P10071 (GLI3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1580 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.13 Ref.14
Subcellular location	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. Ref.8 Ref.13
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.15 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.15
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.17 Ref.19 Ref.20 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]: Autosomal dominant trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. The extra digit is well formed and articulates with the fifth, or extra, metacarpal/metatarsal, and thus it is usually functional. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Polydactyly postaxial B (PAPB) [MIM:174200]: A trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. 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.18 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 process	Transcription Transcription regulation
Cellular component	Cell projection Cilium Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior semicircular canal development Inferred from electronic annotation. Source: Compara anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara artery development Inferred from electronic annotation. Source: Compara axon guidance Inferred from electronic annotation. Source: Compara branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara cell differentiation involved in kidney development Inferred from electronic annotation. Source: Compara cerebral cortex radial glia guided migration Inferred from electronic annotation. Source: Compara developmental growth Inferred from electronic annotation. Source: Compara embryonic digestive tract development Traceable author statement PubMed 11001584. Source: BHF-UCL embryonic digestive tract morphogenesis Inferred from electronic annotation. Source: Compara embryonic digit morphogenesis Traceable author statement PubMed 11001584. Source: BHF-UCL embryonic skeletal system morphogenesis Inferred from electronic annotation. Source: Compara forebrain dorsal/ventral pattern formation Inferred from electronic annotation. Source: Compara forebrain radial glial cell differentiation Inferred from electronic annotation. Source: Compara frontal suture morphogenesis Inferred from electronic annotation. Source: Compara heart development Inferred from electronic annotation. Source: Compara hindgut morphogenesis Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara lambdoid suture morphogenesis Inferred from electronic annotation. Source: Compara lateral ganglionic eminence cell proliferation Inferred from electronic annotation. Source: Compara lateral semicircular canal development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara mammary gland specification Inferred from electronic annotation. Source: Compara melanocyte differentiation Inferred from electronic annotation. Source: Compara metanephros development Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17331723. Source: UniProtKB negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara 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 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: Compara oligodendrocyte differentiation Inferred from electronic annotation. Source: Compara optic nerve morphogenesis Inferred from electronic annotation. Source: Compara palate development Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of protein import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17000779. Source: UniProtKB protein processing Inferred from electronic annotation. Source: Compara proximal/distal pattern formation Inferred from electronic annotation. Source: Compara sagittal suture morphogenesis Inferred from electronic annotation. Source: Compara 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: Compara smoothened signaling pathway involved in spinal cord motor neuron cell fate specification Inferred from electronic annotation. Source: Compara smoothened signaling pathway involved in ventral spinal cord interneuron specification Inferred from electronic annotation. Source: Compara thymocyte apoptotic process Inferred from sequence or structural similarity. Source: BHF-UCL tongue development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cilium Inferred from direct assay Ref.13. Source: UniProtKB cytosol Inferred from direct assay PubMed 18559511. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA transcriptional repressor complex Inferred from electronic annotation. Source: Compara
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara histone deacetylase binding Inferred from direct assay PubMed 12435627. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 10077605PubMed 17000779Ref.12. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Zic1	P46684	2	EBI-308055,EBI-308006	From a different organism.
Zic2	Q62520	2	EBI-308055,EBI-308076	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1580	1580	Transcriptional activator GLI3		PRO_0000047202
	Chain	1 – ?		Transcriptional repressor GLI3R		PRO_0000406137
Regions
	Zinc finger	480 – 505	26	C2H2-type 1
	Zinc finger	513 – 540	28	C2H2-type 2
	Zinc finger	546 – 570	25	C2H2-type 3
	Zinc finger	576 – 601	26	C2H2-type 4
	Zinc finger	607 – 632	26	C2H2-type 5
	Compositional bias	1492 – 1512	21	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	664	1	Phosphoserine Ref.16
	Modified residue	849	1	Phosphoserine; by PKA Ref.7
	Modified residue	865	1	Phosphoserine; by PKA Ref.7
	Modified residue	877	1	Phosphoserine; by PKA Ref.7
	Modified residue	907	1	Phosphoserine; by PKA Ref.7
	Modified residue	980	1	Phosphoserine; by PKA Ref.7
	Modified residue	1006	1	Phosphoserine; by PKA Ref.7
	Cross-link	773		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
	Cross-link	779		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
	Cross-link	784		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
	Cross-link	800		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9
Natural variations
	Natural variant	169	1	P → L in a colorectal cancer sample; somatic mutation. Ref.21		VAR_035560
	Natural variant	183	1	T → A. Ref.1 Ref.2 Ref.5 Corresponds to variant rs846266 [ dbSNP | Ensembl ].		VAR_028276
	Natural variant	440	1	D → E. Ref.2		VAR_010052
	Natural variant	515	1	C → G in GCPS. Ref.2		VAR_010053
	Natural variant	520	1	C → Y in GCPS. Ref.2		VAR_010054
	Natural variant	625	1	R → W in GCPS. Ref.20		VAR_021481
	Natural variant	707	1	P → S in GCPS. Ref.17		VAR_010055
	Natural variant	727	1	G → R in PAPA1 and PAPB. Ref.18		VAR_009876
	Natural variant	808	1	I → M in GCPS. Ref.2		VAR_010056
	Natural variant	934	1	A → P in GCPS; the patient was originally classifed as being affected by acrocallosal syndrome due to the absence of corpus callosum. Ref.19 Corresponds to variant rs28933372 [ dbSNP | Ensembl ].		VAR_021482
	Natural variant	998	1	P → L. Ref.1 Ref.2 Ref.5 Corresponds to variant rs929387 [ dbSNP | Ensembl ].		VAR_028278
	Natural variant	1304	1	S → P in a colorectal cancer sample; somatic mutation. Ref.21		VAR_035561
	Natural variant	1336	1	G → E. Corresponds to variant rs35280470 [ dbSNP | Ensembl ].		VAR_034865
	Natural variant	1537	1	R → C. Ref.2 Corresponds to variant rs35364414 [ dbSNP | Ensembl ].		VAR_010057
Experimental info
	Mutagenesis	773	1	K → R: Loss of proteolytic processing. Ref.9
	Mutagenesis	779	1	K → R: Loss of proteolytic processing. Ref.9
	Mutagenesis	784	1	K → R: Loss of proteolytic processing. Ref.9
	Mutagenesis	800	1	K → R: Loss of proteolytic processing. Ref.9
	Mutagenesis	849	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
	Mutagenesis	855	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	856	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	861	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	864	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	865	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7
	Mutagenesis	873	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	877	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
	Mutagenesis	903	1	S → A: Loss of proteolytic processing. Ref.9
	Mutagenesis	907	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7 Ref.9
	Mutagenesis	980	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7
	Mutagenesis	1006	1	S → A: Loss of phosphorylation and proteolytic processing. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P10071 [UniParc]. Last modified November 24, 2009. Version 6. Checksum: 423B7495FCE3C37C	FASTA	1,580	169,863
	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

