FOS_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FOS_MOUSE
• UniProt AC: P01101
• Protein Name: Proto-oncogene c-Fos
• Gene Name: Fos
• Organism: Mus musculus (Mouse).
• Sequence Length: 380
• Subcellular Localization: Nucleus . Endoplasmic reticulum. Cytoplasm, cytosol. In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the
• Protein Description: 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. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum..
• Protein Sequence: MMFSGFNADYEASSSRCSSASPAGDSLSYYHSPADSFSSMGSPVNTQDFCADLSVSSANFIPTVTAISTSPDLQWLVQPTLVSSVAPSQTRAPHPYGLPTQSAGAYARAGMVKTVSGGRAQSIGRRGKVEQLSPEEEEKRRIRRERNKMAAAKCRNRRRELTDTLQAETDQLEDEKSALQTEIANLLKEKEKLEFILAAHRPACKIPDDLGFPEEMSVASLDLTGGLPEASTPESEEAFTLPLLNDPEPKPSLEPVKSISNVELKAEPFDDFLFPASSRPSGSETSRSVPDVDLSGSFYAADWEPLHSNSLGMGPMVTELEPLCTPVVTCTPGCTTYTSSFVFTYPEADSFPSCAAAHRKGSSSNEPSSDSLSSPTLLAL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
10	Phosphorylation	FSGFNADYEASSSRC CCCCCCCCCCCCCCC	15.81	-
30	Phosphorylation	AGDSLSYYHSPADSF CCCCCEECCCCCCCC	7.76	-
232	Phosphorylation	GGLPEASTPESEEAF CCCCCCCCCCCHHCC	37.82	22817900
258	Phosphorylation	PSLEPVKSISNVELK CCCCCCCCCCCEEEE	31.33	25338131
265	Sumoylation	SISNVELKAEPFDDF CCCCEEEEEEECCCC	36.88	-
325	Phosphorylation	TELEPLCTPVVTCTP CCCCCCCCCEEEECC	27.14	12134156
331	Phosphorylation	CTPVVTCTPGCTTYT CCCEEEECCCCEEEC	17.22	12134156
362	Phosphorylation	AAAHRKGSSSNEPSS HHHHHCCCCCCCCCC	33.36	12134156
363	Phosphorylation	AAHRKGSSSNEPSSD HHHHCCCCCCCCCCC	45.94	26745281
364	Phosphorylation	AHRKGSSSNEPSSDS HHHCCCCCCCCCCCC	47.08	26745281
368	Phosphorylation	GSSSNEPSSDSLSSP CCCCCCCCCCCCCCC	40.37	26745281
369	Phosphorylation	SSSNEPSSDSLSSPT CCCCCCCCCCCCCCC	41.77	26643407
371	Phosphorylation	SNEPSSDSLSSPTLL CCCCCCCCCCCCCEE	31.90	26643407
373	Phosphorylation	EPSSDSLSSPTLLAL CCCCCCCCCCCEECC	37.92	26643407
374	Phosphorylation	PSSDSLSSPTLLAL- CCCCCCCCCCEECC-	27.48	12134156
376	Phosphorylation	SDSLSSPTLLAL--- CCCCCCCCEECC---	36.03	26643407

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
10	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
30	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
232	T	Phosphorylation	Kinase	FRK	P42685	PSP
325	T	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
325	T	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
331	T	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
331	T	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
362	S	Phosphorylation	Kinase	PRKACA	P05132	GPS
362	S	Phosphorylation	Kinase	RSK2	P18654	PSP
362	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
362	S	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
374	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
374	S	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
232	T	Phosphorylation	Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation.	12972619
232	T	Phosphorylation	Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).	12972619
232	T	Sumoylation	Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation.	12972619
232	T	Sumoylation	Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).	12972619
325	T	Phosphorylation	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.	12134156
331	T	Phosphorylation	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.	12134156
362	S	Phosphorylation	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.	12134156
362	S	Phosphorylation	Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation (By similarity).	12134156
362	S	Phosphorylation	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.	12134156
374	S	Phosphorylation	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.	12134156
374	S	Phosphorylation	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.	12134156

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of FOS_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SMCA2_MOUSE	Smarca2	physical	11053448
SNF5_MOUSE	Smarcb1	physical	11053448
JUN_MOUSE	Jun	physical	1631061
JUN_MOUSE	Jun	physical	21478324
CYLD_MOUSE	Cyld	physical	21478324
TYY1_MOUSE	Yy1	physical	22322974
P85A_MOUSE	Pik3r1	physical	9115297
RIT2_MOUSE	Rit2	physical	15867431
ATF7_MOUSE	Atf7	physical	15867431
SNPC5_MOUSE	Snapc5	physical	15867431
PRS8_MOUSE	Psmc5	physical	15867431
JUND_MOUSE	Jund	physical	15867431
OPTN_MOUSE	Optn	physical	15867431
EF1D_MOUSE	Eef1d	physical	15867431
JUN_MOUSE	Jun	physical	15867431
SIR1_MOUSE	Sirt1	physical	20042607

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"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).
Cited for: PHOSPHORYLATION AT SER-362, AND FUNCTION.
PubMed: 15719069

"Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates thetranscriptional activation of AP-1 and cellular transformation inducedby platelet-derived growth factor.";
Monje P., Marinissen M.J., Gutkind J.S.;
Mol. Cell. Biol. 23:7030-7043(2003).
Cited for: PHOSPHORYLATION AT THR-232; THR-325; THR-331; SER-362 AND SER-374,FUNCTION, AND MUTAGENESIS OF THR-232; THR-325; THR-331 AND SER-374.
PubMed: 12972619

"Molecular interpretation of ERK signal duration by immediate earlygene products.";
Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J.;
Nat. Cell Biol. 4:556-564(2002).
Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION,AND MUTAGENESIS OF THR-325; THR-331; PHE-343; TYR-345; SER-362 ANDSER-374.
PubMed: 12134156