GLI1_HUMAN
ID GLI1_HUMAN Reviewed; 1106 AA.
AC P08151; D0EUY3; E9PQQ9; F5H6H8; Q8TDN9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Zinc finger protein GLI1;
DE AltName: Full=Glioma-associated oncogene;
DE AltName: Full=Oncogene GLI;
GN Name=GLI1; Synonyms=GLI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2832761; DOI=10.1038/332371a0;
RA Kinzler K.W., Ruppert J.M., Bigner S.H., Vogelstein B.;
RT "The GLI gene is a member of the Kruppel family of zinc finger proteins.";
RL Nature 332:371-374(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-933 AND GLN-1100.
RA Yoon J.W., Kent P., Clark A., Patterson J., Villavicencio E.,
RA Iannaccone P., Walterhouse D.;
RT "Polymorphic variants of the human oncogene GLI1 function similarly.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, FUNCTION,
RP SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=19706761; DOI=10.1158/0008-5472.can-09-0886;
RA Lo H.W., Zhu H., Cao X., Aldrich A., Ali-Osman F.;
RT "A novel splice variant of GLI1 that promotes glioblastoma cell migration
RT and invasion.";
RL Cancer Res. 69:6790-6798(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=2105456; DOI=10.1128/mcb.10.2.634-642.1990;
RA Kinzler K.W., Vogelstein B.;
RT "The GLI gene encodes a nuclear protein which binds specific sequences in
RT the human genome.";
RL Mol. Cell. Biol. 10:634-642(1990).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STK36 AND SUFU.
RX PubMed=10806483; DOI=10.1038/35010610;
RA Murone M., Luoh S.-L., Stone D., Li W., Gurney A., Armanini M., Grey C.,
RA Rosenthal A., de Sauvage F.J.;
RT "Gli regulation by the opposing activities of fused and suppressor of
RT fused.";
RL Nat. Cell Biol. 2:310-312(2000).
RN [8]
RP FUNCTION, INTERACTION WITH ZIC1, AND SUBCELLULAR LOCATION.
RX PubMed=11238441; DOI=10.1074/jbc.c000773200;
RA Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.;
RT "Physical and functional interactions between Zic and Gli proteins.";
RL J. Biol. Chem. 276:6889-6892(2001).
RN [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND FUNCTION.
RX PubMed=19878745; DOI=10.1016/j.yexcr.2009.10.018;
RA Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.;
RT "Identification of a novel serine/threonine kinase ULK3 as a positive
RT regulator of Hedgehog pathway.";
RL Exp. Cell Res. 316:627-637(2010).
RN [10]
RP ACETYLATION AT LYS-518.
RX PubMed=20081843; DOI=10.1038/ncb2013;
RA Canettieri G., Di Marcotullio L., Greco A., Coni S., Antonucci L.,
RA Infante P., Pietrosanti L., De Smaele E., Ferretti E., Miele E.,
RA Pelloni M., De Simone G., Pedone E.M., Gallinari P., Giorgi A.,
RA Steinkuhler C., Vitagliano L., Pedone C., Schinin M.E., Screpanti I.,
RA Gulino A.;
RT "Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay
RT regulates Hedgehog signalling through Gli acetylation.";
RL Nat. Cell Biol. 12:132-142(2010).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=24076122; DOI=10.1016/j.bbrc.2013.09.090;
RA Gilder A.S., Chen Y.B., Jackson R.J. III, Jiang J., Maher J.F.;
RT "Fem1b promotes ubiquitylation and suppresses transcriptional activity of
RT Gli1.";
RL Biochem. Biophys. Res. Commun. 440:431-436(2013).
RN [12]
RP INTERACTION WITH SUFU.
