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Protein

Transcriptional activator GLI3

Gene

GLI3

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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'. Plays a role in limb and brain development (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri480 – 50526C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri513 – 54028C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri546 – 57025C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri576 – 60126C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri607 – 63226C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
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:
Alternative name(s):
GLI3 C-terminally truncated form
GLI3 form of 83 kDa
Short name:
GLI3-83
Gene namesi
Name:GLI3
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 Componenti: Unplaced

Subcellular locationi

  • Nucleus
  • Cytoplasm By similarity
  • Cell projectioncilium By similarity

  • 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 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15801580Transcriptional activator GLI3PRO_0000047204Add
BLAST
Chaini1 – ?Transcriptional repressor GLI3RPRO_0000406139

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei664 – 6641PhosphoserineBy similarity
Cross-linki773 – 773Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki779 – 779Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki784 – 784Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki800 – 800Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei849 – 8491Phosphoserine; by PKABy similarity
Modified residuei865 – 8651Phosphoserine; by PKABy similarity
Modified residuei877 – 8771Phosphoserine; by PKABy similarity
Modified residuei907 – 9071Phosphoserine; by PKABy similarity
Modified residuei980 – 9801Phosphoserine; by PKABy similarity
Modified residuei1006 – 10061Phosphoserine; by PKABy similarity

Post-translational modificationi

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 (By similarity).By similarity
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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ5IS56.

Interactioni

Subunit structurei

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000032656.

Structurei

3D structure databases

ProteinModelPortaliQ5IS56.
SMRiQ5IS56. Positions 479-633.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1492 – 151221Asp/Glu-rich (acidic)Add
BLAST

Sequence similaritiesi

Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri480 – 50526C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri513 – 54028C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri546 – 57025C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri576 – 60126C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri607 – 63226C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000290688.
HOVERGENiHBG005844.
InParanoidiQ5IS56.
KOiK06230.

Family and domain databases

Gene3Di3.30.160.60. 5 hits.
InterProiIPR032851. GLI3.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR19818:SF5. PTHR19818:SF5. 4 hits.
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q5IS56-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAQSHSSTT TEKKKVENSI VKCSTRTDVS EKAVASSTTS NEDESPGQTY
60 70 80 90 100
HRERRNAITM QPQNVQGLSK VSEEPSTSSD ERASLIKKEI HGSLPHVAEP
110 120 130 140 150
SVPYRGTVFA MDPRNGYMEP HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP
160 170 180 190 200
SPIPPLHMTS ALSSSPTYPD LPFIRISPHR NPAAASESPF SPPHPYINPY
210 220 230 240 250
MDYIRSLHSS PSLSMISATR GLSPTDAPHA GVSPAEYYHQ MALLTGQRSP
260 270 280 290 300
YADIIPSAAT AGTGAIHMEY LHAMDSTRFP SPRLSARPSR KRTLSISPLS
310 320 330 340 350
DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY
360 370 380 390 400
SSAPVSLHMH QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL
410 420 430 440 450
NPVQVSSGPS ESSQNKPTSE SAVSSTGDPM HNKRSKIKPD EDLPSPGARG
460 470 480 490 500
QQEQPEGTTL VKEEGDKDES KQEPEVIYET NCHWEGCARE FDTQEQLVHH
510 520 530 540 550
INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH TGEKPHKCTF
560 570 580 590 600
EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT
610 620 630 640 650
HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDIHPRP
660 670 680 690 700
PPPRDSGSHS QSRSPGRPTQ GALGEQQDLS NTTSKREECL QVKTVKAEKP
710 720 730 740 750
MTSQPSPGGQ SSCSSQQSPI SNYSNSGLEL PLTDGGSIGD LSAIDETPIM
760 770 780 790 800
DSTISTATTA LALQARRNPA GTKWMEHVKL ERLKQVNGMF PRLNPILPPK
810 820 830 840 850
APAVSPLIGN GTQSNNTCSL GGPMTLLPGR SDLSGVDVTM LNMLNRRDSS
860 870 880 890 900
ASTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST
910 920 930 940 950
DASRRSSEAS QSDGLPSLLS LTPAQQYRLK AKYAAATGGP PPTPLPNMER
960 970 980 990 1000
MSLKTRLALL GDALEPGVAL PPVHAPRRCS DGGAHGYGRR HLQPHDAPGH
1010 1020 1030 1040 1050
GVRRASDPVR TGSEGLALPR VPRFSSLSSC NPPAMATSAE KRSLVLQNYT
1060 1070 1080 1090 1100
RPEGGQSRNF HSSPCPPSIT ENVTLESLTM DADANLNDED FLPDDVVQYL
1110 1120 1130 1140 1150
NSQNQAGYEQ HFPSTLPDDS KVPHGPGDFD APGLPDSHAG QQFHALEQPC
1160 1170 1180 1190 1200
PEGSKTDLPI QWNEVSSGSA DLSSSKLKCG PRPAVPQTRA FGFCNGMVVH
1210 1220 1230 1240 1250
PQNPLRSGPA GGYQTLGENS NPYGGPEHLM LHNSPGSGTS GNAFHEQPCK
1260 1270 1280 1290 1300
APQYGNCLNR QPVAPGALDG ACGAGIQASK LKSTPMQGSG GQLNFGLPVA
1310 1320 1330 1340 1350
PNESAGSMVN GMQNQDPVGQ GYLAHQLLGD SMQHPGAGRP GQQMLGQISA
1360 1370 1380 1390 1400
TSHINIYQGP ESCLPGAHGM GSQPSSLAVV RGYQPCASFG GSRRQAMPRD
1410 1420 1430 1440 1450
SLALQSGQLS DTSQTCRVNG IKMEMKGQPH PLCSNLQNYS GQFYDQTVGF
1460 1470 1480 1490 1500
SQQDTKAGSF SISDASCLLQ GTSAKNSELL SPGANQVTST VDSLDSHDLE
1510 1520 1530 1540 1550
GVQIDFDAII DDGDHSSLMS GALSPSIIQN LSYSSSRLTT PRASLPFPAL
1560 1570 1580
SMSTTNMAIG DMSSLLTSLA EESKFLAVMQ
Length:1,580
Mass (Da):169,899
Last modified:February 15, 2005 - v1
Checksum:i1901B7A83403B11B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY665272 mRNA. Translation: AAV74310.1.
RefSeqiNP_001029362.1. NM_001034190.1.
UniGeneiPtr.6521.

Genome annotation databases

GeneIDi463369.
KEGGiptr:463369.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY665272 mRNA. Translation: AAV74310.1.
RefSeqiNP_001029362.1. NM_001034190.1.
UniGeneiPtr.6521.

3D structure databases

ProteinModelPortaliQ5IS56.
SMRiQ5IS56. Positions 479-633.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000032656.

Proteomic databases

PaxDbiQ5IS56.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi463369.
KEGGiptr:463369.

Organism-specific databases

CTDi2737.

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000290688.
HOVERGENiHBG005844.
InParanoidiQ5IS56.
KOiK06230.

Family and domain databases

Gene3Di3.30.160.60. 5 hits.
InterProiIPR032851. GLI3.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR19818:SF5. PTHR19818:SF5. 4 hits.
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 5 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Accelerated evolution of nervous system genes in the origin of Homo sapiens."
    Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L., Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.
    Cell 119:1027-1040(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiGLI3_PANTR
AccessioniPrimary (citable) accession number: Q5IS56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: February 15, 2005
Last modified: July 6, 2016
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.