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   10-FEB-2021, entry version 158.
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   SMR; Q9H2S9; -.
DR   BioGRID; 122146; 24.
DR   CORUM; Q9H2S9; -.
DR   ELM; Q9H2S9; -.
DR   IntAct; Q9H2S9; 13.
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; 174 antibodies.
DR   DNASU; 64375; -.
DR   Ensembl; ENST00000262032; ENSP00000262032; ENSG00000123411. [Q9H2S9-1]
DR   Ensembl; ENST00000431367; ENSP00000412101; ENSG00000123411. [Q9H2S9-1]
DR   Ensembl; ENST00000547167; ENSP00000448419; ENSG00000123411. [Q9H2S9-1]
DR   GeneID; 64375; -.
DR   KEGG; hsa:64375; -.
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:ENSG00000123411.14; -.
DR   eggNOG; KOG1721; Eukaryota.
DR   GeneTree; ENSGT00940000158308; -.
DR   HOGENOM; CLU_025502_0_0_1; -.
DR   InParanoid; Q9H2S9; -.
DR   OMA; MHPVDLD; -.
DR   OrthoDB; 385551at2759; -.
DR   PhylomeDB; Q9H2S9; -.
DR   TreeFam; TF331189; -.
DR   PathwayCommons; Q9H2S9; -.
DR   SIGNOR; Q9H2S9; -.
DR   BioGRID-ORCS; 64375; 9 hits in 895 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 right adrenal gland and 200 other tissues.
DR   ExpressionAtlas; Q9H2S9; baseline and differential.
DR   Genevisible; Q9H2S9; HS.
DR   GO; GO:0016604; C:nuclear body; IDA:HPA.
DR   GO; GO:0000790; C:nuclear chromatin; IBA:GO_Central.
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          281..585
FT                   /note="Interaction with FOXP3"
FT                   /evidence="ECO:0000250|UniProtKB:Q8C208"
FT   MOTIF           425..429
FT                   /note="CTBP-binding motif PEDLA"
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:0000244|PubMed:28112733"
FT   CROSSLNK        500
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000244|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:0000244|PDB:2MA7"
FT   STRAND          187..189
FT                   /evidence="ECO:0000244|PDB:2MA7"
FT   TURN            190..193
FT                   /evidence="ECO:0000244|PDB:2MA7"
FT   STRAND          194..197
FT                   /evidence="ECO:0000244|PDB:2MA7"
FT   HELIX           199..205
FT                   /evidence="ECO:0000244|PDB:2MA7"
FT   TURN            206..209
FT                   /evidence="ECO:0000244|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
//