GLI3_PANTR
ID GLI3_PANTR Reviewed; 1580 AA.
AC Q5IS56;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Transcriptional activator GLI3;
DE AltName: Full=GLI3 form of 190 kDa;
DE Short=GLI3-190;
DE AltName: Full=GLI3 full-length protein;
DE Short=GLI3FL;
DE Contains:
DE RecName: Full=Transcriptional repressor GLI3R;
DE AltName: Full=GLI3 C-terminally truncated form;
DE AltName: Full=GLI3 form of 83 kDa;
DE Short=GLI3-83;
GN Name=GLI3;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
CC -!- FUNCTION: Has a dual function as a transcriptional activator and a
CC repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb
CC development. The full-length GLI3 form (GLI3FL) after phosphorylation
CC and nuclear translocation, acts as an activator (GLI3A) while GLI3R,
CC its C-terminally truncated form, acts as a repressor. A proper balance
CC between the GLI3 activator and the repressor GLI3R, rather than the
CC repressor gradient itself or the activator/repressor ratio gradient,
CC specifies limb digit number and identity. In concert with TRPS1, plays
CC a role in regulating the size of the zone of distal chondrocytes, in
CC restricting the zone of PTHLH expression in distal cells and in
CC activating chondrocyte proliferation. Binds to the minimal GLI-
CC consensus sequence 5'-GGGTGGTC-3'. Plays a role in limb and brain
CC development (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: The full-length GLI3 form (GLI3FL) interacts with SUFU and
CC this interaction regulates the formation of either repressor or
CC activator forms of GLI3. Its association with SUFU is regulated by Hh
CC signaling and dissociation of the SUFU-GLI3 interaction requires the
CC presence of the ciliary motor KIF3A (By similarity). Interacts with
CC KIF7. The activator form of GLI3 (GLI3A) but not the repressor form
CC (GLI3R) can interact with TRPS1. The phosphorylated form interacts with
CC BTRC. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains
CC 3, 4 and 5); the interaction enhances its transcriptional activity (By
CC similarity). Interacts with WRD11; the interaction associates EMX1 with
CC GLI3 (By similarity). Interacts with DZIP1; retains GLI3 within the
CC cytoplasm (By similarity). {ECO:0000250|UniProtKB:P10071,
CC ECO:0000250|UniProtKB:Q61602}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Cell
CC projection, cilium {ECO:0000250}. Note=GLI3FL is localized
CC predominantly in the cytoplasm while GLI3R resides mainly in the
CC nucleus. Ciliary accumulation requires the presence of KIF7 and SMO.
CC Translocation to the nucleus is promoted by interaction with ZIC1 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on multiple sites by protein kinase A (PKA) and
CC phosphorylation by PKA primes further phosphorylation by CK1 and GSK3.
CC Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for
CC its proteolytic processing (By similarity). {ECO:0000250}.
CC -!- PTM: Transcriptional repressor GLI3R, a C-terminally truncated form, is
CC generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through
CC proteolytic processing. This process requires PKA-primed
CC phosphorylation of GLI3, ubiquitination of GLI3 and the presence of
CC BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained
CC in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is
CC recruited to cilia, leading to the efficient processing of GLI3FL into
CC GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it
CC to translocate into the nucleus, and repress Hh target genes. When Hh
CC signaling is initiated, SUFU dissociates from GLI3FL and this has two
CC consequences. First, GLI3R production is halted. Second, free GLI3FL
CC translocates to the nucleus, where it is phosphorylated, destabilized,
CC and converted to a transcriptional activator (GLI3A). Phosphorylated in
CC vitro by ULK3 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AY665272; AAV74310.1; -; mRNA.
DR RefSeq; NP_001029362.1; NM_001034190.1.
DR AlphaFoldDB; Q5IS56; -.
DR SMR; Q5IS56; -.
DR STRING; 9598.ENSPTRP00000032656; -.
DR PaxDb; Q5IS56; -.
DR GeneID; 463369; -.
DR KEGG; ptr:463369; -.
DR CTD; 2737; -.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; Q5IS56; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:InterPro.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:InterPro.
DR GO; GO:0048568; P:embryonic organ development; IEA:InterPro.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; IBA:GO_Central.
DR InterPro; IPR043359; GLI-like.
DR InterPro; IPR032851; GLI3.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR45718; PTHR45718; 1.
