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Protein

Forkhead box protein M1

Gene

FOXM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi235 – 327Fork-headPROSITE-ProRule annotationAdd BLAST93

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
  • sequence-specific DNA binding Source: InterPro
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
  • DNA repair Source: UniProtKB-KW
  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • negative regulation of cell aging Source: UniProtKB
  • negative regulation of stress-activated MAPK cascade Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of double-strand break repair Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of cell cycle Source: Reactome
  • regulation of cell cycle arrest Source: BHF-UCL
  • regulation of cell growth Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • regulation of Ras protein signal transduction Source: BHF-UCL
  • regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
  • transcription from RNA polymerase II promoter Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000111206-MONOMER.
ReactomeiR-HSA-156711. Polo-like kinase mediated events.
R-HSA-69273. Cyclin A/B1 associated events during G2/M transition.
SIGNORiQ08050.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:FOXM1
Synonyms:FKHL16, HFH11, MPP2, WIN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3818. FOXM1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi611T → A: Prevents phosphorylation by CDK1 and subsequent binding of POLO box domains of PLK1; when associated with A-693. 1 Publication1
Mutagenesisi693S → A: Prevents phosphorylation by CDK1 and subsequent binding of POLO box domains of PLK1; when associated with A-611. 1 Publication1
Mutagenesisi730S → A: Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-739. 1 Publication1
Mutagenesisi739S → A: Prevents phosphorylation by PLK1 and impairs transcription activity; when associated with A-730. 1 Publication1

Organism-specific databases

DisGeNETi2305.
OpenTargetsiENSG00000111206.
PharmGKBiPA28236.

Polymorphism and mutation databases

BioMutaiFOXM1.
DMDMi12644391.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918631 – 763Forkhead box protein M1Add BLAST763

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki201Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei331PhosphoserineCombined sources1
Cross-linki356Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei376Phosphoserine; by CHEK21 Publication1
Cross-linki422Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki440Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei522PhosphoserineCombined sources1
Modified residuei611Phosphothreonine; by CDK11 Publication1
Modified residuei620PhosphothreonineCombined sources1
Modified residuei627PhosphothreonineCombined sources1
Modified residuei662PhosphothreonineCurated1
Modified residuei693Phosphoserine; by CDK11 Publication1
Modified residuei730Phosphoserine; by PLK1Combined sources1 Publication1
Modified residuei739Phosphoserine; by PLK1Combined sources1 Publication1

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ08050.
PeptideAtlasiQ08050.
PRIDEiQ08050.

PTM databases

iPTMnetiQ08050.
PhosphoSitePlusiQ08050.

Expressioni

Tissue specificityi

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 stagei

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

Inductioni

Induced during liver regeneration and oxidative stress.

Gene expression databases

BgeeiENSG00000111206.
CleanExiHS_FOXM1.
HS_MPP2.
ExpressionAtlasiQ08050. baseline and differential.
GenevisibleiQ08050. HS.

Organism-specific databases

HPAiCAB017832.
HPA029974.
HPA029975.
HPA029976.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CCNE1P248642EBI-866480,EBI-519526
CDK6Q005342EBI-866499,EBI-295663
CTNNB1P3522216EBI-866480,EBI-491549
DARSP148682EBI-866480,EBI-358730
E7P031293EBI-866499,EBI-866453From a different organism.
FOXO3O435242EBI-866480,EBI-1644164
ORC2Q134162EBI-866480,EBI-374957
PES1O005412EBI-866480,EBI-1053271
ZC3H11AO751522EBI-866480,EBI-748480

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108594. 69 interactors.
DIPiDIP-36754N.
IntActiQ08050. 59 interactors.
MINTiMINT-107757.
STRINGi9606.ENSP00000342307.

Structurei

Secondary structure

1763
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi241 – 250Combined sources10
Beta strandi255 – 257Combined sources3
Helixi259 – 269Combined sources11
Helixi272 – 275Combined sources4
Helixi281 – 291Combined sources11
Beta strandi295 – 299Combined sources5
Beta strandi306 – 310Combined sources5
Turni312 – 314Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3G73X-ray2.21A/B222-360[»]
ProteinModelPortaliQ08050.
SMRiQ08050.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08050.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi480 – 513Glu/Pro/Ser/Thr-richAdd BLAST34

Domaini

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.

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000112633.
HOVERGENiHBG051652.
InParanoidiQ08050.
KOiK09406.
OMAiFKTPIKE.
OrthoDBiEOG091G03GL.
PhylomeDBiQ08050.
TreeFamiTF333250.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

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) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MKTSPRRPLI LKRRRLPLPV QNAPSETSEE EPKRSPAQQE SNQAEASKEV
60 70 80 90 100
AESNSCKFPA GIKIINHPTM PNTQVVAIPN NANIHSIITA LTAKGKESGS
110 120 130 140 150
SGPNKFILIS CGGAPTQPPG LRPQTQTSYD AKRTEVTLET LGPKPAARDV
160 170 180 190 200
NLPRPPGALC EQKRETCADG EAAGCTINNS LSNIQWLRKM SSDGLGSRSI
210 220 230 240 250
KQEMEEKENC HLEQRQVKVE EPSRPSASWQ NSVSERPPYS YMAMIQFAIN
260 270 280 290 300
STERKRMTLK DIYTWIEDHF PYFKHIAKPG WKNSIRHNLS LHDMFVRETS
310 320 330 340 350
ANGKVSFWTI HPSANRYLTL DQVFKPLDPG SPQLPEHLES QQKRPNPELR
360 370 380 390 400
RNMTIKTELP LGARRKMKPL LPRVSSYLVP IQFPVNQSLV LQPSVKVPLP
410 420 430 440 450
LAASLMSSEL ARHSKRVRIA PKVLLAEEGI APLSSAGPGK EEKLLFGEGF
460 470 480 490 500
SPLLPVQTIK EEEIQPGEEM PHLARPIKVE SPPLEEWPSP APSFKEESSH
510 520 530 540 550
SWEDSSQSPT PRPKKSYSGL RSPTRCVSEM LVIQHRERRE RSRSRRKQHL
560 570 580 590 600
LPPCVDEPEL LFSEGPSTSR WAAELPFPAD SSDPASQLSY SQEVGGPFKT
610 620 630 640 650
PIKETLPISS TPSKSVLPRT PESWRLTPPA KVGGLDFSPV QTSQGASDPL
660 670 680 690 700
PDPLGLMDLS TTPLQSAPPL ESPQRLLSSE PLDLISVPFG NSSPSDIDVP
710 720 730 740 750
KPGSPEPQVS GLAANRSLTE GLVLDTMNDS LSKILLDISF PGLDEDPLGP
760
DNINWSQFIP ELQ
Length:763
Mass (Da):84,283
Last modified:December 1, 2000 - v3
Checksum:i963CAC8FE7498E9B
GO
Isoform 2 (identifier: Q08050-2) [UniParc]FASTAAdd to basket
Also known as: FoxM1B, FOXM1-b

The sequence of this isoform differs from the canonical sequence as follows:
     326-340: Missing.

Show »
Length:748
Mass (Da):82,685
Checksum:i3224A22B1434A531
GO
Isoform 4 (identifier: Q08050-3) [UniParc]FASTAAdd to basket
Also known as: FoxM1A, FOXM1-a

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

Show »
Length:801
Mass (Da):88,596
Checksum:i82416A3FA271C5D5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3T → A in AAC63595 (PubMed:9242644).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025239402A → E.1 PublicationCorresponds to variant rs28990715dbSNPEnsembl.1
Natural variantiVAR_025240450F → L.1 PublicationCorresponds to variant rs28919868dbSNPEnsembl.1
Natural variantiVAR_020024643S → P.2 PublicationsCorresponds to variant rs3742076dbSNPEnsembl.1
Natural variantiVAR_025241669P → R.1 PublicationCorresponds to variant rs28919869dbSNPEnsembl.1
Natural variantiVAR_025242673P → L.1 PublicationCorresponds to variant rs28919870dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001547326 – 340Missing in isoform 2. 2 PublicationsAdd BLAST15
Alternative sequenceiVSP_001548423V → VFGEQVVFGYMSKFFSGDLR DFGTPITSLFNFIFLCLSV in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8515.1. [Q08050-1]
CCDS8516.1. [Q08050-3]
CCDS8517.1. [Q08050-2]
PIRiB36881.
RefSeqiNP_001230017.1. NM_001243088.1.
NP_001230018.1. NM_001243089.1.
NP_068772.2. NM_021953.3. [Q08050-1]
NP_973731.1. NM_202002.2. [Q08050-3]
NP_973732.1. NM_202003.2. [Q08050-2]
UniGeneiHs.239.
Hs.735243.

