IKZF3_MOUSE
ID IKZF3_MOUSE Reviewed; 507 AA.
AC O08900; B1AQE6;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Zinc finger protein Aiolos;
DE AltName: Full=Ikaros family zinc finger protein 3;
GN Name=Ikzf3; Synonyms=Zfpn1a3, Znfn1a3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IKZF1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9155026; DOI=10.1093/emboj/16.8.2004;
RA Morgan B., Sun L., Avitahl N., Andrikopoulos K., Ikeda T., Gonzales E.,
RA Wu P., Neben S., Georgopoulos K.;
RT "Aiolos, a lymphoid restricted transcription factor that interacts with
RT Ikaros to regulate lymphocyte differentiation.";
RL EMBO J. 16:2004-2013(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=9806640; DOI=10.1016/s1074-7613(00)80637-8;
RA Wang J.H., Avitahl N., Cariappa A., Friedrich C., Ikeda T., Renold A.,
RA Andrikopoulos K., Liang L., Pillai S., Morgan B.A., Georgopoulos K.;
RT "Aiolos regulates B cell activation and maturation to effector state.";
RL Immunity 9:543-553(1998).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-20; SER-22; SER-42 AND
RP SER-377, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF GLY-158.
RX PubMed=34155405; DOI=10.1038/s41590-021-00951-z;
RA Yamashita M., Kuehn H.S., Okuyama K., Okada S., Inoue Y., Mitsuiki N.,
RA Imai K., Takagi M., Kanegane H., Takeuchi M., Shimojo N., Tsumura M.,
RA Padhi A.K., Zhang K.Y.J., Boisson B., Casanova J.L., Ohara O.,
RA Rosenzweig S.D., Taniuchi I., Morio T.;
RT "A variant in human AIOLOS impairs adaptive immunity by interfering with
RT IKAROS.";
RL Nat. Immunol. 22:893-903(2021).
CC -!- FUNCTION: Transcription factor that plays an important role in the
CC regulation of lymphocyte differentiation. Binds to GGGAA. Plays an
CC essential role in regulation of B-cell differentiation, proliferation
CC and maturation to an effector state. Involved in regulating BCL2
CC expression and controlling apoptosis in T-cells in an IL2-dependent
CC manner. {ECO:0000269|PubMed:34155405, ECO:0000269|PubMed:9155026,
CC ECO:0000269|PubMed:9806640}.
CC -!- SUBUNIT: Homodimer. Heterodimer with other IKAROS family members.
CC Interacts with IKZF4 AND IKZF5. Interacts with HRAS. Interacts with
CC FOXP3; this interaction may be required for silencing target genes and
CC regulating the suppressive activity of FOXP3-positive regulatory T-
CC cells (Treg). Interacts with BCL21L isoform Bcl-X(L); this interaction
CC blocks the anti-apoptotic role of BCL21L. Associates with histone
CC deacetylase complexes containing HDAC1, MTA2 and SIN3A (By similarity).
CC Interacts with IKZF1. {ECO:0000250|UniProtKB:Q9UKT9,
CC ECO:0000269|PubMed:9155026}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9155026}. Cytoplasm
CC {ECO:0000269|PubMed:9155026}.
CC -!- TISSUE SPECIFICITY: Expression is restricted to lymphoid tissues.
CC Expressed at highest levels in spleen and at lower levels in the thymus
CC and bone marrow. First detected in more committed lymphoid progenitors
CC and strongly up-regulated as these differentiate into pre-T and pre-B
CC cell precursors. {ECO:0000269|PubMed:9155026}.
CC -!- DOMAIN: C2H2-type 5 and C2H2-type 6 mediate homodimerization and
CC heterodimerization. {ECO:0000250|UniProtKB:Q9UKT9}.
CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF001293; AAB58795.1; -; mRNA.
DR EMBL; AL591125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466556; EDL16146.1; -; Genomic_DNA.
DR CCDS; CCDS25352.1; -.
DR RefSeq; NP_035901.1; NM_011771.1.
DR AlphaFoldDB; O08900; -.
DR SMR; O08900; -.
DR BioGRID; 204702; 26.
DR CORUM; O08900; -.
DR IntAct; O08900; 3.
DR STRING; 10090.ENSMUSP00000099430; -.
DR iPTMnet; O08900; -.
DR PhosphoSitePlus; O08900; -.
DR EPD; O08900; -.
DR jPOST; O08900; -.
DR MaxQB; O08900; -.
DR PaxDb; O08900; -.
DR PeptideAtlas; O08900; -.
DR PRIDE; O08900; -.
DR ProteomicsDB; 267116; -.
DR Antibodypedia; 4475; 504 antibodies from 39 providers.
DR DNASU; 22780; -.
DR Ensembl; ENSMUST00000103141; ENSMUSP00000099430; ENSMUSG00000018168.
DR GeneID; 22780; -.
DR KEGG; mmu:22780; -.
DR UCSC; uc007lgl.1; mouse.
DR CTD; 22806; -.
DR MGI; MGI:1342542; Ikzf3.
DR VEuPathDB; HostDB:ENSMUSG00000018168; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160462; -.
DR HOGENOM; CLU_025502_1_0_1; -.
DR InParanoid; O08900; -.
DR OMA; CCNVYEF; -.
DR OrthoDB; 385551at2759; -.
DR PhylomeDB; O08900; -.
DR TreeFam; TF331189; -.
DR BioGRID-ORCS; 22780; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Ikzf3; mouse.
DR PRO; PR:O08900; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O08900; protein.
DR Bgee; ENSMUSG00000018168; Expressed in mesenteric lymph node and 75 other tissues.
DR Genevisible; O08900; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; IMP:UniProtKB.
DR GO; GO:0030888; P:regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0045619; P:regulation of lymphocyte differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 6.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW B-cell activation; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..507
FT /note="Zinc finger protein Aiolos"
FT /id="PRO_0000047091"
FT ZN_FING 117..139
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 145..167
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 173..195
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 201..223
FT /note="C2H2-type 4; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 450..472
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 478..502
FT /note="C2H2-type 6; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..502
FT /note="Mediates homodimerization and heterodimerization"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT COMPBIAS 34..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 325
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 61
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT CROSSLNK 100
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT CROSSLNK 244
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT9"
FT MUTAGEN 158
FT /note="G->R: No effect on protein abundance. Changed DNA-
FT binding transcription factor activity. Changed sequence-
FT specific DNA binding. Binds novel and non-specific DNA
FT motifs and acts as a dominant negative through its
FT homodimerization and heterodimerization activities.
FT Profound B cell development defects observed in homozygous
FT or heterozygous animals. Impairs the differentiation of
FT cells in adaptive immunity."
FT /evidence="ECO:0000269|PubMed:34155405"
FT CONFLICT 114
FT /note="G -> S (in Ref. 1; AAB58795)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="L -> F (in Ref. 1; AAB58795)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="N -> M (in Ref. 1; AAB58795)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 57967 MW; 103D46D0C6E236F7 CRC64;
MEDIQPTVEL KSTEEQPLPT ESPDALNDYS LPKPHEIENV DSREAPANED EDAGEDSMKV
KDEYSDRDEN IMKPEPMGDA EESEMPYSYA REYSDYESIK LERHVPYDNS RPTGGKMNCD
VCGLSCISFN VLMVHKRSHT GERPFQCNQC GASFTQKGNL LRHIKLHTGE KPFKCHLCNY
ACQRRDALTG HLRTHSVEKP YKCEFCGRSY KQRSSLEEHK ERCRAFLQNP DLGDAASVEA
RHIKAEMGSE RALVLDRLAS NVAKRKSSMP QKFIGEKRHC FDANYNPGYM YEKENEMMQT
RMMDQAINNA ISYLGAEALR PLVQTPPAPT SEMVPVISSV YPIALTRADM PNGAPQEMEK
KRILLPEKIL PSERGLSPNN SAQDSTDTDS NHEDRQHLYQ QSHVVLPQAR NGMPLLKEVP
RSFELLKPPP ICLRDSIKVI NKEGEVMDVF RCDHCHVLFL DYVMFTIHMG CHGFRDPFEC
NMCGYRSHDR YEFSSHIARG EHRAMLK
