Gli3
entrez
14634
canonical
uniprot
Q61602
canonical
ensembl
ENSMUSG00000021318
resolver
ensp
ENSMUSP00000106137
resolver
enst
ENSMUST00000110510
resolver
genesymbol
Gli3
resolver
uniprot
B2RUG4
resolver
uniprot
Q3TYX7
resolver
uniprot_entry
B2RUG4_MOUSE
resolver
uniprot_entry
GLI3_MOUSE
resolver
uniprot_entry
Q3TYX7_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which sequesters GLI3 in the cytoplasm (PubMed:20360384, PubMed:20956384). In presence of hedgehog (DHH, IHH or SHH), smoothened is activated, leading to phosphorylation by DYRK2 and dissociation from SUFU and translocation to the nucleus (PubMed:20360384, PubMed:20956384). In absence of hedgehog, smoothened is inhibited, promoting processing of GLI3 into Transcription repressor GLI3R, which dissociates from SUFU and translocates to the nucleus (By similarity). {ECO:0000250|UniProtKB:P10071, ECO:0000269|PubMed:20360384, ECO:0000269|PubMed:20956384}.
uniprot
proteins
amino_acid_sequence
MEAQAHSSTATERKKAENSIGKCPTRTDVSEKAVASSTTSNEDESPGQIYHRERRNAITMQPQSVQGLNKISEEPSTSSDERASLIKKEIHGSLPHLAEPSLPYRGTVFAMDPRNGYMEPHYHPPHLFPAFHPPVPIDARHHEGRYHYDPSPIPPLHVPSALSSSPTYPDLPFIRISPHRNPTAASESPFSPPHPYINPYMDYIRSLHSSPSLSMISAARGLSPTDAPHAGVSPAEYYHQMALLTGQRSPYADILPSAATAGAGAIHMEYLHAMDSTRFPSPRLSARPSRKRTLSISPLSDHSFDLQTMIRTSPNSLVTILNNSRSSSSASGSYGHLSASAISPALSFTYPSAPVSLHMHQQILSRQQSLGSAFGHSPPLIHPAPTFPTQRPIPGIPTVLNPVQVSSGPSESSQSKPTSESAVSSTGDPMHNKRSKIKPDEDLPSPGSRGQQEQPEGTTLVKEEADKDESKQEPEVIYETNCHWEGCTREFDTQDQLVHHINNDHIHGEKKEFVCRWLDCSREQKPFKAQYMLVVHMRRHTGEKPHKCTFEGCTKAYSRLENLKTHLRSHTGEKPYVCEHEGCNKAFSNASDRAKHQNRTHSNEKPYVCKIPGCTKRYTDPSSLRKHVKTVHGPEAHVTKKQRGDMHPRPPPPRDSGSHSQSRSPGRPTQGAFGEQKELSNTTSKREECLQVKTVKAEKPMTSQPSPGGQSSCSSQQSPISNYSNSGLELPLTDGGSVADLSAIDETPIMDSTISTATTALALQARRNPAGTKWMEHIKLERLKQVNGMFPRLNPILPSKAPAVSPLIGNGTQSNNNYSSGGPGTLLPSRSDLSGVDFTVLNTLNRRDSNTSTISSAYLSSRRSSGISPCFSSRRSSEASQAEGRPQNVSVADSYDPISTDASRRSSEASQGDGLPSLLSLTPVQQYRLKAKYAAATGGPPPTPLPHMERLSLKTKMALLGEGRDSGVTLPPVHPPRRCSDGGGHTYRGRHLMPHDALANSVRRASDPVRTVSENMSLARVQRFSSLNSFNPPNLPPSVEKRSLVLQNYTRQESSQPRYFQASPCPPSITENVALEALTMDADANLNDEDLLPDDVVQYLNSQNQTGYGQQLQSGISEDSKVAHEPEDLDLAGLPDSHVGQEYPALEQPCSEGSKTDLPIQWNEVSSGTSDLSSSKLKCGQQRPSAQQPRGFGLYNNMVVHPHNLWKVGTGPAGGYQTLGENSSTYNGPEHFAIHSGDGLGTNGNTFHEQPFKTQQYGSQLNRQPLTSSALDHACGTGIQGSKLKGNSLQENGGLLDFSLSVAPNELAGNTVNGMQTQDQMGQGYIAHQLLSGSMQHQGPSRPGQQVLGQVGATSHINIYQGTESCLPGTQDNSSQPSSMAAIRGYQPCASYGGNRRQAMPRGNLTLQQGQLSDMSQSSRVNSIKMEAQGQSQQLCSTVQNYSGQFYDQTMGFSQQDRKAGSFSLSDANCLLQGNGTENSELLSPGANQVTSTVDSFESHDLEGVQIDFDAIIDDGDHTSLMSGALSPSIIQNLSHSSSRLTTPRASLPFPSLSMGTTNMAIGDMSSLLTSLAEESKFLAVMQ
uniprot
proteins
disease_involvement
