ID GLI2_HUMAN Reviewed; 1586 AA. AC P10070; O60252; O60253; O60254; O60255; Q15590; Q15591; Q4JHT4; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 4. DT 27-MAR-2024, entry version 230. DE RecName: Full=Zinc finger protein GLI2 {ECO:0000305}; DE AltName: Full=GLI family zinc finger protein 2 {ECO:0000312|HGNC:HGNC:4318}; DE AltName: Full=Tax helper protein {ECO:0000303|PubMed:9557682}; GN Name=GLI2 {ECO:0000312|HGNC:HGNC:4318}; GN Synonyms=THP {ECO:0000303|PubMed:9557682}; 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] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, DNA-BINDING, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANTS SER-1156 AND RP ASN-1306. RX PubMed=9557682; DOI=10.1128/jvi.72.5.3958-3964.1998; RA Tanimura A., Dan S., Yoshida M.; RT "Cloning of novel isoforms of the human Gli2 oncogene and their activities RT to enhance tax-dependent transcription of the human T-cell leukemia virus RT type 1 genome."; RL J. Virol. 72:3958-3964(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, AND INVOLVEMENT IN CJS. RX PubMed=15994174; DOI=10.1093/hmg/ddi222; RA Roessler E., Ermilov A.N., Grange D.K., Wang A., Grachtchouk M., RA Dlugosz A.A., Muenke M.; RT "A previously unidentified amino-terminal domain regulates transcriptional RT activity of wild-type and disease-associated human GLI2."; RL Hum. Mol. Genet. 14:2181-2188(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-857 (ISOFORMS 1; 2; 3 AND 4). RX PubMed=8350401; DOI=10.1128/jvi.67.9.5375-5382.1993; RA Tanimura A., Teshima H., Fujisawa J., Yoshida M.; RT "A new regulatory element that augments the Tax-dependent enhancer of human RT T-cell leukemia virus type 1 and cloning of cDNAs encoding its binding RT proteins."; RL J. Virol. 67:5375-5382(1993). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 456-560 (ISOFORMS 1; 2; 3 AND 4). RX PubMed=2850480; DOI=10.1128/mcb.8.8.3104-3113.1988; RA Ruppert J.M., Kinzler K.W., Wong A.J., Bigner S.H., Kao F.T., Law M.L., RA Seuanez H.N., O'Brien S.J., Vogelstein B.; RT "The GLI-Kruppel family of human genes."; RL Mol. Cell. Biol. 8:3104-3113(1988). RN [6] RP INTERACTION WITH STK36. 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 [7] RP INVOLVEMENT IN HPE9. RX PubMed=14581620; DOI=10.1073/pnas.2235734100; RA Roessler E., Du Y.-Z., Mullor J.L., Casas E., Allen W.P., RA Gillessen-Kaesbach G., Roeder E.R., Ming J.E., Ruiz i Altaba A., Muenke M.; RT "Loss-of-function mutations in the human GLI2 gene are associated with RT pituitary anomalies and holoprosencephaly-like features."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13424-13429(2003). RN [8] RP FUNCTION, AND PHOSPHORYLATION AT SER-388 AND SER-1011. RX PubMed=18455992; DOI=10.1016/j.cell.2008.02.047; RA Varjosalo M., Bjorklund M., Cheng F., Syvanen H., Kivioja T., Kilpinen S., RA Sun Z., Kallioniemi O., Stunnenberg H.G., He W.W., Ojala P., Taipale J.; RT "Application of active and kinase-deficient kinome collection for RT identification of kinases regulating hedgehog signaling."; RL Cell 133:537-548(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-234 AND SER-236, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149; SER-234; SER-236 AND RP SER-242, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP ACETYLATION AT LYS-757. RX PubMed=23762415; DOI=10.1371/journal.pone.0065718; RA Coni S., Antonucci L., D'Amico D., Di Magno L., Infante P., De Smaele E., RA Giannini G., Di Marcotullio L., Screpanti I., Gulino A., Canettieri G.; RT "Gli2 acetylation at lysine 757 regulates hedgehog-dependent RT transcriptional output by preventing its promoter occupancy."; RL PLoS ONE 8:E65718-E65718(2013). RN [13] RP FUNCTION, AND INTERACTION WITH SUFU. 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 [14] RP INVOLVEMENT BY HPE9, INVOLVEMENT IN CJS, VARIANT CJS LEU-608, AND FUNCTION. RX PubMed=20685856; DOI=10.1210/jc.2010-1050; RA Franca M.M., Jorge A.A., Carvalho L.R., Costalonga E.F., Vasques G.A., RA Leite C.C., Mendonca B.B., Arnhold I.J.; RT "Novel heterozygous nonsense GLI2 mutations in patients with RT hypopituitarism and ectopic posterior pituitary lobe without RT holoprosencephaly."; RL J. Clin. Endocrinol. Metab. 95:E384-E391(2010). RN [15] RP FUNCTION, INTERACTION WITH FOXC1, AND SUBCELLULAR LOCATION. RX PubMed=26565916; DOI=10.1016/j.celrep.2015.09.063; RA Han B., Qu Y., Jin Y., Yu Y., Deng N., Wawrowsky K., Zhang X., Li N., RA Bose S., Wang Q., Sakkiah S., Abrol R., Jensen T.W., Berman B.P., RA Tanaka H., Johnson J., Gao B., Hao J., Liu Z., Buttyan R., Ray P.S., RA Hung M.C., Giuliano A.E., Cui X.; RT "FOXC1 activates smoothened-independent Hedgehog signaling in basal-like RT breast cancer."; RL Cell Rep. 13:1046-1058(2015). RN [16] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-50 (ISOFORMS 2 AND 4), AND RP IDENTIFICATION BY MASS 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 [17] RP VARIANTS HPE9 GLY-479; SER-932 AND LEU-1554, AND VARIANT ILE-1444. RX PubMed=17096318; DOI=10.1002/ajmg.a.31370; RA Rahimov F., Ribeiro L.A., de Miranda E., Richieri-Costa A., Murray J.C.; RT "GLI2 mutations in four Brazilian patients: how wide is the phenotypic RT spectrum?"; RL Am. J. Med. Genet. A 140:2571-2576(2006). RN [18] RP VARIANTS CJS PRO-516 AND 1444-MET-LEU-1445 DELINS ILE-PHE, CHARACTERIZATION RP OF VARIANTS CJS PRO-516 AND 1444-MET-LEU-1445 DELINS ILE-PHE, VARIANTS RP VAL-1352; ASN-1520 AND HIS-1543, AND CHARACTERIZATION OF VARIANTS VAL-1352; RP ASN-1520 AND HIS-1543. RX PubMed=23408573; DOI=10.1210/jc.2012-3224; RA Flemming G.M., Klammt J., Ambler G., Bao Y., Blum W.F., Cowell C., RA Donaghue K., Howard N., Kumar A., Sanchez J., Stobbe H., Pfaeffle R.W.; RT "Functional characterization of a heterozygous GLI2 missense mutation in RT patients with multiple pituitary hormone deficiency."; RL J. Clin. Endocrinol. Metab. 98:E567-E575(2013). RN [19] RP VARIANT ILE-1444. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). RN [20] RP VARIANTS VAL-1352 AND ASN-1520. 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). CC -!- FUNCTION: Functions as a transcription regulator in the hedgehog (Hh) CC pathway (PubMed:18455992, PubMed:26565916). Functions as a CC transcriptional activator (PubMed:9557682, PubMed:19878745, CC PubMed:24311597). May also function as transcriptional repressor (By CC similarity). Requires STK36 for full transcriptional activator CC activity. Required for normal embryonic development (PubMed:15994174, CC PubMed:20685856). {ECO:0000250|UniProtKB:Q0VGT2, CC ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:18455992, CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24311597, CC ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:9557682, CC ECO:0000305|PubMed:20685856}. CC -!