FOS_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FOS_RAT
• UniProt AC: P12841
• Protein Name: Proto-oncogene c-Fos
• Gene Name: Fos
• Organism: Rattus norvegicus (Rat).
• 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 (By similarity)..
• Protein Sequence: MMFSGFNADYEASSSRCSSASPAGDSLSYYHSPADSFSSMGSPVNTQDFCADLSVSSANFIPTVTAISTSPDLQWLVQPTLVSSVAPSQTRAPHPYGLPTPSTGAYARAGVVKTMSGGRAQSIGRRGKVEQLSPEEEEKRRIRRERNKMAAAKCRNRRRELTDTLQAETDQLEDEKSALQTEIANLLKEKEKLEFILAAHRPACKIPNDLGFPEEMSVTSLDLTGGLPEATTPESEEAFTLPLLNDPEPKPSLEPVKNISNMELKAEPFDDFLFPASSRPSGSETARSVPDVDLSGSFYAADWEPLHSSSLGMGPMVTELEPLCTPVVTCTPSCTTYTSSFVFTYPEADSFPSCAAAHRKGSSSNEPSSDSLSSPTLLAL

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	GGLPEATTPESEEAF CCCCCCCCCCCHHCC	31.91	7816602
325	Phosphorylation	TELEPLCTPVVTCTP EECCCCCCCEEEECC	27.14	17223854
331	Phosphorylation	CTPVVTCTPSCTTYT CCCEEEECCCCCEEC	14.63	17223854
362	Phosphorylation	AAAHRKGSSSNEPSS HHHHHCCCCCCCCCC	33.36	27097102
363	Phosphorylation	AAHRKGSSSNEPSSD HHHHCCCCCCCCCCC	45.94	27097102
364	Phosphorylation	AHRKGSSSNEPSSDS HHHCCCCCCCCCCCC	47.08	27097102
368	Phosphorylation	GSSSNEPSSDSLSSP CCCCCCCCCCCCCCC	40.37	27097102
369	Phosphorylation	SSSNEPSSDSLSSPT CCCCCCCCCCCCCCC	41.77	27097102
371	Phosphorylation	SNEPSSDSLSSPTLL CCCCCCCCCCCCCEE	31.90	27097102
373	Phosphorylation	EPSSDSLSSPTLLAL CCCCCCCCCCCEECC	37.92	27097102
374	Phosphorylation	PSSDSLSSPTLLAL- CCCCCCCCCCEECC-	27.48	27097102
376	Phosphorylation	SDSLSSPTLLAL--- CCCCCCCCEECC---	36.03	27097102

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	Q9WUD9	Uniprot
30	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
325	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
325	T	Phosphorylation	Kinase	ERK2	P63085	PSP
325	T	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
325	T	Phosphorylation	Kinase	ERK-SUBFAMILY	-	GPS
325	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
325	T	Phosphorylation	Kinase	MAPK3	P21708	Uniprot
331	T	Phosphorylation	Kinase	ERK2	P28482	PSP
331	T	Phosphorylation	Kinase	ERK2	P63086	PSP
331	T	Phosphorylation	Kinase	ERK-SUBFAMILY	-	GPS
331	T	Phosphorylation	Kinase	ERK1	P21708	PSP
362	S	Phosphorylation	Kinase	RPS6KA3	-	Uniprot
362	S	Phosphorylation	Kinase	RPS6KA3	D3Z8E0	GPS
362	S	Phosphorylation	Kinase	RSK-SUBFAMILY	-	GPS
362	S	Phosphorylation	Kinase	MAPK3	P21708	Uniprot
362	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
362	S	Phosphorylation	Kinase	RPS6KA1	Q63531	GPS
374	S	Phosphorylation	Kinase	ERK1	P21708	PSP
374	S	Phosphorylation	Kinase	ERK1	P27361	PSP
374	S	Phosphorylation	Kinase	ERK2	P63086	PSP
374	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS

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.	7816602
232	T	Phosphorylation	Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).	7816602
232	T	Sumoylation	Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation.	7816602
232	T	Sumoylation	Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).	7816602
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.	17223854
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.	17223854
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.	17223854
362	S	Phosphorylation	Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation.	17223854
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.	17223854
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.	17223854
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.	17223854

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_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of FOS_RAT !!

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Sustained activation of extracellular signal-regulated kinase bynerve growth factor regulates c-fos protein stabilization andtransactivation in PC12 cells.";
Pellegrino M.J., Stork P.J.;
J. Neurochem. 99:1480-1493(2006).
Cited for: PHOSPHORYLATION AT THR-325; THR-331; SER-362 AND SER-374, FUNCTION,AND MUTAGENESIS OF THR-325; THR-331; 343-PHE--TYR-345; SER-362 ANDSER-374.
PubMed: 17223854

"Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates itsactivation capacity.";
Bannister A.J., Brown H.J., Sutherland J.A., Kouzarides T.;
Nucleic Acids Res. 22:5173-5176(1994).
Cited for: PHOSPHORYLATION AT THR-232, FUNCTION, AND MUTAGENESIS OF THR-232.
PubMed: 7816602