dbPTM

SHC1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	SHC1_MOUSE
UniProt AC	P98083
Protein Name	SHC-transforming protein 1
Gene Name	Shc1
Organism	Mus musculus (Mouse).
Sequence Length	579
Subcellular Localization	Cytoplasm. Isoform p47Shc: Mitochondrion matrix. Targeting of isoform p47Shc to mitochondria is mediated by its first 32 amino acids, which behave as a bona fide mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc, that contain the s
Protein Description	Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis (By similarity). Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p47Shc and isoform p52Shc, once phosphorylated, couple activated receptor kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p47Shc and isoform p52 may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span..
Protein Sequence	MDLLPPKPKYNPLRNESLSSLEEGASGSTPPEELPSPSASSLGPILPPLPGDDSPTTLCSFFPRMSNLKLANPAGGRLGPKGEPGKAAEDGEGSAGAALRDSGLLPLLQDMNKLSGGGGRRTRVEGGQLGGEEWTRHGSFVNKPTRGWLHPNDKVMGPGVSYLVRYMGCVEVLQSMRALDFNTRTQVTREAISLVCEAVPGAKGATRRRKPCSRPLSSILGRSNLKFAGMPITLTVSTSSLNLMAADCKQIIANHHMQSISFASGGDPDTAEYVAYVAKDPVNQRACHILECPEGLAQDVISTIGQAFELRFKQYLRNPPKLVTPHDRMAGFDGSAWDEEEEEPPDHQYYNDFPGKEPPLGGVVDMRLREGAARPTLPSAQMSSHLGATLPIGQHAAGDHEVRKQMLPPPPCPGRELFDDPSYVNIQNLDKARQAGGGAGPPNPSLNGSAPRDLFDMKPFEDALRVPPPPQSMSMAEQLQGEPWFHGKLSRREAEALLQLNGDFLVRESTTTPGQYVLTGLQSGQPKHLLLVDPEGVVRTKDHRFESVSHLISYHMDNHLPIISAGSELCLQQPVDRKV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDLLPPKP -------CCCCCCCC	8.06	-
3 (in isoform 2)	Neddylation	-	8.15	-
5 (in isoform 2)	Phosphorylation	-	42.01	29514104
36	Phosphorylation	TPPEELPSPSASSLG CCCHHCCCCCHHHCC	44.08	20547441
41	Phosphorylation	LPSPSASSLGPILPP CCCCCHHHCCCCCCC	36.74	25338131
54	Phosphorylation	PPLPGDDSPTTLCSF CCCCCCCCCCCHHHH	28.96	25338131
81	Acetylation	AGGRLGPKGEPGKAA CCCCCCCCCCCCCCC	74.28	126230401
115	Phosphorylation	LQDMNKLSGGGGRRT HHHHHHHCCCCCCCC	36.68	25338131
139	Phosphorylation	EEWTRHGSFVNKPTR CCCCCCCCCCCCCCC	21.64	12052829
145	Phosphorylation	GSFVNKPTRGWLHPN CCCCCCCCCCCCCCC	43.34	23429704
154	Acetylation	GWLHPNDKVMGPGVS CCCCCCCCCCCCCHH	40.54	23806337
161	Phosphorylation	KVMGPGVSYLVRYMG CCCCCCHHHHHHHHH	20.75	29233185
162	Phosphorylation	VMGPGVSYLVRYMGC CCCCCHHHHHHHHHH	13.55	29233185
188	Phosphorylation	FNTRTQVTREAISLV CCCCCHHHHHHHHHH	16.99	29899451
193	Phosphorylation	QVTREAISLVCEAVP HHHHHHHHHHHHHCC	23.07	29899451
264	Phosphorylation	MQSISFASGGDPDTA CCHHEECCCCCCCHH	41.10	11897789
315	Phosphorylation	FELRFKQYLRNPPKL HHHHHHHHHHCCCCC	14.28	14963047
324	Phosphorylation	RNPPKLVTPHDRMAG HCCCCCCCCCHHHCC	25.91	25159016
335	Phosphorylation	RMAGFDGSAWDEEEE HHCCCCCCCCCCCCC	28.20	25367039
349	Phosphorylation	EEPPDHQYYNDFPGK CCCCCCCCCCCCCCC	10.79	11713219
350	Phosphorylation	EPPDHQYYNDFPGKE CCCCCCCCCCCCCCC	11.16	11713219
376	Phosphorylation	REGAARPTLPSAQMS CCCCCCCCCCHHHHH	45.83	29514104
389	Phosphorylation	MSSHLGATLPIGQHA HHHHCCCCCCCCCCC	31.13	29514104
422	Phosphorylation	RELFDDPSYVNIQNL CCCCCCCCCCCCCCH	49.02	27087446
423	Phosphorylation	ELFDDPSYVNIQNLD CCCCCCCCCCCCCHH	11.69	27087446
433	Methylation	IQNLDKARQAGGGAG CCCHHHHHHCCCCCC	32.40	18964959
433	Dimethylation	IQNLDKARQAGGGAG CCCHHHHHHCCCCCC	32.40	-
445	Phosphorylation	GAGPPNPSLNGSAPR CCCCCCCCCCCCCCH	40.90	25619855
449	Phosphorylation	PNPSLNGSAPRDLFD CCCCCCCCCCHHHCC	33.74	25619855
554	Phosphorylation	SVSHLISYHMDNHLP CHHHHHHHHHCCCCC	8.31	22802335
564	Phosphorylation	DNHLPIISAGSELCL CCCCCEEECCCCHHH	27.57	22802335
567	Phosphorylation	LPIISAGSELCLQQP CCEEECCCCHHHCCC	27.41	22802335

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	PRKCD	P28867	GPS
36	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
36	S	Phosphorylation	Kinase	ERK1	P27361	PSP
36	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
36	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
36	S	Phosphorylation	Kinase	MAPK9	P45984	GPS
36	S	Phosphorylation	Kinase	MAPK10	P53779	GPS
36	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
36	S	Phosphorylation	Kinase	JNK-SUBFAMILY	-	GPS
36	S	Phosphorylation	Kinase	JNK_GROUP	-	PhosphoELM
349	Y	Phosphorylation	Kinase	SRC	P05480	GPS
349	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
36	S	Phosphorylation		9165038
Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of SHC1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ERBB3_HUMAN	ERBB3	physical	9694850
SHIP1_MOUSE	Inpp5d	physical	8723348
A4_HUMAN	APP	physical	17384289
SHIP1_MOUSE	Inpp5d	physical	9393882
SHIP2_MOUSE	Inppl1	physical	20697350
GRB2_MOUSE	Grb2	physical	20697350
SHIP1_MOUSE	Inpp5d	physical	20697350
PTN12_MOUSE	Ptpn12	physical	20697350
LRRK1_MOUSE	Lrrk1	physical	20697350
TBA4A_MOUSE	Tuba4a	physical	20697350
ALK_MOUSE	Alk	physical	15226403
EGFR_MOUSE	Egfr	physical	7538132
GRB2_MOUSE	Grb2	physical	7538132
SRC_MOUSE	Src	physical	15716419
PTN12_MOUSE	Ptpn12	physical	12052829
RET_HUMAN	RET	physical	10995764
GRB2_MOUSE	Grb2	physical	10995764

Drug and Disease Associations

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

Regulatory Network of SHC1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"The phagosomal proteome in interferon-gamma-activated macrophages."; Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.; Immunity 30:143-154(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND MASSSPECTROMETRY.	19144319 [Abstract]
"Protein kinase C beta and prolyl isomerase 1 regulate mitochondrialeffects of the life-span determinant p66Shc."; Pinton P., Rimessi A., Marchi S., Orsini F., Migliaccio E.,Giorgio M., Contursi C., Minucci S., Mantovani F., Wieckowski M.R.,Del Sal G., Pelicci P.G., Rizzuto R.; Science 315:659-663(2007). Cited for: FUNCTION, SUBCELLULAR LOCATION (ISOFORM P66SHC), AND PHOSPHORYLATIONAT SER-36 (ISOFORM P66SHC).	17272725 [Abstract]
"Insulin stimulates the phosphorylation of the 66- and 52-kilodaltonShc isoforms by distinct pathways."; Kao A.W., Waters S.B., Okada S., Pessin J.E.; Endocrinology 138:2474-2480(1997). Cited for: PHOSPHORYLATION AT SER-36.	9165038 [Abstract]
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-423, AND MASSSPECTROMETRY.	18034455 [Abstract]
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-423, AND MASSSPECTROMETRY.	17947660 [Abstract]
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.; Nat. Biotechnol. 23:94-101(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-349; TYR-350 ANDTYR-423, AND MASS SPECTROMETRY.	15592455 [Abstract]

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