- FUNCTION: [Isoform 1]: Involved in the smoothened (SHH) signaling CC pathway. {ECO:0000269|PubMed:18455992}. CC -!- FUNCTION: [Isoform 2]: Involved in the smoothened (SHH) signaling CC pathway. {ECO:0000269|PubMed:18455992}. CC -!- FUNCTION: [Isoform 3]: Involved in the smoothened (SHH) signaling CC pathway. {ECO:0000269|PubMed:18455992}. CC -!- FUNCTION: [Isoform 4]: Involved in the smoothened (SHH) signaling CC pathway. {ECO:0000269|PubMed:18455992}. CC -!- FUNCTION: [Isoform 1]: Acts as a transcriptional activator in T-cell CC leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent CC manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the CC Tax-responsive element (TRE-2S) regulatory element that augments the CC Tax-dependent enhancer of HTLV-1 (PubMed:9557682). CC {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}. CC -!- FUNCTION: [Isoform 2]: (Microbial infection) Acts as a transcriptional CC activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a CC Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which CC is part of the Tax-responsive element (TRE-2S) regulatory element that CC augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). CC {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}. CC -!- FUNCTION: [Isoform 3]: (Microbial infection) Acts as a transcriptional CC activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a CC Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which CC is part of the Tax-responsive element (TRE-2S) regulatory element that CC augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). CC {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}. CC -!- FUNCTION: [Isoform 4]: (Microbial infection) Acts as a transcriptional CC activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a CC Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which CC is part of the Tax-responsive element (TRE-2S) regulatory element that CC augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). CC {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}. CC -!- FUNCTION: [Isoform 5]: Acts as a transcriptional repressor. CC {ECO:0000269|PubMed:15994174}. CC -!- SUBUNIT: Interaction with ZIC1 and ZIC2 (By similarity). Interacts with CC STK36 (PubMed:10806483). Interacts with SUFU; this inhibits CC transcriptional activation mediated by GLI2 (PubMed:24311597). CC Interacts (via C-terminal internal region) with FOXC1 (via N-terminus); CC this interaction is direct and increases GLI2 DNA-binding and CC transcriptional activity through a smoothened (SMO)-independent CC Hedgehog (Hh) signaling pathway (PubMed:26565916). CC {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:10806483, CC ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:26565916}. CC -!- INTERACTION: CC P10070; Q9Y297: BTRC; NbExp=4; IntAct=EBI-10821567, EBI-307461; CC P10070; P84022: SMAD3; NbExp=4; IntAct=EBI-10821567, EBI-347161; CC P10070; Q99816: TSG101; NbExp=2; IntAct=EBI-10821567, EBI-346882; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26565916}. Cytoplasm CC {ECO:0000250|UniProtKB:Q0VGT2}. Cell projection, cilium CC {ECO:0000250|UniProtKB:Q0VGT2}. Note=STK36 promotes translocation to CC the nucleus. In keratinocytes, it is sequestered in the cytoplasm by CC SUFU. In the absence of