DISEASE: Note=Several spontaneous mutations result in developmental defects of cranofacial and limb structures (PubMed:10051311, PubMed:1983115). In particular the add (anterior digit-pattern deformity), Xt (extra-toes) and pdn (polydactyly Nagoya) alleles (PubMed:10051311, PubMed:1983115, PubMed:8387379). Homozygotes Xt (extra-toes) mice show a high incidence of neural tube closure defects and severe forebrain malformation: they die at birth with severe defects in their craniofacial, axial and appendicular skeletons including an enlarged maxillary region, open skull vault, severe fore limb polydactyly, tibial hemimelia, an unfused sternum and fusion of neural arches (PubMed:8387379). {ECO:0000269|PubMed:10051311, ECO:0000269|PubMed:1983115, ECO:0000269|PubMed:8387379}.
uniprot
proteins
function
FUNCTION: Transcription factor that acts as a key effector of the smoothened signaling pathway, and which plays a role in the development and patterning of various body structures, including the brain and limbs (PubMed:10693759, PubMed:11053430, PubMed:17400206, PubMed:19389374, PubMed:20360384). Specifically binds to the minimal GLI-consensus sequence 5'-GACCACCCA-3' to activate or repress the expression of target genes (PubMed:11053430). Functions both as a transcriptional activator and repressor: the full-length GLI3 form (Transcription activator GLI3) acts as a transcription activator following smoothened activation, while the Transcription repressor GLI3R, which is generated in absence of smoothened, acts as a transcription repressor (By similarity). The repressor form (GLI3R) constitutes the major form of GLI3 (By similarity). {ECO:0000250|UniProtKB:P10071, ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:11053430, ECO:0000269|PubMed:17400206, ECO:0000269|PubMed:19389374, ECO:0000269|PubMed:20360384}.; FUNCTION: [Transcription repressor GLI3R]: Major transcription repressor, which inhibits expression of target genes in the absence of smoothened (SMO) signaling (PubMed:10693759, PubMed:16611981). Generated by proteolytic processing of the full-length GLI3 form in the absence of hedgehog (DHH, IHH or SHH), when SMO transducer is inhibited (PubMed:10693759, PubMed:16611981). Constitutes the major form of GLI3, while the transcription activator form only plays a minor role (PubMed:10693759). {ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16611981}.; FUNCTION: [Transcription activator GLI3]: Transcription factor, which activates expression of target genes in response to smoothened (SMO) activation (PubMed:19389374). Constitutes a minor form of GLI3, while the transcription repressor form (GLI3R) plays a major role (By similarity). In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation (By similarity). {ECO:0000250|UniProtKB:P10071, ECO:0000269|PubMed:19389374}.
