InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GLI3

Summary

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

Synonyms

ACLS; GCPS; GLI3-190; GLI3FL; PAP-A; PAPA; PAPA1; PAPB; PHS; PPDIV;

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.

Comments

Interactions

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]
RNA-RNA	0
DNA-RNA	0

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