RX PubMed=28965847; DOI=10.1016/j.ajhg.2017.08.017;
RA De Mori R., Romani M., D'Arrigo S., Zaki M.S., Lorefice E., Tardivo S.,
RA Biagini T., Stanley V., Musaev D., Fluss J., Micalizzi A., Nuovo S.,
RA Illi B., Chiapparini L., Di Marcotullio L., Issa M.Y., Anello D.,
RA Casella A., Ginevrino M., Leggins A.S., Roosing S., Alfonsi R., Rosati J.,
RA Schot R., Mancini G.M.S., Bertini E., Dobyns W.B., Mazza T., Gleeson J.G.,
RA Valente E.M.;
RT "Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway
RT and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.";
RL Am. J. Hum. Genet. 101:552-563(2017).
RN [13]
RP FUNCTION, INVOLVEMENT IN PAPA8, VARIANTS PAPA8 113-ARG--ALA-1106 DEL;
RP 644-GLN--ALA-1106 DEL AND 780-TRP--ALA-1106 DEL, AND CHARACTERIZATION OF
RP VARIANT 780-TRP--ALA-1106 DEL.
RX PubMed=28973407; DOI=10.1093/hmg/ddx335;
RA Palencia-Campos A., Ullah A., Nevado J., Yildirim R., Unal E., Ciorraga M.,
RA Barruz P., Chico L., Piceci-Sparascio F., Guida V., De Luca A.,
RA Kayserili H., Ullah I., Burmeister M., Lapunzina P., Ahmad W.,
RA Morales A.V., Ruiz-Perez V.L.;
RT "GLI1 inactivation is associated with developmental phenotypes overlapping
RT with Ellis-van Creveld syndrome.";
RL Hum. Mol. Genet. 26:4556-4571(2017).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1003, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 234-388 IN COMPLEX WITH DNA, AND
RP DNA-BINDING.
RX PubMed=8378770; DOI=10.1126/science.8378770;
RA Pavletich N.P., Pabo C.O.;
RT "Crystal structure of a five-finger GLI-DNA complex: new perspectives on
RT zinc fingers.";
RL Science 261:1701-1707(1993).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 115-131 IN COMPLEX WITH SUFU,
RP INTERACTION WITH SUFU, AND FUNCTION.
RX PubMed=24311597; DOI=10.1107/s0907444913028473;
RA Cherry A.L., Finta C., Karlstrom M., Jin Q., Schwend T., Astorga-Wells J.,
RA Zubarev R.A., Del Campo M., Criswell A.R., de Sanctis D., Jovine L.,
RA Toftgard R.;
RT "Structural basis of SUFU-GLI interaction in human Hedgehog signalling
RT regulation.";
RL Acta Crystallogr. D 69:2563-2579(2013).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 112-128 IN COMPLEX WITH SUFU,
RP INTERACTION WITH SUFU, AND FUNCTION.
RX PubMed=24217340; DOI=10.1038/ncomms3608;
RA Zhang Y., Fu L., Qi X., Zhang Z., Xia Y., Jia J., Jiang J., Zhao Y., Wu G.;
RT "Structural insight into the mutual recognition and regulation between
RT Suppressor of Fused and Gli/Ci.";
RL Nat. Commun. 4:2608-2608(2013).
RN [18]
RP VARIANTS ALA-884; ASP-933 AND GLN-1100.
RX PubMed=10951255; DOI=10.1046/j.1523-1747.2000.00065.x;
RA Wang X.Q., Chan N., Rothnagel J.A.;
RT "Identification of polymorphic variants of the GLI1 oncogene.";
RL J. Invest. Dermatol. 115:328-329(2000).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] ALA-210; ILE-514 AND GLN-817.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [20]
RP VARIANT PPD1 GLN-506, AND INVOLVEMENT IN PPD1.
RX PubMed=30620395; DOI=10.1111/cge.13495;
RA Ullah A., Umair M., Majeed A.I., Abdullah Jan A., Ahmad W.;
RT "A novel homozygous sequence variant in GLI1 underlies first case of
RT autosomal recessive pre-axial polydactyly.";
RL Clin. Genet. 95:540-541(2019).
CC -!- FUNCTION: Acts as a transcriptional activator (PubMed:19706761,
CC PubMed:10806483, PubMed:19878745, PubMed:24076122, PubMed:24311597,
CC PubMed:24217340). Binds to the DNA consensus sequence 5'-GACCACCCA-3'
CC (PubMed:2105456, PubMed:8378770, PubMed:24217340). Regulates the
CC transcription of specific genes during normal development
CC (PubMed:19706761). Plays a role in craniofacial development and digital
CC development, as well as development of the central nervous system and
CC gastrointestinal tract. Mediates SHH signaling (PubMed:19706761,
CC PubMed:28973407). Plays a role in cell proliferation and
CC differentiation via its role in SHH signaling (PubMed:11238441,
CC PubMed:28973407). {ECO:0000269|PubMed:10806483,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761,
CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456,
CC ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:24217340,
CC ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:28973407,
CC ECO:0000269|PubMed:8378770}.
CC -!- FUNCTION: [Isoform 2]: Acts as a transcriptional activator, but
CC activates a different set of genes than isoform 1. Activates expression
CC of CD24, unlike isoform 1. Mediates SHH signaling. Promotes cancer cell
CC migration. {ECO:0000269|PubMed:19706761}.
CC -!- SUBUNIT: Interacts with KIF7 (By similarity). Interacts with STK36
CC (PubMed:10806483). Interacts with ZIC1; the interaction enhances
CC transcription activation (PubMed:11238441). Interacts with SUFU; this
CC inhibits transcriptional activation by GLI1 (PubMed:10806483,
CC PubMed:24311597, PubMed:24217340, PubMed:28965847).
CC {ECO:0000250|UniProtKB:P47806, ECO:0000269|PubMed:10806483,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:24217340,
CC ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:28965847}.
CC -!- INTERACTION:
CC P08151; P29972: AQP1; NbExp=3; IntAct=EBI-308084, EBI-745213;
CC P08151; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-308084, EBI-744545;
CC P08151; P53673: CRYBA4; NbExp=3; IntAct=EBI-308084, EBI-7519711;
CC P08151; Q96CN9: GCC1; NbExp=3; IntAct=EBI-308084, EBI-746252;
CC P08151; Q96J02: ITCH; NbExp=4; IntAct=EBI-308084, EBI-1564678;
CC P08151; Q13526: PIN1; NbExp=3; IntAct=EBI-308084, EBI-714158;
CC P08151; P54646: PRKAA2; NbExp=3; IntAct=EBI-308084, EBI-1383852;
CC P08151; P23443: RPS6KB1; NbExp=4; IntAct=EBI-308084, EBI-1775921;
CC P08151; P23443-2: RPS6KB1; NbExp=2; IntAct=EBI-308084, EBI-6093204;
CC P08151; Q9UMX1: SUFU; NbExp=27; IntAct=EBI-308084, EBI-740595;
CC P08151; Q9UMX1-1: SUFU; NbExp=2; IntAct=EBI-308084, EBI-740615;
CC P08151; Q9UMX1-2: SUFU; NbExp=4; IntAct=EBI-308084, EBI-740621;
CC P08151; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-308084, EBI-5235829;
CC P08151; P40337-1: VHL; NbExp=2; IntAct=EBI-308084, EBI-3504450;
CC P08151; P40337-3: VHL; NbExp=2; IntAct=EBI-308084, EBI-301270;
CC P08151; Q9QZS3-2: Numb; Xeno; NbExp=4; IntAct=EBI-308084, EBI-3896014;
CC P08151; P46684: Zic1; Xeno; NbExp=2; IntAct=EBI-308084, EBI-308006;
CC P08151-1; P41743: PRKCI; NbExp=3; IntAct=EBI-16038799, EBI-286199;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10806483,
CC ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745,
CC ECO:0000269|PubMed:24076122}. Nucleus {ECO:0000269|PubMed:10806483,
CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761,
CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456}. Note=Tethered
CC in the cytoplasm by binding to SUFU (PubMed:10806483). Activation and
CC translocation to the nucleus is promoted by interaction with STK36
CC (PubMed:10806483). Phosphorylation by ULK3 may promote nuclear
CC localization (PubMed:19878745). Translocation to the nucleus is
CC promoted by interaction with ZIC1 (PubMed:11238441).
