dbPTM

INSR_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	INSR_MOUSE
UniProt AC	P15208
Protein Name	Insulin receptor
Gene Name	Insr
Organism	Mus musculus (Mouse).
Sequence Length	1372
Subcellular Localization	Cell membrane Single-pass type I membrane protein.
Protein Description	Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). When present in a hybrid receptor with IGF1R, binds IGF1 (By similarity)..
Protein Sequence	MGFGRGCETTAVPLLVAVAALLVGTAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECLGNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPGCHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVYWERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPTSQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELGQGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
43	N-linked_Glycosylation	PGMDIRNNLTRLHEL CCCCCCCCHHHHHHH	32.70	-
52	N-linked_Glycosylation	TRLHELENCSVIEGH HHHHHHCCCEEEECE	35.67	-
105	N-linked_Glycosylation	SLKDLFPNLTVIRGS HHHHHCCCCEEEECC	40.80	-
138	N-linked_Glycosylation	LGLYNLMNITRGSVR CCHHHHHCCCCCCEE	35.33	-
242	N-linked_Glycosylation	CHKECLGNCSEPDDP ECHHHHCCCCCCCCC	17.13	-
282	N-linked_Glycosylation	FQDWRCVNFSFCQDL CCCEEEEEEHHHCCC	30.39	-
284	Phosphorylation	DWRCVNFSFCQDLHF CEEEEEEHHHCCCCH	21.65	28418008
322	N-linked_Glycosylation	CPSGYTMNSSNLMCT CCCCCEECCCCCEEC	34.19	-
364	N-linked_Glycosylation	LRGCTVINGSLIINI HCCCEEECCEEEEEE	29.66	-
400	Phosphorylation	GFLKIRRSYALVSLS HHHHHHHHHHHHHHH	12.62	-
401	Phosphorylation	FLKIRRSYALVSLSF HHHHHHHHHHHHHHH	11.35	-
407	Phosphorylation	SYALVSLSFFRKLHL HHHHHHHHHHHHHCC	18.16	-
419	Phosphorylation	LHLIRGETLEIGNYS HCCCCCCEEEECCEE	32.30	24719451
424	N-linked_Glycosylation	GETLEIGNYSFYALD CCEEEECCEEEEEEC	34.63	-
426	Phosphorylation	TLEIGNYSFYALDNQ EEEECCEEEEEECCC	18.77	24719451
445	N-linked_Glycosylation	LWDWSKHNLTITQGK HHHHHHCCEEEECCE	42.49	19656770
447	Phosphorylation	DWSKHNLTITQGKLF HHHHCCEEEECCEEE	27.56	-
457	Phosphorylation	QGKLFFHYNPKLCLS CCEEEEECCHHHHHH	28.18	-
541	N-linked_Glycosylation	YKEAPYQNVTEFDGQ CCCCCCCCCEEECCC	36.51	-
635	N-linked_Glycosylation	LDPISVSNSSSQIIL CCCEECCCCCCEEEE	43.70	-
653	N-linked_Glycosylation	PPSDPNGNITHYLVY CCCCCCCCEEEEEEE	42.50	-
700	N-linked_Glycosylation	SDDSQKHNQSEYDDS CCCHHCCCHHHCCCC	54.85	-
717	Phosphorylation	ECCSCPKTDSQILKE HHCCCCCCHHHHHHH	26.48	28059163
759	N-linked_Glycosylation	RSLEEVGNVTATTLT CCHHHHCCEEEEEEE	32.89	-
772	N-linked_Glycosylation	LTLPDFPNVSSTIVP EECCCCCCCCCCCCC	46.42	-
910	N-linked_Glycosylation	LRGLSPGNYSVRVRA CCCCCCCCEEEEEEE	29.32	-
923	N-linked_Glycosylation	RATSLAGNGSWTEPT EEEECCCCCCCCCCE	35.40	-
989	Phosphorylation	YASSNPEYLSASDVF CCCCCCCCCCHHHCC	13.76	22817900
1001	Phosphorylation	DVFPSSVYVPDEWEV HCCCCCCCCCCCCCC	14.28	20332342
1012	Ubiquitination	EWEVPREKITLLREL CCCCCHHHHHHHHHH	42.12	22790023
