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P10071 (GLI3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcriptional activator GLI3
Alternative name(s):
GLI3 form of 190 kDa
Short name=GLI3-190
GLI3 full length protein
Short name=GLI3FL

Cleaved into the following chain:

  1. Transcriptional repressor GLI3R
    Alternative name(s):
    GLI3 C-terminally truncated form
    GLI3 form of 83 kDa
    Short name=GLI3-83
Gene names
Name:GLI3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1580 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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'. Ref.7 Ref.8 Ref.12

Subunit structure

The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3. 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. The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1. The phosphorylated form interacts with BTRC. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity. Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.15

Subcellular location

Nucleus. Cytoplasm. Cell projectioncilium. 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. Ref.8 Ref.14

Tissue specificity

Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.

Post-translational modification

Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for its proteolytic processing. Ref.7 Ref.9 Ref.10 Ref.11 Ref.16

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. Ref.7 Ref.9 Ref.10 Ref.11 Ref.16

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.18 Ref.20 Ref.21

Pallister-Hall syndrome (PHS) [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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

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.

Sequence similarities

Belongs to the GLI C2H2-type zinc-finger protein family.

Contains 5 C2H2-type zinc fingers.

Sequence caution

The sequence AAA52564.1 differs from that shown. Reason: Frameshift at position 1549.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCell projection
Cilium
Cytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Repressor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell differentiation in thymus

Inferred from sequence or structural similarity. Source: BHF-UCL

anterior semicircular canal development

Inferred from electronic annotation. Source: Ensembl

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

artery development

Inferred from electronic annotation. Source: Ensembl

axon guidance

Inferred from electronic annotation. Source: Ensembl

branching involved in ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

camera-type eye morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell differentiation involved in kidney development

Inferred from electronic annotation. Source: Ensembl

cerebral cortex radial glia guided migration

Inferred from electronic annotation. Source: Ensembl

developmental growth

Inferred from electronic annotation. Source: Ensembl

embryonic digestive tract development

Traceable author statement PubMed 11001584. Source: BHF-UCL

embryonic digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Traceable author statement PubMed 11001584. Source: BHF-UCL

embryonic skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

forebrain dorsal/ventral pattern formation

Inferred from electronic annotation. Source: Ensembl

forebrain radial glial cell differentiation

Inferred from electronic annotation. Source: Ensembl

frontal suture morphogenesis

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from electronic annotation. Source: Ensembl

hindgut morphogenesis

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

lambdoid suture morphogenesis

Inferred from electronic annotation. Source: Ensembl

lateral ganglionic eminence cell proliferation

Inferred from electronic annotation. Source: Ensembl

lateral semicircular canal development

Inferred from electronic annotation. Source: Ensembl

limb morphogenesis

Inferred from mutant phenotype PubMed 18478223PubMed 9354785. Source: UniProtKB

lung development

Inferred from electronic annotation. Source: Ensembl

mammary gland specification

Inferred from electronic annotation. Source: Ensembl

melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

metanephros development

Inferred from electronic annotation. Source: Ensembl

negative regulation of alpha-beta T cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 17331723. Source: UniProtKB

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of smoothened signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12435627PubMed 19084012. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12435627PubMed 19084012. Source: UniProtKB

negative thymic T cell selection

Inferred from sequence or structural similarity. Source: BHF-UCL

nose morphogenesis

Traceable author statement PubMed 11001584. Source: BHF-UCL

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

optic nerve morphogenesis

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

positive regulation of alpha-beta T cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17000779. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

protein processing

Inferred from electronic annotation. Source: Ensembl

proximal/distal pattern formation

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

sagittal suture morphogenesis

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway

Traceable author statement PubMed 11001584. Source: BHF-UCL

smoothened signaling pathway involved in dorsal/ventral neural tube patterning

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway involved in spinal cord motor neuron cell fate specification

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway involved in ventral spinal cord interneuron specification

