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Q08050 (FOXM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein M1
Alternative name(s):
Forkhead-related protein FKHL16
Hepatocyte nuclear factor 3 forkhead homolog 11
Short name=HFH-11
Short name=HNF-3/fork-head homolog 11
M-phase phosphoprotein 2
MPM-2 reactive phosphoprotein 2
Transcription factor Trident
Winged-helix factor from INS-1 cells
Gene names
Name:FOXM1
Synonyms:FKHL16, HFH11, MPP2, WIN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length763 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. Plays a role in the control of cell proliferation. Plays also a role in DNA breaks repair participating in the DNA damage checkpoint response. Ref.6 Ref.7 Ref.10

Subcellular location

Nucleus.

Tissue specificity

Expressed in thymus, testis, small intestine, colon followed by ovary. Appears to be expressed only in adult organs containing proliferating/cycling cells or in response to growth factors. Also expressed in epithelial cell lines derived from tumors. Not expressed in resting cells. Isoform 2 is highly expressed in testis.

Developmental stage

Embryonic expression pattern: liver, lung, intestine, kidney, urinary tract; adult expression pattern: intestine, colon, testis and thymus.

Induction

Induced during liver regeneration and oxidative stress.

Domain

Within the protein there is a domain which acts as a transcriptional activator. Insertion of a splicing sequence within it inactivates this transcriptional activity, as it is the case for isoform 4.

Post-translational modification

Phosphorylated in M (mitotic) phase. Phosphorylation by the checkpoint kinase CHEK2 in response to DNA damage increases the FOXM1 protein stability probably stimulating the transcription of genes involved in DNA repair. Phosphorylated by CDK1 in late S and G2 phases, creating docking sites for the POLO box domains of PLK1. Subsequently, PLK1 binds and phosphorylates FOXM1, leading to activation of transcriptional activity and subsequent enhanced expression of key mitotic regulators. Ref.6 Ref.7

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

Inferred from mutant phenotype Ref.6. Source: UniProtKB

DNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

G2/M transition of mitotic cell cycle

Inferred from direct assay Ref.7. Source: UniProtKB

cell cycle

Traceable author statement PubMed 10523841. Source: UniProtKB

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

liver development

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of cell aging

Inferred from mutant phenotype PubMed 19696738. Source: UniProtKB

negative regulation of stress-activated MAPK cascade

Inferred from mutant phenotype PubMed 19696738. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 20531406. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 20531406. Source: BHF-UCL

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 19696738. Source: BHF-UCL

positive regulation of double-strand break repair

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.7. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.6. Source: UniProtKB

regulation of Ras protein signal transduction

Inferred from mutant phenotype PubMed 19696738. Source: BHF-UCL

regulation of cell cycle

Traceable author statement. Source: Reactome

regulation of cell cycle arrest

Inferred from mutant phenotype PubMed 19696738. Source: BHF-UCL

regulation of cell growth

Traceable author statement PubMed 10523841. Source: UniProtKB

regulation of cell proliferation

Non-traceable author statement PubMed 9441747. Source: UniProtKB

regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 19696738. Source: BHF-UCL

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10523841Ref.1. Source: GOC

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

vasculogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein kinase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 10523841Ref.1. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoform 1 and isoform 2 appear to be the only activators of gene transcription. Isoform 3, found in rat, does not seem to exist in human.
Isoform 1 (identifier: Q08050-1)

Also known as: FoxM1C; FOXM1-c;

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.
Isoform 2 (identifier: Q08050-2)

Also known as: FoxM1B; FOXM1-b;

The sequence of this isoform differs from the canonical sequence as follows:
     326-340: Missing.
Isoform 4 (identifier: Q08050-3)

Also known as: FoxM1A; FOXM1-a;

The sequence of this isoform differs from the canonical sequence as follows:
     423-423: V → VFGEQVVFGYMSKFFSGDLRDFGTPITSLFNFIFLCLSV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 763763Forkhead box protein M1
PRO_0000091863

Regions

DNA binding235 – 32793Fork-head
Compositional bias480 – 51334Glu/Pro/Ser/Thr-rich

Amino acid modifications

Modified residue3311Phosphoserine Ref.8
Modified residue3761Phosphoserine; by CHEK2 Ref.6
Modified residue6111Phosphothreonine; by CDK1 Ref.7
Modified residue6201Phosphothreonine Ref.8
Modified residue6271Phosphothreonine Ref.8
Modified residue6621Phosphothreonine Probable
Modified residue6931Phosphoserine; by CDK1 Ref.7
Modified residue7301Phosphoserine; by PLK1 Ref.7 Ref.9
Modified residue7391Phosphoserine; by PLK1 Ref.7 Ref.9