CC {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441,
CC ECO:0000269|PubMed:19878745}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:19706761}. Nucleus {ECO:0000269|PubMed:19706761}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P08151-1; Sequence=Displayed;
CC Name=2; Synonyms=tGLI1;
CC IsoId=P08151-2; Sequence=VSP_042215;
CC Name=3;
CC IsoId=P08151-3; Sequence=VSP_054829;
CC -!- TISSUE SPECIFICITY: Detected in testis (at protein level)
CC (PubMed:2105456). Testis, myometrium and fallopian tube. Also expressed
CC in the brain with highest expression in the cerebellum, optic nerve and
CC olfactory tract (PubMed:19878745). Isoform 1 is detected in brain,
CC spleen, pancreas, liver, kidney and placenta; isoform 2 is not
CC detectable in these tissues (PubMed:19706761).
CC {ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745,
CC ECO:0000269|PubMed:2105456}.
CC -!- INDUCTION: Isoform 1 and isoform 2 are amplified in glioblastoma cells.
CC {ECO:0000269|PubMed:19706761}.
CC -!- PTM: Phosphorylated in vitro by ULK3. {ECO:0000269|PubMed:19878745}.
CC -!- PTM: Acetylation at Lys-518 down-regulates transcriptional activity.
CC Deacetylated by HDAC1. {ECO:0000269|PubMed:20081843}.
CC -!- PTM: Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1
CC transcriptional activator activity. {ECO:0000269|PubMed:24076122}.
CC -!- DISEASE: Polydactyly, postaxial, A8 (PAPA8) [MIM:618123]: A form of
CC postaxial polydactyly, a condition characterized by the occurrence of
CC supernumerary digits in the upper and/or lower extremities. In
CC postaxial polydactyly type A, the extra digit is well-formed and
CC articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is
CC an autosomal recessive condition characterized by the presence of
CC postaxial extra digits (hexadactyly) on the hands and/or the feet.
CC {ECO:0000269|PubMed:28973407}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Polydactyly, preaxial 1 (PPD1) [MIM:174400]: A form of
CC polydactyly, a condition defined by the occurrence of supernumerary
CC digits in the upper and/or lower extremities. Preaxial or radial
CC polydactyly refers to the presence of extra digits on the radial side
CC of the hand. PPD1 is an autosomal recessive form characterized by
CC duplication of the distal phalanx of the thumb.
CC {ECO:0000269|PubMed:30620395}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Undetectable in normal cells but highly
CC expressed in cancer cells. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GLIID310ch12q13.html";
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DR EMBL; X07384; CAA30297.1; -; mRNA.
DR EMBL; AF316573; AAM13391.1; -; Genomic_DNA.
DR EMBL; GQ890670; ACX35434.1; -; mRNA.
DR EMBL; AC022506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013000; AAH13000.1; -; mRNA.
DR CCDS; CCDS53806.1; -. [P08151-2]
DR CCDS; CCDS53807.1; -. [P08151-3]
DR CCDS; CCDS8940.1; -. [P08151-1]
DR PIR; S00672; TVHUGL.
DR RefSeq; NP_001153517.1; NM_001160045.1. [P08151-3]
DR RefSeq; NP_001161081.1; NM_001167609.1. [P08151-2]
DR RefSeq; NP_005260.1; NM_005269.2. [P08151-1]
DR RefSeq; XP_011536491.1; XM_011538189.2. [P08151-1]
DR PDB; 2GLI; X-ray; 2.60 A; A=234-388.