Inferred from electronic annotation. Source: Ensembl

thymocyte apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

tongue development

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcilium

Inferred from direct assay Ref.14. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 10077605Ref.8PubMed 12435627. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 18559511. Source: UniProtKB

nuclear speck

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.8PubMed 12435627PubMed 18559511. Source: UniProtKB

primary cilium

Inferred from electronic annotation. Source: Ensembl

transcriptional repressor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from direct assay Ref.1. Source: MGI

beta-catenin binding

Inferred from physical interaction PubMed 17331723. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

histone acetyltransferase binding

Inferred from physical interaction PubMed 10075717. Source: UniProtKB

histone deacetylase binding

Inferred from direct assay PubMed 12435627. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.8PubMed 12435627Ref.10PubMed 17000779Ref.12Ref.15Ref.14. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 10077605PubMed 17000779Ref.12. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Zic1P466842EBI-308055,EBI-308006From a different organism.
Zic2Q625202EBI-308055,EBI-308076From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15801580Transcriptional activator GLI3
PRO_0000047202
Chain1 – ?Transcriptional repressor GLI3RPRO_0000406137

Regions

Zinc finger480 – 50526C2H2-type 1
Zinc finger513 – 54028C2H2-type 2
Zinc finger546 – 57025C2H2-type 3
Zinc finger576 – 60126C2H2-type 4
Zinc finger607 – 63226C2H2-type 5
Compositional bias1492 – 151221Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue11N-acetylmethionine Ref.13
Modified residue6641Phosphoserine Ref.17
Modified residue8491Phosphoserine; by PKA Ref.7
Modified residue8651Phosphoserine; by PKA Ref.7
Modified residue8771Phosphoserine; by PKA Ref.7
Modified residue9071Phosphoserine; by PKA Ref.7
Modified residue9801Phosphoserine; by PKA Ref.7
Modified residue10061Phosphoserine; by PKA Ref.7
Cross-link773Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Cross-link779Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Cross-link784Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Cross-link800Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Natural variations

Natural variant1691P → L in a colorectal cancer sample; somatic mutation. Ref.22
VAR_035560
Natural variant1831T → A. Ref.1 Ref.2 Ref.5
Corresponds to variant rs846266 [ dbSNP | Ensembl ].
VAR_028276
Natural variant4401D → E. Ref.2
VAR_010052
Natural variant5151C → G in GCPS. Ref.2
VAR_010053
Natural variant5201C → Y in GCPS. Ref.2
VAR_010054
Natural variant6251R → W in GCPS. Ref.21
VAR_021481
Natural variant7071P → S in GCPS. Ref.18
VAR_010055
Natural variant7271G → R in PAPA1 and PAPB. Ref.19
Corresponds to variant rs121917710 [ dbSNP | Ensembl ].
VAR_009876
Natural variant8081I → M in GCPS. Ref.2
Corresponds to variant rs62622373 [ dbSNP | Ensembl ].
VAR_010056
Natural variant9341A → P in GCPS; the patient was originally classifed as being affected by acrocallosal syndrome due to the absence of corpus callosum. Ref.20
Corresponds to variant rs28933372 [ dbSNP | Ensembl ].
VAR_021482
Natural variant9981P → L. Ref.1 Ref.2 Ref.5
Corresponds to variant rs929387 [ dbSNP | Ensembl ].
VAR_028278
Natural variant13041S → P in a colorectal cancer sample; somatic mutation. Ref.22
VAR_035561
Natural variant13361G → E.
Corresponds to variant rs35280470 [ dbSNP | Ensembl ].
VAR_034865
Natural variant15371R → C. Ref.2
Corresponds to variant rs35364414 [ dbSNP | Ensembl ].
VAR_010057

Experimental info

Mutagenesis7731K → R: Loss of proteolytic processing. Ref.9
Mutagenesis7791K → R: Loss of proteolytic processing. Ref.9
Mutagenesis7841K → R: Loss of proteolytic processing. Ref.9
Mutagenesis8001K → R: Loss of proteolytic processing. Ref.9
Mutagenesis8491S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
Mutagenesis8551S → A: Loss of proteolytic processing. Ref.9
Mutagenesis8561S → A: Loss of proteolytic processing. Ref.9
Mutagenesis8611S → A: Loss of proteolytic processing. Ref.9
Mutagenesis8641S → A: Loss of proteolytic processing. Ref.9
Mutagenesis8651S → A: Loss of phosphorylation and proteolytic processing. Ref.7
Mutagenesis8731S → A: Loss of proteolytic processing. Ref.9
Mutagenesis8771S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
Mutagenesis9031S → A: Loss of proteolytic processing. Ref.9
Mutagenesis9071S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
Mutagenesis9801S → A: Loss of phosphorylation and proteolytic processing. Ref.7
Mutagenesis10061S → A: Loss of phosphorylation and proteolytic processing. Ref.7

Secondary structure

... 1580
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10071 [UniParc].

Last modified November 24, 2009. Version 6.
Checksum: 423B7495FCE3C37C

FASTA1,580169,863
        10         20         30         40         50         60 
MEAQSHSSTT TEKKKVENSI VKCSTRTDVS EKAVASSTTS NEDESPGQTY HRERRNAITM 

        70         80         90        100        110        120 
QPQNVQGLSK VSEEPSTSSD ERASLIKKEI HGSLPHVAEP SVPYRGTVFA MDPRNGYMEP 

       130        140        150        160        170        180 
HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP SPIPPLHMTS ALSSSPTYPD LPFIRISPHR 

       190        200        210        220        230        240 
NPTAASESPF SPPHPYINPY MDYIRSLHSS PSLSMISATR GLSPTDAPHA GVSPAEYYHQ 

       250        260        270        280        290        300 
MALLTGQRSP YADIIPSAAT AGTGAIHMEY LHAMDSTRFS SPRLSARPSR KRTLSISPLS 

       310        320        330        340        350        360 
DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY SSAPVSLHMH 

       370        380        390        400        410        420 
QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL NPVQVSSGPS ESSQNKPTSE 

       430        440        450        460        470        480 
SAVSSTGDPM HNKRSKIKPD EDLPSPGARG QQEQPEGTTL VKEEGDKDES KQEPEVIYET 

       490        500        510        520        530        540 
NCHWEGCARE FDTQEQLVHH INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH 

       550        560        570        580        590        600 
TGEKPHKCTF EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT 

       610        620        630        640        650        660 
HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDIHPRP PPPRDSGSHS 

       670        680        690        700        710        720 
QSRSPGRPTQ GALGEQQDLS NTTSKREECL QVKTVKAEKP MTSQPSPGGQ SSCSSQQSPI 

       730        740        750        760        770        780 
SNYSNSGLEL PLTDGGSIGD LSAIDETPIM DSTISTATTA LALQARRNPA GTKWMEHVKL 

       790        800        810        820        830        840 
ERLKQVNGMF PRLNPILPPK APAVSPLIGN GTQSNNTCSL GGPMTLLPGR SDLSGVDVTM 

       850        860        870        880        890        900 
LNMLNRRDSS ASTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST 

       910        920        930        940        950        960 
DASRRSSEAS QSDGLPSLLS LTPAQQYRLK AKYAAATGGP PPTPLPNMER MSLKTRLALL 

       970        980        990       1000       1010       1020 
GDALEPGVAL PPVHAPRRCS DGGAHGYGRR HLQPHDAPGH GVRRASDPVR TGSEGLALPR 

      1030       1040       1050       1060       1070       1080 
VPRFSSLSSC NPPAMATSAE KRSLVLQNYT RPEGGQSRNF HSSPCPPSIT ENVTLESLTM 

      1090       1100       1110       1120       1130       1140 
DADANLNDED FLPDDVVQYL NSQNQAGYEQ HFPSALPDDS KVPHGPGDFD APGLPDSHAG 

      1150       1160       1170       1180       1190       1200 
QQFHALEQPC PEGSKTDLPI QWNEVSSGSA DLSSSKLKCG PRPAVPQTRA FGFCNGMVVH 

      1210       1220       1230       1240       1250       1260 
PQNPLRSGPA GGYQTLGENS NPYGGPEHLM LHNSPGSGTS GNAFHEQPCK APQYGNCLNR 

      1270       1280       1290       1300       1310       1320 
QPVAPGALDG ACGAGIQASK LKSTPMQGSG GQLNFGLPVA PNESAGSMVN GMQNQDPVGQ 

      1330       1340       1350       1360       1370       1380 
GYLAHQLLGD SMQHPGAGRP GQQMLGQISA TSHINIYQGP ESCLPGAHGM GSQPSSLAVV 

      1390       1400       1410       1420       1430       1440 
RGYQPCASFG GSRRQAMPRD SLALQSGQLS DTSQTCRVNG IKMEMKGQPH PLCSNLQNYS 