DR PANTHER; PTHR45718:SF5; PTHR45718:SF5; 1.
DR Pfam; PF00096; zf-C2H2; 4.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Cell projection; Cilium; Cytoplasm; DNA-binding;
KW Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1580
FT /note="Transcriptional activator GLI3"
FT /id="PRO_0000047204"
FT CHAIN 1..?
FT /note="Transcriptional repressor GLI3R"
FT /id="PRO_0000406139"
FT ZN_FING 480..505
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 513..540
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 546..570
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 576..601
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 607..632
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..845
FT /note="Mediates interaction with DZIP1"
FT /evidence="ECO:0000250|UniProtKB:Q61602"
FT REGION 863..918
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 981..1042
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 620..652
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..688
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 697..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 983..1003
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1024..1042
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 175
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q61602"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 849
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 865
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 877
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 907
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 980
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT MOD_RES 1006
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 462
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 773
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 779
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 779
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 784
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10071"
FT CROSSLNK 800
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10071"
SQ SEQUENCE 1580 AA; 169899 MW; 1901B7A83403B11B CRC64;
MEAQSHSSTT TEKKKVENSI VKCSTRTDVS EKAVASSTTS NEDESPGQTY HRERRNAITM
QPQNVQGLSK VSEEPSTSSD ERASLIKKEI HGSLPHVAEP SVPYRGTVFA MDPRNGYMEP
HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP SPIPPLHMTS ALSSSPTYPD LPFIRISPHR
NPAAASESPF SPPHPYINPY MDYIRSLHSS PSLSMISATR GLSPTDAPHA GVSPAEYYHQ
MALLTGQRSP YADIIPSAAT AGTGAIHMEY LHAMDSTRFP SPRLSARPSR KRTLSISPLS
DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY SSAPVSLHMH
QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL NPVQVSSGPS ESSQNKPTSE
SAVSSTGDPM HNKRSKIKPD EDLPSPGARG QQEQPEGTTL VKEEGDKDES KQEPEVIYET
NCHWEGCARE FDTQEQLVHH INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH
TGEKPHKCTF EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT
HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDIHPRP PPPRDSGSHS
QSRSPGRPTQ GALGEQQDLS NTTSKREECL QVKTVKAEKP MTSQPSPGGQ SSCSSQQSPI
SNYSNSGLEL PLTDGGSIGD LSAIDETPIM DSTISTATTA LALQARRNPA GTKWMEHVKL
ERLKQVNGMF PRLNPILPPK APAVSPLIGN GTQSNNTCSL GGPMTLLPGR SDLSGVDVTM
LNMLNRRDSS ASTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST
DASRRSSEAS QSDGLPSLLS LTPAQQYRLK AKYAAATGGP PPTPLPNMER MSLKTRLALL
GDALEPGVAL PPVHAPRRCS DGGAHGYGRR HLQPHDAPGH GVRRASDPVR TGSEGLALPR
VPRFSSLSSC NPPAMATSAE KRSLVLQNYT RPEGGQSRNF HSSPCPPSIT ENVTLESLTM
DADANLNDED FLPDDVVQYL NSQNQAGYEQ HFPSTLPDDS KVPHGPGDFD APGLPDSHAG
QQFHALEQPC PEGSKTDLPI QWNEVSSGSA DLSSSKLKCG PRPAVPQTRA FGFCNGMVVH
PQNPLRSGPA GGYQTLGENS NPYGGPEHLM LHNSPGSGTS GNAFHEQPCK APQYGNCLNR
QPVAPGALDG ACGAGIQASK LKSTPMQGSG GQLNFGLPVA PNESAGSMVN GMQNQDPVGQ
GYLAHQLLGD SMQHPGAGRP GQQMLGQISA TSHINIYQGP ESCLPGAHGM GSQPSSLAVV
RGYQPCASFG GSRRQAMPRD SLALQSGQLS DTSQTCRVNG IKMEMKGQPH PLCSNLQNYS
GQFYDQTVGF SQQDTKAGSF SISDASCLLQ GTSAKNSELL SPGANQVTST VDSLDSHDLE
GVQIDFDAII DDGDHSSLMS GALSPSIIQN LSYSSSRLTT PRASLPFPAL SMSTTNMAIG
DMSSLLTSLA EESKFLAVMQ