uniprot
proteins
mass_dalton
171655
uniprot
proteins
post_translational_modification
PTM: In absence of smoothened, phosphorylated on multiple sites by protein kinase A (PKA), priming further phosphorylation by CK1 and GSK3B: phosphorylation promotes ubiquitination by the SCF(BTRC) complex and partial proteolysis to generate the Transcription repressor GLI3R form (PubMed:16611981, PubMed:20360384). Phosphorylated by DYRK2 and ULK3 (in vitro) (By similarity). {ECO:0000250|UniProtKB:P10071, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:20360384}.; PTM: [Transcription activator GLI3]: Phosphorylation at Ser-313 by DYRK2 in response to smoothened activation, promotes GLI3 dissociation from SUFU inhibitor and translocation to the nucleus. {ECO:0000250|UniProtKB:P10071}.; PTM: [Transcription activator GLI3]: Monomethylation at Lys-436 and Lys-595 by SETD7 enhances its ability to bind DNA, thereby increasing the transcription activator activity. {ECO:0000250|UniProtKB:P10071}.; PTM: In absence of smoothened signaling, ubiquitinated by the SCF(BTRC) complex following phosphorylation by PKA and GSK3B, generating the Transcription repressor GLI3R form. {ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:19622347}.; PTM: [Transcription repressor GLI3R]: Generated from the full-length GLI3 protein through proteolytic processing (PubMed:10693759, PubMed:16611981, PubMed:19622347, PubMed:20360384). This process requires PKA-primed phosphorylation of GLI3, ubiquitination by the SCF(BTRC) complex and limited proteolysis (PubMed:16611981, PubMed:19622347, PubMed:20360384). {ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:19622347, ECO:0000269|PubMed:20360384}.
uniprot
proteins
protein_family
GLI C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10051311
uniprot
proteins
pubmed
10693759
uniprot
proteins
pubmed
11053430
uniprot
proteins
pubmed
16611981
uniprot
proteins
pubmed
17400206
uniprot
proteins
pubmed
19389374
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19549984
uniprot
proteins
pubmed
19592253
uniprot
proteins
pubmed
19622347
uniprot
proteins
pubmed
1983115
uniprot
proteins
pubmed
20360384
uniprot
proteins
pubmed
20956384
uniprot
proteins
pubmed
23955340
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
29263200
uniprot
proteins
pubmed
38261656
uniprot
proteins
pubmed
8387379
uniprot
proteins
pubmed
8688459
uniprot
proteins
pubmed
9731531
uniprot
proteins
sequence_length
1583
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20360384, ECO:0000269|PubMed:38261656}. Cytoplasm {ECO:0000269|PubMed:20360384}. Cell projection, cilium {ECO:0000269|PubMed:20360384, ECO:0000269|PubMed:20956384}. Note=Full-length GLI3 is sequestered in the cytoplasm by SUFU in absence of smoothened signaling. {ECO:0000269|PubMed:20956384}.; SUBCELLULAR LOCATION: [Transcription repressor GLI3R]: Nucleus {ECO:0000250|UniProtKB:P10071}. Note=Following generation by proteolytic processing in absence of smoothened, translocates to the nucleus, where is represses transcription of target genes. {ECO:0000250|UniProtKB:P10071}.; SUBCELLULAR LOCATION: [Transcription activator GLI3]: Nucleus {ECO:0000250|UniProtKB:P10071}. Cytoplasm {ECO:0000250|UniProtKB:P10071}. Cell projection, cilium {ECO:0000269|PubMed:20956384}. Note=Sequestered in the cytoplasm by SUFU in absence of smoothened signaling (PubMed:20956384). Accumulates in primary cilia following smoothened activation: cilium localization requires the presence of KIF7 (PubMed:20956384). It then translocates to the nucleus, where is activates transcription of target genes. Translocation to the nucleus is promoted by interaction with ZIC1 (By similarity). TMEM216 reduces its nuclear localization (PubMed:38261656). {ECO:0000250|UniProtKB:P10071, ECO:0000269|PubMed:20956384, ECO:0000269|PubMed:38261656}.
uniprot
proteins