Q03267
uniprot
Q03267
canonical
amino_acid_sequence
MDVDEGQDMSQVSGKESPPVSDTPDEGDEPMPVPEDLSTTSGAQQNSKSDRGMGSNVKVETQSDEENGRACEMNGEECAEDLRMLDASGEKMNGSHRDQGSSALSGVGGIRLPNGKLKCDICGIVCIGPNVLMVHKRSHTERPFQCNQCGASFTQKGNLLRHIKLHSGEKPFKCHLCNYACRRRDALTGHLRTHSVGKPHKCGYCGRSYKQRSSLEEHKERCHNYLESMGLPGVCPVIKEETNHNEMAEDLCKIGAERSLVLDRLASNVAKRKSSMPQKFLGDKCLSDMPYDSANYEKEDMMTSHVMDQAINNAINYLGAESLRPLVQTPPGSSEVVPVISSMYQLHKPPSDGPPRSNHSAQDAVDNLLLLSKAKSVSSEREASPSNSCQDSTDTESNAEEQRSGLIYLTNHINPHARNGLALKEEQRAYEVLRAASENSQDAFRVVSTSGEQLKVYKCEHCRVLFLDHVMYTIHMGCHGCHGFRDPFECNMCGYHSQDRYEFSSHITRGEHRYHLS
uniprot
proteins
function
FUNCTION: Transcription regulator of hematopoietic cell differentiation (PubMed:1439790). Binds gamma-satellite DNA (By similarity). Binds with higher affinity to gamma satellite A. 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 (terminal 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 (PubMed:11003653). Increases normal apoptosis in adult erythroid cells (PubMed:16369973). Confers early temporal competence to retinal progenitor cells (RPCs) (PubMed:18940586). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (By similarity). Recognized by CRBN and is targeted for degradation by DCX (DDB1-CUL4-X-box) E3 protein ligase complex (By similarity). {ECO:0000250|UniProtKB:Q13422, ECO:0000269|PubMed:11003653, ECO:0000269|PubMed:1439790, ECO:0000269|PubMed:15024069, ECO:0000269|PubMed:15767674, ECO:0000269|PubMed:16369973, ECO:0000269|PubMed:18223295, ECO:0000269|PubMed:18940586}.
uniprot
proteins
mass_dalton
57336
uniprot
proteins
mutagenesis
MUTAGEN 13; /note="S->A: Abolishes phosphorylation. No change in binding to gamma satellites A and B. No change in pericentromeric location. Increased DNA binding affinity toward TDT."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 13; /note="S->D: Decreased binding to gamma satellite A by 5-fold and to gamma satellite B by 3-fold. Diffuse nuclear location."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 23; /note="T->A: Abolishes phosphorylation. No change in binding to gamma satellites A and B. No change in pericentromeric location."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 23; /note="T->D: Decreased binding to gamma satellites A and B by 3-fold. Little change in pericentromeric location."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 58; /note="K->R: Some loss of sumoylation. Complete loss of sumoylation, increased repressor activity but no change in pericentromeric heterochromatin location; when associated with R-240 and R-459."; /evidence="ECO:0000269|PubMed:15767674"; MUTAGEN 63; /note="S->A: No change in pericentromeric location. Greatly reduced phosphorylation; when associated with A-384; A-386; A-388; A392 and A-393. No effect on DNA-binding activity. Increased DNA-binding activity; when associated with A-384; A-386; A-388; A-392 and A-393."; /evidence="ECO:0000269|PubMed:15024069, ECO:0000269|PubMed:18223295"; MUTAGEN 63; /note="S->D: No change in binding to gamma satellites A and B. No change in pericentromeric location."; /evidence="ECO:0000269|PubMed:15024069, ECO:0000269|PubMed:18223295"; MUTAGEN 101; /note="S->A: Abolishes phosphorylation. No change in pericentromeric location."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 101; /note="S->D: No change in binding to gamma satellites A and B. No change in pericentromeric location."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 140; /note="T->A: Abolishes phosphorylation, DNA binding and pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with A-167 and A-195."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 140; /note="T->E: Abolishes phosphorylation, DNA binding and pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with E-167 and D-195."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 152; /note="S->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 153; /note="F->A: Disrupts pericentromeric heterochromatin location. Partial cytoplasmic location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 154; /note="T->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 155; /note="Q->A: Loss of pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 156; /note="K->A: Disrupts pericentromeric heterochromatin location. Partial cytoplasmic location."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 157; /note="G->A: Loss of pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 158; /note="N->A: Loss of pericentromeric heterochromatin location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 159; /note="L->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 160; /note="L->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 161; /note="R->A: Disrupts pericentromeric heterochromatin location. Partial cytoplasmic location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 167; /note="S->A: Abolishes phosphorylation, no effect on DNA binding nor on pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with A-140 and A-195."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 167; /note="S->E: Abolishes phosphorylation, no effect on DNA binding nor on pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with E-140 and D-195."