      1450       1460       1470       1480       1490       1500 
GQFYDQTVGF SQQDTKAGSF SISDASCLLQ GTSAKNSELL SPGANQVTST VDSLDSHDLE 

      1510       1520       1530       1540       1550       1560 
GVQIDFDAII DDGDHSSLMS GALSPSIIQN LSHSSSRLTT PRASLPFPAL SMSTTNMAIG 

      1570       1580 
DMSSLLTSLA EESKFLAVMQ 

« Hide

References

« Hide 'large scale' references
[1]"GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity."
Ruppert J.M., Vogelstein B., Arheden K., Kinzler K.W.
Mol. Cell. Biol. 10:5408-5415(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-183 AND LEU-998.
[2]"Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactylysyndrome."
Kalff-Suske M., Wild A., Topp J., Wessling M., Jacobsen E.-M., Bornholdt D., Engel H., Heuer H., Aalfs C.M., Ausems M.G.E.M., Barone R., Herzog A., Heutink P., Homfray T., Gillessen-Kaesbach G., Koenig R., Kunze J., Meinecke P. expand/collapse author list , Mueller D., Rizzo R., Strenge S., Superti-Furga A., Grzeschik K.-H.
Hum. Mol. Genet. 8:1769-1777(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GCPS GLY-515; TYR-520 AND MET-808, VARIANTS ALA-183; GLU-440; LEU-998 AND CYS-1537.
[3]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-183 AND LEU-998.
Tissue: Cerebellum.
[6]"The GLI-Kruppel family of human genes."
Ruppert J.M., Kinzler K.W., Wong A.J., Bigner S.H., Kao F.T., Law M.L., Seuanez H.N., O'Brien S.J., Vogelstein B.
Mol. Cell. Biol. 8:3104-3113(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-549.
[7]"Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb."
Wang B., Fallon J.F., Beachy P.A.
Cell 100:423-434(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PROTEOLYTIC PROCESSING, PHOSPHORYLATION AT SER-849; SER-865; SER-877; SER-907; SER-980 AND SER-1006, MUTAGENESIS OF SER-849; SER-865; SER-877; SER-907; SER-980 AND SER-1006.
[8]"Physical and functional interactions between Zic and Gli proteins."
Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.
J. Biol. Chem. 276:6889-6892(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZIC1, SUBCELLULAR LOCATION.
[9]"Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP."
Tempe D., Casas M., Karaz S., Blanchet-Tournier M.F., Concordet J.P.
Mol. Cell. Biol. 26:4316-4326(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, PHOSPHORYLATION, INTERACTION WITH BTRC, UBIQUITINATION AT LYS-773; LYS-779; LYS-784 AND LYS-800, MUTAGENESIS OF LYS-773; LYS-779; LYS-784; LYS-800; SER-849; SER-855; SER-856; SER-861; SER-864; SER-873; SER-877; SER-903 AND SER-907.
[10]"Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing."
Wang B., Li Y.
Proc. Natl. Acad. Sci. U.S.A. 103:33-38(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, PHOSPHORYLATION, POLYUBIQUITINATION, INTERACTION WITH BTRC.
[11]"Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling."
Varjosalo M., Bjorklund M., Cheng F., Syvanen H., Kivioja T., Kilpinen S., Sun Z., Kallioniemi O., Stunnenberg H.G., He W.W., Ojala P., Taipale J.
Cell 133:537-548(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[12]"Characterization of the interactions of human ZIC3 mutants with GLI3."
Zhu L., Zhou G., Poole S., Belmont J.W.
Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZIC3.
[13]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development."
Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W., Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J., Peterson A.S.
Curr. Biol. 19:1320-1326(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KIF7.
[15]"Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3."
Wuelling M., Kaiser F.J., Buelens L.A., Braunholz D., Shivdasani R.A., Depping R., Vortkamp A.
Dev. Biol. 328:40-53(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRPS1.
[16]"Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway."
Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.
Exp. Cell Res. 316:627-637(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[17]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Point mutations in human GLI3 cause Greig syndrome."
Wild A., Kalff-Suske M., Vortkamp A., Bornholdt D., Koenig R., Grzeschik K.-H.
Hum. Mol. Genet. 6:1979-1984(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GCPS SER-707.
[19]"The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; no phenotype prediction from the position of GLI3 mutations."
Radhakrishna U., Bornholdt D., Scott H.S., Patel U.C., Rossier C., Engel H., Bottani A., Chandal D., Blouin J.-L., Solanki J.V., Grzeschik K.-H., Antonarakis S.E.
Am. J. Hum. Genet. 65:645-655(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PAPA1 ARG-727, VARIANT PAPB ARG-727.
[20]"De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models."
Elson E., Perveen R., Donnai D., Wall S., Black G.C.M.
J. Med. Genet. 39:804-806(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GCPS PRO-934.
[21]"Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations."
Debeer P., Peeters H., Driess S., De Smet L., Freese K., Matthijs G., Bornholdt D., Devriendt K., Grzeschik K.-H., Fryns J.-P., Kalff-Suske M.
Am. J. Med. Genet. A 120:49-58(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GCPS TRP-625.
[22]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-169 AND PRO-1304.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57609 mRNA. Translation: AAA52564.1. Frameshift.
AJ250408 Genomic DNA. Translation: CAB59315.1.
AC005026 Genomic DNA. Translation: AAP21869.1.
AC005028 Genomic DNA. Translation: AAS01998.1.
AC005158 Genomic DNA. Translation: AAS02015.1.
AC073852 Genomic DNA. No translation available.
CH236951 Genomic DNA. Translation: EAL24002.1.
M20674 Genomic DNA. No translation available.
BC113616 mRNA. Translation: AAI13617.1.
BC117168 mRNA. Translation: AAI17169.1.
CCDSCCDS5465.1.
PIRA35927.
RefSeqNP_000159.3. NM_000168.5.
XP_005249760.1. XM_005249703.1.
XP_005249761.1. XM_005249704.1.
UniGeneHs.21509.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BLDX-ray2.80E/F/G/H328-344[»]
ProteinModelPortalP10071.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108999. 20 interactions.
DIPDIP-32538N.
IntActP10071. 9 interactions.
MINTMINT-189869.
STRING9606.ENSP00000379255.

