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Q9QWV4

- MLF1_MOUSE

UniProt

Q9QWV4 - MLF1_MOUSE

Protein

Myeloid leukemia factor 1

Gene

Mlf1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 87 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation. Interferes with erythropoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels. Suppresses RFWD2/COP1 activity via CSN3 which activates p53 and induces cell cycle arrest. Binds DNA and affects the expression of a number of genes so may function as a transcription factor in the nucleus.2 Publications

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle arrest Source: UniProtKB
    2. myeloid progenitor cell differentiation Source: UniProtKB
    3. transcription, DNA-templated Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Cell cycle, Differentiation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Myeloid leukemia factor 1
    Alternative name(s):
    Hematopoietic lineage switch 7
    Myelodysplasia-myeloid leukemia factor 1
    Gene namesi
    Name:Mlf1
    Synonyms:Hls7
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:1341819. Mlf1.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: In non-hematopoietic cells, resides primarily in the cytoplasm with some punctate nuclear localization. Shuttles between the cytoplasm and nucleus. In hematopoietic cells, located preferentially in the nucleus.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi34 – 341S → A: 70% reduction in binding to YWHAZ and increased nuclear localization. 1 Publication
    Mutagenesisi149 – 1491S → A: No effect on binding to YWHAZ. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 267267Myeloid leukemia factor 1PRO_0000220753Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei34 – 341PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation is required for binding to YWHAZ.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ9QWV4.
    PRIDEiQ9QWV4.

    PTM databases

    PhosphoSiteiQ9QWV4.

    Expressioni

    Tissue specificityi

    Highly expressed in skeletal muscle, heart, testis. Also found in lung, but not in spleen, thymus, bone marrow, liver and kidney.1 Publication

    Gene expression databases

    ArrayExpressiQ9QWV4.
    BgeeiQ9QWV4.
    CleanExiMM_MLF1.
    GenevestigatoriQ9QWV4.

    Interactioni

    Subunit structurei

    Interacts with CENPU By similarity. Also interacts with NRBP1/MADM, YWHAZ/14-3-3-zeta and HNRPUL2/MANP. NRBP1 recruits a serine kinase which phosphorylates both itself and MLF1. Phosphorylated MLF1 then binds to YWHAZ and is retained in the cytoplasm. Retained in the nucleus by binding to HNRPUL2. Binds to COPS3/CSN3 which is required for suppression of RFWD2 and activation of p53.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Nrbp1Q99J455EBI-354765,EBI-767484
    YwhazP631013EBI-354765,EBI-354751

    Protein-protein interaction databases

    BioGridi201434. 2 interactions.
    IntActiQ9QWV4. 6 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9QWV4.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni50 – 12576Interaction with COPS3By similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the MLF family.Curated

    Phylogenomic databases

    eggNOGiNOG238823.
    GeneTreeiENSGT00390000005023.
    HOGENOMiHOG000045671.
    HOVERGENiHBG019060.
    KOiK15622.
    OrthoDBiEOG7H1JN6.
    PhylomeDBiQ9QWV4.

    Family and domain databases

    InterProiIPR019376. Myeloid_leukemia_factor.
    [Graphical view]
    PfamiPF10248. Mlf1IP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9QWV4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFRMLSSSFE DDPFFADSFL AHRESMRNMM RSFSEPLGRD LLSISDGRGR    50
    THNRRERDDG EDSLTHADVN PFQTMDRMMA NMRSGIQELQ RNFGQLSMDP 100
    NGHSFCSSSV MTYSKVGDEP PKVFQASTQT RRAPGGVKET RKAMRDSDSG 150
    LERMAVGHHI HDRGHVIRKS KNNKTGDEEV NQEFINMNES DAHAFDDEWQ 200
    NEVLKYKSIG RSGNTGMRSV GHEHPGSREL KRREKIHRNS AIESGRRSNV 250
    FVDKLNVKGS PVKITKK 267
    Length:267
    Mass (Da):30,432
    Last modified:May 1, 2000 - v1
    Checksum:i0DEF99C708CBE6B8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti172 – 1721N → Y in AAC17946. (PubMed:10523300)Curated
    Sequence conflicti214 – 2141N → H in AAC17946. (PubMed:10523300)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100171 mRNA. Translation: AAD02876.1.
    AF009515 mRNA. Translation: AAC17946.1.
    CCDSiCCDS17396.1.
    RefSeqiNP_034931.2. NM_010801.3.
    UniGeneiMm.10414.

    Genome annotation databases

    EnsembliENSMUST00000077916; ENSMUSP00000077072; ENSMUSG00000048416.
    GeneIDi17349.
    KEGGimmu:17349.
    UCSCiuc008pll.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100171 mRNA. Translation: AAD02876.1 .
    AF009515 mRNA. Translation: AAC17946.1 .
    CCDSi CCDS17396.1.
    RefSeqi NP_034931.2. NM_010801.3.
    UniGenei Mm.10414.

    3D structure databases

    ProteinModelPortali Q9QWV4.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201434. 2 interactions.
    IntActi Q9QWV4. 6 interactions.

    PTM databases

    PhosphoSitei Q9QWV4.

    Proteomic databases

    PaxDbi Q9QWV4.
    PRIDEi Q9QWV4.

    Protocols and materials databases

    DNASUi 17349.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000077916 ; ENSMUSP00000077072 ; ENSMUSG00000048416 .
    GeneIDi 17349.
    KEGGi mmu:17349.
    UCSCi uc008pll.1. mouse.

    Organism-specific databases

    CTDi 4291.
    MGIi MGI:1341819. Mlf1.

    Phylogenomic databases

    eggNOGi NOG238823.
    GeneTreei ENSGT00390000005023.
    HOGENOMi HOG000045671.
    HOVERGENi HBG019060.
    KOi K15622.
    OrthoDBi EOG7H1JN6.
    PhylomeDBi Q9QWV4.

    Miscellaneous databases

    NextBioi 291942.
    PROi Q9QWV4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9QWV4.
    Bgeei Q9QWV4.
    CleanExi MM_MLF1.
    Genevestigatori Q9QWV4.

    Family and domain databases

    InterProi IPR019376. Myeloid_leukemia_factor.
    [Graphical view ]
    Pfami PF10248. Mlf1IP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "cDNA cloning, expression pattern, and chromosomal localization of Mlf1, murine homologue of a gene involved in myelodysplasia and acute myeloid leukemia."
      Hitzler J.K., Witte D.P., Jenkins N.A., Copeland N.G., Gilbert D.J., Naeve C.W., Look A.T., Morris S.W.
      Am. J. Pathol. 155:53-59(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Testis.
    2. "HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1."
      Williams J.H., Daly L.N., Ingley E., Beaumont J.G., Tilbrook P.A., Lalonde J.-P., Stillitano J.P., Klinken S.P.
      EMBO J. 18:5559-5566(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
      Tissue: Embryo.
    3. "MADM, a novel adaptor protein that mediates phosphorylation of the 14-3-3 binding site of myeloid leukemia factor 1."
      Lim R., Winteringham L.N., Williams J.H., McCulloch R.K., Ingley E., Tiao J.Y.-H., Lalonde J.-P., Tsai S., Tilbrook P.A., Sun Y., Wu X., Morris S.W., Klinken S.P.
      J. Biol. Chem. 277:40997-41008(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NRBP1 AND YWHAZ, SUBCELLULAR LOCATION, PHOSPHORYLATION.
    4. "Myeloid leukemia factor 1 inhibits erythropoietin-induced differentiation, cell cycle exit and p27Kip1 accumulation."
      Winteringham L.N., Kobelke S., Williams J.H., Ingley E., Klinken S.P.
      Oncogene 23:5105-5109(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Myeloid leukemia factor 1 associates with a novel heterogeneous nuclear ribonucleoprotein U-like molecule."
      Winteringham L.N., Endersby R., Kobelke S., McCulloch R.K., Williams J.H., Stillitano J., Cornwall S.M., Ingley E., Klinken S.P.
      J. Biol. Chem. 281:38791-38800(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HNRPUL2 AND YWHAZ, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-34 AND SER-149.

    Entry informationi

    Entry nameiMLF1_MOUSE
    AccessioniPrimary (citable) accession number: Q9QWV4
    Secondary accession number(s): O70217
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 2, 2001
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 87 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3