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 173; /note="K->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 178; /note="N->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 179; /note="Y->A: Loss of pericentromeric heterochromatin location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 180; /note="A->L: Loss of pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 181; /note="C->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 182; /note="R->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 183; /note="R->A: Disrupts pericentromeric heterochromatin location. Partial cytoplasmic location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 184; /note="R->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 185; /note="D->A: No effect on pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 186; /note="A->L: No effect on pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 187; /note="L->A: Loss of pericentromeric heterochromatin location. Abolishes DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 188; /note="T->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 189; /note="G->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 191; /note="L->A: No effect on pericentromeric heterochromatin location. Disrupted DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 192; /note="R->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 193; /note="T->A: No effect on pericentromeric heterochromatin location. No change in DNA binding."; /evidence="ECO:0000269|PubMed:10970879"; MUTAGEN 195; /note="S->A: Abolishes phosphorylation, no effect on DNA binding nor on pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with A-140 and A-167."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 195; /note="S->D: Abolishes phosphorylation, no effect on DNA binding nor on pericentromeric location. Loss of DNA binding and pericentromeric location; when associated with E-140 and E-167."; /evidence="ECO:0000269|PubMed:12464629"; MUTAGEN 239; /note="K->R: Some loss of sumoylation. Complete loss of sumoylation, increased repressor activity but no change in pericentromeric heterochromatin location.; when associated with R-58 and R-459."; /evidence="ECO:0000269|PubMed:15767674"; MUTAGEN 293; /note="S->A: Abolishes phosphorylation. No change in binding to gamma satellites A and B. No change in pericentromeric location. Increased DNA binding affinity toward TDT."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 293; /note="S->D: Decreased binding to gamma satellite A by 5-fold and to gamma satellite B by 3-fold. Diffuse nuclear location. Decreased DNA binding affinity toward TdT by 3-fold."; /evidence="ECO:0000269|PubMed:18223295"; MUTAGEN 384; /note="S->A: Significantly reduced phosphorylation and 2- to 3-fold increase in ability to arrest in G(1); when associated with A-386; A-388; A-392 and A-393. and A-392. Further reduction in phosphorylation; when associated with A-63; A-386; A-388; A-392 and A-393."; /evidence="ECO:0000269|PubMed:15024069"; MUTAGEN 386; /note="S->A: Significantly reduced phosphorylation and 2- to 3-fold increase in ability to arrest in G(1); when associated with A-384; A-388; A-392 and A-393. Further reduction in phosphorylation; when associated with A-63; A-384; A-388; A-392 and A-393."; /evidence="ECO:0000269|PubMed:15024069"; MUTAGEN 388; /note="S->A: Significantly reduced phosphorylation and 2- to 3-fold increase in ability to arrest in G(1); when associated with A-384; A-386; A-392 and A-393. Further reduction in phosphorylation; when associated with A-63; A-384; A-386; A-392 and A-393."; /evidence="ECO:0000269|PubMed:15024069"; MUTAGEN 392; /note="S->A: Significantly reduced phosphorylation and 2- to 3-fold increase in ability to arrest in G(1); when associated with A-384; A-386; A-388 and A-392. Further reduction in phosphorylation; when associated with A-63; A-384; A-386; A-386 and A-388."; /evidence="ECO:0000269|PubMed:15024069"; MUTAGEN 393; /note="T->A: Significantly reduced phosphorylation and 2- to 3-fold increase in ability to arrest in G(1); when associated with A-384; A-386; A-388 and A-392. Further reduction in phosphorylation; when associated with A-63; A-384; A-386; A-388 and A-392."; /evidence="ECO:0000269|PubMed:15024069"; MUTAGEN 424; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:15767674"; MUTAGEN 458; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:15767674"; MUTAGEN 465..467; /note="LFL->AFA: Abolishes binding of PP1CC, decreases DNA binding, abolishes pericentromeric location, and results in IKAROS degradation."; /evidence="ECO:0000269|PubMed:19282287
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-357 and Ser-360 downstream of SYK induces nuclear translocation (By similarity). 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-293 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. {ECO:0000250, ECO:0000269|PubMed:12464629, ECO:0000269|PubMed:15024069, ECO:0000269|PubMed:18223295, ECO:0000269|PubMed:19282287}.; 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. {ECO:0000269|PubMed:15767674}.; PTM: Polyubiquitinated. {ECO:0000269|PubMed:19282287}.
uniprot
proteins
protein_family
Ikaros C2H2-type zinc-finger protein family
uniprot
proteins
pubmed
10544193
uniprot
proteins
pubmed
10970879
uniprot
proteins
pubmed
11003653
uniprot
proteins
pubmed
12464629
uniprot
proteins
pubmed
1439790
uniprot
proteins
pubmed
15024069
uniprot
proteins
pubmed
15767674
uniprot
proteins
pubmed
16369973
uniprot
proteins
pubmed
18223295
uniprot
proteins
pubmed
18940586
uniprot
proteins
pubmed
19282287
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
7935426
uniprot
proteins
pubmed
9155026
uniprot
proteins
sequence_length
517
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10970879, ECO:0000269|PubMed:12464629, ECO:0000269|PubMed:18223295, ECO:0000269|PubMed:19282287}. Note=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. {ECO:0000250|UniProtKB:Q13422}.; SUBCELLULAR LOCATION: [Isoform V]: Nucleus. Note=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: [Isoform I]: Cytoplasm.
uniprot
proteins