1012	Ubiquitination	EWEVPREKITLLREL CCCCCHHHHHHHHHH	42.12	22790023
1037	Ubiquitination	GNAKDIIKGEAETRV CCHHHHHCCCCEEEE	51.54	22790023
1037	Ubiquitination	GNAKDIIKGEAETRV CCHHHHHCCCCEEEE	51.54	22790023
1047	Ubiquitination	AETRVAVKTVNESAS CEEEEEEEECCCCCC	36.70	22790023
1047	Ubiquitination	AETRVAVKTVNESAS CEEEEEEEECCCCCC	36.70	22790023
1052	Phosphorylation	AVKTVNESASLRERI EEEECCCCCCHHHHH	20.25	-
1054	Phosphorylation	KTVNESASLRERIEF EECCCCCCHHHHHHH	36.92	-
1122	Phosphorylation	NPGRPPPTLQEMIQM CCCCCCCCHHHHHHH	47.01	28059163
1171	Phosphorylation	KIGDFGMTRDIYETD EECCCCCCCCEEECC	26.10	23375375
1175	Phosphorylation	FGMTRDIYETDYYRK CCCCCCEEECCCCCC	19.64	8940173
1177	Phosphorylation	MTRDIYETDYYRKGG CCCCEEECCCCCCCC	16.60	22499769
1179	Phosphorylation	RDIYETDYYRKGGKG CCEEECCCCCCCCCC	16.76	25521595
1180	Phosphorylation	DIYETDYYRKGGKGL CEEECCCCCCCCCCC	14.52	25521595
1185	Ubiquitination	DYYRKGGKGLLPVRW CCCCCCCCCCCCEEE	55.86	22790023
1185	Ubiquitination	DYYRKGGKGLLPVRW CCCCCCCCCCCCEEE	55.86	22790023
1337	Phosphorylation	AGGREGGSSLSIKRT CCCCCCCCCCEEEEE	38.67	23737553
1338	Phosphorylation	GGREGGSSLSIKRTY CCCCCCCCCEEEEEC	29.43	27180971
1340	Phosphorylation	REGGSSLSIKRTYDE CCCCCCCEEEEECCC	28.19	25521595
1344	Phosphorylation	SSLSIKRTYDEHIPY CCCEEEEECCCCCCC	30.26	22817900
1345	Phosphorylation	SLSIKRTYDEHIPYT CCEEEEECCCCCCCC	24.30	22817900
1351	Phosphorylation	TYDEHIPYTHMNGGK ECCCCCCCCCCCCCC	14.52	22817900
1352	Phosphorylation	YDEHIPYTHMNGGKK CCCCCCCCCCCCCCC	14.86	23684622
1365	Phosphorylation	KKNGRVLTLPRSNPS CCCCEEEECCCCCCC	31.68	21454597
1369	Phosphorylation	RVLTLPRSNPS---- EEEECCCCCCC----	51.67	29514104

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
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo2	Q80UW2	PMID:27932386

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of INSR_MOUSE !!

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 INSR_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SRBS1_MOUSE	Sorbs1	physical	9447983
SH2B2_MOUSE	Sh2b2	physical	10196204
FLOT1_MOUSE	Flot1	physical	16455755
CAV3_MOUSE	Cav3	physical	16455755
GRB10_MOUSE	Grb10	physical	9062339
PLAK_MOUSE	Jup	physical	24567360
AKT1_MOUSE	Akt1	physical	19122674
SRC_MOUSE	Src	physical	19122674
ARRB2_MOUSE	Arrb2	physical	19122674
CLK1_HUMAN	CLK1	physical	26496610
PDIA3_HUMAN	PDIA3	physical	26496610
IGF1R_HUMAN	IGF1R	physical	26496610
FAF2_HUMAN	FAF2	physical	26496610
NSF1C_HUMAN	NSFL1C	physical	26496610
UBE2O_HUMAN	UBE2O	physical	26496610

Drug and Disease Associations

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

Regulatory Network of INSR_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-445, AND MASSSPECTROMETRY.	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-445, AND MASSSPECTROMETRY.	19656770 [Abstract]