DR PDB; 4BLB; X-ray; 2.80 A; E/F/G/H=115-131.
DR PDB; 4KMD; X-ray; 1.70 A; B=112-128.
DR PDB; 5OM0; X-ray; 3.20 A; A/B=637-645.
DR PDBsum; 2GLI; -.
DR PDBsum; 4BLB; -.
DR PDBsum; 4KMD; -.
DR PDBsum; 5OM0; -.
DR AlphaFoldDB; P08151; -.
DR SMR; P08151; -.
DR BioGRID; 108997; 125.
DR ComplexPortal; CPX-56; GLI1-SUFU complex.
DR DIP; DIP-32536N; -.
DR ELM; P08151; -.
DR IntAct; P08151; 46.
DR MINT; P08151; -.
DR STRING; 9606.ENSP00000228682; -.
DR BindingDB; P08151; -.
DR ChEMBL; CHEMBL5461; -.
DR GlyGen; P08151; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P08151; -.
DR PhosphoSitePlus; P08151; -.
DR BioMuta; GLI1; -.
DR DMDM; 121323; -.
DR EPD; P08151; -.
DR jPOST; P08151; -.
DR MassIVE; P08151; -.
DR MaxQB; P08151; -.
DR PaxDb; P08151; -.
DR PeptideAtlas; P08151; -.
DR PRIDE; P08151; -.
DR ProteomicsDB; 27194; -.
DR ProteomicsDB; 52074; -. [P08151-1]
DR ProteomicsDB; 52075; -. [P08151-2]
DR Antibodypedia; 4004; 871 antibodies from 44 providers.
DR DNASU; 2735; -.
DR Ensembl; ENST00000228682.7; ENSP00000228682.2; ENSG00000111087.10. [P08151-1]
DR Ensembl; ENST00000528467.1; ENSP00000434408.1; ENSG00000111087.10. [P08151-2]
DR Ensembl; ENST00000543426.5; ENSP00000437607.1; ENSG00000111087.10. [P08151-3]
DR Ensembl; ENST00000546141.5; ENSP00000441006.1; ENSG00000111087.10. [P08151-2]
DR GeneID; 2735; -.
DR KEGG; hsa:2735; -.
DR MANE-Select; ENST00000228682.7; ENSP00000228682.2; NM_005269.3; NP_005260.1.
DR UCSC; uc001snx.4; human. [P08151-1]
DR CTD; 2735; -.
DR DisGeNET; 2735; -.
DR GeneCards; GLI1; -.
DR HGNC; HGNC:4317; GLI1.
DR HPA; ENSG00000111087; Tissue enhanced (cervix).
DR MalaCards; GLI1; -.
DR MIM; 165220; gene.
DR MIM; 174400; phenotype.
DR MIM; 618123; phenotype.
DR neXtProt; NX_P08151; -.
DR OpenTargets; ENSG00000111087; -.
DR Orphanet; 289; Ellis Van Creveld syndrome.
DR Orphanet; 93339; Polydactyly of a biphalangeal thumb.
DR Orphanet; 93334; Postaxial polydactyly type A.
DR Orphanet; 93335; Postaxial polydactyly type B.
DR PharmGKB; PA28720; -.
DR VEuPathDB; HostDB:ENSG00000111087; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160235; -.
DR HOGENOM; CLU_003666_0_0_1; -.
DR InParanoid; P08151; -.
DR OMA; CTEAPLF; -.
DR OrthoDB; 135929at2759; -.
DR PhylomeDB; P08151; -.
DR TreeFam; TF350216; -.
DR PathwayCommons; P08151; -.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635851; GLI proteins bind promoters of Hh responsive genes to promote transcription.
DR SignaLink; P08151; -.
DR SIGNOR; P08151; -.
DR BioGRID-ORCS; 2735; 29 hits in 1096 CRISPR screens.
DR EvolutionaryTrace; P08151; -.
DR GeneWiki; GLI1; -.
DR GenomeRNAi; 2735; -.
DR Pharos; P08151; Tchem.
DR PRO; PR:P08151; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P08151; protein.
DR Bgee; ENSG00000111087; Expressed in tibial nerve and 127 other tissues.
DR ExpressionAtlas; P08151; baseline and differential.
DR Genevisible; P08151; HS.
DR GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR GO; GO:0097546; C:ciliary base; TAS:Reactome.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1990788; C:GLI-SUFU complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; NAS:BHF-UCL.
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:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0021696; P:cerebellar cortex morphogenesis; IEA:Ensembl.
DR GO; GO:0048546; P:digestive tract morphogenesis; TAS:BHF-UCL.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0009913; P:epidermal cell differentiation; IDA:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:1990787; P:negative regulation of hh target transcription factor activity; IDA:ComplexPortal.
DR GO; GO:0060032; P:notochord regression; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IDA:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:2000345; P:regulation of hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; TAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0021938; P:smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR GO; GO:0007418; P:ventral midline development; IEA:Ensembl.
DR InterPro; IPR043359; GLI-like.
DR InterPro; IPR032850; GLI1.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR45718; PTHR45718; 2.
DR PANTHER; PTHR45718:SF2; PTHR45718:SF2; 2.
DR Pfam; PF00096; zf-C2H2; 3.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1106
FT /note="Zinc finger protein GLI1"
FT /id="PRO_0000047197"
FT ZN_FING 235..260
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 268..295
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 301..325
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 331..356
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 362..387
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..20
FT /note="SNAG domain"
FT /evidence="ECO:0000250"
FT REGION 120..124
FT /note="Interaction with SUFU"
FT /evidence="ECO:0000269|PubMed:24217340,
FT ECO:0000269|PubMed:24311597"
FT REGION 283..291
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:8378770"
FT REGION 345..350
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:8378770"
FT REGION 375..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 375..381
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:8378770"
FT REGION 516..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..792
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 817..889
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 914..942
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1054..1087
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..402
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..426
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..770
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 837..876
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 927..942
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 518
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20081843"
FT CROSSLNK 1003
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..128
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054829"
FT VAR_SEQ 34..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19706761"
FT /id="VSP_042215"
FT VARIANT 113..1106
FT /note="Missing (in PAPA8)"
FT /evidence="ECO:0000269|PubMed:28973407"
FT /id="VAR_081480"
FT VARIANT 210
FT /note="P -> A (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035557"
FT VARIANT 506
FT /note="L -> Q (in PPD1; unknown pathological significance;
FT dbSNP:rs753690500)"
FT /evidence="ECO:0000269|PubMed:30620395"
FT /id="VAR_082590"
FT VARIANT 514
FT /note="T -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035558"
FT VARIANT 644..1106
FT /note="Missing (in PAPA8)"
FT /evidence="ECO:0000269|PubMed:28973407"
FT /id="VAR_081481"
FT VARIANT 780..1106
FT /note="Missing (in PAPA8; decreased transcriptional
FT activity; reduced expression of the GLI1 target PTCH1
FT observed in patient fibroblasts after chemical induction of
FT the hedgehog pathway)"
FT /evidence="ECO:0000269|PubMed:28973407"
FT /id="VAR_081482"
FT VARIANT 817
FT /note="E -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035559"
FT VARIANT 884
FT /note="D -> A"
FT /evidence="ECO:0000269|PubMed:10951255"
FT /id="VAR_015114"
FT VARIANT 933
FT /note="G -> D (in dbSNP:rs2228224)"
FT /evidence="ECO:0000269|PubMed:10951255, ECO:0000269|Ref.2"
FT /id="VAR_015115"
FT VARIANT 1012
FT /note="G -> V (in dbSNP:rs2229300)"
FT /id="VAR_052723"
FT VARIANT 1100
FT /note="E -> Q (in dbSNP:rs2228226)"
FT /evidence="ECO:0000269|PubMed:10951255, ECO:0000269|Ref.2"
FT /id="VAR_015116"
FT CONFLICT 1106
FT /note="A -> AS (in Ref. 3; ACX35434)"
FT /evidence="ECO:0000305"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:4KMD"
FT HELIX 249..259
FT /evidence="ECO:0007829|PDB:2GLI"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:2GLI"
FT TURN 276..279
FT /evidence="ECO:0007829|PDB:2GLI"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:2GLI"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:2GLI"
FT HELIX 315..324
FT /evidence="ECO:0007829|PDB:2GLI"
FT STRAND 341..346
FT /evidence="ECO:0007829|PDB:2GLI"
FT HELIX 349..354
FT /evidence="ECO:0007829|PDB:2GLI"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:2GLI"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:2GLI"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:2GLI"
FT TURN 382..384
FT /evidence="ECO:0007829|PDB:2GLI"
SQ SEQUENCE 1106 AA; 117904 MW; E29B11D1A6CD3D91 CRC64;
MFNSMTPPPI SSYGEPCCLR PLPSQGAPSV GTEGLSGPPF CHQANLMSGP HSYGPARETN
SCTEGPLFSS PRSAVKLTKK RALSISPLSD ASLDLQTVIR TSPSSLVAFI NSRCTSPGGS
YGHLSIGTMS PSLGFPAQMN HQKGPSPSFG VQPCGPHDSA RGGMIPHPQS RGPFPTCQLK
SELDMLVGKC REEPLEGDMS SPNSTGIQDP LLGMLDGRED LEREEKREPE SVYETDCRWD
GCSQEFDSQE QLVHHINSEH IHGERKEFVC HWGGCSRELR PFKAQYMLVV HMRRHTGEKP
HKCTFEGCRK SYSRLENLKT HLRSHTGEKP YMCEHEGCSK AFSNASDRAK HQNRTHSNEK
PYVCKLPGCT KRYTDPSSLR KHVKTVHGPD AHVTKRHRGD GPLPRAPSIS TVEPKREREG
GPIREESRLT VPEGAMKPQP SPGAQSSCSS DHSPAGSAAN TDSGVEMTGN AGGSTEDLSS
LDEGPCIAGT GLSTLRRLEN LRLDQLHQLR PIGTRGLKLP SLSHTGTTVS RRVGPPVSLE
RRSSSSSSIS SAYTVSRRSS LASPFPPGSP PENGASSLPG LMPAQHYLLR ARYASARGGG
TSPTAASSLD RIGGLPMPPW RSRAEYPGYN PNAGVTRRAS DPAQAADRPA PARVQRFKSL
GCVHTPPTVA GGGQNFDPYL PTSVYSPQPP SITENAAMDA RGLQEEPEVG TSMVGSGLNP
YMDFPPTDTL GYGGPEGAAA EPYGARGPGS LPLGPGPPTN YGPNPCPQQA SYPDPTQETW
GEFPSHSGLY PGPKALGGTY SQCPRLEHYG QVQVKPEQGC PVGSDSTGLA PCLNAHPSEG
PPHPQPLFSH YPQPSPPQYL QSGPYTQPPP DYLPSEPRPC LDFDSPTHST GQLKAQLVCN
YVQSQQELLW EGGGREDAPA QEPSYQSPKF LGGSQVSPSR AKAPVNTYGP GFGPNLPNHK
SGSYPTPSPC HENFVVGANR ASHRAAAPPR LLPPLPTCYG PLKVGGTNPS CGHPEVGRLG
GGPALYPPPE GQVCNPLDSL DLDNTQLDFV AILDEPQGLS PPPSHDQRGS SGHTPPPSGP
PNMAVGNMSV LLRSLPGETE FLNSSA
