GLIS2_MOUSE
ID GLIS2_MOUSE Reviewed; 521 AA.
AC Q8VDL9; Q8R4X9; Q99MY6; Q99P73;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Zinc finger protein GLIS2;
DE AltName: Full=GLI-similar 2;
DE AltName: Full=Neuronal Krueppel-like protein;
DE AltName: Full=Zinc finger protein GLI5;
GN Name=Glis2; Synonyms=Gli5, Nkl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=11262234; DOI=10.1242/dev.128.8.1335;
RA Lamar E., Kintner C., Goulding M.;
RT "Identification of NKL, a novel Gli-Kruppel zinc-finger protein that
RT promotes neuronal differentiation.";
RL Development 128:1335-1346(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND FUNCTION.
RC STRAIN=129/SvJ, and BALB/cJ; TISSUE=Kidney;
RX PubMed=11741991; DOI=10.1074/jbc.m108062200;
RA Zhang F., Nakanishi G., Kurebayashi S., Yoshino K., Perantoni A.,
RA Kim Y.-S., Jetten A.M.;
RT "Characterization of Glis2, a novel gene encoding a Gli-related, Kruppel-
RT like transcription factor with transactivation and repressor functions.
RT Roles in kidney development and neurogenesis.";
RL J. Biol. Chem. 277:10139-10149(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, INTERACTION WITH CTBP1 AND HDAC3, CLEAVAGE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16326862; DOI=10.1093/nar/gki985;
RA Kim S.-C., Kim Y.-S., Jetten A.M.;
RT "Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses
RT transcription through interaction with C-terminal binding protein 1
RT (CtBP1).";
RL Nucleic Acids Res. 33:6805-6815(2005).
RN [5]
RP FUNCTION, INTERACTION WITH CTNNB1, MUTAGENESIS OF CYS-175, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17289029; DOI=10.1016/j.febslet.2007.01.058;
RA Kim Y.-S., Kang H.S., Jetten A.M.;
RT "The Kruppel-like zinc finger protein Glis2 functions as a negative
RT modulator of the Wnt/beta-catenin signaling pathway.";
RL FEBS Lett. 581:858-864(2007).
RN [6]
RP FUNCTION, INTERACTION WITH CTNND1, CLEAVAGE SITE, DNA-BINDING, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF CYS-170; TYR-288 AND ASP-290.
RX PubMed=17344476; DOI=10.1091/mbc.e06-10-0941;
RA Hosking C.R., Ulloa F., Hogan C., Ferber E.C., Figueroa A., Gevaert K.,
RA Birchmeier W., Briscoe J., Fujita Y.;
RT "The transcriptional repressor Glis2 is a novel binding partner for p120
RT catenin.";
RL Mol. Biol. Cell 18:1918-1927(2007).
RN [7]
RP FUNCTION, AND INTERACTION WITH SUFU.
RX PubMed=21816948; DOI=10.1093/hmg/ddr339;
RA Li B., Rauhauser A.A., Dai J., Sakthivel R., Igarashi P., Jetten A.M.,
RA Attanasio M.;
RT "Increased hedgehog signaling in postnatal kidney results in aberrant
RT activation of nephron developmental programs.";
RL Hum. Mol. Genet. 20:4155-4166(2011).
CC -!- FUNCTION: Can act either as a transcriptional repressor or as a
CC transcriptional activator, depending on the cell context. Acts as a
CC repressor of the Hedgehog signaling pathway. Represses the Hedgehog-
CC dependent expression of Wnt4. Necessary to maintain the differentiated
CC epithelial phenotype in renal cells through the inhibition of SNAI1,
CC which itself induces the epithelial-to-mesenchymal transition.
CC Represses transcriptional activation by CTNNB1 in the Wnt signaling
CC pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be
CC involved in neuron differentiation. {ECO:0000269|PubMed:11262234,
CC ECO:0000269|PubMed:11741991, ECO:0000269|PubMed:16326862,
CC ECO:0000269|PubMed:17289029, ECO:0000269|PubMed:17344476,
CC ECO:0000269|PubMed:21816948}.
CC -!- SUBUNIT: Interacts with CTBP1 and HDAC3. Interacts with CTNNB1 and
CC CTNND1. Interacts with SUFU. {ECO:0000269|PubMed:16326862,
CC ECO:0000269|PubMed:17289029, ECO:0000269|PubMed:17344476,
CC ECO:0000269|PubMed:21816948}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in kidney, and at lower
CC levels in heart and lung. {ECO:0000269|PubMed:11741991}.
CC -!- DEVELOPMENTAL STAGE: Expression begins at 9.5 dpc in cranial ganglia,
CC dorsal root ganglia and neural tube. At 10.5 dpc, broadly expressed in
CC the intermediate zone of the hindbrain, spinal cord and dorsal root
CC ganglia. By 12.5 dpc, expression in the spinal cord becomes restricted
CC to a narrow band of cells in the ventricular zone.
CC {ECO:0000269|PubMed:11262234}.
CC -!- DOMAIN: The C2H2-type zinc finger 1 has a major repressor function and
CC is required for CTNNB1 binding.
CC -!- PTM: C-terminus cleavage is induced by interaction with CTNND1 and
CC enhances by Src tyrosine kinase. {ECO:0000269|PubMed:16326862,
CC ECO:0000269|PubMed:17344476}.
CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF249340; AAK28410.1; -; mRNA.
