UniProt:Q61602 Gli3

chain
  • chain:1-1583
  • chain:1-
checksum 37ECC0C3ACF26C24
comment
  • FUNCTION Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. 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. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.SUBUNIT The phosphorylated form interacts with BTRC (By similarity). The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3 (PubMed:20360384, PubMed:38261656). Its association with SUFU is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A (By similarity). Interacts with KIF7 (PubMed:19549984). The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1 (PubMed:19389374). Interacts with ZIC1 (By similarity). Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity (By similarity). Interacts with WRD11; the interaction associates EMX1 with GLI3 (PubMed:29263200). Interacts with DZIP1; retains GLI3 within the cytoplasm (PubMed:23955340). Interacts with TMEM216; this interaction reduces nuclear localization of GLI3 (PubMed:38261656).SUBCELLULAR LOCATION Translocation to the nucleus is promoted by interaction with ZIC1 (By similarity). GLI3FL is localized predominantly in the cytoplasm while GLI3R resides mainly in the nucleus. Ciliary accumulation requires the presence of KIF7 and SMO (By similarity). TMEM216 reduces its nuclear localization (PubMed:38261656).PTM Phosphorylated by DYRK2 (in vitro) (By similarity). Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylation is essential for its proteolytic processing.PTM Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.DISEASE Several mutations result in developmental defects of cranofacial and limb structures. In particular the add (anterior digit-pattern deformity) and pdn (polydactyly Nagoya) alleles.SIMILARITY Belongs to the GLI C2H2-type zinc-finger protein family.
crossReference
databaseName UniProt
dbId 91361
description
  • recommendedName: Transcriptional activator GLI3 alternativeName: GLI3 form of 190 kDa shortName: GLI3-190 alternativeName: GLI3 full-length protein shortName: GLI3FL component recommendedName: Transcriptional repressor GLI3R alternativeName: GLI3 C-terminally truncated form alternativeName: GLI3 form of 83 kDa shortName: GLI3-83 /component
displayName UniProt:Q61602 Gli3
geneName
  • Gli3
identifier Q61602
isSequenceChanged false
keyword
  • Acetylation
  • Activator
  • Cell projection
  • Cilium
  • Cytoplasm
  • DNA-binding
  • Isopeptide bond
  • Metal-binding
  • Methylation
  • Nucleus
  • Phosphoprotein
  • Reference proteome
  • Repeat
  • Repressor
  • Transcription
  • Transcription regulation
  • Ubl conjugation
  • Zinc
  • Zinc-finger
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • Gli3
otherIdentifier
  • 101182_at
  • 10403727
  • 137022_at
  • 1450525_at
  • 1455154_at
  • 1456067_at
  • 14634
  • 17285414
  • 4347294
  • 4375806
  • 4387331
  • 4392179
  • 4441816
  • 4459831
  • 4479251
  • 4522165
  • 4595928
  • 4748636
  • 4805123
  • 4829825
  • 4927942
  • 4984719
  • 5013352
  • 5029570
  • 5311279
  • 5361910
  • 5367931
  • 5391329
  • 5410409
  • 5411992
  • 5592626
  • 5609791
  • A_51_P171288
  • GE34488
  • GO:0000122
  • GO:0000977
  • GO:0000978
  • GO:0000981
  • GO:0001649
  • GO:0001656
  • GO:0001658
  • GO:0001701
  • GO:0001822
  • GO:0002052
  • GO:0002062
  • GO:0002376
  • GO:0003677
  • GO:0003682
  • GO:0003700
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005730
  • GO:0005737
  • GO:0005829
  • GO:0005929
  • GO:0005930
  • GO:0006355
  • GO:0006357
  • GO:0006606
  • GO:0006886
  • GO:0006913
  • GO:0006915
  • GO:0007224
  • GO:0007389
  • GO:0007405
  • GO:0007411
  • GO:0007417
  • GO:0007420
  • GO:0007442
  • GO:0007507
  • GO:0008013
  • GO:0008270
  • GO:0008283
  • GO:0008285
  • GO:0008589
  • GO:0009952
  • GO:0009953
  • GO:0009954
  • GO:0010467
  • GO:0010468
  • GO:0016020
  • GO:0016485
  • GO:0016607
  • GO:0017053
  • GO:0021513
  • GO:0021520
  • GO:0021521
  • GO:0021522
  • GO:0021537
  • GO:0021543
  • GO:0021544
  • GO:0021631
  • GO:0021766
  • GO:0021775
  • GO:0021776
  • GO:0021798
  • GO:0021801
  • GO:0021819
  • GO:0021861
  • GO:0021904
  • GO:0021915
  • GO:0021953
  • GO:0022018
  • GO:0030154
  • GO:0030318
  • GO:0030324
  • GO:0030326
  • GO:0030850
  • GO:0030879
  • GO:0030900
  • GO:0032331
  • GO:0032332
  • GO:0033077
  • GO:0035035
  • GO:0035108
  • GO:0035295
  • GO:0036033
  • GO:0042127
  • GO:0042307
  • GO:0042475
  • GO:0042733
  • GO:0042826
  • GO:0042981
  • GO:0042995
  • GO:0043010
  • GO:0043066
  • GO:0043226
  • GO:0043565
  • GO:0043586
  • GO:0043627
  • GO:0045060
  • GO:0045595
  • GO:0045665
  • GO:0045669
  • GO:0045879
  • GO:0045892
  • GO:0045893
  • GO:0045944
  • GO:0046632
  • GO:0046638
  • GO:0046639
  • GO:0046872
  • GO:0048557
  • GO:0048562
  • GO:0048566
  • GO:0048589
  • GO:0048593
  • GO:0048598
  • GO:0048646
  • GO:0048663
  • GO:0048702
  • GO:0048704
  • GO:0048709
  • GO:0048732
  • GO:0048754
  • GO:0048839
  • GO:0048856
  • GO:0048870
  • GO:0060021
  • GO:0060173
  • GO:0060364
  • GO:0060366
  • GO:0060367
  • GO:0060594
  • GO:0060831
  • GO:0060840
  • GO:0060873
  • GO:0060875
  • GO:0061005
  • GO:0070242
  • GO:0071625
  • GO:0072089
  • GO:0090090
  • GO:0097421
  • GO:0120223
  • GO:1903010
  • GO:1990788
  • GO:1990837
  • GO:2000647
  • ILMN_1215183
  • ILMN_2449396
  • X95255_s_at
  • mMC006557
  • mMC011030
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • GLI3_MOUSE
sequenceLength 1583
species [Species:48892] Mus musculus
stId uniprot:Q61602
url http://purl.uniprot.org/uniprot/Q61602

Referrals

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