References

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[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. , 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. , 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. , 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]	"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.
[14]	"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.
[15]	"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.
[16]	"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, MASS SPECTROMETRY.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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. , 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.

Web resources

GeneReviews

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.
IPI	IPI00018889.
PIR	A35927.
RefSeq	NP_000159.3. NM_000168.5.
UniGene	Hs.21509.
3D structure databases
ProteinModelPortal	P10071.
SMR	P10071. Positions 479-633.
ModBase	Search...
Protein-protein interaction databases
IntAct	P10071. 8 interactions.
MINT	MINT-189869.
STRING	9606.ENSP00000379255.
PTM databases
PhosphoSite	P10071.
Polymorphism databases
DMDM	269849770.
Proteomic databases
PaxDb	P10071.
PRIDE	P10071.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000395925; ENSP00000379258; ENSG00000106571.
GeneID	2737.
KEGG	hsa:2737.
UCSC	uc011kbg.2. human.
Organism-specific databases
CTD	2737.
GeneCards	GC07M041970.
H-InvDB	HIX0033636.
HGNC	HGNC:4319. GLI3.
HPA	HPA005534.
MIM	146510. phenotype. 165240. gene. 174200. phenotype. 174700. phenotype. 175700. phenotype.
neXtProt	NX_P10071.
Orphanet	36. 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.
PharmGKB	PA28722.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOVERGEN	HBG005844.
InParanoid	P10071.
KO	K06230.
OMA	NSQNQAG.
OrthoDB	EOG45HRWN.
Enzyme and pathway databases
Pathway_Interaction_DB	hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
Gene expression databases
ArrayExpress	P10071.
Bgee	P10071.
CleanEx	HS_GLI3.
Genevestigator	P10071.
GermOnline	ENSG00000106571. Homo sapiens.
Family and domain databases
Gene3D	3.30.160.60. 5 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 5 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 4 hits. PS50157. ZINC_FINGER_C2H2_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GLI3. human.
GenomeRNAi	2737.
NextBio	10788.
SOURCE	Search...

Entry information

Entry name

GLI3_HUMAN

Accession

Primary (citable) accession number: P10071
Secondary accession number(s): A4D1W1 , O75219, Q17RW4, Q75MT0, Q75MU9, Q9UDT5, Q9UJ39

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 143 of the entry and version 6 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.