SUFU, it translocates to the nucleus. CC {ECO:0000250|UniProtKB:Q0VGT2}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus CC {ECO:0000269|PubMed:9557682}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus CC {ECO:0000269|PubMed:9557682}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=5; Synonyms=GLI2 {ECO:0000303|PubMed:15994174}; CC IsoId=P10070-5; Sequence=Displayed; CC Name=1; Synonyms=Alpha, GLI2star, GLI2deltaN CC {ECO:0000303|PubMed:15994174, ECO:0000303|PubMed:9557682}; CC IsoId=P10070-1; Sequence=VSP_035708; CC Name=2; Synonyms=Beta {ECO:0000303|PubMed:9557682}; CC IsoId=P10070-2; Sequence=VSP_035708, VSP_006877; CC Name=3; Synonyms=Gamma {ECO:0000303|PubMed:9557682}; CC IsoId=P10070-3; Sequence=VSP_035708, VSP_006878, VSP_006879; CC Name=4; Synonyms=Delta {ECO:0000303|PubMed:9557682}; CC IsoId=P10070-4; Sequence=VSP_035708, VSP_006877, VSP_006878, CC VSP_006879; CC -!- TISSUE SPECIFICITY: Expressed in breast cancers (at protein level) CC (PubMed:26565916). Isoform 1 and isoform 4 are expressed in HTLV-1- CC infected T-cell lines (at protein level) (PubMed:9557682). Isoform 1 CC and isoform 2 are strongly expressed in HTLV-1-infected T-cell lines CC (PubMed:9557682). Isoform 3 and isoform 4 are weakly expressed in HTLV- CC 1-infected T-cell lines (PubMed:9557682). {ECO:0000269|PubMed:26565916, CC ECO:0000269|PubMed:9557682}. CC -!- DOMAIN: The N-terminal domain confers transcriptional repressor CC activity, while the C-terminal domain mediates transcriptional CC activation. {ECO:0000250|UniProtKB:Q0VGT2}. CC -!- PTM: Phosphorylated in vitro by ULK3. Phosphorylated by DYRK2; this CC inhibits GLI2 transcription factor activity and promotes proteasomal CC degradation of GLI2. {ECO:0000269|PubMed:18455992, CC ECO:0000269|PubMed:19878745}. CC -!- PTM: Acetylation at Lys-757 inhibits Hh target gene expression, CC probably by impeding entry into chromatin thus preventing promoter CC occupancy. {ECO:0000269|PubMed:23762415}. CC -!- DISEASE: Holoprosencephaly 9 (HPE9) [MIM:610829]: A structural anomaly CC of the brain, in which the developing forebrain fails to correctly CC separate into right and left hemispheres. Holoprosencephaly is CC genetically heterogeneous and associated with several distinct facies CC and phenotypic variability. Holoprosencephaly type 9 is characterized CC by defective anterior pituitary formation and pan-hypopituitarism, with CC or without overt forebrain cleavage abnormalities, and CC holoprosencephaly-like midfacial hypoplasia. CC {ECO:0000269|PubMed:14581620, ECO:0000269|PubMed:17096318, CC ECO:0000269|PubMed:20685856}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Culler-Jones syndrome (CJS) [MIM:615849]: An autosomal CC dominant disorder characterized by a wide range of clinical CC manifestations. Clinical features include hypothalamic hamartoma, CC pituitary dysfunction, central or postaxial polydactyly, and CC syndactyly. Malformations are frequent in the viscera, e.g. anal CC atresia, bifid uvula, congenital heart malformations, pulmonary or CC renal dysplasia. {ECO:0000269|PubMed:15994174, CC ECO:0000269|PubMed:20685856, ECO:0000269|PubMed:23408573, CC ECO:0000269|PubMed:28973407}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA03568.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA03569.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA25665.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAA25667.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB007295; BAA25665.1; ALT_FRAME; mRNA. DR EMBL; AB007296; BAA25666.1; -; mRNA. DR EMBL; AB007297; BAA25667.1; ALT_FRAME; mRNA. DR EMBL; AB007298; BAA25668.1; -; mRNA. DR EMBL; DQ086814; AAY87165.1; -; mRNA. DR EMBL; AC016764; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC017033; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D14827; BAA03568.1; ALT_FRAME; mRNA. DR EMBL; D14828; BAA03569.1; ALT_FRAME; mRNA. DR EMBL; M20672; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M20673; AAA35898.1; -; Genomic_DNA. DR CCDS; CCDS33283.1; -. [P10070-5] DR PIR; A31201; A31201. DR PIR; A40679; A40679. DR PIR; B40679; B40679. DR RefSeq; NP_005261.2; NM_005270.4. [P10070-5] DR AlphaFoldDB; P10070; -. DR SMR; P10070; -. DR BioGRID; 108998; 61. DR ComplexPortal; CPX-148; GLI2-SUFU complex. DR IntAct; P10070; 40. DR STRING; 9606.ENSP00000390436; -. DR BindingDB; P10070; -. DR ChEMBL; CHEMBL5119; -. DR GlyCosmos; P10070; 4 sites, 1 glycan. DR GlyGen; P10070; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; P10070; -. DR PhosphoSitePlus; P10070; -. DR BioMuta; GLI2; -. DR DMDM; 215274258; -. DR EPD; P10070; -. DR jPOST; P10070; -. DR MassIVE; P10070; -. DR MaxQB; P10070; -. DR PaxDb; 9606-ENSP00000390436; -. DR PeptideAtlas; P10070; -. DR ProteomicsDB; 52552; -. [P10070-5] DR ProteomicsDB; 52553; -. [P10070-1] DR ProteomicsDB; 52554; -. [P10070-2] DR ProteomicsDB; 52555; -. [P10070-3] DR ProteomicsDB; 52556; -. [P10070-4] DR Pumba; P10070; -. DR Antibodypedia; 3768; 419 antibodies from 39 providers. DR DNASU; 2736; -. DR Ensembl; ENST00000452319.6; ENSP00000390436.1; ENSG00000074047.22. [P10070-5] DR GeneID; 2736; -. DR KEGG; hsa:2736; -. DR UCSC; uc010flp.4; human. [P10070-5] DR AGR; HGNC:4318; -. DR CTD; 2736; -. DR DisGeNET; 2736; -. DR GeneCards; GLI2; -. DR GeneReviews; GLI2; -. DR HGNC; HGNC:4318; GLI2. DR HPA; ENSG00000074047; Tissue enhanced (ovary). DR MalaCards; GLI2; -. DR MIM; 165230; gene. DR MIM; 610829; phenotype. DR MIM; 615849; phenotype. DR neXtProt; NX_P10070; -. DR OpenTargets; ENSG00000074047; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 95494; Combined pituitary hormone deficiencies, genetic forms. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 280200; Microform holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 420584; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA28721; -. DR VEuPathDB; HostDB:ENSG00000074047; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000159213; -. DR HOGENOM; CLU_003666_2_0_1; -. DR InParanoid; P10070; -. DR OMA; PPESTCF; -. DR OrthoDB; 3304552at2759; -. DR PhylomeDB; P10070; -. DR TreeFam; TF350216; -. DR PathwayCommons; P10070; -. DR Reactome; R-HSA-5610783; Degradation of GLI2 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 Reactome; R-HSA-8941284; RUNX2 regulates chondrocyte maturation. DR SignaLink; P10070; -. DR SIGNOR; P10070; -. DR BioGRID-ORCS; 2736; 16 hits in 1175 CRISPR screens. DR GeneWiki; GLI2; -. DR GenomeRNAi; 2736; -. DR Pharos; P10070; Tchem. DR PRO; PR:P10070; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P10070; Protein. DR Bgee; ENSG00000074047; Expressed in tibia and 154 other cell types or tissues. DR ExpressionAtlas; P10070; baseline and differential. DR GO; GO:0097546; C:ciliary base; TAS:Reactome. DR GO; GO:0097542; C:ciliary tip; TAS:Reactome. DR GO; GO:0005929; C:cilium; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:1990788; C:GLI-SUFU complex; ISS:ComplexPortal. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB. DR GO; GO:0021696; P:cerebellar cortex morphogenesis; ISS:UniProtKB. DR GO; GO:0048589; P:developmental growth; ISS:UniProtKB. DR GO; GO:0048566; P:embryonic digestive tract development; ISS:UniProtKB. DR GO; GO:0009913; P:epidermal cell differentiation; IDA:UniProtKB. DR GO; GO:0021508; P:floor plate formation; ISS:UniProtKB. DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:UniProtKB. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0030902; P:hindbrain development; ISS:UniProtKB. DR GO; GO:0007442; P:hindgut morphogenesis; ISS:UniProtKB. DR GO; GO:0001822; P:kidney development; ISS:UniProtKB. DR GO; GO:0030324; P:lung development; ISS:UniProtKB. DR GO; GO:0030879; P:mammary gland development; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0048666; P:neuron development; ISS:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:UniProtKB. DR GO; GO:0002076; P:osteoblast development; ISS:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB. DR GO; GO:0007389; P:pattern specification process; ISS:UniProtKB. DR GO; GO:0021983; P:pituitary gland development; ISS:UniProtKB. DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0009954; P:proximal/distal pattern formation; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001501; P:skeletal system development; ISS:UniProtKB. DR GO; GO:0007224; P:smoothened signaling pathway; IDA:UniProtKB. DR GO; GO:0021775; P:smoothened signaling pathway involved in ventral spinal cord interneuron specification; ISS:UniProtKB. DR GO; GO:0021513; P:spinal cord dorsal/ventral patterning; ISS:UniProtKB. DR GO; GO:0021965; P:spinal cord ventral commissure morphogenesis; ISS:UniProtKB. DR GO; GO:0035295; P:tube development; ISS:UniProtKB. DR GO; GO:0007418; P:ventral midline development; ISS:UniProtKB. DR GO; GO:0021517; P:ventral spinal cord development; ISS:UniProtKB. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 5. DR InterPro; IPR043359; GLI-like. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR45718; TRANSCRIPTIONAL ACTIVATOR CUBITUS INTERRUPTUS; 1. DR PANTHER; PTHR45718:SF6; ZINC FINGER PROTEIN GLI2; 1. DR Pfam; PF00096; zf-C2H2; 2. DR SMART; SM00355; ZnF_C2H2; 5. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. DR Genevisible; P10070; HS. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative splicing; Cell projection; Cilium; KW Cytoplasm; Developmental protein; Disease variant; DNA-binding; KW Holoprosencephaly; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1586 FT /note="Zinc finger protein GLI2" FT /id="PRO_0000354050" FT ZN_FING 437..464 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 475..497 FT /note="C2H2-type 2; degenerate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 503..527 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 533..558 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 564..589 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 342..389 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 577..636 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 650..716 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 742..879 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 925..1030 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1182..1215 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1421..1441 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1469..1498 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 342..370 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 577..611 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 650..680 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 746..760 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 790..838 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 852..879 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1187..1209 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 234 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 236 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 242 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 388 FT /note="Phosphoserine; by DYRK2" FT /evidence="ECO:0000269|PubMed:18455992" FT MOD_RES 725 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q0VGT2" FT MOD_RES 757 FT /note="N6-acetyllysine; by EP300" FT /evidence="ECO:0000269|PubMed:23762415" FT MOD_RES 1011 FT /note="Phosphoserine; by DYRK2" FT /evidence="ECO:0000269|PubMed:18455992" FT VAR_SEQ 1..328 FT /note="Missing (in isoform 1, isoform 2, isoform 3 and FT isoform 4)" FT /evidence="ECO:0000303|PubMed:8350401, FT ECO:0000303|PubMed:9557682" FT /id="VSP_035708" FT VAR_SEQ 394..410 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:8350401, FT ECO:0000303|PubMed:9557682" FT /id="VSP_006877" FT VAR_SEQ 1149..1157 FT /note="VSSGTVDAL -> ASATWLSGT (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:8350401, FT ECO:0000303|PubMed:9557682" FT /id="VSP_006878" FT VAR_SEQ 1158..1586 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:8350401, FT ECO:0000303|PubMed:9557682" FT /id="VSP_006879" FT VARIANT 449 FT /note="D -> H (in dbSNP:rs13427953)" FT /id="VAR_047303" FT VARIANT 479 FT /note="R -> G (in HPE9; uncertain significance; FT dbSNP:rs121917708)" FT /evidence="ECO:0000269|PubMed:17096318" FT /id="VAR_032975" FT VARIANT 516 FT /note="R -> P (in CJS; loss of DNA-binding; loss of FT transcription factor activity)" FT /evidence="ECO:0000269|PubMed:23408573" FT /id="VAR_075214" FT VARIANT 579 FT /note="S -> I (in dbSNP:rs12618388)" FT /id="VAR_047304" FT VARIANT 608 FT /note="P -> L (in CJS; dbSNP:rs149800897)" FT /evidence="ECO:0000269|PubMed:20685856" FT /id="VAR_071700" FT VARIANT 625 FT /note="P -> S (in dbSNP:rs3099537)" FT /id="VAR_047305" FT VARIANT 932 FT /note="P -> S (in HPE9; uncertain significance; FT dbSNP:rs1272759660)" FT /evidence="ECO:0000269|PubMed:17096318" FT /id="VAR_032976" FT VARIANT 1156 FT /note="A -> S (in dbSNP:rs3738880)" FT /evidence="ECO:0000269|PubMed:9557682" FT /id="VAR_047306" FT VARIANT 1306 FT /note="D -> N (in dbSNP:rs12711538)" FT /evidence="ECO:0000269|PubMed:9557682" FT /id="VAR_047307" FT VARIANT 1352 FT /note="M -> V (found in Culler-Jones syndrome; when FT associated in cis with N-1520; decreased transcription FT factor activity when associated in cis with N-1520; FT dbSNP:rs149140724)" FT /evidence="ECO:0000269|PubMed:23408573, FT ECO:0000269|PubMed:28973407" FT /id="VAR_075215" FT