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Q9QWV4 (MLF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Myeloid leukemia factor 1
Alternative name(s):
Hematopoietic lineage switch 7
Myelodysplasia-myeloid leukemia factor 1
Gene names
Name:Mlf1
Synonyms:Hls7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length267 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.4

Subunit structure

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. Ref.3 Ref.5

Subcellular location

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. Ref.2 Ref.3 Ref.5

Tissue specificity

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

Post-translational modification

Phosphorylation is required for binding to YWHAZ.

Sequence similarities

Belongs to the MLF family.

Ontologies

Keywords
   Biological processCell cycle
Differentiation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

myeloid progenitor cell differentiation

Inferred from direct assay Ref.2. Source: UniProtKB

transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.3. Source: UniProtKB

nucleus

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.5. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.3Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Nrbp1Q99J455EBI-354765,EBI-767484
YwhazP631013EBI-354765,EBI-354751

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 267267Myeloid leukemia factor 1
PRO_0000220753

Regions

Region50 – 12576Interaction with COPS3 By similarity

Amino acid modifications

Modified residue341Phosphoserine By similarity

Experimental info

Mutagenesis341S → A: 70% reduction in binding to YWHAZ and increased nuclear localization. Ref.5
Mutagenesis1491S → A: No effect on binding to YWHAZ. Ref.5
Sequence conflict1721N → Y in AAC17946. Ref.2
Sequence conflict2141N → H in AAC17946. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9QWV4 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 0DEF99C708CBE6B8

FASTA26730,432
        10         20         30         40         50         60 
MFRMLSSSFE DDPFFADSFL AHRESMRNMM RSFSEPLGRD LLSISDGRGR THNRRERDDG 

        70         80         90        100        110        120 
EDSLTHADVN PFQTMDRMMA NMRSGIQELQ RNFGQLSMDP NGHSFCSSSV MTYSKVGDEP 

       130        140        150        160        170        180 
PKVFQASTQT RRAPGGVKET RKAMRDSDSG LERMAVGHHI HDRGHVIRKS KNNKTGDEEV 

       190        200        210        220        230        240 
NQEFINMNES DAHAFDDEWQ NEVLKYKSIG RSGNTGMRSV GHEHPGSREL KRREKIHRNS 

       250        260 
AIESGRRSNV FVDKLNVKGS PVKITKK 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF100171 mRNA. Translation: AAD02876.1.
AF009515 mRNA. Translation: AAC17946.1.
CCDSCCDS17396.1.
RefSeqNP_034931.2. NM_010801.3.
UniGeneMm.10414.

3D structure databases

ProteinModelPortalQ9QWV4.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201434. 2 interactions.
IntActQ9QWV4. 6 interactions.

PTM databases

PhosphoSiteQ9QWV4.

Proteomic databases

PaxDbQ9QWV4.
PRIDEQ9QWV4.

Protocols and materials databases

DNASU17349.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000077916; ENSMUSP00000077072; ENSMUSG00000048416.
GeneID17349.
KEGGmmu:17349.
UCSCuc008pll.1. mouse.

Organism-specific databases

CTD4291.
MGIMGI:1341819. Mlf1.

Phylogenomic databases

eggNOGNOG238823.
GeneTreeENSGT00390000005023.
HOGENOMHOG000045671.
HOVERGENHBG019060.
KOK15622.
OrthoDBEOG7H1JN6.
PhylomeDBQ9QWV4.

Gene expression databases

ArrayExpressQ9QWV4.
BgeeQ9QWV4.
CleanExMM_MLF1.
GenevestigatorQ9QWV4.

Family and domain databases

InterProIPR019376. Myeloid_leukemia_factor.
[Graphical view]
PfamPF10248. Mlf1IP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio291942.
PROQ9QWV4.
SOURCESearch...

Entry information

Entry nameMLF1_MOUSE
AccessionPrimary (citable) accession number: Q9QWV4
Secondary accession number(s): O70217
Entry history
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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot