GLI2_HUMAN
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 03-AUG-2022, entry version 221.
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-ILE-PHE-1445, CHARACTERIZATION OF VARIANTS
RP CJS PRO-516 AND 1444-ILE-PHE-1445, VARIANTS VAL-1352; ASN-1520 AND
RP HIS-1543, AND CHARACTERIZATION OF VARIANTS VAL-1352; 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 transcription regulator in the hedgehog (Hh)
CC pathway (PubMed:18455992, PubMed:26565916). Functions as
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; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-10821567, EBI-740595;
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};
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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; 57.
DR ComplexPortal; CPX-148; GLI2-SUFU complex.
DR IntAct; P10070; 41.
DR STRING; 9606.ENSP00000390436; -.
DR BindingDB; P10070; -.
DR ChEMBL; CHEMBL5119; -.
DR GlyGen; P10070; 4 sites, 1 O-linked glycan (4 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; P10070; -.
DR PeptideAtlas; P10070; -.
DR PRIDE; 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 Antibodypedia; 3768; 354 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 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; FHSAHDV; -.
DR OrthoDB; 56870at2759; -.
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 1097 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 152 other tissues.
DR ExpressionAtlas; P10070; baseline and differential.
DR Genevisible; P10070; HS.
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: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: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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; ISS:UniProtKB.
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 InterPro; IPR043359; GLI-like.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR45718; PTHR45718; 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; 4.
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; unknown pathological 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; unknown pathological 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 (likely benign variant; associated with N-
FT 1520 in Culler-Jones syndrome; decreased transcription
FT factor activity when associated 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; unknown pathological significance;
FT decreased 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 (likely benign variant; associated with V-
FT 1352 in Culler-Jones syndrome; decreased transcription
FT factor activity when associated with V-1352;
FT 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; unknown pathological 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; BAA25665/BAA25667/BAA25666/
FT BAA25668)"
FT /evidence="ECO:0000305"
FT CONFLICT 966
FT /note="A -> T (in Ref. 1; BAA25665/BAA25667/BAA25666/
FT 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