DR EMBL; AF325913; AAK00953.1; -; mRNA.
DR EMBL; AF336135; AAL93213.1; -; Genomic_DNA.
DR EMBL; BC021517; AAH21517.1; -; mRNA.
DR CCDS; CCDS27920.1; -.
DR RefSeq; NP_112461.2; NM_031184.3.
DR RefSeq; XP_006522831.1; XM_006522768.3.
DR AlphaFoldDB; Q8VDL9; -.
DR SMR; Q8VDL9; -.
DR BioGRID; 219913; 2.
DR CORUM; Q8VDL9; -.
DR STRING; 10090.ENSMUSP00000014447; -.
DR iPTMnet; Q8VDL9; -.
DR PhosphoSitePlus; Q8VDL9; -.
DR PaxDb; Q8VDL9; -.
DR PRIDE; Q8VDL9; -.
DR ProteomicsDB; 267453; -.
DR Antibodypedia; 11033; 121 antibodies from 23 providers.
DR DNASU; 83396; -.
DR Ensembl; ENSMUST00000014447; ENSMUSP00000014447; ENSMUSG00000014303.
DR GeneID; 83396; -.
DR KEGG; mmu:83396; -.
DR UCSC; uc007xzw.1; mouse.
DR CTD; 84662; -.
DR MGI; MGI:1932535; Glis2.
DR VEuPathDB; HostDB:ENSMUSG00000014303; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000158383; -.
DR HOGENOM; CLU_031801_1_0_1; -.
DR InParanoid; Q8VDL9; -.
DR OMA; APKDKCL; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q8VDL9; -.
DR TreeFam; TF351425; -.
DR BioGRID-ORCS; 83396; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Glis1; mouse.
DR PRO; PR:Q8VDL9; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8VDL9; protein.
DR Bgee; ENSMUSG00000014303; Expressed in ciliary body and 204 other tissues.
DR ExpressionAtlas; Q8VDL9; baseline and differential.
DR Genevisible; Q8VDL9; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0097730; C:non-motile cilium; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; ISS:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0061005; P:cell differentiation involved in kidney development; IMP:MGI.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR InterPro; IPR030432; Glis2.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR19818:SF84; PTHR19818:SF84; 1.
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; 4.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Developmental protein; Differentiation; DNA-binding;
KW Metal-binding; Neurogenesis; Nucleus; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..521
FT /note="Zinc finger protein GLIS2"
FT /id="PRO_0000286984"
FT ZN_FING 168..193
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 202..229
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 235..257
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 263..287
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 293..317
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 35..174
FT /note="Interaction with CTNND1"
FT /evidence="ECO:0000269|PubMed:17344476"
FT REGION 41..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 71..137
FT /note="Transcription activation"
FT REGION 84..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..171
FT /note="Transcription repression"
FT REGION 436..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..103
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 457..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 287..288
FT /note="Cleavage"
FT MUTAGEN 170
FT /note="C->A: Impairs DNA-binding."
FT /evidence="ECO:0000269|PubMed:17344476"
FT MUTAGEN 175
FT /note="C->A: Abolishes interaction with CTNNB1. No effect
FT on nuclear localization."
FT /evidence="ECO:0000269|PubMed:17289029"
FT MUTAGEN 288
FT /note="Y->A: No effect on C-terminus cleavage."
FT /evidence="ECO:0000269|PubMed:17344476"
FT MUTAGEN 290
FT /note="D->A: Impairs C-terminus cleavage."
FT /evidence="ECO:0000269|PubMed:17344476"
FT CONFLICT 87..88
FT /note="SG -> CE (in Ref. 2; AAL93213)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="G -> D (in Ref. 2; AAK00953)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="Missing (in Ref. 1; AAK28410)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="N -> K (in Ref. 2; AAL93213)"
FT /evidence="ECO:0000305"
FT CONFLICT 315..318
FT /note="KAHG -> RPW (in Ref. 2; AAL93213)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="G -> A (in Ref. 1; AAK28410)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="D -> N (in Ref. 2; AAL93213/AAK00953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 55842 MW; 6B5F78F4A742C72D CRC64;
MHSLDEPLDL KLSITKLRAA REKRERTLGV VRHHALHREL GLVDDSPAPG SPGSPPPGFL
LNPKFPEKVD GRFSAAPLVD LSLSPPSGLD SPNGSSSLSP ECQGNGDLPP LPTAVDFQPL
RYLDGVPSSF QFFLPLGSGG ALHLPASSFL PPPKDKCLSP ELPLAKQLVC RWAKCNQLFE
LLQDLVDHVN DHHVKPEQDA RYCCHWEGCA RHGRGFNARY KMLIHIRTHT NEKPHRCPTC
NKSFSRLENL KIHNRSHTGE KPYVCPYEGC NKRYSNSSDR FKHTRTHYVD KPYYCKMPGC
HKRYTDPSSL RKHIKAHGHF VSHEQQELLQ LRPPPKPPLP TPDSGSYVSG AQIIIPNPAA
LFGGPSLPGL PLPLPPGPLD LSALACGNGG GGGGGIGPGL PGSVLPLNLA KNPLLPSPFG
AGGLGLPVVS LLGGSAGSKA EGEKGRGSVP ARVLGLEDHK TPLERTERSR SRPSPDGLPL
LPGTVLDLST GNSAASSPEV LTPGWVVIPP GSVLLKPAVV N
