Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9BZE0 (GLIS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc finger protein GLIS2
Alternative name(s):
GLI-similar 2
Neuronal Krueppel-like protein
Gene names
Name:GLIS2
Synonyms:NKL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Represses the Hedgehog-dependent expression of Wnt4 By similarity. Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition By similarity. Represses transcriptional activation mediated by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation By similarity.

Subunit structure

Interacts with CTBP1 and HDAC3 By similarity. Interacts with CTNNB1 By similarity. Interacts with SUFU By similarity. Interacts with CTNND1. Ref.7

Subcellular location

Nucleus speckle By similarity. Cytoplasm By similarity.

Tissue specificity

Expressed at high levels in kidney and at low levels in heart, lung and placenta. Expressed in colon. Ref.1 Ref.6

Domain

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

Post-translational modification

C-terminus cleavage is induced by interaction with CTNND1 and enhanced by Src tyrosine kinase By similarity.

Involvement in disease

Nephronophthisis 7 (NPHP7) [MIM:611498]: An autosomal recessive disorder resulting in end-stage renal disease during childhood or adolescence. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the GLI C2H2-type zinc-finger protein family.

Contains 5 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseCiliopathy
Nephronophthisis
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Developmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of smoothened signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from sequence or structural similarity. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CTNNB1P352226EBI-7251368,EBI-491549

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 524524Zinc finger protein GLIS2
PRO_0000286983

Regions

Zinc finger168 – 19326C2H2-type 1
Zinc finger202 – 22928C2H2-type 2; atypical
Zinc finger235 – 25723C2H2-type 3
Zinc finger263 – 28725C2H2-type 4
Zinc finger293 – 31725C2H2-type 5
Region35 – 174140Interaction with CTNND1 By similarity
Region71 – 13767Transcription activation By similarity
Region148 – 17124Transcription repression By similarity
Compositional bias363 – 46098Gly-rich

Sites

Site287 – 2882Cleavage By similarity

Natural variations

Natural variant4921T → A.
Corresponds to variant rs8057701 [ dbSNP | Ensembl ].
VAR_032256

Experimental info

Sequence conflict491P → L in AAK00954. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9BZE0 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: F38BA80C477FDC24

FASTA52455,689
        10         20         30         40         50         60 
MHSLDEPLDL KLSITKLRAA REKRERTLGV VRPRALHREL GLVDDSPTPG SPGSPPSGFL 

        70         80         90        100        110        120 
LNSKFPEKVE GRFSAAPLVD LSLSPPSGLD SPNGSSSLSP ERQGNGDLPP VPSASDFQPL 

       130        140        150        160        170        180 
RYLDGVPSSF QFFLPLGSGG ALHLPASSFL TPPKDKCLSP DLPLPKQLVC RWAKCNQLFE 

       190        200        210        220        230        240 
LLQDLVDHVN DYHVKPEKDA GYCCHWEGCA RHGRGFNARY KMLIHIRTHT NEKPHRCPTC 

       250        260        270        280        290        300 
SKSFSRLENL KIHNRSHTGE KPYVCPYEGC NKRYSNSSDR FKHTRTHYVD KPYYCKMPGC 

       310        320        330        340        350        360 
HKRYTDPSSL RKHIKAHGHF VSHEQQELLQ LRPPPKPPLP APDGGPYVSG AQIIIPNPAA 

       370        380        390        400        410        420 
LFGGPGLPGL PLPLAPGPLD LSALACGNGG GSGGGGGMGP GLPGPVLPLN LAKNPLLPSP 

       430        440        450        460        470        480 
FGAGGLGLPV VSLLAGAAGG KAEGEKGRGS VPTRALGMEG HKTPLERTES SCSRPSPDGL 

       490        500        510        520 
PLLPGTVLDL STGVNSAASS PEALAPGWVV IPPGSVLLKP AVVN 

« Hide

References

« Hide 'large scale' references
[1]"Genomic structure of the gene encoding the human GLI-related, Kruppel-like zinc finger protein GLIS2."
Zhang F., Jetten A.M.
Gene 280:49-57(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Kidney.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: IDENTIFICATION.
[6]"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: TISSUE SPECIFICITY.
[7]"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: INTERACTION WITH CTNND1.
[8]"Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis."
Attanasio M., Uhlenhaut N.H., Sousa V.H., O'Toole J.F., Otto E., Anlag K., Klugmann C., Treier A.-C., Helou J., Sayer J.A., Seelow D., Nuernberg G., Becker C., Chudley A.E., Nuernberg P., Hildebrandt F., Treier M.
Nat. Genet. 39:1018-1024(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NPHP7.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF325914 mRNA. Translation: AAK00954.1.
AK126918 mRNA. Translation: BAG54396.1.
AC005356 Genomic DNA. No translation available.
AC012676 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85317.1.
CH471112 Genomic DNA. Translation: EAW85318.1.
RefSeqNP_115964.2. NM_032575.2.
XP_005255698.1. XM_005255641.2.
XP_005255699.1. XM_005255642.1.
UniGeneHs.592087.

3D structure databases

ProteinModelPortalQ9BZE0.
SMRQ9BZE0. Positions 170-318.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124182. 8 interactions.
IntActQ9BZE0. 8 interactions.
MINTMINT-2816833.
STRING9606.ENSP00000262366.

PTM databases

PhosphoSiteQ9BZE0.

Polymorphism databases

DMDM296434515.

Proteomic databases

PaxDbQ9BZE0.
PRIDEQ9BZE0.

Protocols and materials databases

DNASU84662.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262366; ENSP00000262366; ENSG00000126603.
ENST00000433375; ENSP00000395547; ENSG00000126603.
GeneID84662.
KEGGhsa:84662.
UCSCuc002cwc.1. human.

Organism-specific databases

CTD84662.
GeneCardsGC16P004365.
HGNCHGNC:29450. GLIS2.
MIM608539. gene.
611498. phenotype.
neXtProtNX_Q9BZE0.
Orphanet329469. Acute megakaryoblastic leukemia without Down syndrome.
93592. Juvenile autosomal recessive medullary cystic kidney disease.
PharmGKBPA134919876.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000065778.
HOVERGENHBG101807.
InParanoidQ9BZE0.
KOK09233.
OMADKCLSPE.
OrthoDBEOG70CR6P.
PhylomeDBQ9BZE0.
TreeFamTF351425.

Enzyme and pathway databases

SignaLinkQ9BZE0.

Gene expression databases

ArrayExpressQ9BZE0.
BgeeQ9BZE0.
CleanExHS_GLIS2.
GenevestigatorQ9BZE0.

Family and domain databases

Gene3D3.30.160.60. 5 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 5 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGLIS2. human.
GenomeRNAi84662.
NextBio74642.
PROQ9BZE0.
SOURCESearch...

Entry information

Entry nameGLIS2_HUMAN
AccessionPrimary (citable) accession number: Q9BZE0
Secondary accession number(s): B3KX84
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM