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Details on Person UniProt:Q13422 IKZF1

Class:Id	ReferenceGeneProduct:57206
_chainChangeLog	chain:1-519 added on Sat February 7 2015
_displayName	UniProt:Q13422 IKZF1
_timestamp	2024-11-03 19:36:51
chain	chain:1-519
checksum	7B0129C4E3FE41A8
comment	FUNCTION Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067).SUBUNIT Heterodimer formed by the various isoforms; this modulates transcription regulator activity (PubMed:17135265, PubMed:17934067). Heterodimer with other IKAROS family members. Interacts with IKZF4 AND IKZF5 (PubMed:10978333). Component of the chromatin-remodeling NuRD repressor complex which includes at least HDAC1, HDAC2, RBBP4, RBBP7, IKZF1, MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4. Interacts directly with the CHD4 component of the NuRD complex. Interacts directly with SMARCA4; the interaction associates IKFZ1 with the BAF complex (PubMed:10204490). Interacts with SUMO1; the interaction sumoylates IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform alpha); the interaction promotes sumoylation and reduces transcription repression. Interacts, to a lesser extent, with PIAS3. Interacts with PPP1CC; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with IKZF3 (By similarity).INTERACTION In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events.SUBCELLULAR LOCATION In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events (By similarity).SUBCELLULAR LOCATION Abundantly expressed in thymus, spleen and peripheral blood Leukocytes and lymph nodes. Lower expression in bone marrow and small intestine.DOMAIN The N-terminal zinc-fingers 2 and 3 are required for DNA binding as well as for targeting IKFZ1 to pericentromeric heterochromatin.DOMAIN The C-terminal zinc-finger domain is required for dimerization.PTM Phosphorylation controls cell-cycle progression from late G(1) stage to S stage. Hyperphosphorylated during G2/M phase. Dephosphorylated state during late G(1) phase. Phosphorylation on Thr-140 is required for DNA and pericentromeric location during mitosis. CK2 is the main kinase, in vitro. GSK3 and CDK may also contribute to phosphorylation of the C-terminal serine and threonine residues. Phosphorylation on these C-terminal residues reduces the DNA-binding ability. Phosphorylation/dephosphorylation events on Ser-13 and Ser-295 regulate TDT expression during thymocyte differentiation. Dephosphorylation by protein phosphatase 1 regulates stability and pericentromeric heterochromatin location. Phosphorylated in both lymphoid and non-lymphoid tissues (By similarity). Phosphorylation at Ser-361 and Ser-364 downstream of SYK induces nuclear translocation.PTM Sumoylated. Simultaneous sumoylation on the 2 sites results in a loss of both HDAC-dependent and HDAC-independent repression. Has no effect on pericentromeric heterochromatin location. Desumoylated by SENP1 (By similarity).PTM Polyubiquitinated.DISEASE Defects in IKZF1 are frequent occurrences (28.6%) in acute lymphoblasic leukemia (ALL). Such alterations or deletions lead to poor prognosis for ALL.DISEASE Chromosomal aberrations involving IKZF1 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), with BCL6.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the Ikaros C2H2-type zinc-finger protein family.
description	recommendedName: DNA-binding protein Ikaros alternativeName: Ikaros family zinc finger protein 1 alternativeName: Lymphoid transcription factor LyF-1
geneName	IKZF1 IK1 IKAROS LYF1 ZNFN1A1
identifier	Q13422
isSequenceChanged	FALSE
keyword	3D-structure Activator Alternative splicing Cell cycle Chromatin regulator Chromosomal rearrangement Cytoplasm Developmental protein Disease variant DNA-binding Isopeptide bond Metal-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Repressor Transcription Transcription regulation Ubl conjugation Zinc Zinc-finger
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	IKZF1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8989009] ENSEMBL:ENSG00000185811 IKZF1 [Homo sapiens]
secondaryIdentifier	IKZF1_HUMAN A4D260 B4E0Z1 D3DVM5 O00598 Q53XL2 Q69BM4 Q8WVA3
sequenceLength	519
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:148760] UniProt:Q13422-2 IKZF1 [Homo sapiens] [ReferenceIsoform:148761] UniProt:Q13422-3 IKZF1 [Homo sapiens] [ReferenceIsoform:148762] UniProt:Q13422-4 IKZF1 [Homo sapiens] [ReferenceIsoform:148763] UniProt:Q13422-5 IKZF1 [Homo sapiens] [ReferenceIsoform:148764] UniProt:Q13422-6 IKZF1 [Homo sapiens] [ReferenceIsoform:148765] UniProt:Q13422-7 IKZF1 [Homo sapiens] [ReferenceIsoform:405607] UniProt:Q13422-1 IKZF1 [Homo sapiens] [ReferenceIsoform:8977874] UniProt:Q13422-8 IKZF1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:158567] IKZF1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9944878] IKZF1 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q13422 IKZF1 (57206)