Proto-oncogene c-Fos - Mus musculus (Mouse)

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P01101 (FOS_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified October 31, 2012. Version 112. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Proto-oncogene c-Fos

Alternative name(s):
Cellular oncogene fos

Gene names

Name:

Fos

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling By similarity. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. Ref.5 Ref.6 Ref.7
Subunit structure	Heterodimer; with JUN By similarity. Interacts with MAFB. Component of the SMAD3/SMAD4/JUN/FOS complex required for syngernistic TGF-beta-mediated transcription at the AP1 promoter site. Interacts with SMAD3; the interaction is weak even on TGF-beta activation. Interacts with MAFB By similarity. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Ref.4
Subcellular location	Nucleus By similarity.
Post-translational modification	Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-374 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and Thr-331 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation By similarity. Ref.5 Ref.6 Ref.7 Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 By similarity.
Sequence similarities	Belongs to the bZIP family. Fos subfamily. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	aging Inferred from electronic annotation. Source: Compara cellular response to calcium ion Inferred from direct assay PubMed 19365557. Source: MGI cellular response to extracellular stimulus Inferred from mutant phenotype PubMed 9294610. Source: MGI cellular response to hormone stimulus Inferred from electronic annotation. Source: Compara conditioned taste aversion Inferred from electronic annotation. Source: Compara female pregnancy Inferred from electronic annotation. Source: Compara nervous system development Inferred from mutant phenotype PubMed 11925568. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 9294610. Source: MGI response to cAMP Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara response to corticosterone stimulus Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from direct assay PubMed 9098922. Source: MGI response to gravity Inferred from electronic annotation. Source: Compara response to light stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara response to progesterone stimulus Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara sleep Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular component	transcription factor complex Inferred from direct assay PubMed 12943993. Source: MGI
Molecular function	DNA binding Inferred from direct assay PubMed 12486129. Source: MGI double-stranded DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 12220541. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Esr2	O08537	2	EBI-4288185,EBI-2526214

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 380

380

Proto-oncogene c-Fos

PRO_0000076467

Regions

Domain

137 – 200

bZIP

Region

139 – 159

Basic motif By similarity

Region

165 – 193

Leucine-zipper By similarity

Amino acid modifications

Modified residue

232

Phosphothreonine Ref.6

Modified residue

325

Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6

Modified residue

331

Phosphothreonine; by MAPK1 and MAPK3 Ref.5 Ref.6

Modified residue

362

Phosphoserine; by MAPK1, MAPK3 and RPS6KA3 Ref.5 Ref.6 Ref.7

Modified residue

374

Phosphoserine; by MAPK1 and MAPK3 Ref.5 Ref.6

Cross-link

113

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

265

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis

232

T → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-325; A-331 and A-374. Ref.6

Mutagenesis

325

T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-331. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-331 and A-374. Ref.5 Ref.6

Mutagenesis

331

T → A: Almost no EGF-mediated phosphorylation, greatly reduced cellular transformation, and reduced AP1 activity by 20%; when associated with A-325. No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325;and A-374. Ref.5 Ref.6

Mutagenesis

343

F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. Ref.5

Mutagenesis

345

Y → A: Reduced phosphorylation by ERK. Ref.5

Mutagenesis

362

S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. Ref.5

Mutagenesis

362

S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. Ref.5

Mutagenesis

374

S → A: No effect on PDGF-stimulated enhancement of transcriptional activity. Completely abolishes PDGF-stimulated enhancement of transcriptional activity; when associated with A-232; A-325 and A-331. Ref.5 Ref.6

Mutagenesis

374

S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. Ref.5 Ref.6

Mutagenesis

374

S → E: Increased enhanced EGF- and RSK-mediated tranformation; when associated with E-362. Ref.5 Ref.6

Secondary structure

380

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P01101 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 475966265952B624
Show »

FASTA

380

40,838

        10         20         30         40         50         60 
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC ADLSVSSANF 

        70         80         90        100        110        120 
IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT QSAGAYARAG MVKTVSGGRA 

       130        140        150        160        170        180 
QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD QLEDEKSALQ 

       190        200        210        220        230        240 
TEIANLLKEK EKLEFILAAH RPACKIPDDL GFPEEMSVAS LDLTGGLPEA STPESEEAFT 

       250        260        270        280        290        300 
LPLLNDPEPK PSLEPVKSIS NVELKAEPFD DFLFPASSRP SGSETSRSVP DVDLSGSFYA 

       310        320        330        340        350        360 
ADWEPLHSNS LGMGPMVTEL EPLCTPVVTC TPGCTTYTSS FVFTYPEADS FPSCAAAHRK 

       370        380 
GSSSNEPSSD SLSSPTLLAL

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Analysis of FBJ-MuSV provirus and c-fos (mouse) gene reveals that viral and cellular fos gene products have different carboxy termini." van Beveren C., van Straaten F., Curran T., Mueller R., Verma I.M. Cell 32:1241-1255(1983) [PubMed: 6301687] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Removal of a 67-base-pair sequence in the noncoding region of protooncogene fos converts it to a transforming gene." Meijlink F., Curran T., Miller A.D., Verma I.M. Proc. Natl. Acad. Sci. U.S.A. 82:4987-4991(1985) [PubMed: 2991903] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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]. Strain: FVB/N. Tissue: Mammary gland.
[4]	"Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ." Mittelstadt P.R., Ashwell J.D. J. Biol. Chem. 276:29603-29610(2001) [PubMed: 11397794] [Abstract] Cited for: INTERACTION WITH DSIPI.
[5]	"Molecular interpretation of ERK signal duration by immediate early gene products." Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J. Nat. Cell Biol. 4:556-564(2002) [PubMed: 12134156] [Abstract] Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; PHE-343; TYR-345; SER-362 AND SER-374.
[6]	"Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor." Monje P., Marinissen M.J., Gutkind J.S. Mol. Cell. Biol. 23:7030-7043(2003) [PubMed: 12972619] [Abstract] Cited for: PHOSPHORYLATION AT THR-232; THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-232; THR-325; THR-331 AND SER-374.
[7]	"Essential role of RSK2 in c-Fos-dependent osteosarcoma development." David J.-P., Mehic D., Bakiri L., Schilling A.F., Mandic V., Priemel M., Idarraga M.H., Reschke M.O., Hoffmann O., Amling M., Wagner E.F. J. Clin. Invest. 115:664-672(2005) [PubMed: 15719069] [Abstract] Cited for: PHOSPHORYLATION AT SER-362, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V00727 Genomic DNA. Translation: CAA24105.1.
J00370 Genomic DNA. Translation: AAA96699.1.
BC029814 mRNA. Translation: AAH29814.1.

IPI

IPI00131985.

PIR

TVMSF. A01343.

RefSeq

NP_034364.1. NM_010234.2.

UniGene

Mm.246513.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WT7	X-ray	2.30	A	138-200	[»]

ProteinModelPortal

P01101.

SMR

P01101. Positions 138-200.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1066N.

IntAct

P01101. 1 interaction.

MINT

MINT-1500015.

STRING

P01101.

PTM databases

PhosphoSite

P01101.

Proteomic databases

PRIDE

P01101.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000021674; ENSMUSP00000021674; ENSMUSG00000021250.

GeneID

14281.

KEGG

mmu:14281.

UCSC

uc007oha.1. mouse.

Organism-specific databases

CTD

2353.

MGI

MGI:95574. Fos.

Phylogenomic databases

eggNOG

NOG258795.

GeneTree

ENSGT00550000074426.

HOGENOM

HOG000234334.

HOVERGEN

HBG005743.

InParanoid

P01101.

K04379.

OMA

QPICKIP.

OrthoDB

EOG42BX9D.

Gene expression databases

ArrayExpress

P01101.

Bgee

P01101.

CleanEx

MM_FOS.

Genevestigator

P01101.

GermOnline

ENSMUSG00000021250. Mus musculus.

Family and domain databases

InterPro

IPR004827. bZIP.
IPR011616. bZIP_1.
IPR000837. Leuzip_Fos.
[Graphical view]

Pfam

PF00170. bZIP_1. 1 hit.
[Graphical view]

PRINTS

PR00042. LEUZIPPRFOS.

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

285657.

SOURCE

Search...

Entry information

Entry name

FOS_MOUSE

Accession

Primary (citable) accession number: P01101

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	October 31, 2012
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Oct	NOV	Dec
	11
2011	2012	2013

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents