Reviewed, UniProtKB/Swiss-Prot P58340 (MLF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Myeloid leukemia factor 1
Alternative name(s):
    Myelodysplasia-myeloid leukemia factor 1

Gene names

Name:

MLF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	268 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 erythopoietin-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.
Subunit structure	Interacts with MLF1IP. 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.
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. Found in the nucleolus when fused to NPM.
Tissue specificity	Most abundant in testis, ovary, skeletal muscle, heart, kidney and colon. Low expression in spleen, thymus and peripheral blood leukocytes.
Post-translational modification	Phosphorylation is required for binding to YWHAZ By similarity.
Involvement in disease	A chromosomal aberration involving MLF1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with NPM1/NPM.
Sequence similarities	Belongs to the MLF family.

Ontologies

Keywords
Biological process	Cell cycle Differentiation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle arrest Ref.4 Inferred from direct assay. Source: UniProtKB myeloid progenitor cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB protein domain specific binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 268	268	Myeloid leukemia factor 1		PRO_0000220752
Regions
	Region	50 – 125	76	Interaction with COPS3
Sites
	Site	16 – 17	2	Breakpoint for translocation to form NPM-MLF1
Natural variations
	Natural variant	226	1	P → T: dbSNP rs17629834.		VAR_022070

Sequences

	Sequence		Length	Mass (Da)
	P58340-1 [UniParc]. Last modified November 2, 2001. Version 1. Checksum: 08774217329F737A	FASTA	268	30,627
	10 20 30 40 50 60 MFRMLNSSFE DDPFFSESIL AHRENMRQMI RSFSEPFGRD LLSISDGRGR AHNRRGHNDG 70 80 90 100 110 120 EDSLTHTDVS SFQTMDQMVS NMRNYMQKLE RNFGQLSVDP NGHSFCSSSV MTYSKIGDEP 130 140 150 160 170 180 PKVFQASTQT RRAPGGIKET RKAMRDSDSG LEKMAIGHHI HDRAHVIKKS KNKKTGDEEV 190 200 210 220 230 240 NQEFINMNES DAHAFDEEWQ SEVLKYKPGR HNLGNTRMRS VGHENPGSRE LKRREKPQQS 250 260 PAIEHGRRSN VLGDKLHIKG SSVKSNKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1." Yoneda-Kato N., Look A.T., Kirstein M.N., Valentine M.B., Raimondi S.C., Cohen K.J., Carroll A.J., Morris S.W. Oncogene 12:265-275(1996) [PubMed: 8570204] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION. Tissue: Skeletal muscle and Testis.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[3]	"cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP." Hanissian S.H., Akbar U., Teng B., Janjetovic Z., Hoffmann A., Hitzler J.K., Iscove N., Hamre K., Du X., Tong Y., Mukatira S., Robertson J.H., Morris S.W. Oncogene 23:3700-3707(2004) [PubMed: 15116101] [Abstract] Cited for: INTERACTION WITH MLF1IP.
[4]	"Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome subunit 3." Yoneda-Kato N., Tomoda K., Umehara M., Arata Y., Kato J.-Y. EMBO J. 24:1739-1749(2005) [PubMed: 15861129] [Abstract] Cited for: FUNCTION, INTERACTION WITH COPS3.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	L49054 mRNA. Translation: AAA99997.1. BC007045 mRNA. Translation: AAH07045.1.
RefSeq	NP_071888.1.
UniGene	Hs.85195
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P58340.
PTM databases
PhosphoSite	P58340.
Genome annotation databases
Ensembl	ENSG00000178053. Homo sapiens. [Contig view]
GeneID	4291.
KEGG	hsa:4291.
Organism-specific databases
H-InvDB	HIX0019510.
HGNC	HGNC:7125. MLF1.
HPA	HPA017903.
MIM	601402. gene.
PharmGKB	PA30843.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P58340.
Gene expression databases
ArrayExpress	P58340.
CleanEx	HS_MLF1.
GermOnline	ENSG00000178053. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other Resources
LinkHub	P58340.
NextBio	16889.
SOURCE	Search...

Entry information

Entry name

MLF1_HUMAN

Accession

Primary (citable) accession number: P58340

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 2, 2001
Last sequence update:	November 2, 2001
Last modified:	November 4, 2008
This is version 52 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)