Homo sapiens Protein: GLI3
InnateDB Protein IDBP-238557.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol GLI3
Protein Name GLI family zinc finger 3
Species Homo sapiens
Ensembl Protein ENSP00000379258
InnateDB Gene IDBG-13536 (GLI3)
Protein Structure
UniProt Annotation
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'. {ECO:0000269PubMed:10693759, ECO:0000269PubMed:11238441, ECO:0000269PubMed:17764085}.
Subcellular Localization Nucleus. Cytoplasm. Cell projection, cilium. Note=GLI3FL is localized predominantly in the cytoplasm while GLI3R resides mainly in the nucleus. Ciliary accumulation requires the presence of KIF7 and SMO. Translocation to the nucleus is promoted by interaction with ZIC1.
Disease Associations 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:0000269PubMed:10441342, ECO:0000269PubMed:12414818, ECO:0000269PubMed:12794692, ECO:0000269PubMed:9302279}. Note=The disease is caused by mutations affecting the gene represented in this entry.Pallister-Hall syndrome 1 (PHS1) [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. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:10441570}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:10441570}. Note=The disease is caused by mutations affecting the gene represented in this entry.Polydactyly preaxial 4 (POP4) [MIM:174700]: Preaxial polydactyly (i.e., polydactyly on the radial/tibial side of the hand/foot) covers a heterogeneous group of entities. In preaxial polydactyly type IV, the thumb shows only the mildest degree of duplication, and syndactyly of various degrees affects fingers 3 and 4. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.
Number of Interactions This gene and/or its encoded proteins are associated with 37 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.
Experimentally validated
Total 37 [view]
Protein-Protein 30 [view]
Protein-DNA 3 [view]
Protein-RNA 0
DNA-DNA 4 [view]
Predicted by orthology
Total 9 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0003682 chromatin binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0035035 histone acetyltransferase binding
GO:0042826 histone deacetylase binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001656 metanephros development
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001701 in utero embryonic development
GO:0001822 kidney development
GO:0002052 positive regulation of neuroblast proliferation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007224 smoothened signaling pathway
GO:0007389 pattern specification process
GO:0007411 axon guidance
GO:0007417 central nervous system development
GO:0007420 brain development
GO:0007442 hindgut morphogenesis
GO:0007507 heart development
GO:0008285 negative regulation of cell proliferation
GO:0009952 anterior/posterior pattern specification
GO:0009953 dorsal/ventral pattern formation
GO:0009954 proximal/distal pattern formation
GO:0010468 regulation of gene expression
GO:0016485 protein processing
GO:0021513 spinal cord dorsal/ventral patterning
GO:0021522 spinal cord motor neuron differentiation
GO:0021537 telencephalon development
GO:0021543 pallium development
GO:0021544 subpallium development
GO:0021631 optic nerve morphogenesis
GO:0021766 hippocampus development
GO:0021775 smoothened signaling pathway involved in ventral spinal cord interneuron specification
GO:0021776 smoothened signaling pathway involved in spinal cord motor neuron cell fate specification
GO:0021798 forebrain dorsal/ventral pattern formation
GO:0021801 cerebral cortex radial glia guided migration
GO:0021861 forebrain radial glial cell differentiation
GO:0021915 neural tube development
GO:0022018 lateral ganglionic eminence cell proliferation
GO:0030318 melanocyte differentiation
GO:0030324 lung development
GO:0030326 embryonic limb morphogenesis
GO:0030879 mammary gland development
GO:0030900 forebrain development
GO:0032332 positive regulation of chondrocyte differentiation
GO:0033077 T cell differentiation in thymus
GO:0035108 limb morphogenesis
GO:0035295 tube development
GO:0042060 wound healing
GO:0042127 regulation of cell proliferation
GO:0042307 positive regulation of protein import into nucleus
GO:0042475 odontogenesis of dentin-containing tooth
GO:0042733 embryonic digit morphogenesis
GO:0042981 regulation of apoptotic process
GO:0043010 camera-type eye development
GO:0043066 negative regulation of apoptotic process
GO:0043585 nose morphogenesis
GO:0043586 tongue development
GO:0043627 response to estrogen
GO:0045060 negative thymic T cell selection
GO:0045595 regulation of cell differentiation
GO:0045596 negative regulation of cell differentiation
GO:0045665 negative regulation of neuron differentiation
GO:0045669 positive regulation of osteoblast differentiation
GO:0045879 negative regulation of smoothened signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046638 positive regulation of alpha-beta T cell differentiation
GO:0046639 negative regulation of alpha-beta T cell differentiation
GO:0048557 embryonic digestive tract morphogenesis
GO:0048566 embryonic digestive tract development
GO:0048589 developmental growth
GO:0048593 camera-type eye morphogenesis
GO:0048598 embryonic morphogenesis
GO:0048646 anatomical structure formation involved in morphogenesis
GO:0048663 neuron fate commitment
GO:0048704 embryonic skeletal system morphogenesis
GO:0048709 oligodendrocyte differentiation
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048839 inner ear development
GO:0048856 anatomical structure development
GO:0060021 palate development
GO:0060173 limb development
GO:0060364 frontal suture morphogenesis
GO:0060366 lambdoid suture morphogenesis
GO:0060367 sagittal suture morphogenesis
GO:0060594 mammary gland specification
GO:0060831 smoothened signaling pathway involved in dorsal/ventral neural tube patterning
GO:0060840 artery development
GO:0060873 anterior semicircular canal development
GO:0060875 lateral semicircular canal development
GO:0061005 cell differentiation involved in kidney development
GO:0070242 thymocyte apoptotic process
GO:0090090 negative regulation of canonical Wnt signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005929 cilium
GO:0016592 mediator complex
GO:0016607 nuclear speck
GO:0017053 transcriptional repressor complex
GO:0072372 primary cilium
Protein Structure and Domains
InterPro IPR007087 Zinc finger, C2H2
IPR015880 Zinc finger, C2H2-like
PFAM PF00096
Post-translational Modifications
SwissProt P10071
PhosphoSite PhosphoSite-P10071
UniProt Splice Variant
Entrez Gene 2737
UniGene Hs.707641
RefSeq NP_000159
OMIM 165240
HPRD 01313
EMBL AC005026 AC005028 AC005158 AC073852 AJ250408 BC113616 BC117168 CH236951 M20674 M57609
GenPept AAA52564 AAI13617 AAI17169 AAP21869 AAS01998 AAS02015 CAB59315 EAL24002