RAF1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RAF1_RAT
• UniProt AC: P11345
• Protein Name: RAF proto-oncogene serine/threonine-protein kinase
• Gene Name: Raf1
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 648
• Subcellular Localization: Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphoryla
• Protein Description: Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation (By similarity). Phosphorylates TNNT2/cardiac muscle troponin T..
• Protein Sequence: MEHIQGAWKTISNGFGLKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDSSKTSNTIRVFLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLQEHKGKKARLDWNTDAASLIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKVPTMCVDWSNIRQLLLFPNSTASDSGVPAPPSFTMRRMRESVSRMPASSQHRYSTPHAFTFNTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNLSPTGWSQPKTPVPAQRERAPGSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQLQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYASPDLSRLYKNCPKAMKRLVADCVKKVKEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF

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
25	Phosphorylation	KDAVFDGSSCISPTI CCCEECCCCCCCHHH	24.71	23984901
26	Phosphorylation	DAVFDGSSCISPTIV CCEECCCCCCCHHHH	22.47	27097102
29	Phosphorylation	FDGSSCISPTIVQQF ECCCCCCCHHHHHHH	21.96	29779826
31	Phosphorylation	GSSCISPTIVQQFGY CCCCCCHHHHHHHCC	27.30	27097102
43	Phosphorylation	FGYQRRASDDGKLTD HCCCCCCCCCCCCCC	34.13	29779826
49	Phosphorylation	ASDDGKLTDSSKTSN CCCCCCCCCCCCCCC	37.00	28432305
51	Phosphorylation	DDGKLTDSSKTSNTI CCCCCCCCCCCCCEE	28.62	28432305
52	Phosphorylation	DGKLTDSSKTSNTIR CCCCCCCCCCCCEEE	42.64	28432305
220	Phosphorylation	TMRRMRESVSRMPAS HHHHHHHHHHCCCCC	18.28	29779826
222	Phosphorylation	RRMRESVSRMPASSQ HHHHHHHHCCCCCCC	31.94	28432305
227	Phosphorylation	SVSRMPASSQHRYST HHHCCCCCCCCCCCC	25.35	23984901
228	Phosphorylation	VSRMPASSQHRYSTP HHCCCCCCCCCCCCC	31.92	23984901
232	Phosphorylation	PASSQHRYSTPHAFT CCCCCCCCCCCCEEE	18.12	27097102
233	Phosphorylation	ASSQHRYSTPHAFTF CCCCCCCCCCCEEEE	35.10	27097102
234	Phosphorylation	SSQHRYSTPHAFTFN CCCCCCCCCCEEEEE	15.34	27097102
239	Phosphorylation	YSTPHAFTFNTSSPS CCCCCEEEEECCCCC	19.43	27097102
242	Phosphorylation	PHAFTFNTSSPSSEG CCEEEEECCCCCCCC	26.79	28432305
243	Phosphorylation	HAFTFNTSSPSSEGS CEEEEECCCCCCCCC	41.16	23984901
244	Phosphorylation	AFTFNTSSPSSEGSL EEEEECCCCCCCCCC	27.11	23984901
246	Phosphorylation	TFNTSSPSSEGSLSQ EEECCCCCCCCCCCH	42.86	23984901
247	Phosphorylation	FNTSSPSSEGSLSQR EECCCCCCCCCCCHH	49.73	23984901
250	Phosphorylation	SSPSSEGSLSQRQRS CCCCCCCCCCHHHHC	22.31	27097102
252	Phosphorylation	PSSEGSLSQRQRSTS CCCCCCCCHHHHCCC	25.64	28689409
257	Phosphorylation	SLSQRQRSTSTPNVH CCCHHHHCCCCCCEE	20.55	27097102
258	Phosphorylation	LSQRQRSTSTPNVHM CCHHHHCCCCCCEEE	38.52	21738781
259	Phosphorylation	SQRQRSTSTPNVHMV CHHHHCCCCCCEEEE	43.01	14688280
260	Phosphorylation	QRQRSTSTPNVHMVS HHHHCCCCCCEEEEE	20.97	27097102
267	Phosphorylation	TPNVHMVSTTLPVDS CCCEEEEECEECCCC	14.22	27097102
268	Phosphorylation	PNVHMVSTTLPVDSR CCEEEEECEECCCCH	22.42	27097102
269	Phosphorylation	NVHMVSTTLPVDSRM CEEEEECEECCCCHH	22.89	27097102
274	Phosphorylation	STTLPVDSRMIEDAI ECEECCCCHHHHHHH	24.79	25575281
283	Phosphorylation	MIEDAIRSHSESASP HHHHHHHHCCCCCCH	25.83	27097102
285	Phosphorylation	EDAIRSHSESASPSA HHHHHHCCCCCCHHH	34.20	27097102
287	Phosphorylation	AIRSHSESASPSALS HHHHCCCCCCHHHHC	36.74	27097102
289	Phosphorylation	RSHSESASPSALSSS HHCCCCCCHHHHCCC	28.77	27097102
291	Phosphorylation	HSESASPSALSSSPN CCCCCCHHHHCCCCC	39.07	27097102
294	Phosphorylation	SASPSALSSSPNNLS CCCHHHHCCCCCCCC	28.61	27097102
295	Phosphorylation	ASPSALSSSPNNLSP CCHHHHCCCCCCCCC	51.14	27097102
296	Phosphorylation	SPSALSSSPNNLSPT CHHHHCCCCCCCCCC	28.42	21738781
301	Phosphorylation	SSSPNNLSPTGWSQP CCCCCCCCCCCCCCC	23.65	27097102
303	Phosphorylation	SPNNLSPTGWSQPKT CCCCCCCCCCCCCCC	48.16	27097102
306	Phosphorylation	NLSPTGWSQPKTPVP CCCCCCCCCCCCCCC	37.64	27097102
338	Phosphorylation	RPRGQRDSSYYWEIE CCCCCCCCCEEEEEE	23.56	14688280
339	Phosphorylation	PRGQRDSSYYWEIEA CCCCCCCCEEEEEEE	26.91	-
340	Phosphorylation	RGQRDSSYYWEIEAS CCCCCCCEEEEEEEE	19.29	14688280
341	Phosphorylation	GQRDSSYYWEIEASE CCCCCCEEEEEEEEE	9.86	14688280
357	Phosphorylation	MLSTRIGSGSFGTVY EEEEEECCCCCCCEE	28.97	27097102
359	Phosphorylation	STRIGSGSFGTVYKG EEEECCCCCCCEECC	23.38	27097102
471	Phosphorylation	IIHRDMKSNNIFLHE CCCCCCCCCCEEEEC	28.59	-
491	Phosphorylation	IGDFGLATVKSRWSG ECCEEEEEECCCCCC	33.24	-
494	Phosphorylation	FGLATVKSRWSGSQQ EEEEEECCCCCCCCC	34.35	27097102
497	Phosphorylation	ATVKSRWSGSQQVEQ EEECCCCCCCCCEEC	27.70	27097102
499	Phosphorylation	VKSRWSGSQQVEQPT ECCCCCCCCCEECCC	16.36	27097102
506	Phosphorylation	SQQVEQPTGSVLWMA CCCEECCCCCEEEEC	41.61	27097102
508	Phosphorylation	QVEQPTGSVLWMAPE CEECCCCCEEEECCE	19.26	27097102
