MLF1_MOUSE
ID MLF1_MOUSE Reviewed; 267 AA.
AC Q9QWV4; O70217;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Myeloid leukemia factor 1;
DE AltName: Full=Hematopoietic lineage switch 7;
DE AltName: Full=Myelodysplasia-myeloid leukemia factor 1;
GN Name=Mlf1; Synonyms=Hls7;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10393836; DOI=10.1016/s0002-9440(10)65098-5;
RA Hitzler J.K., Witte D.P., Jenkins N.A., Copeland N.G., Gilbert D.J.,
RA Naeve C.W., Look A.T., Morris S.W.;
RT "cDNA cloning, expression pattern, and chromosomal localization of Mlf1,
RT murine homologue of a gene involved in myelodysplasia and acute myeloid
RT leukemia.";
RL Am. J. Pathol. 155:53-59(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Embryo;
RX PubMed=10523300; DOI=10.1093/emboj/18.20.5559;
RA Williams J.H., Daly L.N., Ingley E., Beaumont J.G., Tilbrook P.A.,
RA Lalonde J.-P., Stillitano J.P., Klinken S.P.;
RT "HLS7, a hemopoietic lineage switch gene homologous to the leukemia-
RT inducing gene MLF1.";
RL EMBO J. 18:5559-5566(1999).
RN [3]
RP INTERACTION WITH NRBP1 AND YWHAZ, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION.
RX PubMed=12176995; DOI=10.1074/jbc.m206041200;
RA Lim R., Winteringham L.N., Williams J.H., McCulloch R.K., Ingley E.,
RA Tiao J.Y.-H., Lalonde J.-P., Tsai S., Tilbrook P.A., Sun Y., Wu X.,
RA Morris S.W., Klinken S.P.;
RT "MADM, a novel adaptor protein that mediates phosphorylation of the 14-3-3
RT binding site of myeloid leukemia factor 1.";
RL J. Biol. Chem. 277:40997-41008(2002).
RN [4]
RP FUNCTION.
RX PubMed=15122318; DOI=10.1038/sj.onc.1207661;
RA Winteringham L.N., Kobelke S., Williams J.H., Ingley E., Klinken S.P.;
RT "Myeloid leukemia factor 1 inhibits erythropoietin-induced differentiation,
RT cell cycle exit and p27Kip1 accumulation.";
RL Oncogene 23:5105-5109(2004).
RN [5]
RP INTERACTION WITH HNRPUL2 AND YWHAZ, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF SER-34 AND SER-149.
RX PubMed=17008314; DOI=10.1074/jbc.m605401200;
RA Winteringham L.N., Endersby R., Kobelke S., McCulloch R.K., Williams J.H.,
RA Stillitano J., Cornwall S.M., Ingley E., Klinken S.P.;
RT "Myeloid leukemia factor 1 associates with a novel heterogeneous nuclear
RT ribonucleoprotein U-like molecule.";
RL J. Biol. Chem. 281:38791-38800(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Testis;
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 [7]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=27914912; DOI=10.1016/j.ydbio.2016.11.019;
RA Stauber M., Weidemann M., Dittrich-Breiholz O., Lobschat K., Alten L.,
RA Mai M., Beckers A., Kracht M., Gossler A.;
RT "Identification of FOXJ1 effectors during ciliogenesis in the foetal
RT respiratory epithelium and embryonic left-right organiser of the mouse.";
RL Dev. Biol. 423:170-188(2017).
CC -!- FUNCTION: Involved in lineage commitment of primary hemopoietic
CC progenitors by restricting erythroid formation and enhancing myeloid
CC formation. Interferes with erythropoietin-induced erythroid terminal
CC differentiation by preventing cells from exiting the cell cycle through
CC suppression of CDKN1B/p27Kip1 levels. Suppresses COP1 activity via CSN3
CC which activates p53 and induces cell cycle arrest. Binds DNA and
CC affects the expression of a number of genes so may function as a
CC transcription factor in the nucleus. {ECO:0000269|PubMed:10523300,
CC ECO:0000269|PubMed:15122318}.
CC -!- SUBUNIT: Interacts with CENPU (By similarity). Also interacts with
CC NRBP1/MADM, YWHAZ/14-3-3-zeta and HNRPUL2/MANP. NRBP1 recruits a serine
CC kinase which phosphorylates both itself and MLF1. Phosphorylated MLF1
CC then binds to YWHAZ and is retained in the cytoplasm. Retained in the
CC nucleus by binding to HNRPUL2. Binds to COPS3/CSN3 which is required
CC for suppression of COP1 and activation of p53. {ECO:0000250,
CC ECO:0000269|PubMed:12176995, ECO:0000269|PubMed:17008314}.
CC -!- INTERACTION:
CC Q9QWV4; Q99J45: Nrbp1; NbExp=5; IntAct=EBI-354765, EBI-767484;
CC Q9QWV4; P63101: Ywhaz; NbExp=3; IntAct=EBI-354765, EBI-354751;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10523300}. Nucleus
CC {ECO:0000269|PubMed:10523300}. Cell projection, cilium
CC {ECO:0000269|PubMed:27914912}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:27914912}. Note=Shuttles between the cytoplasm
CC and nucleus. {ECO:0000269|PubMed:17008314}.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, heart, testis.
CC Also found in lung, but not in spleen, thymus, bone marrow, liver and
CC kidney. {ECO:0000269|PubMed:10393836}.
CC -!- INDUCTION: Expression is activated by FOXJ1.
CC {ECO:0000269|PubMed:27914912}.
CC -!- PTM: Phosphorylation is required for binding to YWHAZ.
CC {ECO:0000269|PubMed:12176995}.
CC -!- SIMILARITY: Belongs to the MLF family. {ECO:0000305}.
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DR EMBL; AF100171; AAD02876.1; -; mRNA.
DR EMBL; AF009515; AAC17946.1; -; mRNA.
DR CCDS; CCDS17396.1; -.
DR RefSeq; NP_034931.2; NM_010801.3.
DR AlphaFoldDB; Q9QWV4; -.
DR BioGRID; 201434; 3.
DR IntAct; Q9QWV4; 6.
DR MINT; Q9QWV4; -.
DR STRING; 10090.ENSMUSP00000058596; -.
DR MoonDB; Q9QWV4; Predicted.
DR iPTMnet; Q9QWV4; -.
DR PhosphoSitePlus; Q9QWV4; -.
DR MaxQB; Q9QWV4; -.
DR PRIDE; Q9QWV4; -.
DR ProteomicsDB; 295956; -.
DR Antibodypedia; 18436; 572 antibodies from 34 providers.
DR DNASU; 17349; -.
DR Ensembl; ENSMUST00000077916; ENSMUSP00000077072; ENSMUSG00000048416.
DR GeneID; 17349; -.
DR KEGG; mmu:17349; -.
DR UCSC; uc008pll.1; mouse.
DR CTD; 4291; -.
DR MGI; MGI:1341819; Mlf1.
DR VEuPathDB; HostDB:ENSMUSG00000048416; -.
DR eggNOG; KOG4049; Eukaryota.
DR GeneTree; ENSGT00390000005023; -.
DR HOGENOM; CLU_063313_0_1_1; -.
DR InParanoid; Q9QWV4; -.
DR PhylomeDB; Q9QWV4; -.
DR BioGRID-ORCS; 17349; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Mlf1; mouse.
DR PRO; PR:Q9QWV4; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9QWV4; protein.
DR Bgee; ENSMUSG00000048416; Expressed in spermatid and 168 other tissues.
DR ExpressionAtlas; Q9QWV4; baseline and differential.
DR Genevisible; Q9QWV4; MM.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0097546; C:ciliary base; IDA:MGI.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; IDA:MGI.
DR GO; GO:0097730; C:non-motile cilium; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IDA:UniProtKB.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR InterPro; IPR019376; Myeloid_leukemia_factor.
DR PANTHER; PTHR13105; PTHR13105; 1.
DR Pfam; PF10248; Mlf1IP; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Differentiation; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..267
FT /note="Myeloid leukemia factor 1"
FT /id="PRO_0000220753"
FT REGION 39..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 50..125
FT /note="Interaction with COPS3"
FT /evidence="ECO:0000250"
FT COMPBIAS 45..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 6
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58340"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58340"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58340"
FT MUTAGEN 34
FT /note="S->A: 70% reduction in binding to YWHAZ and
FT increased nuclear localization."
FT /evidence="ECO:0000269|PubMed:17008314"
FT MUTAGEN 149
FT /note="S->A: No effect on binding to YWHAZ."
FT /evidence="ECO:0000269|PubMed:17008314"
FT CONFLICT 172
FT /note="N -> Y (in Ref. 2; AAC17946)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="N -> H (in Ref. 2; AAC17946)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 267 AA; 30432 MW; 0DEF99C708CBE6B8 CRC64;
MFRMLSSSFE DDPFFADSFL AHRESMRNMM RSFSEPLGRD LLSISDGRGR THNRRERDDG
EDSLTHADVN PFQTMDRMMA NMRSGIQELQ RNFGQLSMDP NGHSFCSSSV MTYSKVGDEP
PKVFQASTQT RRAPGGVKET RKAMRDSDSG LERMAVGHHI HDRGHVIRKS KNNKTGDEEV
NQEFINMNES DAHAFDDEWQ NEVLKYKSIG RSGNTGMRSV GHEHPGSREL KRREKIHRNS
AIESGRRSNV FVDKLNVKGS PVKITKK
