IKZF2 (IKAROS family zinc finger 2)

2007-04-01   Rupa Sridharan , Stephen Smale 

Room 6730 MacDonald Research Laboratories, Howard Hughes Medical Institute, 675 Charles Young Drive South, University of California, Los Angeles, CA 90095-1662, USA.

Identity

HGNC
LOCATION
2q34
LOCUSID
ALIAS
ANF1A2,HELIOS,ZNF1A2,ZNFN1A2
FUSION GENES

DNA/RNA

Description

143kb encoding 7 exons.

Transcription

12kb transcript, alternatively spliced to give two predominant isoforms.

Proteins

Note

526 amino acids. Mouse protein migrates at 70kD.
Atlas Image
Helios with the zinc finger domain shown as blocks and the exon junctions in black lines.

Description

Largest isoform contains four N-terminal zinc fingers used for DNA binding and two C terminal zinc fingers for homodimerization and heterodimerization with other Ikaros family members.

Expression

Largely restricted to the thymus. In mice, besides thymocytes and T cells, low levels are found in proB cells and bone marrow multipotent progenitors.

Localisation

Nuclear. Often localizes to the pericentric heterochromatin as punctate spots in cycling cells, with diffuse nuclear localization in non-cycling cells.

Function

Helios is thought to be important for T cell development and may function as a repressor of transcription. However, Helios mutant mice have not been reported. In mice, Helios can recruit the NuRD chromatin remodeling complex to the pericentric heterochromatin.

Homology

High level of identity to Ikaros over the zinc finger domains.

Implicated in

Entity name
Leukemia
Note
Shorter isoforms of Helios are expressed in certain human leukemias. They may function as dominant negative inhibitors of full-length proteins due to the lack of DNA binding domain. However, dominant negative functions have not been demonstrated experimentally.
Entity name
Lymphoma
Note
Overexpression of Helios in B cells of mice promotes lymphomagenesis. Overexpression of a DNA binding mutant in hematopoietic progenitors leads to aggressive and transplantable T cell lymphomas in 60% of the mice.

Bibliography

Pubmed IDLast YearTitleAuthors
161480932005Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.Dovat S et al
95125131998Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin.Hahm K et al
105418171999Human Helios, an Ikaros-related zinc finger DNA binding protein: cDNA cloning and tissue expression pattern.Hosokawa Y et al
95603391998Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors.Kelley CM et al
119372652002Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia.Nakase K et al
171104632007Expression of a non-DNA-binding isoform of Helios induces T-cell lymphoma in mice.Zhang Z et al

Other Information

Locus ID:

NCBI: 22807
MIM: 606234
HGNC: 13177
Ensembl: ENSG00000030419

Variants:

dbSNP: 22807
ClinVar: 22807
TCGA: ENSG00000030419
COSMIC: IKZF2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000030419ENST00000342002B4DWF2
ENSG00000030419ENST00000374319Q9UKS7
ENSG00000030419ENST00000374326Q9UKS7
ENSG00000030419ENST00000412444Q9UKS7
ENSG00000030419ENST00000431520Q9UKS7
ENSG00000030419ENST00000433134E7EUI1
ENSG00000030419ENST00000434687Q9UKS7
ENSG00000030419ENST00000439848Q9UKS7
ENSG00000030419ENST00000442445E7ES26
ENSG00000030419ENST00000451136A0A0A0MSL2
ENSG00000030419ENST00000452786E7EPU0
ENSG00000030419ENST00000453575Q9UKS7
ENSG00000030419ENST00000457361A0A0A0MT14

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
219186852011Helios expression is a marker of T cell activation and proliferation.151
233595042013Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans.88
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
202265312010A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells.75
176819522007Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes.64
264959862015Differences in Expression Level of Helios and Neuropilin-1 Do Not Distinguish Thymus-Derived from Extrathymically-Induced CD4+Foxp3+ Regulatory T Cells.46
232643412013Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus.38
255865482015Concomitant analysis of Helios and Neuropilin-1 as a marker to detect thymic derived regulatory T cells in naïve mice.37
215709172011Expanded subpopulation of FoxP3+ T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs.21
227539282012Cutting edge: in the absence of TGF-β signaling in T cells, fewer CD103+ regulatory T cells develop, but exuberant IFN-γ production renders mice more susceptible to helminth infection.16

Citation

Rupa Sridharan ; Stephen Smale

IKZF2 (IKAROS family zinc finger 2)

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

Online version: http://atlasgeneticsoncology.org/gene/42885/ikzf2