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Protein

Myeloid leukemia factor 1

Gene

Mlf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 domain specific binding Source: MGI

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 Componenti: 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. nucleoplasm Source: MGI
  3. 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 – 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

BgeeiQ9QWV4.
CleanExiMM_MLF1.
ExpressionAtlasiQ9QWV4. baseline and differential.
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.
InParanoidiQ9QWV4.
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

        10         20         30         40         50
MFRMLSSSFE DDPFFADSFL AHRESMRNMM RSFSEPLGRD LLSISDGRGR
60 70 80 90 100
THNRRERDDG EDSLTHADVN PFQTMDRMMA NMRSGIQELQ RNFGQLSMDP
110 120 130 140 150
NGHSFCSSSV MTYSKVGDEP PKVFQASTQT RRAPGGVKET RKAMRDSDSG
160 170 180 190 200
LERMAVGHHI HDRGHVIRKS KNNKTGDEEV NQEFINMNES DAHAFDDEWQ
210 220 230 240 250
NEVLKYKSIG RSGNTGMRSV GHEHPGSREL KRREKIHRNS AIESGRRSNV
260
FVDKLNVKGS PVKITKK
Length:267
Mass (Da):30,432
Last modified:April 30, 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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
AF100171 mRNA. Translation: AAD02876.1.
AF009515 mRNA. Translation: AAC17946.1.
CCDSiCCDS17396.1.
RefSeqiNP_034931.2. NM_010801.3.
UniGeneiMm.10414.

3D structure databases

ProteinModelPortaliQ9QWV4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201434. 2 interactions.
IntActiQ9QWV4. 6 interactions.

PTM databases

PhosphoSiteiQ9QWV4.

Proteomic databases

PaxDbiQ9QWV4.
PRIDEiQ9QWV4.

Protocols and materials databases

DNASUi17349.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4291.
MGIiMGI:1341819. Mlf1.

Phylogenomic databases

eggNOGiNOG238823.
GeneTreeiENSGT00390000005023.
HOGENOMiHOG000045671.
HOVERGENiHBG019060.
InParanoidiQ9QWV4.
KOiK15622.
OrthoDBiEOG7H1JN6.
PhylomeDBiQ9QWV4.

Miscellaneous databases

NextBioi291942.
PROiQ9QWV4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QWV4.
CleanExiMM_MLF1.
ExpressionAtlasiQ9QWV4. baseline and differential.
GenevestigatoriQ9QWV4.

Family and domain databases

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

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(1998) [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(1998) [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(2001) [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(2003) [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(2005) [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 1, 2001
Last sequence update: April 30, 2000
Last modified: March 3, 2015
This is version 91 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.