dbPTM

IGF1R_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IGF1R_MOUSE
UniProt AC	Q60751
Protein Name	Insulin-like growth factor 1 receptor
Gene Name	Igf1r
Organism	Mus musculus (Mouse).
Sequence Length	1373
Subcellular Localization	Cell membrane Single-pass type I membrane protein.
Protein Description	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R (By similarity). When present in a hybrid receptor with INSR, binds IGF1 (By similarity)..
Protein Sequence	MKSGSGGGSPTSLWGLVFLSAALSLWPTSGEICGPGIDIRNDYQQLKRLENCTVIEGFLHILLISKAEDYRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGWKLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTIDWSLILDAVSNNYIVGNKPPKECGDLCPGTLEEKPMCEKTTINNEYNYRCWTTNRCQKMCPSVCGKRACTENNECCHPECLGSCHTPDDNTTCVACRHYYYKGVCVPACPPGTYRFEGWRCVDRDFCANIPNAESSDSDGFVIHDDECMQECPSGFIRNSTQSMYCIPCEGPCPKVCGDEEKKTKTIDSVTSAQMLQGCTILKGNLLINIRRGNNIASELENFMGLIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLEGNYSFYVLDNQNLQQLWDWNHRNLTVRSGKMYFAFNPKLCVSEIYRMEEVTGTKGRQSKGDINTRNNGERASCESDVLRFTSTTTWKNRIIITWHRYRPPDYRDLISFTVYYKEAPFKNVTEYDGQDACGSNSWNMVDVDLPPNKEGEPGILLHGLKPWTQYAVYVKAVTLTMVENDHIRGAKSEILYIRTNASVPSIPLDVLSASNSSSQLIVKWNPPTLPNGNLSYYIVRWQRQPQDGYLYRHNYCSKDKIPIRKYADGTIDVEEVTENPKTEVCGGDKGPCCACPKTEAEKQAEKEEAEYRKVFENFLHNSIFVPRPERRRRDVMQVANTTMSSRSRNTTVADTYNITDPEEFETEYPFFESRVDNKERTVISNLRPFTLYRIDIHSCNHEAEKLGCSASNFVFARTMPAEGADDIPGPVTWEPRPENSIFLKWPEPENPNGLILMYEIKYGSQVEDQRECVSRQEYRKYGGAKLNRLNPGNYTARIQATSLSGNGSWTDPVFFYVPAKTTYENFMHLIIALPVAILLIVGGLVIMLYVFHRKRNNSRLGNGVLYASVNPEYFSAADVYVPDEWEVAREKITMNRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEVEQNNLVLIPPSLSKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTTHSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIIGSIKDEMEPSFQEVSFYYSEENKPPEPEELEMELEMEPENMESVPLDPSASSASLPLPERHSGHKAENGPGPGVLVLRASFDERQPYAHMNGGRANERALPLPQSSTC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
51	N-linked_Glycosylation	QQLKRLENCTVIEGF HHHHHHCCCEEECCH	31.20	-
102	N-linked_Glycosylation	SLGDLFPNLTVIRGW HHHHHCCCCEEEECC	40.80	-
135	N-linked_Glycosylation	IGLYNLRNITRGAIR CEEEHHCCCCCCCEE	43.05	-
245	N-linked_Glycosylation	SCHTPDDNTTCVACR CCCCCCCCCEEEECC	44.67	-
314	N-linked_Glycosylation	CPSGFIRNSTQSMYC CCCCEEECCCCCEEE	44.59	-
315	Phosphorylation	PSGFIRNSTQSMYCI CCCEEECCCCCEEEE	20.27	22871156
316	Phosphorylation	SGFIRNSTQSMYCIP CCEEECCCCCEEEEE	28.36	22871156
318	Phosphorylation	FIRNSTQSMYCIPCE EEECCCCCEEEEECC	16.29	22871156
418	N-linked_Glycosylation	GEEQLEGNYSFYVLD CHHHHCCCEEEEEEC	21.65	-
439	N-linked_Glycosylation	LWDWNHRNLTVRSGK HHCCCCCCEEECCCC	32.29	-
535	N-linked_Glycosylation	YKEAPFKNVTEYDGQ EECCCCCCCEEECCC	46.45	-
608	N-linked_Glycosylation	EILYIRTNASVPSIP EEEEEECCCCCCCCC	21.99	-
623	N-linked_Glycosylation	LDVLSASNSSSQLIV CHHHCCCCCCCCEEE	45.70	-
639	N-linked_Glycosylation	WNPPTLPNGNLSYYI ECCCCCCCCCEEEEE	55.91	19349973
641	N-linked_Glycosylation	PPTLPNGNLSYYIVR CCCCCCCCEEEEEEE	32.24	19349973
748	N-linked_Glycosylation	RDVMQVANTTMSSRS HHHHHHHHHHCCCCC	36.91	19656770
757	N-linked_Glycosylation	TMSSRSRNTTVADTY HCCCCCCCCEECEEC	41.15	19349973
765	N-linked_Glycosylation	TTVADTYNITDPEEF CEECEECCCCCHHHH	32.54	19349973
901	N-linked_Glycosylation	LNRLNPGNYTARIQA CCCCCCCCCEEEEEE	32.04	19656770
914	N-linked_Glycosylation	QATSLSGNGSWTDPV EEEECCCCCCCCCCE	37.64	-
974	Phosphorylation	RLGNGVLYASVNPEY CCCCCEEEEECCHHH	8.40	9480911
981	Phosphorylation	YASVNPEYFSAADVY EEECCHHHCCCCCEE	12.23	9480911
1024	Acetylation	GVAKGVVKDEPETRV CHHHCCCCCCCCCEE	54.70	6568873
1034	Ubiquitination	PETRVAIKTVNEAAS CCCEEEEEEHHHHHH	36.36	22790023
1041	Phosphorylation	KTVNEAASMRERIEF EEHHHHHHHHHHHHH	25.97	23984901
1159	Phosphorylation	KIGDFGMTRDIYETD EECCCCCCCEEEECC	26.10	23375375
1163	Phosphorylation	FGMTRDIYETDYYRK CCCCCEEEECCCCCC	19.64	8940173
1165	Phosphorylation	MTRDIYETDYYRKGG CCCEEEECCCCCCCC	16.60	22499769
1167	Phosphorylation	RDIYETDYYRKGGKG CEEEECCCCCCCCCC	16.76	25521595
1168	Phosphorylation	DIYETDYYRKGGKGL EEEECCCCCCCCCCC	14.52	25521595
1173	Ubiquitination	DYYRKGGKGLLPVRW CCCCCCCCCCCCEEE	55.86	-
1280	Phosphorylation	EPSFQEVSFYYSEEN CCCCEEEEEEECCCC	13.53	22685298
1282	Phosphorylation	SFQEVSFYYSEENKP CCEEEEEEECCCCCC	9.89	14963047
1283	Phosphorylation	FQEVSFYYSEENKPP CEEEEEEECCCCCCC	13.95	14963047
1284	Phosphorylation	QEVSFYYSEENKPPE EEEEEEECCCCCCCC	27.36	22685298
1319	Phosphorylation	DPSASSASLPLPERH CCCCCCCCCCCCCCC	32.25	25338131
1345	Phosphorylation	GVLVLRASFDERQPY CEEEEEECCCCCCCC	27.14	26824392
1352	Phosphorylation	SFDERQPYAHMNGGR CCCCCCCCCCCCCCC	10.78	8940173
1370	Phosphorylation	RALPLPQSSTC---- CCCCCCCCCCC----	26.19	25619855
1371	Phosphorylation	ALPLPQSSTC----- CCCCCCCCCC-----	28.66	25619855
1372	Phosphorylation	LPLPQSSTC------ CCCCCCCCC------	27.73	25521595

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
974	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
974	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
974	Y	Phosphorylation	Kinase	SRC	P05480	PSP
981	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
981	Y	Phosphorylation	Kinase	SRC	P05480	PSP
981	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
1163	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
1163	Y	Phosphorylation	Kinase	SRC	P05480	PSP
1163	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
1167	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
1167	Y	Phosphorylation	Kinase	SRC	P05480	PSP
1167	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
1168	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
1168	Y	Phosphorylation	Kinase	SRC	P05480	PSP
1168	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
1280	S	Phosphorylation	Kinase	GSK3-BETA	Q9WV60	Uniprot
1352	Y	Phosphorylation	Kinase	IGF1R	Q60751	PSP
1352	Y	Phosphorylation	Kinase	SRC	P05480	PSP
1352	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
29	K	ubiquitylation	-
Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome.
48	K	ubiquitylation	-
Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome.
1170	K	ubiquitylation	-
Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome.
1173	K	ubiquitylation	-
Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome.
1280	S	Phosphorylation	22685298
Phosphorylation of Ser-1280 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1284.
1284	S	Phosphorylation	22685298
Phosphorylation of Ser-1280 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1284.

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 IGF1R_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GRB10_MOUSE	Grb10	physical	20980250
GRB10_MOUSE	Grb10	physical	9062339
IRS1_MOUSE	Irs1	physical	22033112

Drug and Disease Associations

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

Regulatory Network of IGF1R_MOUSE

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."; Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,Schiess R., Aebersold R., Watts J.D.; Nat. Biotechnol. 27:378-386(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-639; ASN-641; ASN-757 ANDASN-765, AND MASS SPECTROMETRY.	19349973 [Abstract]
"The mouse C2C12 myoblast cell surface N-linked glycoproteome:identification, glycosite occupancy, and membrane orientation."; Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I.,Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E.,Wollscheid B.; Mol. Cell. Proteomics 8:2555-2569(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-748 AND ASN-901, AND MASSSPECTROMETRY.	19656770 [Abstract]

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