563	Methylation	QIIFMVGRGYASPDL EEEEEECCCCCCCHH	24.44	-
563	Symmetric dimethylarginine	QIIFMVGRGYASPDL EEEEEECCCCCCCHH	24.44	-
571	Phosphorylation	GYASPDLSRLYKNCP CCCCCHHHHHHHHCH	27.85	26022182
604	Phosphorylation	PLFPQILSSIELLQH CCHHHHHHHHHHHHC	30.79	27097102
605	Phosphorylation	LFPQILSSIELLQHS CHHHHHHHHHHHHCC	19.35	27097102
612	Phosphorylation	SIELLQHSLPKINRS HHHHHHCCCCCCCCC	33.15	27097102
619	Phosphorylation	SLPKINRSASEPSLH CCCCCCCCCCCCCHH	31.49	23984901
621	Phosphorylation	PKINRSASEPSLHRA CCCCCCCCCCCHHHH	51.81	14688280
624	Phosphorylation	NRSASEPSLHRAAHT CCCCCCCCHHHHHCC	32.53	23984901
638	Phosphorylation	TEDINACTLTTSPRL CCCCCCCCCCCCCCC	25.40	22108457
640	Phosphorylation	DINACTLTTSPRLPV CCCCCCCCCCCCCCC	13.69	22108457
641	Phosphorylation	INACTLTTSPRLPVF CCCCCCCCCCCCCCC	39.59	27097102
642	Phosphorylation	NACTLTTSPRLPVF- CCCCCCCCCCCCCC-	11.64	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
29	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
233	S	Phosphorylation	Kinase	PKA	-	Uniprot
259	S	Phosphorylation	Kinase	AKT1	P47196	PSP
269	T	Phosphorylation	Kinase	PKA	-	Uniprot
289	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
296	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
301	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
338	S	Phosphorylation	Kinase	PAK1	P35465	Uniprot
338	S	Phosphorylation	Kinase	PAK2	Q64303	Uniprot
338	S	Phosphorylation	Kinase	PAK3	Q62829	Uniprot
338	S	Phosphorylation	Kinase	PAK5	D4A280	Uniprot
339	S	Phosphorylation	Kinase	PAK2	Q64303	Uniprot
339	S	Phosphorylation	Kinase	PAK3	Q62829	Uniprot
339	S	Phosphorylation	Kinase	PAK1	P35465	Uniprot
340	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
341	Y	Phosphorylation	Kinase	SRC	Q9WUD9	Uniprot
497	S	Phosphorylation	Kinase	PKC	-	Uniprot
499	S	Phosphorylation	Kinase	PKC	-	Uniprot
642	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
29	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	-
43	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	22673903
259	S	Phosphorylation	Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity.	22673903
259	S	Phosphorylation	Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity.	22673903
269	T	Phosphorylation	Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation.	-
289	S	Methylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
289	S	Phosphorylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
289	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	-
296	S	Phosphorylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
296	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	-
296	S	Phosphorylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
296	S	Methylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
296	S	Methylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
301	S	Methylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
301	S	Methylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
301	S	Phosphorylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
301	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	-
301	S	Phosphorylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
338	S	Methylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
338	S	Phosphorylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
338	S	Phosphorylation	Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation.	-
338	S	Phosphorylation	Phosphorylation at Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization (By similarity).	-
338	S	Phosphorylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
338	S	Phosphorylation	Dephosphorylation at SER-338 by PPP5C results in a decreased of activity (By similarity).	-
338	S	Methylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
339	S	Phosphorylation	Phosphorylation at Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization (By similarity).	-
491	T	Phosphorylation	Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation.	-
494	S	Phosphorylation	Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation.	-
621	S	Methylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
621	S	Methylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
621	S	Phosphorylation	Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells.	-
621	S	Phosphorylation	Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation.	-
621	S	Phosphorylation	Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338.	-
642	S	Phosphorylation	Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of RAF1_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PEBP1_RAT	Pebp1	physical	12551925

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS.";
Moser K., White F.M.;
J. Proteome Res. 5:98-104(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, AND MASSSPECTROMETRY.
PubMed: 16396499