Natural variations

Alternative sequence326 – 34015Missing in isoform 2.
VSP_001547
Alternative sequence4231V → VFGEQVVFGYMSKFFSGDLR DFGTPITSLFNFIFLCLSV in isoform 4.
VSP_001548
Natural variant4021A → E. Ref.3
Corresponds to variant rs28990715 [ dbSNP | Ensembl ].
VAR_025239
Natural variant4501F → L. Ref.3
Corresponds to variant rs28919868 [ dbSNP | Ensembl ].
VAR_025240
Natural variant6431S → P. Ref.3 Ref.4
Corresponds to variant rs3742076 [ dbSNP | Ensembl ].
VAR_020024
Natural variant6691P → R. Ref.3
Corresponds to variant rs28919869 [ dbSNP | Ensembl ].
VAR_025241
Natural variant6731P → L. Ref.3
Corresponds to variant rs28919870 [ dbSNP | Ensembl ].
VAR_025242

Experimental info

Mutagenesis6111T → A: Prevents phosphorylation by CDK1 and subsequent binding of POLO box domains of PLK1; when associated with A-693. Ref.7
Mutagenesis6931S → A: Prevents phosphorylation by CDK1 and subsequent binding of POLO box domains of PLK1; when associated with A-611. Ref.7
Mutagenesis7301S → A: Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-739. Ref.7
Mutagenesis7391S → A: Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-730. Ref.7
Sequence conflict31T → A in AAC63595. Ref.2

Secondary structure

................. 763
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FoxM1C) (FOXM1-c) [UniParc].

Last modified December 1, 2000. Version 3.
Checksum: 963CAC8FE7498E9B

FASTA76384,283
        10         20         30         40         50         60 
MKTSPRRPLI LKRRRLPLPV QNAPSETSEE EPKRSPAQQE SNQAEASKEV AESNSCKFPA 

        70         80         90        100        110        120 
GIKIINHPTM PNTQVVAIPN NANIHSIITA LTAKGKESGS SGPNKFILIS CGGAPTQPPG 

       130        140        150        160        170        180 
LRPQTQTSYD AKRTEVTLET LGPKPAARDV NLPRPPGALC EQKRETCADG EAAGCTINNS 

       190        200        210        220        230        240 
LSNIQWLRKM SSDGLGSRSI KQEMEEKENC HLEQRQVKVE EPSRPSASWQ NSVSERPPYS 

       250        260        270        280        290        300 
YMAMIQFAIN STERKRMTLK DIYTWIEDHF PYFKHIAKPG WKNSIRHNLS LHDMFVRETS 

       310        320        330        340        350        360 
ANGKVSFWTI HPSANRYLTL DQVFKPLDPG SPQLPEHLES QQKRPNPELR RNMTIKTELP 

       370        380        390        400        410        420 
LGARRKMKPL LPRVSSYLVP IQFPVNQSLV LQPSVKVPLP LAASLMSSEL ARHSKRVRIA 

       430        440        450        460        470        480 
PKVLLAEEGI APLSSAGPGK EEKLLFGEGF SPLLPVQTIK EEEIQPGEEM PHLARPIKVE 

       490        500        510        520        530        540 
SPPLEEWPSP APSFKEESSH SWEDSSQSPT PRPKKSYSGL RSPTRCVSEM LVIQHRERRE 

       550        560        570        580        590        600 
RSRSRRKQHL LPPCVDEPEL LFSEGPSTSR WAAELPFPAD SSDPASQLSY SQEVGGPFKT 

       610        620        630        640        650        660 
PIKETLPISS TPSKSVLPRT PESWRLTPPA KVGGLDFSPV QTSQGASDPL PDPLGLMDLS 

       670        680        690        700        710        720 
TTPLQSAPPL ESPQRLLSSE PLDLISVPFG NSSPSDIDVP KPGSPEPQVS GLAANRSLTE 

       730        740        750        760 
GLVLDTMNDS LSKILLDISF PGLDEDPLGP DNINWSQFIP ELQ 

« Hide

Isoform 2 (FoxM1B) (FOXM1-b) [UniParc].

Checksum: 3224A22B1434A531
Show »

FASTA74882,685
Isoform 4 (FoxM1A) (FOXM1-a) [UniParc].