PTM databases

PhosphoSiteP10071.

Polymorphism databases

DMDM269849770.

Proteomic databases

MaxQBP10071.
PaxDbP10071.
PRIDEP10071.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000395925; ENSP00000379258; ENSG00000106571.
GeneID2737.
KEGGhsa:2737.
UCSCuc011kbg.2. human.

Organism-specific databases

CTD2737.
GeneCardsGC07M041970.
GeneReviewsGLI3.
H-InvDBHIX0033636.
HGNCHGNC:4319. GLI3.
HPAHPA005534.
MIM146510. phenotype.
165240. gene.
174200. phenotype.
174700. phenotype.
175700. phenotype.
neXtProtNX_P10071.
Orphanet36. Acrocallosal syndrome.
380. Greig cephalopolysyndactyly syndrome.
672. Pallister-Hall syndrome.
295161. Polysyndactyly, bilateral.
295159. Polysyndactyly, unilateral.
295165. Postaxial polydactyly type A, bilateral.
295163. Postaxial polydactyly type A, unilateral.
295169. Postaxial polydactyly type B, bilateral.
295167. Postaxial polydactyly type B, unilateral.
PharmGKBPA28722.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOVERGENHBG005844.
InParanoidP10071.
KOK06230.
OMAPRDSGSH.
OrthoDBEOG7X6KZ8.
PhylomeDBP10071.
TreeFamTF350216.

Enzyme and pathway databases

SignaLinkP10071.

Gene expression databases

ArrayExpressP10071.
BgeeP10071.
CleanExHS_GLI3.
GenevestigatorP10071.

Family and domain databases

Gene3D3.30.160.60. 5 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGLI3. human.
GeneWikiGLI3.
GenomeRNAi2737.
NextBio10788.
PROP10071.
SOURCESearch...

Entry information

Entry nameGLI3_HUMAN
AccessionPrimary (citable) accession number: P10071
Secondary accession number(s): A4D1W1 expand/collapse secondary AC list , O75219, Q17RW4, Q75MT0, Q75MU9, Q9UDT5, Q9UJ39
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 24, 2009
Last modified: July 9, 2014
This is version 156 of the entry and version 6 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM