Reviewed, UniProtKB/Swiss-Prot P12841 (FOS_RAT)

Names and origin

Protein names

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

Gene names

Name:

Fos

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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
Subunit structure	Heterodimer. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA By similarity. Interacts with MAFB.
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	aging Inferred from expression pattern. Source: RGD cellular response to hormone stimulus Inferred from expression pattern. Source: RGD conditioned taste aversion Inferred from expression pattern. Source: RGD female pregnancy Inferred from expression pattern. Source: RGD response to cAMP Inferred from expression pattern. Source: RGD response to cold Inferred from expression pattern. Source: RGD response to corticosterone stimulus Inferred from expression pattern. Source: RGD response to cytokine stimulus Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to gravity Inferred from expression pattern. Source: RGD response to light stimulus Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to mechanical stimulus Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to progesterone stimulus Inferred from expression pattern. Source: RGD response to toxin Inferred from expression pattern. Source: RGD sleep Inferred from expression pattern. Source: RGD transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: RGD
Cellular component	synaptosome Inferred from direct assay. Source: RGD
Molecular function	double-stranded DNA binding Ref.3 Inferred from direct assay. Source: RGD protein heterodimerization activity Ref.3 Inferred from direct assay. Source: RGD sequence-specific DNA binding Inferred from direct assay. Source: RGD transcription factor activity Ref.3 Inferred from mutant phenotype. Source: RGD
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_0000076469
Regions
	Domain	165 – 193	29	Leucine-zipper
	DNA binding	139 – 160	22	Basic motif Ref.3
Amino acid modifications
	Modified residue	232	1	Phosphothreonine Ref.5
	Modified residue	325	1	Phosphothreonine Ref.6
	Modified residue	331	1	Phosphothreonine Ref.6
	Modified residue	362	1	Phosphoserine; by MAPK and RPS6KA3 Ref.6
	Modified residue	374	1	Phosphoserine; by MAPK 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: Abolishes HA-RAS-mediated activation. Loss of in vitro ERK2-mediated phosphorylation. No change in sumoylation levels. Ref.5
	Mutagenesis	325	1	T → A: Loss of NGF-mediated phosphorylation; when associated with A-331. Ref.6
	Mutagenesis	331	1	T → A: Loss of NGF-mediated phosphorylation; when associated with A-325. Ref.6
	Mutagenesis	343 – 345	3	FTY → ATA: Decreased phosphorylation levels. Reduced NGF-mediated enhanced transactivation. Ref.6
	Mutagenesis	362	1	S → A: Some loss of protein stabilization on NGF-treatment; when associated with D-374. Ref.6
	Mutagenesis	362	1	S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-374. Ref.6
	Mutagenesis	374	1	S → A: Greatly reduced protein stabilization on NGF stimulation. Ref.6
	Mutagenesis	374	1	S → D: Increased protein stabilization on NGF-treatment, but no increase when treated with MAPK-inhibitor; when associated with D-362. Some loss of protein stablization on NGF-treatment; wnen associated with A-362. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P12841-1 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: E62D16A88CB2BEE9	FASTA	380	40,927
	10 20 30 40 50 60 MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNTQDFC ADLSVSSANF 70 80 90 100 110 120 IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGLPT PSTGAYARAG VVKTMSGGRA 130 140 150 160 170 180 QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD QLEDEKSALQ 190 200 210 220 230 240 TEIANLLKEK EKLEFILAAH RPACKIPNDL GFPEEMSVTS LDLTGGLPEA TTPESEEAFT 250 260 270 280 290 300 LPLLNDPEPK PSLEPVKNIS NMELKAEPFD DFLFPASSRP SGSETARSVP DVDLSGSFYA 310 320 330 340 350 360 ADWEPLHSSS LGMGPMVTEL EPLCTPVVTC TPSCTTYTSS FVFTYPEADS FPSCAAAHRK 370 380 GSSSNEPSSD SLSSPTLLAL

References

[1]	"Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro." Curran T., Gordon M.B., Rubino K.L., Sambucetti L.C. Oncogene 2:79-84(1987) [PubMed: 3325886] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cFOS expression in rat." Weiler E. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Sprague-Dawley. Tissue: Liver.
[3]	"Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly." Abate C., Luk D., Gentz R., Rauscher F.J. III, Curran T. Proc. Natl. Acad. Sci. U.S.A. 87:1032-1036(1990) [PubMed: 2105492] [Abstract] Cited for: DNA-BINDING.
[4]	"Rat maf-related factors: the specificities of DNA binding and heterodimer formation." Matsushima-Hibiya Y., Nishi S., Sakai M. Biochem. Biophys. Res. Commun. 245:412-418(1998) [PubMed: 9571165] [Abstract] Cited for: INTERACTION WITH MAFB.
[5]	"Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation capacity." Bannister A.J., Brown H.J., Sutherland J.A., Kouzarides T. Nucleic Acids Res. 22:5173-5176(1994) [PubMed: 7816602] [Abstract] Cited for: PHOSPHORYLATION AT THR-232, FUNCTION, MUTAGENESIS OF THR-232.
[6]	"Sustained activation of extracellular signal-regulated kinase by nerve growth factor regulates c-fos protein stabilization and transactivation in PC12 cells." Pellegrino M.J., Stork P.J. J. Neurochem. 99:1480-1493(2006) [PubMed: 17223854] [Abstract] Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION, MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 AND SER-374.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X06769 mRNA. Translation: CAA29937.1. DQ089699 Genomic DNA. Translation: AAZ13764.1.
IPI	IPI00368000.
PIR	TVRTFS. A28263.
RefSeq	NP_071533.1.
UniGene	Rn.103750
3D structure databases
HSSP	HSSP built from PDB template 1FOS based on UniProtKB P01100.
SMR	P12841. Positions 139-198.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:6001N.
PTM databases
PhosphoSite	P12841.
Genome annotation databases
Ensembl	ENSRNOG00000008015. Rattus norvegicus. [Contig view]
GeneID	314322.
KEGG	rno:314322.
Organism-specific databases
RGD	2626. Fos.
Phylogenomic databases
HOVERGEN	P12841.
OMA	P12841. TYTSSFV.
Gene expression databases
ArrayExpress	P12841.
GermOnline	ENSRNOG00000008015. Rattus norvegicus.
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	667476.

Entry information

Entry name

FOS_RAT

Accession

Primary (citable) accession number: P12841
Secondary accession number(s): Q4FDN1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	June 16, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)