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Q9QWV4

- MLF1_MOUSE

UniProt

Q9QWV4 - MLF1_MOUSE

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Protein

Myeloid leukemia factor 1

Gene
Mlf1, Hls7
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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
Complete GO annotation...

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.3 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

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 – 341Phosphoserine By similarity

Post-translational modificationi

Phosphorylation is required for binding to YWHAZ.

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 p53.2 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.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni50 – 12576Interaction with COPS3 By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the MLF family.

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti172 – 1721N → Y in AAC17946. 1 Publication
Sequence conflicti214 – 2141N → H in AAC17946. 1 Publication

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: July 9, 2014
This is version 86 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

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