Q9BZE0 (GLIS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein GLIS2

Alternative name(s):
GLI-similar 2
Neuronal Krueppel-like protein

Gene names

Name:	GLIS2
Synonyms:	NKL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Ciliopathy Nephronophthisis
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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 nervous system development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	RNA 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 transcription regulatory region DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 524	524	Zinc finger protein GLIS2		PRO_0000286983
Regions
	Zinc finger	168 – 193	26	C2H2-type 1
	Zinc finger	202 – 229	28	C2H2-type 2; atypical
	Zinc finger	235 – 257	23	C2H2-type 3
	Zinc finger	263 – 287	25	C2H2-type 4
	Zinc finger	293 – 317	25	C2H2-type 5
	Region	35 – 174	140	Interaction with CTNND1 By similarity
	Region	71 – 137	67	Transcription activation By similarity
	Region	148 – 171	24	Transcription repression By similarity
	Compositional bias	363 – 460	98	Gly-rich
Sites
	Site	287 – 288	2	Cleavage By similarity
Natural variations
	Natural variant	492	1	T → A. Corresponds to variant rs8057701 [ dbSNP | Ensembl ].		VAR_032256
Experimental info
	Sequence conflict	49	1	P → L in AAK00954. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9BZE0 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: F38BA80C477FDC24	FASTA	524	55,689
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00000274.
RefSeq	NP_115964.2. NM_032575.2.
UniGene	Hs.592087.
3D structure databases
HSSP	HSSP built from PDB template 2GLI based on UniProtKB P08151.
ProteinModelPortal	Q9BZE0.
SMR	Q9BZE0. Positions 170-318.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2816833.
STRING	9606.ENSP00000262366.
PTM databases
PhosphoSite	Q9BZE0.
Polymorphism databases
DMDM	296434515.
Proteomic databases
PaxDb	Q9BZE0.
PRIDE	Q9BZE0.
Protocols and materials databases
DNASU	84662.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262366; ENSP00000262366; ENSG00000126603. ENST00000433375; ENSP00000395547; ENSG00000126603.
GeneID	84662.
KEGG	hsa:84662.
UCSC	uc002cwc.1. human.
Organism-specific databases
CTD	84662.
GeneCards	GC16P004365.
HGNC	HGNC:29450. GLIS2.
MIM	608539. gene. 611498. phenotype.
neXtProt	NX_Q9BZE0.
Orphanet	93592. Juvenile autosomal recessive medullary cystic kidney disease.
PharmGKB	PA134919876.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOGENOM	HOG000065778.
HOVERGEN	HBG101807.
InParanoid	Q9BZE0.
KO	K09233.
OMA	DKCLSPE.
OrthoDB	EOG4RNB8P.
PhylomeDB	Q9BZE0.
Gene expression databases
ArrayExpress	Q9BZE0.
Bgee	Q9BZE0.
CleanEx	HS_GLIS2.
Genevestigator	Q9BZE0.
Family and domain databases
Gene3D	3.30.160.60. 5 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 5 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 4 hits. PS50157. ZINC_FINGER_C2H2_2. 4 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GLIS2. human.
GenomeRNAi	84662.
NextBio	74642.
SOURCE	Search...

Entry information

Entry name

GLIS2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.