Gli2
entrez
14633
canonical
uniprot
Q0VGT2
canonical
ensembl
ENSMUSG00000048402
resolver
ensp
ENSMUSP00000054837
resolver
ensp
ENSMUSP00000125342
resolver
ensp
ENSMUSP00000341935
resolver
enst
ENSMUST00000062483
resolver
enst
ENSMUST00000161301
resolver
genesymbol
Gli2
resolver
uniprot
A5AA27
resolver
uniprot
E9PYJ4
resolver
uniprot
F7CC69
resolver
uniprot
Q8BKI7
resolver
uniprot_entry
A5AA27_MOUSE
resolver
uniprot_entry
F7CC69_MOUSE
resolver
uniprot_entry
GLI2_MOUSE
resolver
uniprot_entry
Q8BKI7_MOUSE
resolver
uniprot_sec
E9PYJ4
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which sequesters GLI2 in the cytoplasm (PubMed:10806483, 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:20956384). Phosphorylated by ULK3 or STK36 in response to smoothened activation, promoting subsequent phosphorylation by CDK1 and dissociation from SUFU and translocation to the nucleus (PubMed:31279575, PubMed:38096226). In absence of hedgehog, smoothened is inhibited, promoting processing of GLI2 into Transcription repressor GLI2R, which dissociates from SUFU and translocates to the nucleus (By similarity). {ECO:0000250|UniProtKB:P10070, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:20956384, ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:38096226}.
uniprot
proteins
amino_acid_sequence
METSAPAPALEKKEAKSGLLEDSSFPDPGKKACPLAVAAAVAAHGVPQQLLPAFHAPLPIDMRHQEGRYHYDPHSVHSVHGPPTLSGSPVISDISLIRLSPHPAGPGESPFSAHHPYVNPHMEHYLRSVHSSPTLSMISAARGLSPADVAHEHLKERGLFSLAAPGTNPSDYYHQMTLMASHPTPYGDLLMQSGGAASAPHLHDYLNPVDASRFSSPRVTPRLSRKRALSISPLSDASLDLQRMIRTSPNSLVAYINNSRSSSAASGSYGHLSAGALSPAFTFPHPINPVAYQQILSQQRGLGSAFGHTPPLIQPSPTFLAQQPMTLTSISTMPTQLSSSSSNCLNDANQNKQNSESAVSSTVNPITIHKRSKVKTEAEGLRPASPLGLTQEQLADLKEDLDRDDCKQEAEVVIYETNCHWADCTKEYDTQEQLVHHINNEHIHGEKKEFVCRWQACTREQKPFKAQYMLVVHMRRHTGEKPHKCTFEGCSKAYSRLENLKTHLRSHTGEKPYVCEHEGCNKAFSNASDRAKHQNRTHSNEKPYICKIPGCTKRYTDPSSLRKHVKTVHGPDAHVTKKQRNDVHVRAPLLKENGDNEASAEPGGRGPEESVEASSTSHTVEDCLHIKAIKTESSGLCQSSPGAQSSCSSEPSPLGSAPNNDSGMEMPGTGPGSLGDLTALADTCPGADTSALAAPSTGGLQLRKHMSTVHRFEQLKREKLKSLKDSCSWAGPAPHTRNTKLPPLPVNGSVLENFNNTGGGGPAGLLPSQRLPELTEVTMLSQLQERRDSSTSTMSSAYTVSRRSSGISPYFSSRRSSEASPLGGLRPHNASSADSYDPISTDASRRSSEASQCSGGGPGLLNLTPAQQYNLRAKYAAATGGPPPTPLPGLDRVSLRTRLALLDAPERALPGACPHPLGPRRGSDGPTYSHGHGHGYAGAAPAFPHEGPNSSTRRASDPVRRPDPLILPRVQRFHSTHNMNPGSLPPCADRRGLHVQSHPSVDSNLTRNAYSPRPPSINENVVMEAVAAGVDGPGLECDLGLVEDELVLPDDVVQYIKAHTGGTLDDGIRQGYPTEGTGFPENSKLPSPGLQGHRRLAAADSNMGPSAPGLGGCQLSYSPSSNLNKSNMPVQWNEVSSGTVDALPTQVKPPPFPHSNLAVVQQKPAFGQYPGYNPQSVQSSSGGLDSTQPHLQLRGAPSASRGSYTQQPRQPAAGSQCLGMSAAMSPQASYSQAHPQLSPNIVSGSLNQFSPSCSNMAAKPSHLGLPQQMEVVPNATIMNGHQREHGVPNSSLAAVSQPHPVLSYPQQDSYQQGSNLLSSHQPGFMESQQNAGFGLMQPRPPLEPNTASRHRGVRSGQQQLYARTTGQAMVTSANQETAEAMPKGPAGTMVSLAPQPSQDTGRAQDQNTLYYYGQIHMYEQNGGCPAVQPQPPQPQACSDSIQPEPLPSPGVNQVSSTVDSQLLEPPQIDFDAIMDDGDHSSLFSGALSPTLLHNLSQNSSRLTTPRNSLTLPSIPAGISNMAVGDMSSMLTSLAEESKFLNMMT
uniprot
proteins
function
FUNCTION: Transcription factor that acts as a key effector of the smoothened signaling pathway, and which plays a role in skeleton development (PubMed:10806483, PubMed:16611981, PubMed:16880529, PubMed:22007132, PubMed:9006072, PubMed:9655799, PubMed:9731531). Specifically binds to the minimal GLI-consensus sequence 5'-GACCACCCA-3' to activate or repress the expression of target genes (By similarity). Functions both as a transcriptional activator and repressor: the full-length GLI2 form (Transcription activator GLI2) acts as a transcription activator following smoothened activation, while the Transcription repressor GLI2R, which is generated in absence of smoothened, acts as a transcription repressor (PubMed:10433919, PubMed:10806483). The transcriptional activator form constitutes the major form of GLI2 (PubMed:16611981). {ECO:0000250|UniProtKB:P10070, ECO:0000269|PubMed:10433919, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:16880529, ECO:0000269|PubMed:22007132, ECO:0000269|PubMed:9006072, ECO:0000269|PubMed:9655799, ECO:0000269|PubMed:9731531}.; FUNCTION: [Transcription activator GLI2]: Transcription factor, which activates expression of target genes in response to smoothened (SMO) activation (PubMed:10806483, PubMed:16611981, PubMed:16880529). Constitutes a major form of GLI2, while the transcription repressor form (GLI2R) plays a minor role (PubMed:16611981). {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:16880529}.; FUNCTION: [Transcription repressor GLI2R]: Transcription repressor, which inhibits expression of target genes in the absence of smoothened (SMO) signaling (PubMed:10433919). Generated by proteolytic processing of the full-length GLI2 form in the absence of hedgehog (DHH, IHH or SHH), when SMO transducer is inhibited (By similarity). Constitutes a minor form of GLI2, while the transcription activator GLI2 form plays a major role in smoothened signaling (PubMed:10433919). {ECO:0000250|UniProtKB:P10070, ECO:0000269|PubMed:10433919}.
uniprot
proteins
mass_dalton
165031
uniprot
proteins
mutagenesis
MUTAGEN 230..232; /note="SIS->AIA: Decreased phosphorylation by ULK3, preventing dissociation from SUFU."; /evidence="ECO:0000269|PubMed:31279575"; MUTAGEN 230; /note="S->A: Decreased phosphorylation by ULK3, preventing dissociation from SUFU."; /evidence="ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:38096226"; MUTAGEN 620..621; /note="VE->KR: Increased generation of theTranscription repressor GLI2R form and decreased degradation in absence of smoothened."; /evidence="ECO:0000269|PubMed:17283082"; MUTAGEN 789; /note="S->A: In Gli2P1-4 mutant; abolished phosphorylation by PKA, preventing degradation; when associated with A-805; A-817 and A-848."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 792; /note="S->A: In Gli2C1-4 mutant; abolished phosphorylation by PK1, preventing degradation; when associated with A-808, A-820 and A-851."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 801; /note="S->A: In Gli2N2-4 mutant; abolished phosphorylation by GSK3B, preventing degradation; when associated with A-813 and A-844."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 805; /note="S->A: In Gli2P1-4 mutant; abolished phosphorylation by PKA, preventing degradation; when associated with A-789; A-817 and A-848."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 808; /note="S->A: In Gli2C1-4 mutant; abolished phosphorylation by PK1, preventing degradation; when associated with A-792, A-820 and A-851."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 813; /note="S->A: In Gli2N2-4 mutant; abolished phosphorylation by GSK3B, preventing degradation; when associated with A-801 and A-844."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 817; /note="S->A: In Gli2P1-4 mutant; abolished phosphorylation by PKA, preventing degradation; when associated with A-789; A-805 and A-848."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 820; /note="S->A: In Gli2C1-4 mutant; abolished phosphorylation by PK1, preventing degradation; when associated with A-792, A-808 and A-851."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 844; /note="S->A: In Gli2N2-4 mutant; abolished phosphorylation by GSK3B, preventing degradation; when associated with A-801 and A-813."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 848; /note="S->A: In Gli2P1-4 mutant; abolished phosphorylation by PKA, preventing degradation; when associated with A-789; A-805 and A-817."; /evidence="ECO:0000269|PubMed:16611981"; MUTAGEN 851; /note="S->A: In Gli2C1-4 mutant; abolished phosphorylation by PK1, preventing degradation; when associated with A-792, A-808 and A-820."; /evidence="ECO:0000269|PubMed:16611981
uniprot
proteins
post_translational_modification
PTM: Acetylation at Lys-740 inhibits Hh target gene expression, probably by impeding entry into chromatin thus preventing promoter occupancy. {ECO:0000250|UniProtKB:P10070}.; 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 GLI2R form (PubMed:16611981, PubMed:22007132). Phosphorylated by DYRK2; this inhibits GLI2 transcription factor activity and promotes proteasomal degradation of GLI2 (By similarity). {ECO:0000250|UniProtKB:P10070, ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:22007132}.; PTM: [Transcription activator GLI2]: Phosphorylation at Ser-248 by DYRK2 in response to smoothened activation, promotes GLI2 dissociation from SUFU inhibitor and translocation to the nucleus (By similarity). Phosphorylated at Ser-230 and Ser-232 by ULK3 or STK36 in response to smoothened activation, promoting subsequent phosphorylation by CDK1 and GLI2 dissociation from SUFU inhibitor, followed by translocation to the nucleus (PubMed:31279575, PubMed:38096226). {ECO:0000250|UniProtKB:P10070, ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:38096226}.; PTM: In absence of smoothened signaling, ubiquitinated by the SCF(BTRC) complex following phosphorylation by PKA and GSK3B, promoting mainly degradation, as well as a small fraction of the Transcription repressor GLI2R form. {ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:17283082}.; PTM: [Transcription repressor GLI2R]: Generated from the full-length GLI2 protein through proteolytic processing (PubMed:16611981). This process requires PKA-primed phosphorylation of GLI2, ubiquitination by the SCF(BTRC) complex and limited proteolysis (PubMed:16611981). In absence of smoothened signaling, only a small fraction of full-length GLI2 is converted into Transcription repressor GLI2R form, the main fraction of the protein beeing degraded (PubMed:16611981, PubMed:17283082). {ECO:0000269|PubMed:16611981, ECO:0000269|PubMed:17283082}.
uniprot
proteins
protein_family
GLI C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10433919
uniprot
proteins
pubmed
10725236
uniprot
proteins
pubmed
10806483
uniprot
proteins
pubmed
11238441
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16611981
uniprot
proteins
pubmed
16880529
uniprot
proteins
pubmed
17283082
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20956384
uniprot
proteins
pubmed
22007132
uniprot
proteins
pubmed
23034632
uniprot
proteins
pubmed
25644602
uniprot
proteins
pubmed
25808752
uniprot
proteins
pubmed
26565916
uniprot
proteins
pubmed
31279575
uniprot
proteins
pubmed
38096226
uniprot
proteins
pubmed
38261656
uniprot
proteins
pubmed
9006072
uniprot
proteins
pubmed
9636069
uniprot
proteins
pubmed
9655799
uniprot
proteins
pubmed
9731531
uniprot
proteins
sequence_length
1544
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:23034632, ECO:0000269|PubMed:38261656}. Cytoplasm {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:17283082, ECO:0000269|PubMed:23034632}. Cell projection, cilium {ECO:0000269|PubMed:20956384, ECO:0000269|PubMed:22007132, ECO:0000269|PubMed:25644602, ECO:0000269|PubMed:31279575}. Note=Full-length GLI2 is sequestered in the cytoplasm by SUFU in absence of smoothened signaling. {ECO:0000269|PubMed:23034632}.; SUBCELLULAR LOCATION: [Transcription activator GLI2]: Nucleus {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:23034632, ECO:0000269|PubMed:38261656}. Cytoplasm {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:23034632}. Cell projection, cilium {ECO:0000269|PubMed:25644602, ECO:0000269|PubMed:31279575}. Note=Sequestered in the cytoplasm by SUFU in absence of smoothened signaling (PubMed:20956384). Accumulates in primary cilia following smoothened activation (PubMed:20956384, PubMed:23034632, PubMed:31279575). It then translocates to the nucleus, where is activates transcription of target genes (PubMed:31279575). TMEM216 promotes its nuclear localization (PubMed:38261656). STK36 promotes translocation to the nucleus (PubMed:10806483). {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:20956384, ECO:0000269|PubMed:23034632, ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:38261656}.; SUBCELLULAR LOCATION: [Transcription repressor GLI2R]: Nucleus {ECO:0000250|UniProtKB:P10070}. Note=Following generation by proteolytic processing in absence of smoothened, translocates to the nucleus, where is represses transcription of target genes. {ECO:0000250|UniProtKB:P10070}.
uniprot
proteins