Genome annotation databases

EnsembliENST00000342628; ENSP00000342307; ENSG00000111206. [Q08050-3]
ENST00000359843; ENSP00000352901; ENSG00000111206. [Q08050-1]
ENST00000361953; ENSP00000354492; ENSG00000111206. [Q08050-2]
GeneIDi2305.
KEGGihsa:2305.
UCSCiuc001qle.4. human. [Q08050-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS8515.1. [Q08050-1]
CCDS8516.1. [Q08050-3]
CCDS8517.1. [Q08050-2]
PIRiB36881.
RefSeqiNP_001230017.1. NM_001243088.1.
NP_001230018.1. NM_001243089.1.
NP_068772.2. NM_021953.3. [Q08050-1]
NP_973731.1. NM_202002.2. [Q08050-3]
NP_973732.1. NM_202003.2. [Q08050-2]
UniGeneiHs.239.
Hs.735243.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3G73X-ray2.21A/B222-360[»]
ProteinModelPortaliQ08050.
SMRiQ08050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108594. 69 interactors.
DIPiDIP-36754N.
IntActiQ08050. 59 interactors.
MINTiMINT-107757.
STRINGi9606.ENSP00000342307.

PTM databases

iPTMnetiQ08050.
PhosphoSitePlusiQ08050.

Polymorphism and mutation databases

BioMutaiFOXM1.
DMDMi12644391.

Proteomic databases

PaxDbiQ08050.
PeptideAtlasiQ08050.
PRIDEiQ08050.

Protocols and materials databases

DNASUi2305.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342628; ENSP00000342307; ENSG00000111206. [Q08050-3]
ENST00000359843; ENSP00000352901; ENSG00000111206. [Q08050-1]
ENST00000361953; ENSP00000354492; ENSG00000111206. [Q08050-2]
GeneIDi2305.
KEGGihsa:2305.
UCSCiuc001qle.4. human. [Q08050-1]

Organism-specific databases

CTDi2305.
DisGeNETi2305.
GeneCardsiFOXM1.
HGNCiHGNC:3818. FOXM1.
HPAiCAB017832.
HPA029974.
HPA029975.
HPA029976.
MIMi602341. gene.
neXtProtiNX_Q08050.
OpenTargetsiENSG00000111206.
PharmGKBiPA28236.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000112633.
HOVERGENiHBG051652.
InParanoidiQ08050.
KOiK09406.
OMAiFKTPIKE.
OrthoDBiEOG091G03GL.
PhylomeDBiQ08050.
TreeFamiTF333250.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000111206-MONOMER.
ReactomeiR-HSA-156711. Polo-like kinase mediated events.
R-HSA-69273. Cyclin A/B1 associated events during G2/M transition.
SIGNORiQ08050.

Miscellaneous databases

EvolutionaryTraceiQ08050.
GeneWikiiFOXM1.
GenomeRNAii2305.
PROiQ08050.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111206.
CleanExiHS_FOXM1.
HS_MPP2.
ExpressionAtlasiQ08050. baseline and differential.
GenevisibleiQ08050. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOXM1_HUMAN
AccessioniPrimary (citable) accession number: Q08050
Secondary accession number(s): O43258
, O43259, O43260, Q4ZGG7, Q9BRL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: December 1, 2000
Last modified: November 30, 2016
This is version 179 of the entry and version 3 of the sequence. [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 12
    Human chromosome 12: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.