Reviewed, UniProtKB/Swiss-Prot Q9BZE0 (GLIS2_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 transcription repressor or as a transcription activator, depending on the cell context. Represses the transcriptional activation mediated by CTNNB1 in the Wnt 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. Interacts with CTNNB1 By similarity. Interacts with CTNND1. Ref.5
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.4
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	Defects in GLIS2 are the cause of nephronophthisis type 7 (NPHP7) [MIM:611498]. NPHP7 is 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. Ref.6
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	Nephronophthisis
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Developmental protein Repressor
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cellular transcription Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cellular transcription Inferred from sequence or structural similarity. Source: UniProtKB nervous system development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cellular transcription Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW transcription activator activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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
Amino acid modifications
	Modified residue	245	1	Phosphoserine Ref.3
Natural variations
	Natural variant	492	1	T → A: dbSNP rs8057701.		VAR_032256

Sequences

	Sequence		Length	Mass (Da)
	Q9BZE0-1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 3E2C27243DE5A85E	FASTA	524	55,705
	10 20 30 40 50 60 MHSLDEPLDL KLSITKLRAA REKRERTLGV VRPRALHREL GLVDDSPTLG 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: 11738817] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Kidney.
[2]	"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: 11262234] [Abstract] Cited for: IDENTIFICATION.
[3]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, MASS SPECTROMETRY. Tissue: Epithelium.
[4]	"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: 17289029] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"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: 17344476] [Abstract] Cited for: INTERACTION WITH CTNND1.
[6]	"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: 17618285] [Abstract] Cited for: INVOLVEMENT IN NPHP7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF325914 mRNA. Translation: AAK00954.1.
IPI	IPI00000274.
RefSeq	NP_115964.2.
UniGene	Hs.592087
3D structure databases
HSSP	HSSP built from PDB template 2GLI based on UniProtKB P08151.
SMR	Q9BZE0. Positions 170-317.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9BZE0.
Proteomic databases
PRIDE	Q9BZE0.
Genome annotation databases
Ensembl	ENST00000262366; ENSP00000262366; ENSG00000126603; Homo sapiens. [Genome view] ENST00000433375; ENSP00000395547; ENSG00000126603; Homo sapiens. [Genome view]
GeneID	84662.
KEGG	hsa:84662.
UCSC	uc002cwc.1. human.
Organism-specific databases
CTD	84662.
GeneCards	GC16P004304.
HGNC	HGNC:29450. GLIS2.
MIM	608539. gene. 611498. phenotype.
Orphanet	655. Medullary cystic kidney disease, autosomal recessive. 93592. Medullary cystic kidney disease, autosomal recessive, juvenile.
PharmGKB	PA134919876.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17876.
HOGENOM	HBG714295.
HOVERGEN	HBG101807.
InParanoid	Q9BZE0.
Gene expression databases
ArrayExpress	Q9BZE0.
Bgee	Q9BZE0.
CleanEx	HS_GLIS2.
Genevestigator	Q9BZE0.
Family and domain databases
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Gene3D	G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 2 hits.
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 Resources
NextBio	74642.
SOURCE	Search...

Entry information

Entry name

GLIS2_HUMAN

Accession

Primary (citable) accession number: Q9BZE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	June 1, 2001
Last modified:	March 2, 2010
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.