GLI2
entrez
2736
canonical
uniprot
P10070
canonical
ensembl
ENSG00000074047
resolver
ensp
ENSP00000354586
resolver
ensp
ENSP00000390436
resolver
ensp
ENSP00000398992
resolver
ensp
ENSP00000604465
resolver
enst
ENST00000361492
resolver
enst
ENST00000418323
resolver
genesymbol
GLI2
resolver
genesymbol_syn
THP
resolver
hgnc
HGNC:4318
resolver
uniprot
A0A7I2PJA1
resolver
uniprot
F6U3E6
resolver
uniprot
O60252
resolver
uniprot
O60253
resolver
uniprot
O60254
resolver
uniprot
O60255
resolver
uniprot
Q15590
resolver
uniprot
Q15591
resolver
uniprot
Q1PSW9
resolver
uniprot
Q4JHT4
resolver
uniprot
Q59FV5
resolver
uniprot_entry
A0A7I2PJA1_HUMAN
resolver
uniprot_entry
F6U3E6_HUMAN
resolver
uniprot_entry
GLI2_HUMAN
resolver
uniprot_entry
Q1PSW9_HUMAN
resolver
uniprot_entry
Q59FV5_HUMAN
resolver
uniprot_sec
O60252
resolver
uniprot_sec
O60253
resolver
uniprot_sec
O60254
resolver
uniprot_sec
O60255
resolver
uniprot_sec
Q15590
resolver
uniprot_sec
Q15591
resolver
uniprot_sec
Q4JHT4
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which sequesters GLI2 in the cytoplasm (PubMed:24311597, PubMed:38968120). 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). Phosphorylated by ULK3 or STK36 in response to smoothened activation, promoting subsequent phosphorylation by CDK1 and dissociation from SUFU and translocation to the nucleus (By similarity). In absence of hedgehog, smoothened is inhibited, promoting processing of GLI2 into Transcription repressor GLI2R, which dissociates from SUFU and translocates to the nucleus (PubMed:38968120). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:38968120}.
uniprot
proteins
amino_acid_sequence
METSASATASEKQEAKSGILEAAGFPDPGKKASPLVVAAAAAAAVAAQGVPQHLLPPFHAPLPIDMRHQEGRYHYEPHSVHGVHGPPALSGSPVISDISLIRLSPHPAGPGESPFNAPHPYVNPHMEHYLRSVHSSPTLSMISAARGLSPADVAQEHLKERGLFGLPAPGTTPSDYYHQMTLVAGHPAPYGDLLMQSGGAASAPHLHDYLNPVDVSRFSSPRVTPRLSRKRALSISPLSDASLDLQRMIRTSPNSLVAYINNSRSSSAASGSYGHLSAGALSPAFTFPHPINPVAYQQILSQQRGLGSAFGHTPPLIQPSPTFLAQQPMALTSINATPTQLSSSSNCLSDTNQNKQSSESAVSSTVNPVAIHKRSKVKTEPEGLRPASPLALTQGQVSGHGSCGCALPLSQEQLADLKEDLDRDDCKQEAEVVIYETNCHWEDCTKEYDTQEQLVHHINNEHIHGEKKEFVCRWQACTREQKPFKAQYMLVVHMRRHTGEKPHKCTFEGCSKAYSRLENLKTHLRSHTGEKPYVCEHEGCNKAFSNASDRAKHQNRTHSNEKPYICKIPGCTKRYTDPSSLRKHVKTVHGPDAHVTKKQRNDVHLRTPLLKENGDSEAGTEPGGPESTEASSTSQAVEDCLHVRAIKTESSGLCQSSPGAQSSCSSEPSPLGSAPNNDSGVEMPGTGPGSLGDLTALDDTPPGADTSALAAPSAGGLQLRKHMTTMHRFEQLKKEKLKSLKDSCSWAGPTPHTRNTKLPPLPGSGSILENFSGSGGGGPAGLLPNPRLSELSASEVTMLSQLQERRDSSTSTVSSAYTVSRRSSGISPYFSSRRSSEASPLGAGRPHNASSADSYDPISTDASRRSSEASQCSGGSGLLNLTPAQQYSLRAKYAAATGGPPPTPLPGLERMSLRTRLALLDAPERTLPAGCPRPLGPRRGSDGPTYGHGHAGAAPAFPHEAPGGGARRASDPVRRPDALSLPRVQRFHSTHNVNPGPLPPCADRRGLRLQSHPSTDGGLARGAYSPRPPSISENVAMEAVAAGVDGAGPEADLGLPEDDLVLPDDVVQYIKAHASGALDEGTGQVYPTESTGFSDNPRLPSPGLHGQRRMVAADSNVGPSAPMLGGCQLGFGAPSSLNKNNMPVQWNEVSSGTVDALASQVKPPPFPQGNLAVVQQKPAFGQYPGYSPQGLQASPGGLDSTQPHLQPRSGAPSQGIPRVNYMQQLRQPVAGSQCPGMTTTMSPHACYGQVHPQLSPSTISGALNQFPQSCSNMPAKPGHLGHPQQTEVAPDPTTMGNRHRELGVPDSALAGVPPPHPVQSYPQQSHHLAASMSQEGYHQVPSLLPARQPGFMEPQTGPMGVATAGFGLVQPRPPLEPSPTGRHRGVRAVQQQLAYARATGHAMAAMPSSQETAEAVPKGAMGNMGSVPPQPPPQDAGGAPDHSMLYYYGQIHMYEQDGGLENLGSCQVMRSQPPQPQACQDSIQPQPLPSPGVNQVSSTVDSQLLEAPQIDFDAIMDDGDHSSLFSGALSPSLLHSLSQNSSRLTTPRNSLTLPSIPAGISNMAVGDMSSMLTSLAEESKFLNMMT
uniprot
proteins
disease_involvement
DISEASE: Holoprosencephaly 9 (HPE9) [MIM:610829]: A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia. HPE9 inheritance is autosomal dominant. {ECO:0000269|PubMed:14581620, ECO:0000269|PubMed:17096318, ECO:0000269|PubMed:20685856}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Culler-Jones syndrome (CJS) [MIM:615849]: An autosomal dominant disorder with incomplete penetrance and variable expressivity, characterized by pituitary abnormalities including ectopic or non-visible posterior pituitary lobe, growth hormone deficiency, combined pituitary hormone deficiency, and, in some patients, additional features such as postaxial polydactyly, midline facial defects, and developmental delay. {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:20685856, ECO:0000269|PubMed:23408573, ECO:0000269|PubMed:28973407}. 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 skeleton development (PubMed:15994174, PubMed:18455992, PubMed:19878745, PubMed:20154143, PubMed:20685856, PubMed:24311597, PubMed:26565916, PubMed:9557682). 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 (By similarity). The transcriptional activator form constitutes the major form of GLI2 (By similarity). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:20685856, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:9557682}.; FUNCTION: [Transcription activator GLI2]: Transcription factor, which activates expression of target genes in response to smoothened (SMO) activation (PubMed:18455992, PubMed:19878745, PubMed:24311597, PubMed:26565916, PubMed:9557682). Constitutes a major form of GLI2, while the transcription repressor form (GLI2R) plays a minor role (By similarity). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:9557682}.; FUNCTION: [Transcription repressor GLI2R]: Transcription repressor, which inhibits expression of target genes in the absence of smoothened (SMO) signaling (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q0VGT2}.; FUNCTION: [Isoform 1]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 2]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 3]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 4]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 5]: Acts as a transcriptional repressor. {ECO:0000269|PubMed:15994174}.; FUNCTION: [Isoform 1]: (Microbial infection) Acts as a transcriptional activator in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 2]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 3]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 4]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.
uniprot
proteins
mass_dalton
167783
uniprot
proteins
mutagenesis
MUTAGEN 252; /note="S->A: Abolished phosphorylation by DYRK2, leading to decreased dossiciation from SUFU."; /evidence="ECO:0000269|PubMed:38968120
uniprot
proteins
post_translational_modification
PTM: Acetylation at Lys-757 inhibits Hh target gene expression, probably by impeding entry into chromatin thus preventing promoter occupancy. {ECO:0000269|PubMed:23762415}.; 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 (By similarity). Phosphorylated by DYRK2; this inhibits GLI2 transcription factor activity and promotes proteasomal degradation of GLI2 (PubMed:18455992). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:18455992}.; PTM: [Transcription activator GLI2]: Phosphorylation at Ser-252 by DYRK2 in response to smoothened activation, promotes GLI2 dissociation from SUFU inhibitor and translocation to the nucleus (PubMed:38968120). Phosphorylated by ULK3 (PubMed:19878745). Phosphorylation by ULK3 or STK36 in response to smoothened activation promotes subsequent phosphorylation by CDK1 and GLI2 dissociation from SUFU inhibitor, followed by translocation to the nucleus (By similarity). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:38968120}.; 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:0000250|UniProtKB:Q0VGT2}.; PTM: [Transcription repressor GLI2R]: Generated from the full-length GLI2 protein through proteolytic processing (By similarity). This process requires PKA-primed phosphorylation of GLI2, ubiquitination by the SCF(BTRC) complex and limited proteolysis (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q0VGT2}.
uniprot
proteins
protein_family
GLI C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10806483
uniprot
proteins
pubmed
14581620
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15994174
uniprot
proteins
pubmed
17096318
uniprot
proteins
pubmed
18455992
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19878745
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20154143
uniprot
proteins
pubmed
20643644
uniprot
proteins
pubmed
20685856
uniprot
proteins
pubmed
23408573
uniprot
proteins
pubmed
23762415
uniprot
proteins
pubmed
24311597
uniprot
proteins
pubmed
26565916
uniprot
proteins
pubmed
27535533
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
2850480
uniprot
proteins
pubmed
28973407
uniprot
proteins
pubmed
38968120
uniprot
proteins
pubmed
8350401
uniprot
proteins
pubmed
9557682
uniprot
proteins
sequence_length
1586
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:26565916}. Cytoplasm {ECO:0000250|UniProtKB:Q0VGT2}. Cell projection, cilium {ECO:0000269|PubMed:20154143}. Note=Full-length GLI2 is sequestered in the cytoplasm by SUFU in absence of smoothened signaling. {ECO:0000250|UniProtKB:Q0VGT2}.; SUBCELLULAR LOCATION: [Transcription activator GLI2]: Nucleus {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:38968120}. Cytoplasm {ECO:0000269|PubMed:38968120}. Cell projection, cilium {ECO:0000269|PubMed:20154143}. Note=Sequestered in the cytoplasm by SUFU in absence of smoothened signaling (PubMed:38968120). Accumulates in primary cilia following smoothened activation (PubMed:20154143). It then translocates to the nucleus, where is activates transcription of target genes (PubMed:38968120). TMEM216 promotes its nuclear localization (By similarity). STK36 promotes translocation to the nucleus (PubMed:10806483). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:20154143, ECO:0000269|PubMed:38968120}.; SUBCELLULAR LOCATION: [Transcription repressor GLI2R]: Nucleus {ECO:0000250|UniProtKB:Q0VGT2}. Note=Following generation by proteolytic processing in absence of smoothened, translocates to the nucleus, where is represses transcription of target genes. {ECO:0000250|UniProtKB:Q0VGT2}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:9557682}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:9557682}.
uniprot
proteins