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Protein

Myeloid leukemia factor 1

Gene

MLF1

Organism
Homo sapiens (Human)
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.1 Publication

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processCell cycle, Differentiation

Enzyme and pathway databases

SIGNORiP58340.

Names & Taxonomyi

Protein namesi
Recommended name:
Myeloid leukemia factor 1
Alternative name(s):
Myelodysplasia-myeloid leukemia factor 1
Gene namesi
Name:MLF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000178053.17.
HGNCiHGNC:7125. MLF1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving MLF1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with NPM1/NPM.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei16 – 17Breakpoint for translocation to form NPM-MLF12

Organism-specific databases

DisGeNETi4291.
MalaCardsiMLF1.
OpenTargetsiENSG00000178053.
PharmGKBiPA30843.

Polymorphism and mutation databases

BioMutaiMLF1.
DMDMi17368170.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002207521 – 268Myeloid leukemia factor 1Add BLAST268

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphoserineCombined sources1
Modified residuei32PhosphoserineCombined sources1
Modified residuei34Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation is required for binding to YWHAZ.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP58340.
PeptideAtlasiP58340.
PRIDEiP58340.

PTM databases

iPTMnetiP58340.
PhosphoSitePlusiP58340.

Expressioni

Tissue specificityi

Most abundant in testis, ovary, skeletal muscle, heart, kidney and colon. Low expression in spleen, thymus and peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000178053.
CleanExiHS_MLF1.
ExpressionAtlasiP58340. baseline and differential.
GenevisibleiP58340. HS.

Organism-specific databases

HPAiHPA069479.

Interactioni

Subunit structurei

Interacts with CENPU. 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 p53.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110437. 72 interactors.
ELMiP58340.
IntActiP58340. 86 interactors.
MINTiMINT-1427321.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UALX-ray1.80P29-42[»]
3UBWX-ray1.90P29-42[»]
ProteinModelPortaliP58340.
SMRiP58340.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni50 – 125Interaction with COPS31 PublicationAdd BLAST76

Sequence similaritiesi

Belongs to the MLF family.Curated

Phylogenomic databases

GeneTreeiENSGT00390000005023.
HOGENOMiHOG000045671.
HOVERGENiHBG019060.
InParanoidiP58340.
KOiK15622.
OMAiLENTRMR.
OrthoDBiEOG091G0JFX.
PhylomeDBiP58340.
TreeFamiTF317561.

Family and domain databases

InterProiView protein in InterPro
IPR019376. Myeloid_leukemia_factor.
PANTHERiPTHR13105. PTHR13105. 1 hit.
PfamiView protein in Pfam
PF10248. Mlf1IP. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P58340-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MFRMLNSSFE DDPFFSESIL AHRENMRQMI RSFSEPFGRD LLSISDGRGR
60 70 80 90 100
AHNRRGHNDG EDSLTHTDVS SFQTMDQMVS NMRNYMQKLE RNFGQLSVDP
110 120 130 140 150
NGHSFCSSSV MTYSKIGDEP PKVFQASTQT RRAPGGIKET RKAMRDSDSG
160 170 180 190 200
LEKMAIGHHI HDRAHVIKKS KNKKTGDEEV NQEFINMNES DAHAFDEEWQ
210 220 230 240 250
SEVLKYKPGR HNLGNTRMRS VGHENPGSRE LKRREKPQQS PAIEHGRRSN
260
VLGDKLHIKG SSVKSNKK
Length:268
Mass (Da):30,627
Last modified:November 2, 2001 - v1
Checksum:i08774217329F737A
GO
Isoform 2 (identifier: P58340-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     94-136: Missing.

Show »
Length:200
Mass (Da):23,117
Checksum:iCFF347E5F40C1BFF
GO
Isoform 3 (identifier: P58340-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MFRMLNSSFEDDPFF → MLKEVLQREGKSYKSETLMYIKKARASENKL
     65-65: T → TATSCSLVPFGDFGGM

Note: No experimental confirmation available.
Show »
Length:299
Mass (Da):33,888
Checksum:i75E81192D63D7948
GO
Isoform 5 (identifier: P58340-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Show »
Length:243
Mass (Da):27,625
Checksum:i061E87A385C3E063
GO
Isoform 4 (identifier: P58340-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     65-65: T → TATSCSLVPFGDFGGM

Note: No experimental confirmation available.
Show »
Length:258
Mass (Da):29,095
Checksum:i68BC1583FCAA0F23
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022070226P → T. Corresponds to variant dbSNP:rs15967Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0431301 – 25Missing in isoform 2, isoform 4 and isoform 5. 2 PublicationsAdd BLAST25
Alternative sequenceiVSP_0437251 – 15MFRML…DDPFF → MLKEVLQREGKSYKSETLMY IKKARASENKL in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_04372665T → TATSCSLVPFGDFGGM in isoform 3 and isoform 4. 1 Publication1
Alternative sequenceiVSP_04313194 – 136Missing in isoform 2. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L49054 mRNA. Translation: AAA99997.1.
AY848700 mRNA. Translation: AAX46015.1.
AY848702 mRNA. Translation: AAX46017.1.
AK056948 mRNA. Translation: BAB71320.1.
AK096889 mRNA. Translation: BAC04885.1.
AK297488 mRNA. Translation: BAG59906.1.
AC025033 Genomic DNA. No translation available.
AC106707 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78689.1.
CH471052 Genomic DNA. Translation: EAW78690.1.
BC007045 mRNA. Translation: AAH07045.1.
CCDSiCCDS3182.1. [P58340-1]
CCDS46945.1. [P58340-5]
CCDS56286.1. [P58340-3]
CCDS56287.1. [P58340-4]
CCDS56288.1. [P58340-2]
RefSeqiNP_001123628.1. NM_001130156.2. [P58340-5]
NP_001123629.1. NM_001130157.2. [P58340-5]
NP_001182361.1. NM_001195432.1. [P58340-3]
NP_001182362.1. NM_001195433.1. [P58340-2]
NP_001182363.1. NM_001195434.1. [P58340-4]
NP_071888.1. NM_022443.4. [P58340-1]
XP_005247537.1. XM_005247480.2. [P58340-4]
XP_011511154.1. XM_011512852.2. [P58340-4]
XP_011511155.1. XM_011512853.2. [P58340-5]
UniGeneiHs.85195.

Genome annotation databases

EnsembliENST00000355893; ENSP00000348157; ENSG00000178053. [P58340-1]
ENST00000359117; ENSP00000352025; ENSG00000178053. [P58340-5]
ENST00000392822; ENSP00000376568; ENSG00000178053. [P58340-3]
ENST00000469452; ENSP00000418595; ENSG00000178053. [P58340-2]
ENST00000471745; ENSP00000420134; ENSG00000178053. [P58340-4]
ENST00000478894; ENSP00000417777; ENSG00000178053. [P58340-4]
ENST00000482628; ENSP00000417141; ENSG00000178053. [P58340-5]
ENST00000484955; ENSP00000417835; ENSG00000178053. [P58340-5]
ENST00000618075; ENSP00000484169; ENSG00000178053. [P58340-2]
ENST00000619577; ENSP00000483337; ENSG00000178053. [P58340-4]
GeneIDi4291.
KEGGihsa:4291.
UCSCiuc003fbx.4. human. [P58340-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMLF1_HUMAN
AccessioniPrimary (citable) accession number: P58340
Secondary accession number(s): E9PEU9
, Q2TLE3, Q2TLE5, Q8N8F8, Q96MH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: November 2, 2001
Last modified: October 25, 2017
This is version 131 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families