| Note | 524 amino acids; molecular weight: 55,688 kD.
Member of the Krüppel-like zinc finger proteins family, forming a subfamily with Glis1 and Glis3 closely related to Gli and Zic protein families. |
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| Description | Similarly to Gli and Zic proteins, Glis2 contains 5 Cys2-His2 zinc finger motifs separated by a conserved consensus region T/SGEKPY/FX (Zhang et al., 2002). |
| Expression | In mouse tissues: high expression level of Glis2 in kidney, moderate level in heart, lung, low level in prostate, brain, colon (Zhang et al., 2002).
In rat embryos: high expression in embryonic kidneys (particularly within the ureteric bud in 16-dpc and 19-dpc rat).
Expression of Glis2 detected in caudal somites and in the neural tubes of 13-dpc in rat embryos (Zhang et al., 2002); high expression level in neural tube in Xenopus, mouse and chick embryos (Lamar et al., 2001).
In human: GLIS2 mRNA is highly expressed in kidney, low level in heart, lung and placenta (Zhang and Jetten, 2001). |
| Localisation | Nuclear localization (Zhang et al., 2002); the 3rd Zinc Finger motif contains a region required for the nuclear localization (Vasanth et al., 2011). |
| Function | Krüppel-like zinc finger family proteins can act as activator or repressor of gene transcription. They are involved in regulation of embryonic development and various physiological mechanisms in adults (Dang et al., 2000).
Kang and colleagues described the regulation of gene expression by Glis1-3 through the interaction with transcriptional mediators that are recruited by specific repressor and activation domains within the respective Glis protein.
According to cell context, Glis2 can thus act as a transcriptional activator or repressor. Glis2 is especially implicated in the maintenance of normal kidney structure and function; both activation and repression roles are involved during embryonic development and adult kidney (Zhang et al., 2002; Attanasio et al., 2007).
GLIS2 has also been described as NKL (neuronal Krüppel-like protein): NKL is broadly expressed in the neural tube and peripheral nervous system when neural precursors are differentiating. NKL is implicated in neurogenesis, promoting neuronal differentiation (Lamar et al., 2001).
In mice, Zhang and colleagues (Zhang et al., 2002) highlighted the presence of an activation domain located between Gly71 and Gly137. Two repressor domains were identified: one is located between Ser148 and Arg171 and the other is located within the first zinc finger motif. CtBP1 (C-terminal binding protein 1) and HDAC3 (histone deacetylase 3) are two co-repressor recruited by Glis2 for its repression activity, though a repression complex (Kim et al., 2005). |
| Homology | GLI proteins are homologous of Cubitus interruptus (Ci) in Drosophila melanogaster which plays an important role in wing development. Ci and GLI are involved in Sonic-Hedgehog pathway in Dosophila and vertebrates. (Zhang and Jetten, 2001).
Glis2 shows high homologies with Gli and Zic Krüppel-like protein families.
In mice highest homology is observed in the zinc finger motifs: 57%, 56%, 56% and 49% homology with Gli1, Gli2, Gli3 and Zic1 respectively. 3rd and 5th zinc finger domains show the highest homology with Gli proteins (70 and 88% homology) (Zhang et al., 2002).
In human: highest homology is observed with GLI1: 58% between Zinc Finger domains. 3rd, 4th and 5th Zinc Finger show the highest homology: 65-80% homology when compared to those of GLI and ZIC proteins (Zhang and Jetten, 2001).
This suggests that Glis2 interacts with DNA in the way Gli and Zic proteins do (Zhang et al., 2002).
In both human and mouse, little homology with Gli and Zic protein family is observed outside the zinc finger domain, which show that Glis2 belongs to another subfamily of Krüppel-like zinc finger proteins (Zhang et al., 2002; Zhang and Jetten, 2001). |
| Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. |
| Attanasio M, Uhlenhaut NH, Sousa VH, O'Toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Helou J, Sayer JA, Seelow D, Nurnberg G, Becker C, Chudley AE, Nurnberg P, Hildebrandt F, Treier M. |
| Nat Genet. 2007 Aug;39(8):1018-24. Epub 2007 Jul 8. |
| PMID 17618285 |
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| The biology of the mammalian Kruppel-like family of transcription factors. |
| Dang DT, Pevsner J, Yang VW. |
| Int J Biochem Cell Biol. 2000 Nov-Dec;32(11-12):1103-21. (REVIEW) |
| PMID 11137451 |
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| An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. |
| Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, Chen SC, Su X, Ogden SK, Dang J, Wu G, Gupta V, Andersson AK, Pounds S, Shi L, Easton J, Barbato MI, Mulder HL, Manne J, Wang J, Rusch M, Ranade S, Ganti R, Parker M, Ma J, Radtke I, Ding L, Cazzaniga G, Biondi A, Kornblau SM, Ravandi F, Kantarjian H, Nimer SD, Dohner K, Dohner H, Ley TJ, Ballerini P, Shurtleff S, Tomizawa D, Adachi S, Hayashi Y, Tawa A, Shih LY, Liang DC, Rubnitz JE, Pui CH, Mardis ER, Wilson RK, Downing JR. |
| Cancer Cell. 2012 Nov 13;22(5):683-97. doi: 10.1016/j.ccr.2012.10.007. |
| PMID 23153540 |
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| Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1). |
| Kim SC, Kim YS, Jetten AM. |
| Nucleic Acids Res. 2005 Dec 2;33(21):6805-15. Print 2005. |
| PMID 16326862 |
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| Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation. |
| Lamar E, Kintner C, Goulding M. |
| Development. 2001 Apr;128(8):1335-46. |
| PMID 11262234 |
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| CBFA2T3-GLIS2 fusion transcript is a novel common feature in pediatric, cytogenetically normal AML, not restricted to FAB M7 subtype. |
| Masetti R, Pigazzi M, Togni M, Astolfi A, Indio V, Manara E, Casadio R, Pession A, Basso G, Locatelli F. |
| Blood. 2013 Apr 25;121(17):3469-72. doi: 10.1182/blood-2012-11-469825. Epub 2013 Feb 13. |
| PMID 23407549 |
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| Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models. |
| Thiollier C, Lopez CK, Gerby B, Ignacimouttou C, Poglio S, Duffourd Y, Guegan J, Rivera-Munoz P, Bluteau O, Mabialah V, Diop M, Wen Q, Petit A, Bauchet AL, Reinhardt D, Bornhauser B, Gautheret D, Lecluse Y, Landman-Parker J, Radford I, Vainchenker W, Dastugue N, de Botton S, Dessen P, Bourquin JP, Crispino JD, Ballerini P, Bernard OA, Pflumio F, Mercher T. |
| J Exp Med. 2012 Oct 22;209(11):2017-31. doi: 10.1084/jem.20121343. Epub 2012 Oct 8. |
| PMID 23045605 |
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| Identification of nuclear localization, DNA binding, and transactivating mechanisms of Kruppel-like zinc finger protein Gli-similar 2 (Glis2). |
| Vasanth S, ZeRuth G, Kang HS, Jetten AM. |
| J Biol Chem. 2011 Feb 11;286(6):4749-59. doi: 10.1074/jbc.M110.165951. Epub 2010 Dec 2. |
| PMID 21127075 |
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| Genomic structure of the gene encoding the human GLI-related, Kruppel-like zinc finger protein GLIS2. |
| Zhang F, Jetten AM. |
| Gene. 2001 Dec 12;280(1-2):49-57. |
| PMID 11738817 |
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| Characterization of Glis2, a novel gene encoding a Gli-related, Kruppel-like transcription factor with transactivation and repressor functions. Roles in kidney development and neurogenesis. |
| Zhang F, Nakanishi G, Kurebayashi S, Yoshino K, Perantoni A, Kim YS, Jetten AM. |
| J Biol Chem. 2002 Mar 22;277(12):10139-49. Epub 2001 Dec 12. |
| PMID 11741991 |
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