IKZF4_HUMAN
ID IKZF4_HUMAN Reviewed; 585 AA.
AC Q9H2S9; Q96JP3;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Zinc finger protein Eos;
DE AltName: Full=Ikaros family zinc finger protein 4;
GN Name=IKZF4; Synonyms=KIAA1782, ZNFN1A4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-585 (ISOFORM 1), FUNCTION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH IKZF1; IKZF2; IKZF3 AND IKZF5.
RX PubMed=10978333; DOI=10.1074/jbc.m005457200;
RA Perdomo J., Holmes M., Chong B., Crossley M.;
RT "Eos and pegasus, two members of the Ikaros family of proteins with
RT distinct DNA binding activities.";
RL J. Biol. Chem. 275:38347-38354(2000).
RN [4]
RP FUNCTION.
RX PubMed=12015313; DOI=10.1074/jbc.m201694200;
RA Koipally J., Georgopoulos K.;
RT "A molecular dissection of the repression circuitry of Ikaros.";
RL J. Biol. Chem. 277:27697-27705(2002).
RN [5]
RP FUNCTION, INTERACTION WITH CTBP2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 425-PRO--ASP-427.
RX PubMed=12444977; DOI=10.1046/j.1432-1033.2002.03313.x;
RA Perdomo J., Crossley M.;
RT "The Ikaros family protein Eos associates with C-terminal-binding protein
RT corepressors.";
RL Eur. J. Biochem. 269:5885-5892(2002).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-100 AND LYS-500, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [8]
RP STRUCTURE BY NMR OF 155-216 IN COMPLEX WITH ZINC IONS.
RG Northeast structural genomics consortium (NESG);
RT "Solution NMR structure of zinc finger protein EOS from Homo sapiens,
RT Northeast structural genomics consortium (NESG) target HR7992A.";
RL Submitted (SEP-2013) to the PDB data bank.
CC -!- FUNCTION: DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-
CC binding sequence. Transcriptional repressor. Interacts with SPI1 and
CC MITF to repress transcription of the CTSK and ACP5 promoters via
CC recruitment of corepressors SIN3A and CTBP2. May be involved in the
CC development of central and peripheral nervous systems. Essential for
CC the inhibitory function of regulatory T-cells (Treg). Mediates FOXP3-
CC mediated gene silencing in regulatory T-cells (Treg) via recruitment of
CC corepressor CTBP1 (By similarity). {ECO:0000250|UniProtKB:Q8C208,
CC ECO:0000269|PubMed:10978333, ECO:0000269|PubMed:12015313,
CC ECO:0000269|PubMed:12444977}.
CC -!- SUBUNIT: Self-associates. Interacts with other family members; IKZF1,
CC IKZF2, IKZF3 and IKZF5. Interacts with CTBP2. Interacts with SPI1,
CC MITF, FOXP3 and CTBP1 (By similarity). {ECO:0000250|UniProtKB:Q8C208,
CC ECO:0000269|PubMed:12444977}.
CC -!- INTERACTION:
CC Q9H2S9; O00311: CDC7; NbExp=3; IntAct=EBI-1640423, EBI-374980;
CC Q9H2S9; P48730: CSNK1D; NbExp=3; IntAct=EBI-1640423, EBI-751621;
CC Q9H2S9; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-1640423, EBI-348259;
CC Q9H2S9; Q9H8S9: MOB1A; NbExp=3; IntAct=EBI-1640423, EBI-748229;
CC Q9H2S9; Q70IA8: MOB3C; NbExp=3; IntAct=EBI-1640423, EBI-9679267;
CC Q9H2S9; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-1640423, EBI-11974855;
CC Q9H2S9; Q15560: TCEA2; NbExp=3; IntAct=EBI-1640423, EBI-710310;
CC Q9H2S9; P42681: TXK; NbExp=3; IntAct=EBI-1640423, EBI-7877438;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12444977}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H2S9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H2S9-2; Sequence=VSP_027688;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, low levels of
CC expression in heart, thymus, kidney, liver, and spleen. Expressed in
CC the hematopoietic cell lines MOLT-4, NALM-6 and K-562. Highly expressed
CC in THP-1 and M-07e cell lines, which have characteristics of myeloid
CC and early megakaryocytic cells respectively.
CC {ECO:0000269|PubMed:10978333}.
CC -!- DOMAIN: The N-terminal zinc fingers are involved in sequence-specific
CC DNA binding and heterotypic associations with other family members.
CC -!- DOMAIN: C-terminal zinc fingers mediate homodimerization.
CC -!- MISCELLANEOUS: 'Eos' means 'rising sun' in Greek.
CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG39221.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB47411.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB058685; BAB47411.1; ALT_INIT; mRNA.
DR EMBL; BX647761; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF230809; AAG39221.1; ALT_INIT; mRNA.
DR CCDS; CCDS44917.1; -. [Q9H2S9-1]
DR RefSeq; NP_071910.3; NM_022465.3. [Q9H2S9-1]
DR RefSeq; XP_016875294.1; XM_017019805.1.
DR RefSeq; XP_016875295.1; XM_017019806.1. [Q9H2S9-1]
DR RefSeq; XP_016875296.1; XM_017019807.1. [Q9H2S9-1]
DR RefSeq; XP_016875297.1; XM_017019808.1. [Q9H2S9-1]
DR RefSeq; XP_016875298.1; XM_017019809.1. [Q9H2S9-1]
DR RefSeq; XP_016875299.1; XM_017019810.1. [Q9H2S9-1]
DR RefSeq; XP_016875300.1; XM_017019811.1. [Q9H2S9-1]
DR PDB; 2MA7; NMR; -; A=155-216.
DR PDBsum; 2MA7; -.
DR AlphaFoldDB; Q9H2S9; -.
DR SMR; Q9H2S9; -.
DR BioGRID; 122146; 49.
DR CORUM; Q9H2S9; -.
DR ELM; Q9H2S9; -.
DR IntAct; Q9H2S9; 14.
DR STRING; 9606.ENSP00000262032; -.
DR iPTMnet; Q9H2S9; -.
DR PhosphoSitePlus; Q9H2S9; -.
DR BioMuta; IKZF4; -.
DR DMDM; 158564025; -.
DR jPOST; Q9H2S9; -.
DR MassIVE; Q9H2S9; -.
DR MaxQB; Q9H2S9; -.
DR PaxDb; Q9H2S9; -.
DR PeptideAtlas; Q9H2S9; -.
DR PRIDE; Q9H2S9; -.
DR ProteomicsDB; 80588; -. [Q9H2S9-1]
DR ProteomicsDB; 80589; -. [Q9H2S9-2]
DR Antibodypedia; 27854; 185 antibodies from 30 providers.
DR DNASU; 64375; -.
DR Ensembl; ENST00000262032.9; ENSP00000262032.5; ENSG00000123411.15. [Q9H2S9-1]
DR Ensembl; ENST00000431367.6; ENSP00000412101.3; ENSG00000123411.15. [Q9H2S9-1]
DR Ensembl; ENST00000547167.6; ENSP00000448419.1; ENSG00000123411.15. [Q9H2S9-1]
DR GeneID; 64375; -.
DR KEGG; hsa:64375; -.
DR MANE-Select; ENST00000547167.6; ENSP00000448419.1; NM_022465.4; NP_071910.3.
DR UCSC; uc001sjb.1; human. [Q9H2S9-1]
DR CTD; 64375; -.
DR DisGeNET; 64375; -.
DR GeneCards; IKZF4; -.
DR HGNC; HGNC:13179; IKZF4.
DR HPA; ENSG00000123411; Low tissue specificity.
DR MIM; 606239; gene.
DR neXtProt; NX_Q9H2S9; -.
DR OpenTargets; ENSG00000123411; -.
DR PharmGKB; PA162391948; -.
DR VEuPathDB; HostDB:ENSG00000123411; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000158308; -.
DR HOGENOM; CLU_025502_0_0_1; -.
DR InParanoid; Q9H2S9; -.
DR OMA; NSTPICN; -.
DR OrthoDB; 385551at2759; -.
DR PhylomeDB; Q9H2S9; -.
DR TreeFam; TF331189; -.
DR PathwayCommons; Q9H2S9; -.
DR SignaLink; Q9H2S9; -.
DR SIGNOR; Q9H2S9; -.
DR BioGRID-ORCS; 64375; 16 hits in 1097 CRISPR screens.
DR ChiTaRS; IKZF4; human.
DR GeneWiki; IKZF4; -.
DR GenomeRNAi; 64375; -.
DR Pharos; Q9H2S9; Tbio.
DR PRO; PR:Q9H2S9; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9H2S9; protein.
DR Bgee; ENSG00000123411; Expressed in buccal mucosa cell and 173 other tissues.
DR ExpressionAtlas; Q9H2S9; baseline and differential.
DR Genevisible; Q9H2S9; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0043425; F:bHLH transcription factor binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IMP:CAFA.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IMP:CAFA.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 6.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..585
FT /note="Zinc finger protein Eos"
FT /id="PRO_0000299468"
FT ZN_FING 159..181
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 187..209
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 215..237
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 248..271
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 530..552
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 558..582
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..585
FT /note="Interaction with FOXP3"
FT /evidence="ECO:0000250|UniProtKB:Q8C208"
FT REGION 410..489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 425..429
FT /note="CTBP-binding motif PEDLA"
FT COMPBIAS 78..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKS7"
FT MOD_RES 335
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKS7"
FT CROSSLNK 100
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..61
FT /note="MHTPPALPRRFQGGGRVRTPGSHRQGKDNLERDPSGGCVPDFLPQAQDSNHF
FT IMESLFCES -> MDSRYLQLQLYLPSCSLLQG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_027688"
FT MUTAGEN 425..427
FT /note="PED->AAA: No effect on CTBP2 interaction."
FT /evidence="ECO:0000269|PubMed:12444977"
FT CONFLICT 145
FT /note="E -> K (in Ref. 3; AAG39221)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="P -> A (in Ref. 3; AAG39221)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="A -> G (in Ref. 3; AAG39221)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="N -> H (in Ref. 3; AAG39221)"
FT /evidence="ECO:0000305"
FT CONFLICT 524
FT /note="G -> S (in Ref. 3; AAG39221)"
FT /evidence="ECO:0000305"
FT HELIX 173..181
FT /evidence="ECO:0007829|PDB:2MA7"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:2MA7"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:2MA7"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:2MA7"
FT HELIX 199..205
FT /evidence="ECO:0007829|PDB:2MA7"
FT TURN 206..209
FT /evidence="ECO:0007829|PDB:2MA7"
SQ SEQUENCE 585 AA; 64106 MW; 42AE169A3E2E14D3 CRC64;
MHTPPALPRR FQGGGRVRTP GSHRQGKDNL ERDPSGGCVP DFLPQAQDSN HFIMESLFCE
SSGDSSLEKE FLGAPVGPSV STPNSQHSSP SRSLSANSIK VEMYSDEESS RLLGPDERLL
EKDDSVIVED SLSEPLGYCD GSGPEPHSPG GIRLPNGKLK CDVCGMVCIG PNVLMVHKRS
HTGERPFHCN QCGASFTQKG NLLRHIKLHS GEKPFKCPFC NYACRRRDAL TGHLRTHSVS
SPTVGKPYKC NYCGRSYKQQ STLEEHKERC HNYLQSLSTE AQALAGQPGD EIRDLEMVPD
SMLHSSSERP TFIDRLANSL TKRKRSTPQK FVGEKQMRFS LSDLPYDVNS GGYEKDVELV
AHHSLEPGFG SSLAFVGAEH LRPLRLPPTN CISELTPVIS SVYTQMQPLP GRLELPGSRE
AGEGPEDLAD GGPLLYRPRG PLTDPGASPS NGCQDSTDTE SNHEDRVAGV VSLPQGPPPQ
PPPTIVVGRH SPAYAKEDPK PQEGLLRGTP GPSKEVLRVV GESGEPVKAF KCEHCRILFL
DHVMFTIHMG CHGFRDPFEC NICGYHSQDR YEFSSHIVRG EHKVG
