRGPFGT EDDFGVPPPA KLTRTEEPKR VLLYVRKESE
EVFDALMLKT PSLKGLMEAI SDKYDVPHDK IGKIFKKCKK GILVNMDDNI VKHYSNEDTF
QLQIEEAGGS YKLTLTEI