VARIANT 1444..1445 FT /note="ML -> IF (in CJS; uncertain significance; decreased FT transcription factor activity)" FT /evidence="ECO:0000269|PubMed:23408573" FT /id="VAR_075216" FT VARIANT 1444 FT /note="M -> I (in dbSNP:rs146467786)" FT /evidence="ECO:0000269|PubMed:17096318, FT ECO:0000269|PubMed:27535533" FT /id="VAR_032977" FT VARIANT 1520 FT /note="D -> N (found in Culler-Jones syndrome; when FT associated in cis with V-1352 in Culler-Jones syndrome; FT decreased transcription factor activity when associated in FT cis with V-1352; dbSNP:rs114814747)" FT /evidence="ECO:0000269|PubMed:23408573, FT ECO:0000269|PubMed:28973407" FT /id="VAR_075217" FT VARIANT 1543 FT /note="R -> H (no effect on transcription factor activity; FT dbSNP:rs138987487)" FT /evidence="ECO:0000269|PubMed:23408573" FT /id="VAR_075218" FT VARIANT 1554 FT /note="P -> L (in HPE9; uncertain significance; FT dbSNP:rs767802807)" FT /evidence="ECO:0000269|PubMed:17096318" FT /id="VAR_032978" FT CONFLICT 456 FT /note="H -> Q (in Ref. 5; M20672)" FT /evidence="ECO:0000305" FT CONFLICT 718..719 FT /note="QL -> HV (in Ref. 4; BAA03568/BAA03569)" FT /evidence="ECO:0000305" FT CONFLICT 923..925 FT /note="PER -> AEG (in Ref. 1; FT BAA25665/BAA25667/BAA25666/BAA25668)" FT /evidence="ECO:0000305" FT CONFLICT 966 FT /note="A -> T (in Ref. 1; FT BAA25665/BAA25667/BAA25666/BAA25668)" FT /evidence="ECO:0000305" FT CROSSLNK P10070-2:50 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK P10070-4:50 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" SQ SEQUENCE 1586 AA; 167783 MW; 86556112E13DE106 CRC64; METSASATAS EKQEAKSGIL EAAGFPDPGK KASPLVVAAA AAAAVAAQGV PQHLLPPFHA PLPIDMRHQE GRYHYEPHSV HGVHGPPALS GSPVISDISL IRLSPHPAGP GESPFNAPHP YVNPHMEHYL RSVHSSPTLS MISAARGLSP ADVAQEHLKE RGLFGLPAPG TTPSDYYHQM TLVAGHPAPY GDLLMQSGGA ASAPHLHDYL NPVDVSRFSS PRVTPRLSRK RALSISPLSD ASLDLQRMIR TSPNSLVAYI NNSRSSSAAS GSYGHLSAGA LSPAFTFPHP INPVAYQQIL SQQRGLGSAF GHTPPLIQPS PTFLAQQPMA LTSINATPTQ LSSSSNCLSD TNQNKQSSES AVSSTVNPVA IHKRSKVKTE PEGLRPASPL ALTQGQVSGH GSCGCALPLS QEQLADLKED LDRDDCKQEA EVVIYETNCH WEDCTKEYDT QEQLVHHINN EHIHGEKKEF VCRWQACTRE QKPFKAQYML VVHMRRHTGE KPHKCTFEGC SKAYSRLENL KTHLRSHTGE KPYVCEHEGC NKAFSNASDR AKHQNRTHSN EKPYICKIPG CTKRYTDPSS LRKHVKTVHG PDAHVTKKQR NDVHLRTPLL KENGDSEAGT EPGGPESTEA SSTSQAVEDC LHVRAIKTES SGLCQSSPGA QSSCSSEPSP LGSAPNNDSG VEMPGTGPGS LGDLTALDDT PPGADTSALA APSAGGLQLR KHMTTMHRFE QLKKEKLKSL KDSCSWAGPT PHTRNTKLPP LPGSGSILEN FSGSGGGGPA GLLPNPRLSE LSASEVTMLS QLQERRDSST STVSSAYTVS RRSSGISPYF SSRRSSEASP LGAGRPHNAS SADSYDPIST DASRRSSEAS QCSGGSGLLN LTPAQQYSLR AKYAAATGGP PPTPLPGLER MSLRTRLALL DAPERTLPAG CPRPLGPRRG SDGPTYGHGH AGAAPAFPHE APGGGARRAS DPVRRPDALS LPRVQRFHST HNVNPGPLPP CADRRGLRLQ SHPSTDGGLA RGAYSPRPPS ISENVAMEAV AAGVDGAGPE ADLGLPEDDL VLPDDVVQYI KAHASGALDE GTGQVYPTES TGFSDNPRLP SPGLHGQRRM VAADSNVGPS APMLGGCQLG FGAPSSLNKN NMPVQWNEVS SGTVDALASQ VKPPPFPQGN LAVVQQKPAF GQYPGYSPQG LQASPGGLDS TQPHLQPRSG APSQGIPRVN YMQQLRQPVA GSQCPGMTTT MSPHACYGQV HPQLSPSTIS GALNQFPQSC SNMPAKPGHL GHPQQTEVAP DPTTMGNRHR ELGVPDSALA GVPPPHPVQS YPQQSHHLAA SMSQEGYHQV PSLLPARQPG FMEPQTGPMG VATAGFGLVQ PRPPLEPSPT GRHRGVRAVQ QQLAYARATG HAMAAMPSSQ ETAEAVPKGA MGNMGSVPPQ PPPQDAGGAP DHSMLYYYGQ IHMYEQDGGL ENLGSCQVMR SQPPQPQACQ DSIQPQPLPS PGVNQVSSTV DSQLLEAPQI DFDAIMDDGD HSSLFSGALS PSLLHSLSQN SSRLTTPRNS LTLPSIPAGI SNMAVGDMSS MLTSLAEESK FLNMMT //