Q9QWV4 (MLF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myeloid leukemia factor 1

Alternative name(s):
Hematopoietic lineage switch 7
Myelodysplasia-myeloid leukemia factor 1

Gene names

Name:	Mlf1
Synonyms:	Hls7

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Protein existence	Evidence 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 MLF1IP 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 process	Cell cycle Differentiation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB myeloid progenitor cell differentiation Inferred from direct assay Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from direct assay Ref.5. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.3. Source: UniProtKB nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Nrbp1	Q99J45	5	EBI-354765,EBI-767484
Ywhaz	P63101	2	EBI-354765,EBI-354751

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 267	267	Myeloid leukemia factor 1		PRO_0000220753
Regions
	Region	50 – 125	76	Interaction with COPS3 By similarity
Amino acid modifications
	Modified residue	34	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	34	1	S → A: 70% reduction in binding to YWHAZ and increased nuclear localization. Ref.5
	Mutagenesis	149	1	S → A: No effect on binding to YWHAZ. Ref.5
	Sequence conflict	172	1	N → Y in AAC17946. Ref.2
	Sequence conflict	214	1	N → H in AAC17946. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9QWV4 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 0DEF99C708CBE6B8	FASTA	267	30,432
	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

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.
IPI	IPI00475175.
RefSeq	NP_034931.2. NM_010801.3.
UniGene	Mm.10414.
3D structure databases
ProteinModelPortal	Q9QWV4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9QWV4. 6 interactions.
PTM databases
PhosphoSite	Q9QWV4.
Proteomic databases
PaxDb	Q9QWV4.
PRIDE	Q9QWV4.
Protocols and materials databases
DNASU	17349.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000077916; ENSMUSP00000077072; ENSMUSG00000048416.
GeneID	17349.
KEGG	mmu:17349.
Organism-specific databases
CTD	4291.
MGI	MGI:1341819. Mlf1.
Phylogenomic databases
eggNOG	NOG238823.
GeneTree	ENSGT00390000005023.
HOGENOM	HOG000045671.
HOVERGEN	HBG019060.
KO	K15622.
Gene expression databases
ArrayExpress	Q9QWV4.
Bgee	Q9QWV4.
CleanEx	MM_MLF1.
Genevestigator	Q9QWV4.
GermOnline	ENSMUSG00000048416. Mus musculus.
Family and domain databases
InterPro	IPR019376. Myeloid_leukemia_factor. [Graphical view]
Pfam	PF10248. Mlf1IP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	291942.
SOURCE	Search...

Entry information

Entry name

MLF1_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program