GLI3
entrez
2737
canonical
uniprot
P10071
canonical
ensembl
ENSG00000106571
resolver
ensp
ENSP00000379258
resolver
ensp
ENSP00000496377
resolver
ensp
ENSP00000502957
resolver
ensp
ENSP00000503743
resolver
ensp
ENSP00000548809
resolver
ensp
ENSP00000548810
resolver
enst
ENST00000395925
resolver
enst
ENST00000479210
resolver
enst
ENST00000677605
resolver
enst
ENST00000678429
resolver
enst
ENST00000878750
resolver
enst
ENST00000878751
resolver
genesymbol
GLI3
resolver
hgnc
HGNC:4319
resolver
uniprot
A0A2R8YGX0
resolver
uniprot
A4D1W1
resolver
uniprot
O75219
resolver
uniprot
Q17RW4
resolver
uniprot
Q75MT0
resolver
uniprot
Q75MU9
resolver
uniprot
Q9UDT5
resolver
uniprot
Q9UJ39
resolver
uniprot_entry
A0A2R8YGX0_HUMAN
resolver
uniprot_entry
GLI3_HUMAN
resolver
uniprot_sec
A4D1W1
resolver
uniprot_sec
O75219
resolver
uniprot_sec
Q17RW4
resolver
uniprot_sec
Q75MT0
resolver
uniprot_sec
Q75MU9
resolver
uniprot_sec
Q9UDT5
resolver
uniprot_sec
Q9UJ39
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which sequesters GLI3 in the cytoplasm (PubMed:24311597). 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:24311597, PubMed:38968120). In absence of hedgehog, smoothened is inhibited, promoting processing of GLI3 into Transcription repressor GLI3R, which dissociates from SUFU and translocates to the nucleus (PubMed:24311597). {ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:38968120}.
uniprot
proteins
amino_acid_sequence
MEAQSHSSTTTEKKKVENSIVKCSTRTDVSEKAVASSTTSNEDESPGQTYHRERRNAITMQPQNVQGLSKVSEEPSTSSDERASLIKKEIHGSLPHVAEPSVPYRGTVFAMDPRNGYMEPHYHPPHLFPAFHPPVPIDARHHEGRYHYDPSPIPPLHMTSALSSSPTYPDLPFIRISPHRNPTAASESPFSPPHPYINPYMDYIRSLHSSPSLSMISATRGLSPTDAPHAGVSPAEYYHQMALLTGQRSPYADIIPSAATAGTGAIHMEYLHAMDSTRFSSPRLSARPSRKRTLSISPLSDHSFDLQTMIRTSPNSLVTILNNSRSSSSASGSYGHLSASAISPALSFTYSSAPVSLHMHQQILSRQQSLGSAFGHSPPLIHPAPTFPTQRPIPGIPTVLNPVQVSSGPSESSQNKPTSESAVSSTGDPMHNKRSKIKPDEDLPSPGARGQQEQPEGTTLVKEEGDKDESKQEPEVIYETNCHWEGCAREFDTQEQLVHHINNDHIHGEKKEFVCRWLDCSREQKPFKAQYMLVVHMRRHTGEKPHKCTFEGCTKAYSRLENLKTHLRSHTGEKPYVCEHEGCNKAFSNASDRAKHQNRTHSNEKPYVCKIPGCTKRYTDPSSLRKHVKTVHGPEAHVTKKQRGDIHPRPPPPRDSGSHSQSRSPGRPTQGALGEQQDLSNTTSKREECLQVKTVKAEKPMTSQPSPGGQSSCSSQQSPISNYSNSGLELPLTDGGSIGDLSAIDETPIMDSTISTATTALALQARRNPAGTKWMEHVKLERLKQVNGMFPRLNPILPPKAPAVSPLIGNGTQSNNTCSLGGPMTLLPGRSDLSGVDVTMLNMLNRRDSSASTISSAYLSSRRSSGISPCFSSRRSSEASQAEGRPQNVSVADSYDPISTDASRRSSEASQSDGLPSLLSLTPAQQYRLKAKYAAATGGPPPTPLPNMERMSLKTRLALLGDALEPGVALPPVHAPRRCSDGGAHGYGRRHLQPHDAPGHGVRRASDPVRTGSEGLALPRVPRFSSLSSCNPPAMATSAEKRSLVLQNYTRPEGGQSRNFHSSPCPPSITENVTLESLTMDADANLNDEDFLPDDVVQYLNSQNQAGYEQHFPSALPDDSKVPHGPGDFDAPGLPDSHAGQQFHALEQPCPEGSKTDLPIQWNEVSSGSADLSSSKLKCGPRPAVPQTRAFGFCNGMVVHPQNPLRSGPAGGYQTLGENSNPYGGPEHLMLHNSPGSGTSGNAFHEQPCKAPQYGNCLNRQPVAPGALDGACGAGIQASKLKSTPMQGSGGQLNFGLPVAPNESAGSMVNGMQNQDPVGQGYLAHQLLGDSMQHPGAGRPGQQMLGQISATSHINIYQGPESCLPGAHGMGSQPSSLAVVRGYQPCASFGGSRRQAMPRDSLALQSGQLSDTSQTCRVNGIKMEMKGQPHPLCSNLQNYSGQFYDQTVGFSQQDTKAGSFSISDASCLLQGTSAKNSELLSPGANQVTSTVDSLDSHDLEGVQIDFDAIIDDGDHSSLMSGALSPSIIQNLSHSSSRLTTPRASLPFPALSMSTTNMAIGDMSSLLTSLAEESKFLAVMQ
uniprot
proteins
disease_involvement
DISEASE: Greig cephalo-poly-syndactyly syndrome (GCPS) [MIM:175700]: Autosomal dominant disorder affecting limb and craniofacial development. It is characterized by pre- and postaxial polydactyly, syndactyly of fingers and toes, macrocephaly and hypertelorism. {ECO:0000269|PubMed:10441342, ECO:0000269|PubMed:12414818, ECO:0000269|PubMed:12794692, ECO:0000269|PubMed:9302279}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pallister-Hall syndrome (PHS) [MIM:146510]: An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia. {ECO:0000269|PubMed:10441570}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Polydactyly, postaxial A1 (PAPA1) [MIM:174200]: A condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. {ECO:0000269|PubMed:10441570}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Polydactyly, postaxial B (PAPB) [MIM:174200]: A condition characterized by an extra digit in the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type B the extra digit is not well formed and is frequently in the form of a skin. {ECO:0000269|PubMed:10441570}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Polydactyly, preaxial 4 (PPD4) [MIM:174700]: A form of polydactyly, a condition defined by the occurrence of supernumerary digits in the upper and/or lower extremities. Preaxial or radial polydactyly refers to the presence of extra digits on the radial side of the hand. PPD4 is an autosomal dominant form characterized by mild duplication of the thumb, syndactyly of various degrees affects fingers 3 and 4, duplication of part or all of the first or second toes and variable toes syndactyly. Some patients have only foot involvement. {ECO:0000269|PubMed:10441570}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:10075717, PubMed:10375510, PubMed:10693759, PubMed:11238441, PubMed:17764085, PubMed:20154143, PubMed:27146893). Specifically binds to the minimal GLI-consensus sequence 5'-GACCACCCA-3' to activate or repress the expression of target genes (PubMed:10075717). 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 (PubMed:10375510). The repressor form (GLI3R) constitutes the major form of GLI3 (PubMed:10375510). {ECO:0000269|PubMed:10075717, ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:27146893}.; FUNCTION: [Transcription repressor GLI3R]: Major transcription repressor, which inhibits expression of target genes in the absence of smoothened (SMO) signaling (PubMed:10375510, PubMed:10693759). 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:10375510). Constitutes the major form of GLI3, while the transcription activator form only plays a minor role (PubMed:10375510). {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:10693759}.; FUNCTION: [Transcription activator GLI3]: Transcription factor, which activates expression of target genes in response to smoothened (SMO) activation (PubMed:10075717, PubMed:27146893). Constitutes a minor form of GLI3, while the transcription repressor form (GLI3R) plays a major role (PubMed:10075717). 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 (PubMed:19389374). {ECO:0000269|PubMed:10075717, ECO:0000269|PubMed:19389374, ECO:0000269|PubMed:27146893}.
uniprot
proteins
mass_dalton
169863
uniprot
proteins
mutagenesis
MUTAGEN 313; /note="S->A: Abolished phosphorylation by DYRK2, leading to decreased dossiciation from SUFU."; /evidence="ECO:0000269|PubMed:38968120"; MUTAGEN 436; /note="K->R: Abolished methylation by SETD7; when associated with R-595."; /evidence="ECO:0000269|PubMed:27146893"; MUTAGEN 595; /note="K->R: Abolished methylation by SETD7; when associated with R-436."; /evidence="ECO:0000269|PubMed:27146893"; MUTAGEN 773; /note="K->R: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 779; /note="K->R: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 784; /note="K->R: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 800; /note="K->R: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 849; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16705181"; MUTAGEN 855; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 856; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 861; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 864; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 865; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759"; MUTAGEN 873; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 877; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16705181"; MUTAGEN 903; /note="S->A: Loss of proteolytic processing."; /evidence="ECO:0000269|PubMed:16705181"; MUTAGEN 907; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16705181"; MUTAGEN 980; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759"; MUTAGEN 1006; /note="S->A: Loss of phosphorylation and proteolytic processing."; /evidence="ECO:0000269|PubMed:10693759
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:10375510, PubMed:10693759, PubMed:16705181, PubMed:20154143). Phosphorylated by DYRK2 and ULK3 (in vitro) (PubMed:18455992, PubMed:19878745). {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20154143}.; 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:0000269|PubMed:38968120}.; 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:0000269|PubMed:27146893}.; 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:16371461, ECO:0000269|PubMed:16705181}.; PTM: [Transcription repressor GLI3R]: Generated from the full-length GLI3 protein through proteolytic processing (PubMed:10375510, PubMed:10693759, PubMed:16371461, PubMed:16705181, PubMed:17283082, PubMed:20154143, PubMed:21921029). This process requires PKA-primed phosphorylation of GLI3, ubiquitination by the SCF(BTRC) complex and limited proteolysis (PubMed:10375510, PubMed:10693759, PubMed:16371461, PubMed:16705181, PubMed:21921029). {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:10693759, ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:17283082, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:21921029}.
uniprot
proteins
protein_family
GLI C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10075717
uniprot
proteins
pubmed
10375510
uniprot
proteins
pubmed
10441342
uniprot
proteins
pubmed
10441570
uniprot
proteins
pubmed
10693759
uniprot
proteins
pubmed
11238441
uniprot
proteins
pubmed
12414818
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12794692
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16371461
uniprot
proteins
pubmed
16705181
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17283082
uniprot
proteins
pubmed
17764085
uniprot
proteins
pubmed
18455992
uniprot
proteins
pubmed
19389374
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19592253
uniprot
proteins
pubmed
19878745
uniprot
proteins
pubmed
20154143
uniprot
proteins
pubmed
2118997
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21921029
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23955340
uniprot
proteins
pubmed
24311597
uniprot
proteins
pubmed
27146893
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
2850480
uniprot
proteins
pubmed
28965847
uniprot
proteins
pubmed
29263200
uniprot
proteins
pubmed
38968120
uniprot
proteins
pubmed
9302279
uniprot
proteins
sequence_length
1580
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:17283082, ECO:0000269|PubMed:38968120}. Cytoplasm {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:17283082, ECO:0000269|PubMed:38968120}. Cell projection, cilium {ECO:0000269|PubMed:19592253, ECO:0000269|PubMed:38968120}. Note=Full-length GLI3 is sequestered in the cytoplasm by SUFU in absence of smoothened signaling. {ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:38968120}.; SUBCELLULAR LOCATION: [Transcription repressor GLI3R]: Nucleus {ECO:0000269|PubMed:10375510, ECO:0000269|PubMed:17283082}. Note=Following generation by proteolytic processing in absence of smoothened, translocates to the nucleus, where is represses transcription of target genes. {ECO:0000269|PubMed:17283082}.; SUBCELLULAR LOCATION: [Transcription activator GLI3]: Nucleus {ECO:0000269|PubMed:11238441}. Cytoplasm {ECO:0000269|PubMed:38968120}. Cell projection, cilium {ECO:0000269|PubMed:19592253, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:38968120}. Note=Sequestered in the cytoplasm by SUFU in absence of smoothened signaling (PubMed:38968120). Accumulates in primary cilia following smoothened activation: cilium localization requires the presence of KIF7 (PubMed:19592253, PubMed:20154143). It then translocates to the nucleus, where is activates transcription of target genes (PubMed:38968120). Translocation to the nucleus is promoted by interaction with ZIC1 (PubMed:11238441). TMEM216 reduces its nuclear localization (By similarity). {ECO:0000250|UniProtKB:Q61602, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19592253, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:38968120}.
uniprot
proteins