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Protein

Zinc finger protein GLIS2

Gene

Glis2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway. Represses the Hedgehog-dependent expression of Wnt4. Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition. Represses transcriptional activation by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation.6 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri168 – 19326C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri202 – 22928C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri235 – 25723C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri263 – 28725C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri293 – 31725C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

  • cell differentiation involved in kidney development Source: MGI
  • kidney development Source: MGI
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of smoothened signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • nervous system development Source: UniProtKB-KW
  • positive regulation of protein localization to nucleus Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of transcription from RNA polymerase II promoter involved in kidney development Source: MGI
  • transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Repressor

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein GLIS2
Alternative name(s):
GLI-similar 2
Neuronal Krueppel-like protein
Zinc finger protein GLI5
Gene namesi
Name:Glis2
Synonyms:Gli5, Nkl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1932535. Glis2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nonmotile primary cilium Source: MGI
  • nuclear speck Source: UniProtKB
  • nucleus Source: BHF-UCL
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi170 – 1701C → A: Impairs DNA-binding. 1 Publication
Mutagenesisi175 – 1751C → A: Abolishes interaction with CTNNB1. No effect on nuclear localization. 1 Publication
Mutagenesisi288 – 2881Y → A: No effect on C-terminus cleavage. 1 Publication
Mutagenesisi290 – 2901D → A: Impairs C-terminus cleavage. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 521521Zinc finger protein GLIS2PRO_0000286984Add
BLAST

Post-translational modificationi

C-terminus cleavage is induced by interaction with CTNND1 and enhances by Src tyrosine kinase.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei287 – 2882Cleavage

Proteomic databases

MaxQBiQ8VDL9.
PaxDbiQ8VDL9.
PRIDEiQ8VDL9.

PTM databases

PhosphoSiteiQ8VDL9.

Expressioni

Tissue specificityi

Expressed at high levels in kidney, and at lower levels in heart and lung.1 Publication

Developmental stagei

Expression begins at E9.5 in cranial ganglia, dorsal root ganglia and neural tube. At E10.5, broadly expressed in the intermediate zone of the hindbrain, spinal cord and dorsal root ganglia. By E12.5, expression in the spinal cord becomes restricted to a narrow band of cells in the ventricular zone.1 Publication

Gene expression databases

BgeeiQ8VDL9.
CleanExiMM_GLIS2.
ExpressionAtlasiQ8VDL9. baseline and differential.
GenevisibleiQ8VDL9. MM.

Interactioni

Subunit structurei

Interacts with CTBP1 and HDAC3. Interacts with CTNNB1 and CTNND1. Interacts with SUFU.4 Publications

Protein-protein interaction databases

BioGridi219913. 2 interactions.
STRINGi10090.ENSMUSP00000014447.

Structurei

3D structure databases

ProteinModelPortaliQ8VDL9.
SMRiQ8VDL9. Positions 170-318.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni35 – 174140Interaction with CTNND1Add
BLAST
Regioni71 – 13767Transcription activationAdd
BLAST
Regioni148 – 17124Transcription repressionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi333 – 37846Pro-richAdd
BLAST
Compositional biasi387 – 44761Gly-richAdd
BLAST

Domaini

The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding.

Sequence similaritiesi

Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri168 – 19326C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri202 – 22928C2H2-type 2; atypicalPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri235 – 25723C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri263 – 28725C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri293 – 31725C2H2-type 5PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000065778.
HOVERGENiHBG101807.
InParanoidiQ8VDL9.
KOiK09233.
OMAiDKCLSPE.
OrthoDBiEOG70CR6P.
PhylomeDBiQ8VDL9.
TreeFamiTF351425.

Family and domain databases

Gene3Di3.30.160.60. 5 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VDL9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHSLDEPLDL KLSITKLRAA REKRERTLGV VRHHALHREL GLVDDSPAPG
60 70 80 90 100
SPGSPPPGFL LNPKFPEKVD GRFSAAPLVD LSLSPPSGLD SPNGSSSLSP
110 120 130 140 150
ECQGNGDLPP LPTAVDFQPL RYLDGVPSSF QFFLPLGSGG ALHLPASSFL
160 170 180 190 200
PPPKDKCLSP ELPLAKQLVC RWAKCNQLFE LLQDLVDHVN DHHVKPEQDA
210 220 230 240 250
RYCCHWEGCA RHGRGFNARY KMLIHIRTHT NEKPHRCPTC NKSFSRLENL
260 270 280 290 300
KIHNRSHTGE KPYVCPYEGC NKRYSNSSDR FKHTRTHYVD KPYYCKMPGC
310 320 330 340 350
HKRYTDPSSL RKHIKAHGHF VSHEQQELLQ LRPPPKPPLP TPDSGSYVSG
360 370 380 390 400
AQIIIPNPAA LFGGPSLPGL PLPLPPGPLD LSALACGNGG GGGGGIGPGL
410 420 430 440 450
PGSVLPLNLA KNPLLPSPFG AGGLGLPVVS LLGGSAGSKA EGEKGRGSVP
460 470 480 490 500
ARVLGLEDHK TPLERTERSR SRPSPDGLPL LPGTVLDLST GNSAASSPEV
510 520
LTPGWVVIPP GSVLLKPAVV N
Length:521
Mass (Da):55,842
Last modified:March 1, 2002 - v1
Checksum:i6B5F78F4A742C72D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti87 – 882SG → CE in AAL93213 (PubMed:11741991).Curated
Sequence conflicti208 – 2081G → D in AAK00953 (PubMed:11741991).Curated
Sequence conflicti210 – 2101Missing in AAK28410 (PubMed:11262234).Curated
Sequence conflicti249 – 2491N → K in AAL93213 (PubMed:11741991).Curated
Sequence conflicti315 – 3184KAHG → RPW in AAL93213 (PubMed:11741991).Curated
Sequence conflicti387 – 3871G → A in AAK28410 (PubMed:11262234).Curated
Sequence conflicti458 – 4581D → N in AAL93213 (PubMed:11741991).Curated
Sequence conflicti458 – 4581D → N in AAK00953 (PubMed:11741991).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF249340 mRNA. Translation: AAK28410.1.
AF325913 mRNA. Translation: AAK00953.1.
AF336135 Genomic DNA. Translation: AAL93213.1.
BC021517 mRNA. Translation: AAH21517.1.
CCDSiCCDS27920.1.
RefSeqiNP_112461.2. NM_031184.3.
XP_006522831.1. XM_006522768.2.
UniGeneiMm.134072.

Genome annotation databases

EnsembliENSMUST00000014447; ENSMUSP00000014447; ENSMUSG00000014303.
GeneIDi83396.
KEGGimmu:83396.
UCSCiuc007xzw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF249340 mRNA. Translation: AAK28410.1.
AF325913 mRNA. Translation: AAK00953.1.
AF336135 Genomic DNA. Translation: AAL93213.1.
BC021517 mRNA. Translation: AAH21517.1.
CCDSiCCDS27920.1.
RefSeqiNP_112461.2. NM_031184.3.
XP_006522831.1. XM_006522768.2.
UniGeneiMm.134072.

3D structure databases

ProteinModelPortaliQ8VDL9.
SMRiQ8VDL9. Positions 170-318.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219913. 2 interactions.
STRINGi10090.ENSMUSP00000014447.

PTM databases

PhosphoSiteiQ8VDL9.

Proteomic databases

MaxQBiQ8VDL9.
PaxDbiQ8VDL9.
PRIDEiQ8VDL9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000014447; ENSMUSP00000014447; ENSMUSG00000014303.
GeneIDi83396.
KEGGimmu:83396.
UCSCiuc007xzw.1. mouse.

Organism-specific databases

CTDi84662.
MGIiMGI:1932535. Glis2.

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00760000118771.
HOGENOMiHOG000065778.
HOVERGENiHBG101807.
InParanoidiQ8VDL9.
KOiK09233.
OMAiDKCLSPE.
OrthoDBiEOG70CR6P.
PhylomeDBiQ8VDL9.
TreeFamiTF351425.

Miscellaneous databases

PROiQ8VDL9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VDL9.
CleanExiMM_GLIS2.
ExpressionAtlasiQ8VDL9. baseline and differential.
GenevisibleiQ8VDL9. MM.

Family and domain databases

Gene3Di3.30.160.60. 5 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF13912. zf-C2H2_6. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of NKL, a novel Gli-Kruppel zinc-finger protein that promotes neuronal differentiation."
    Lamar E., Kintner C., Goulding M.
    Development 128:1335-1346(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, FUNCTION.
  2. "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 Y.-S., Jetten A.M.
    J. Biol. Chem. 277:10139-10149(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION.
    Strain: 129/SvJ and BALB/c.
    Tissue: Kidney.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  4. "Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1)."
    Kim S.-C., Kim Y.-S., Jetten A.M.
    Nucleic Acids Res. 33:6805-6815(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CTBP1 AND HDAC3, CLEAVAGE, SUBCELLULAR LOCATION.
  5. "The Kruppel-like zinc finger protein Glis2 functions as a negative modulator of the Wnt/beta-catenin signaling pathway."
    Kim Y.-S., Kang H.S., Jetten A.M.
    FEBS Lett. 581:858-864(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CTNNB1, MUTAGENESIS OF CYS-175, SUBCELLULAR LOCATION.
  6. "The transcriptional repressor Glis2 is a novel binding partner for p120 catenin."
    Hosking C.R., Ulloa F., Hogan C., Ferber E.C., Figueroa A., Gevaert K., Birchmeier W., Briscoe J., Fujita Y.
    Mol. Biol. Cell 18:1918-1927(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CTNND1, CLEAVAGE SITE, DNA-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-170; TYR-288 AND ASP-290.
  7. "Increased hedgehog signaling in postnatal kidney results in aberrant activation of nephron developmental programs."
    Li B., Rauhauser A.A., Dai J., Sakthivel R., Igarashi P., Jetten A.M., Attanasio M.
    Hum. Mol. Genet. 20:4155-4166(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SUFU.

Entry informationi

Entry nameiGLIS2_MOUSE
AccessioniPrimary (citable) accession number: Q8VDL9
Secondary accession number(s): Q8R4X9, Q99MY6, Q99P73
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: March 1, 2002
Last modified: June 8, 2016
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.