Checksum: 82416A3FA271C5D5
Show »

FASTA80188,596

References

« Hide 'large scale' references
[1]"Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues."
Ye H., Kelly T.F., Samadani U., Lim L., Rubio S., Overdier D.G., Roebuck K.A., Costa R.H.
Mol. Cell. Biol. 17:1626-1641(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4).
Tissue: Colon carcinoma.
[2]"Molecular analysis of a novel winged helix protein, WIN. Expression pattern, DNA binding property, and alternative splicing within the DNA binding domain."
Yao K.-M., Sha M., Lu Z., Wong G.G.
J. Biol. Chem. 272:19827-19836(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Pancreatic carcinoma and Testis.
[3]NIEHS SNPs program
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-402; LEU-450; PRO-643; ARG-669 AND LEU-673.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT PRO-643.
Tissue: Lung, Ovary and Skin.
[5]"Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope."
Westendorf J.M., Rao P.N., Gerace L.
Proc. Natl. Acad. Sci. U.S.A. 91:714-718(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 543-763.
Tissue: Lymphoblast.
[6]"Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes."
Tan Y., Raychaudhuri P., Costa R.H.
Mol. Cell. Biol. 27:1007-1016(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPAIR, PHOSPHORYLATION AT SER-376 BY CHEK2.
[7]"Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression."
Fu Z., Malureanu L., Huang J., Wang W., Li H., van Deursen J.M., Tindall D.J., Chen J.
Nat. Cell Biol. 10:1076-1082(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT THR-611; SER-693; SER-730 AND SER-739, MUTAGENESIS OF THR-611; SER-693; SER-730 AND SER-739.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331; THR-620 AND THR-627, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-730 AND SER-739, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence."
Littler D.R., Alvarez-Fernandez M., Stein A., Hibbert R.G., Heidebrecht T., Aloy P., Medema R.H., Perrakis A.
Nucleic Acids Res. 38:4527-4538(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 222-360 IN COMPLEX WITH PROMOTER DNA, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U74612 mRNA. Translation: AAC51128.1.
U74613 mRNA. Translation: AAC51129.1.
U83113 mRNA. Translation: AAC63595.1.
DQ022289 Genomic DNA. Translation: AAY26401.1.
BC006192 mRNA. Translation: AAH06192.1.
BC006529 mRNA. Translation: AAH06529.1.
BC012863 mRNA. Translation: AAH12863.1.
L16783 mRNA. Translation: AAC37541.1.
PIRB36881.
RefSeqNP_001230017.1. NM_001243088.1.
NP_001230018.1. NM_001243089.1.
NP_068772.2. NM_021953.3.
NP_973731.1. NM_202002.2.
NP_973732.1. NM_202003.2.
UniGeneHs.239.
Hs.735243.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3G73X-ray2.21A/B222-360[»]
ProteinModelPortalQ08050.
SMRQ08050. Positions 234-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108594. 23 interactions.
DIPDIP-36754N.
IntActQ08050. 13 interactions.
MINTMINT-107757.
STRING9606.ENSP00000342307.

PTM databases

PhosphoSiteQ08050.

Polymorphism databases

DMDM12644391.

Proteomic databases

PaxDbQ08050.
PRIDEQ08050.

Protocols and materials databases

DNASU2305.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342628; ENSP00000342307; ENSG00000111206. [Q08050-3]
ENST00000359843; ENSP00000352901; ENSG00000111206. [Q08050-1]
ENST00000361953; ENSP00000354492; ENSG00000111206. [Q08050-2]
GeneID2305.
KEGGhsa:2305.
UCSCuc001qle.3. human. [Q08050-3]
uc001qlf.3. human. [Q08050-1]
uc001qlg.3. human. [Q08050-2]

Organism-specific databases

CTD2305.
GeneCardsGC12M002966.
HGNCHGNC:3818. FOXM1.
HPACAB017832.
HPA029974.
HPA029975.
HPA029976.
MIM602341. gene.
neXtProtNX_Q08050.
PharmGKBPA28236.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000112633.
HOVERGENHBG051652.
KOK09406.
OMAFKTPIKE.
OrthoDBEOG7SJD4C.
PhylomeDBQ08050.
TreeFamTF333250.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressQ08050.
BgeeQ08050.
CleanExHS_FOXM1.
HS_MPP2.
GenevestigatorQ08050.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ08050.
GeneWikiFOXM1.
GenomeRNAi2305.
NextBio9359.
PROQ08050.
SOURCESearch...

Entry information

Entry nameFOXM1_HUMAN
AccessionPrimary (citable) accession number: Q08050
Secondary accession number(s): O43258 expand/collapse secondary AC list , O43259, O43260, Q4ZGG7, Q9BRL2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 149 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM