Reviewed, UniProtKB/Swiss-Prot P01101 (FOS_MOUSE)

Names and origin

Protein names

Recommended name:
    Proto-oncogene protein c-fos
Alternative name(s):
    Cellular oncogene fos

Gene names

Name:

Fos

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	380 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. 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. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Interacts with MAFB By similarity.
Subcellular location	Nucleus.
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. Constitutively sumoylated by 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 domain.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Proto-oncogene
Ligand	DNA-binding
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	cellular response to extracellular stimulus Inferred from mutant phenotype. Source: MGI nervous system development Inferred from mutant phenotype. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: MGI response to drug Inferred from direct assay. Source: MGI response to protein stimulus Inferred from direct assay. Source: MGI
Cellular component	transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 380	380	Proto-oncogene protein c-fos		PRO_0000076467
Regions
	Domain	165 – 193	29	Leucine-zipper
	DNA binding	139 – 160	22	Basic motif
Amino acid modifications
	Modified residue	232	1	Phosphothreonine Ref.6
	Modified residue	325	1	Phosphothreonine Ref.5 Ref.6
	Modified residue	331	1	Phosphothreonine Ref.5 Ref.6
	Modified residue	362	1	Phosphoserine; by MAPK and RPS6KA3 Ref.5 Ref.6 Ref.7
	Modified residue	374	1	Phosphoserine; by MAPK 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	1	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	1	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	1	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	1	F → A: Reduced phosphorylation by ERK. Reduced AP1 activity by 65%. Ref.5
	Mutagenesis	345	1	Y → A: Reduced phosphorylation by ERK. Ref.5
	Mutagenesis	362	1	S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-374. Ref.5
	Mutagenesis	362	1	S → E: Increased enhancement of EGF- and RSK-mediated tranformation; when associated with E-374. Ref.5
	Mutagenesis	374	1	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	1	S → D: Enhanced EGF- and RSK-mediated tranformation; when associated with D-362. Ref.5 Ref.6
	Mutagenesis	374	1	S → E: Increased enhanced EGF- and RSK-mediated tranformation; when associated with E-362. Ref.5 Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P01101-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 475966265952B624	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

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
EMBLGenBankDDBJ	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.
UniGene	Mm.246513
3D structure databases
HSSP	HSSP built from PDB template 1FOS based on UniProtKB P01100.
SMR	P01101. Positions 139-198.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:1066N.
STRING	P01101.
PTM databases
PhosphoSite	P01101.
Proteomic databases
PRIDE	P01101.
Genome annotation databases
Ensembl	ENSMUST00000021674; ENSMUSP00000021674; ENSMUSG00000021250; Mus musculus. [Genome view]
GeneID	14281.
KEGG	mmu:14281.
UCSC	uc007oha.1. mouse.
Organism-specific databases
CTD	14281.
MGI	MGI:95574. Fos.
Phylogenomic databases
HOGENOM	P01101.
HOVERGEN	P01101.
OMA	TYTSSFV.
Gene expression databases
ArrayExpress	P01101.
Bgee	P01101.
CleanEx	MM_FOS.
Genevestigator	P01101.
GermOnline	ENSMUSG00000021250. Mus musculus.
Family and domain databases
InterPro	IPR011616. bZIP_1. IPR000837. Leuzip_Fos. IPR004827. TF_bZIP. [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 Resources
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:	November 3, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)