KLF1_MOUSE
ID KLF1_MOUSE Reviewed; 358 AA.
AC P46099; O70261;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 146.
DE RecName: Full=Krueppel-like factor 1;
DE AltName: Full=Erythroid krueppel-like transcription factor;
DE Short=EKLF;
GN Name=Klf1; Synonyms=Elkf;
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].
RX PubMed=7682653; DOI=10.1128/mcb.13.5.2776-2786.1993;
RA Miller I.J., Bieker J.J.;
RT "A novel, erythroid cell-specific murine transcription factor that binds to
RT the CACCC element and is related to the Kruppel family of nuclear
RT proteins.";
RL Mol. Cell. Biol. 13:2776-2786(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RA Jenkins N.A., Gilbert D.J., Copeland N.G., Gruzglin E., Bieker J.J.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=7565748; DOI=10.1128/mcb.15.11.5957;
RA Anderson K.P., Kern C.B., Crable S.C., Lingrel J.B.;
RT "Isolation of a gene encoding a functional zinc finger protein homologous
RT to erythroid Kruppel-like factor: identification of a new multigene
RT family.";
RL Mol. Cell. Biol. 15:5957-5965(1995).
RN [4]
RP PHOSPHORYLATION AT THR-23, FUNCTION, AND MUTAGENESIS OF THR-23 AND
RP 25-GLU-ASP-26.
RX PubMed=9722526; DOI=10.1074/jbc.273.36.23019;
RA Ouyang L., Chen X., Bieker J.J.;
RT "Regulation of erythroid Krueppel-like factor (EKLF) transcriptional
RT activity by phosphorylation of a protein kinase casein kinase II site
RT within its interaction domain.";
RL J. Biol. Chem. 273:23019-23025(1998).
RN [5]
RP ACETYLATION AT LYS-270 AND LYS-284, FUNCTION, AND MUTAGENESIS OF LYS-270
RP AND LYS-284.
RX PubMed=11259590; DOI=10.1128/mcb.21.7.2413-2422.2001;
RA Zhang W., Kadam S., Emerson B.M., Bieker J.J.;
RT "Site-specific acetylation by p300 or CREB binding protein regulates
RT erythroid Krueppel-like factor transcriptional activity via its interaction
RT with the SWI-SNF complex.";
RL Mol. Cell. Biol. 21:2413-2422(2001).
RN [6]
RP FUNCTION, INTERACTION WITH SIN3A AND HDAC1, AND MUTAGENESIS OF LYS-284;
RP HIS-295; HIS-325 AND HIS-353.
RX PubMed=15542849; DOI=10.1128/mcb.24.23.10416-10424.2004;
RA Chen X., Bieker J.J.;
RT "Stage-specific repression by the EKLF transcriptional activator.";
RL Mol. Cell. Biol. 24:10416-10424(2004).
RN [7]
RP SUMOYLATION AT LYS-56, INTERACTION WITH CHD4, FUNCTION, AND MUTAGENESIS OF
RP LYS-56.
RX PubMed=17938210; DOI=10.1128/mcb.00589-07;
RA Siatecka M., Xue L., Bieker J.J.;
RT "Sumoylation of EKLF promotes transcriptional repression and is involved in
RT inhibition of megakaryopoiesis.";
RL Mol. Cell. Biol. 27:8547-8560(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-178, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Transcription regulator of erythrocyte development. Binds to
CC the CACCC box in the beta-globin gene promoter and activates
CC transcription. Probably serves as a general switch factor for erythroid
CC development. When sumoylated, acts as a transcriptional repressor by
CC promoting interaction with CDH2/MI2beta and also represses
CC megakaryocytic differentiation. {ECO:0000269|PubMed:11259590,
CC ECO:0000269|PubMed:15542849, ECO:0000269|PubMed:17938210,
CC ECO:0000269|PubMed:9722526}.
CC -!- SUBUNIT: Interacts with CBP and EP300; the interactions enhance the
CC transactivation activity. Interacts with PCAF; the interaction does not
CC acetylate EKLF and inhibits its transactivation activity (By
CC similarity). Interacts with CDH4; the interaction is SUMO-dependent and
CC leads to transcriptional repression. {ECO:0000250,
CC ECO:0000269|PubMed:15542849, ECO:0000269|PubMed:17938210}.
CC -!- INTERACTION:
CC P46099; Q16594: TAF9; Xeno; NbExp=3; IntAct=EBI-15761537, EBI-712521;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with SUMO1 in nuclear
CC speckles.
CC -!- TISSUE SPECIFICITY: Erythroid-specific. Only expressed in bone marrow
CC and spleen.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:Q13351}.
CC -!- PTM: Acetylated; can be acetylated on both Lys-270 and Lys-288.
CC Acetylation on Lys-270 (by CBP) appears to be the major site affecting
CC EKLF transactivation activity. {ECO:0000269|PubMed:11259590}.
CC -!- PTM: Sumoylated; sumoylation, promoted by PIAS1, leads to repression of
CC megakaryocyte differentiation. Also promotes the interaction with the
CC CDH4 subunit of the NuRD repression complex.
CC {ECO:0000269|PubMed:17938210}.
CC -!- PTM: Phosphorylated primarily on serine residues in the transactivation
CC domain. Phosphorylation on Thr-23 is critical for the transactivation
CC activity. {ECO:0000269|PubMed:9722526}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA37546.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M97200; AAA37546.1; ALT_INIT; mRNA.
DR EMBL; AF019074; AAB87861.1; -; Genomic_DNA.
DR EMBL; AF033102; AAC24497.1; -; Genomic_DNA.
DR CCDS; CCDS22483.1; -.
DR PIR; A48060; A48060.
DR AlphaFoldDB; P46099; -.
DR SMR; P46099; -.
DR DIP; DIP-48738N; -.
DR IntAct; P46099; 2.
DR STRING; 10090.ENSMUSP00000064366; -.
DR iPTMnet; P46099; -.
DR PhosphoSitePlus; P46099; -.
DR MaxQB; P46099; -.
DR PaxDb; P46099; -.
DR PRIDE; P46099; -.
DR ProteomicsDB; 269222; -.
DR MGI; MGI:1342771; Klf1.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; P46099; -.
DR PhylomeDB; P46099; -.
DR PRO; PR:P46099; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P46099; protein.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
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; IMP:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0006338; P:chromatin remodeling; IDA:MGI.
DR GO; GO:0035162; P:embryonic hemopoiesis; IMP:MGI.
DR GO; GO:0048821; P:erythrocyte development; IMP:MGI.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:MGI.
DR GO; GO:0043249; P:erythrocyte maturation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR InterPro; IPR031786; EKLF_TAD1.
DR InterPro; IPR031784; EKLF_TAD2.
DR InterPro; IPR031785; KLF1.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR23235:SF107; PTHR23235:SF107; 1.
DR Pfam; PF16832; EKLF_TAD1; 1.
DR Pfam; PF16833; EKLF_TAD2; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW Acetylation; Activator; DNA-binding; Isopeptide bond; Metal-binding;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..358
FT /note="Krueppel-like factor 1"
FT /id="PRO_0000047161"
FT ZN_FING 275..299
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 305..329
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 335..357
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 35..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 71..79
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:Q13351"
FT MOD_RES 23
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000305|PubMed:9722526"
FT MOD_RES 178
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 270
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:11259590"
FT MOD_RES 284
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:11259590"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT MUTAGEN 23
FT /note="T->A: Greatly reduced transactivation activity."
FT /evidence="ECO:0000269|PubMed:9722526"
FT MUTAGEN 23
FT /note="T->D: No change in transactivation activity."
FT /evidence="ECO:0000269|PubMed:9722526"
FT MUTAGEN 25..26
FT /note="ED->AG: Abolishes most of transactivation activity."
FT /evidence="ECO:0000269|PubMed:9722526"
FT MUTAGEN 56
FT /note="K->R: Abolishes sumoylation. No change in nuclear
FT localization but no colocalization with SUMO1. Reduces
FT inhibition of megakaryocytic differentiation. No decrease
FT in bone marrow precursors to form megakaryocytic colonies.
FT No effect on erythroid differentiation."
FT /evidence="ECO:0000269|PubMed:17938210"
FT MUTAGEN 270
FT /note="K->A,R: No effect on DNA binding. Transactivation
FT activity reduced by 50%. Loss of superactivation by CBP of
FT EP300."
FT /evidence="ECO:0000269|PubMed:11259590"
FT MUTAGEN 284
FT /note="K->A,R: No effect on DNA binding. No change in
FT transactivation activity. No loss of superactivation by CBP
FT or EP300."
FT /evidence="ECO:0000269|PubMed:11259590,
FT ECO:0000269|PubMed:15542849"
FT MUTAGEN 295
FT /note="H->N: Loss of DNA binding and transactivation
FT activity. No change in interaction with SIN3A nor with
FT HDAC1. No effect on repressive activity."
FT /evidence="ECO:0000269|PubMed:15542849"
FT MUTAGEN 325
FT /note="H->N: Loss of DNA binding and transactivation
FT activity. No change in interaction with SIN3A nor with
FT HDAC1. No effect on repressive activity."
FT /evidence="ECO:0000269|PubMed:15542849"
FT MUTAGEN 353
FT /note="H->N: Loss of DNA binding and transactivation
FT activity. No change in interaction with SIN3A nor with
FT HDAC1. No effect on repressive activity."
FT /evidence="ECO:0000269|PubMed:15542849"
FT CONFLICT 94
FT /note="C -> Y (in Ref. 3; AAC24497)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="A -> T (in Ref. 3; AAC24497)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="G -> P (in Ref. 3; AAC24497)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="S -> T (in Ref. 3; AAC24497)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 358 AA; 37757 MW; 6FD59F294DDA45D1 CRC64;
MASAETVLPS ISTLTTLGQF LDTQEDFLKW WRSEETQDLG PGPPNPTGPS LHVSLKSEDP
SGEDDERDVT CAWDPDLFLT NFPGSESPGT SRTCALAPSV GPVAQFEPPE SLGAYAGGPG
LVTGPLGSEE HTSWAHPTPR PPAPEPFVAP ALAPGLAPKA QPSYSDSRAG SVGGFFPRAG
LAVPAAPGAP YGLLSGYPAL YPAPQYQGHF QLFRGLAAPS AGGTAPPSFL NCLGPGTVAT
ELGATAIAGD AGLSPGTAPP KRSRRTLAPK RQAAHTCGHE GCGKSYSKSS HLKAHLRTHT
GEKPYACSWD GCDWRFARSD ELTRHYRKHT GHRPFCCGLC PRAFSRSDHL ALHMKRHL
