Reviewed, UniProtKB/Swiss-Prot P10071 (GLI3_HUMAN)

Names and origin

Protein names

Recommended name:
    Zinc finger protein GLI3

Gene names

Name:

GLI3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1580 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in limb and brain development. Implicated in the transduction of SHH signal By similarity.
Subcellular location	Nucleus.
Tissue specificity	Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.
Involvement in disease	Defects in GLI3 are the cause of Greig cephalo-poly-syndactyly syndrome (GCPS) [MIM:175700]; an autosomal dominant disorder affecting limb and craniofacial development. GCPS is characterized by pre- and postaxial polydactyly, syndactyly of fingers and toes, macrocephaly and hypertelorism. Ref.2 Ref.8 Ref.11 Defects in GLI3 are a cause of Pallister-Hall syndrome (PHS) [MIM:146510]. Pallister-Hall syndrome is characterized by a wide range of clinical manifestations. It mainly associates central or postaxial polydactyly, syndactyly, and hypothalamic hamartoma. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia. It is an autosomal dominant disorder. Defects in GLI3 are a cause of type A1/B postaxial polydactyly (PAPA1/PAPB) [MIM:174200, 603596]. PAPA in humans is an 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. Ref.9 Defects in GLI3 are a cause of type IV preaxial polydactyly [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. Defects in GLI3 are the cause of acrocallosal syndrome (ACS) [MIM:200990]; also abbreviated ACLS. ACS is characterized by postaxial polydactyly, hallux duplication, macrocephaly, and absence of the corpus callosum, usually with severe developmental delay. Ref.10
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	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	protein import into nucleus, translocation Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cilium Inferred from direct assay. Source: MGI cytoplasm Traceable author statement. Source: ProtInc nucleolus Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: IntAct transcription factor activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STK36	Q9NRP7	1	EBI-308055,EBI-863797
SUFU	Q9UMX1	1	EBI-308055,EBI-740595
Zic1	P46684	2	EBI-308055,EBI-308006	From a different organism.
Zic2	Q62520	2	EBI-308055,EBI-308076	From a different organism.
Zic3	Q62521	1	EBI-308055,EBI-308132	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1580	1580	Zinc finger protein GLI3		PRO_0000047202
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	19	1	Phosphoserine Ref.7
Natural variations
	Natural variant	169	1	P → L in a colorectal cancer sample; somatic mutation. Ref.12		VAR_035560
	Natural variant	183	1	A → T: dbSNP rs846266. Ref.3 Ref.4		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.11		VAR_021481
	Natural variant	707	1	P → S in GCPS. Ref.8		VAR_010055
	Natural variant	727	1	G → R in PAPA1/PAPB. Ref.9		VAR_009876
	Natural variant	808	1	I → M in GCPS. Ref.2		VAR_010056
	Natural variant	934	1	A → P in ACS. dbSNP rs28933372. Ref.10		VAR_021482
	Natural variant	998	1	L → P: dbSNP rs929387. Ref.3 Ref.4		VAR_028278
	Natural variant	1304	1	S → P in a colorectal cancer sample; somatic mutation. Ref.12		VAR_035561
	Natural variant	1336	1	G → E: dbSNP rs35280470.		VAR_034865
	Natural variant	1537	1	R → C: dbSNP rs35364414. Ref.2		VAR_010057

Sequences

	Sequence		Length	Mass (Da)
	P10071-1 [UniParc]. Last modified September 11, 2007. Version 5. Checksum: 51219D62A19AF7FE	FASTA	1,580	169,849
	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 NPAAASESPF 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 HLQPHDALGH 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

	« Hide 'large scale' referencesShow '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: 2118997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 10441342] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GCPS GLY-515; TYR-520 AND MET-808, VARIANTS GLU-440 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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS THR-183 AND PRO-998.
[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: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS THR-183 AND PRO-998.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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: 2850480] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-549.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"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: 9302279] [Abstract] Cited for: VARIANT GCPS SER-707.
[9]	"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: 10441570] [Abstract] Cited for: VARIANT PAPA1/PAPB ARG-727.
[10]	"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: 12414818] [Abstract] Cited for: VARIANT ACS PRO-934.
[11]	"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: 12794692] [Abstract] Cited for: VARIANT GCPS TRP-625.
[12]	"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: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-169 AND PRO-1304.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. 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.
UniGene	Hs.21509
3D structure databases
HSSP	HSSP built from PDB template 2GLI based on UniProtKB P08151.
ModBase	Search...
Protein-protein interaction databases
IntAct	P10071. 5 interactions.
PTM databases
PhosphoSite	P10071.
Proteomic databases
PRIDE	P10071.
Genome annotation databases
Ensembl	ENSG00000106571. Homo sapiens. [Contig view]
GeneID	2737.
KEGG	hsa:2737.
Organism-specific databases
GeneCards	GC07M041970.
HGNC	HGNC:4319. GLI3.
HPA	HPA005534.
MIM	146510. phenotype. 165240. gene. 174200. phenotype. 174700. phenotype. 175700. phenotype. 200990. phenotype. 603596. phenotype.
Orphanet	36. Acrocallosal syndrome, Schinzel type. 380. Greig syndrome. 672. Pallister-Hall syndrome. 2918. Polydactyly postaxial. 2922. Polydactyly, preaxial.
PharmGKB	PA28722.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P10071.
HOVERGEN	P10071.
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.
GermOnline	ENSG00000106571. Homo sapiens.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 1 hit.
Pfam	PF00096. zf-C2H2. 5 hits. [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 Resources
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:	September 11, 2007
Last modified:	June 16, 2009
This is version 100 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)