GLI1
entrez
2735
canonical
uniprot
P08151
canonical
ensembl
ENSG00000111087
resolver
ensp
ENSP00000228682
resolver
ensp
ENSP00000437607
resolver
ensp
ENSP00000441006
resolver
ensp
ENSP00000577114
resolver
genesymbol
GLI1
resolver
genesymbol_syn
GLI
resolver
hgnc
HGNC:4317
resolver
uniprot
B4DNF7
resolver
uniprot
D0EUY3
resolver
uniprot
E9PQQ9
resolver
uniprot
F5H6H8
resolver
uniprot
Q8TDN9
resolver
uniprot_entry
B4DNF7_HUMAN
resolver
uniprot_entry
GLI1_HUMAN
resolver
uniprot_sec
D0EUY3
resolver
uniprot_sec
E9PQQ9
resolver
uniprot_sec
F5H6H8
resolver
uniprot_sec
Q8TDN9
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which sequesters GLI1 in the cytoplasm (PubMed:10806483, PubMed:10559945, PubMed:24311597). In presence of hedgehog (DHH, IHH or SHH), smoothened is activated, leading to phosphorylation by MAPK1/ERK2 and dissociation from SUFU and translocation to the nucleus (PubMed:10806483, PubMed:24311597, PubMed:35831023). In absence of hedgehog, smoothened is inhibited, promoting degradation of GLI1 (PubMed:21921029). {ECO:0000269|PubMed:10559945, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:21921029, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:35831023}.
uniprot
proteins
amino_acid_sequence
MFNSMTPPPISSYGEPCCLRPLPSQGAPSVGTEGLSGPPFCHQANLMSGPHSYGPARETNSCTEGPLFSSPRSAVKLTKKRALSISPLSDASLDLQTVIRTSPSSLVAFINSRCTSPGGSYGHLSIGTMSPSLGFPAQMNHQKGPSPSFGVQPCGPHDSARGGMIPHPQSRGPFPTCQLKSELDMLVGKCREEPLEGDMSSPNSTGIQDPLLGMLDGREDLEREEKREPESVYETDCRWDGCSQEFDSQEQLVHHINSEHIHGERKEFVCHWGGCSRELRPFKAQYMLVVHMRRHTGEKPHKCTFEGCRKSYSRLENLKTHLRSHTGEKPYMCEHEGCSKAFSNASDRAKHQNRTHSNEKPYVCKLPGCTKRYTDPSSLRKHVKTVHGPDAHVTKRHRGDGPLPRAPSISTVEPKREREGGPIREESRLTVPEGAMKPQPSPGAQSSCSSDHSPAGSAANTDSGVEMTGNAGGSTEDLSSLDEGPCIAGTGLSTLRRLENLRLDQLHQLRPIGTRGLKLPSLSHTGTTVSRRVGPPVSLERRSSSSSSISSAYTVSRRSSLASPFPPGSPPENGASSLPGLMPAQHYLLRARYASARGGGTSPTAASSLDRIGGLPMPPWRSRAEYPGYNPNAGVTRRASDPAQAADRPAPARVQRFKSLGCVHTPPTVAGGGQNFDPYLPTSVYSPQPPSITENAAMDARGLQEEPEVGTSMVGSGLNPYMDFPPTDTLGYGGPEGAAAEPYGARGPGSLPLGPGPPTNYGPNPCPQQASYPDPTQETWGEFPSHSGLYPGPKALGGTYSQCPRLEHYGQVQVKPEQGCPVGSDSTGLAPCLNAHPSEGPPHPQPLFSHYPQPSPPQYLQSGPYTQPPPDYLPSEPRPCLDFDSPTHSTGQLKAQLVCNYVQSQQELLWEGGGREDAPAQEPSYQSPKFLGGSQVSPSRAKAPVNTYGPGFGPNLPNHKSGSYPTPSPCHENFVVGANRASHRAAAPPRLLPPLPTCYGPLKVGGTNPSCGHPEVGRLGGGPALYPPPEGQVCNPLDSLDLDNTQLDFVAILDEPQGLSPPPSHDQRGSSGHTPPPSGPPNMAVGNMSVLLRSLPGETEFLNSSA
uniprot
proteins
disease_involvement
DISEASE: Polydactyly, postaxial, A8 (PAPA8) [MIM:618123]: A form of postaxial polydactyly, 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. PAPA8 is an autosomal recessive condition characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet. {ECO:0000269|PubMed:28973407}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Polydactyly, preaxial 1 (PPD1) [MIM:174400]: 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. PPD1 is an autosomal recessive form characterized by duplication of the distal phalanx of the thumb. {ECO:0000269|PubMed:30620395}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Transcription activator that acts as a key effector of the smoothened signaling pathway, and which plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract (PubMed:10806483, PubMed:11238441, PubMed:19706761, PubMed:19878745, PubMed:24076122, PubMed:24217340, PubMed:24311597, PubMed:28973407). Binds to the DNA consensus sequence 5'-GACCACCCA-3' (PubMed:2105456, PubMed:24217340, PubMed:2832761, PubMed:8378770). Activated in response to smoothened signaling: in presence of hedgehog (DHH, IHH or SHH) and subsequent activation of smoothened, GLI1 translocates to the nucleus and promotes expression of target genes (PubMed:2105456). In contrast to GLI2 and GLI3, does not contain a repressor domain and only acts as a transcription activator (PubMed:10075717). {ECO:0000269|PubMed:10075717, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456, ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:2832761, ECO:0000269|PubMed:28973407, ECO:0000269|PubMed:8378770}.; FUNCTION: [Isoform 2]: Acts as a transcriptional activator, but activates a different set of genes than isoform 1 (PubMed:19706761). Activates expression of CD24, unlike isoform 1 (PubMed:19706761). {ECO:0000269|PubMed:19706761}.
uniprot
proteins
mass_dalton
117904
uniprot
proteins
mutagenesis
MUTAGEN 70; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-86, A-102- A-116, A-130, A-146 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 86; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-102- A-116, A-130, A-146 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 102; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-86, A-116, A-130, A-146 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 102; /note="S->E: Mimics phosphorylation; promotes dissociation from SUFU; when associated with E-116 and E-130."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 116; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-86, A-102- A-130, A-146 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 116; /note="S->E: Mimics phosphorylation; promotes dissociation from SUFU; when associated with E-102 and E-130."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 130; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-86, A-102- A-116, A-146 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 130; /note="S->E: Mimics phosphorylation; promotes dissociation from SUFU; when associated with E-102 and E-116."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 146; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-86, A-102- A-116, A-130 and A-201."; /evidence="ECO:0000269|PubMed:35831023"; MUTAGEN 201; /note="S->A: In 7A mutant; abolished phosphorylation by MAPK1/ERK2, preventing dissociation from SUFU; when associated with A-70, A-86, A-102- A-116, A-130 and A-146."; /evidence="ECO:0000269|PubMed:35831023
uniprot
proteins
post_translational_modification
PTM: Phosphorylated in vitro by ULK3 (PubMed:19878745). Phosphorylation by PRKCD inhibits its activity by decreasing its localization to the nucleus (By similarity). Phosphorylation at Ser-102, Ser-116 and Ser-130 by MAPK1/ERK2 in response to smoothened activation, promotes GLI1 dissociation from SUFU inhibitor and translocation to the nucleus (PubMed:35831023). {ECO:0000250|UniProtKB:P47806, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:35831023}.; PTM: Acetylation at Lys-518 down-regulates transcriptional activity. Deacetylated by HDAC1. {ECO:0000269|PubMed:20081843}.; PTM: Degradaded by the proteasome in absence of smoothened signaling. {ECO:0000269|PubMed:21921029}.; PTM: Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1 transcriptional activator activity. {ECO:0000269|PubMed:24076122}.
uniprot
proteins
protein_family
GLI C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10075717
uniprot
proteins
pubmed
10559945
uniprot
proteins
pubmed
10806483
uniprot
proteins
pubmed
10951255
uniprot
proteins
pubmed
11238441
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
19706761
uniprot
proteins
pubmed
19878745
uniprot
proteins
pubmed
20081843
uniprot
proteins
pubmed
2105456
uniprot
proteins
pubmed
21921029
uniprot
proteins
pubmed
24076122
uniprot
proteins
pubmed
24217340
uniprot
proteins
pubmed
24311597
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
2832761
uniprot
proteins
pubmed
28965847
uniprot
proteins
pubmed
28973407
uniprot
proteins
pubmed
30620395
uniprot
proteins
pubmed
35831023
uniprot
proteins
pubmed
8378770
uniprot
proteins
sequence_length
1106
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24076122}. Nucleus {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456}. Cell projection, cilium {ECO:0000250|UniProtKB:P47806}. Note=Sequestered in the cytoplasm by SUFU in absence of smoothened signaling (PubMed:10806483, PubMed:10559945). Accumulates in primary cilia following smoothened activation (By similarity). It then translocates to the nucleus, where is activates transcription of target genes (PubMed:10806483, PubMed:24311597, PubMed:35831023). Activation and translocation to the nucleus is promoted by interaction with STK36 (PubMed:10806483). Phosphorylation by ULK3 may promote nuclear localization (PubMed:19878745). Translocation to the nucleus is promoted by interaction with ZIC1 (PubMed:11238441). {ECO:0000250|UniProtKB:P47806, ECO:0000269|PubMed:10559945, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:35831023}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:19706761}. Nucleus {ECO:0000269|PubMed:19706761}.
uniprot
proteins