dbPTM

INSR_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	INSR_HUMAN
UniProt AC	P06213
Protein Name	Insulin receptor
Gene Name	INSR
Organism	Homo sapiens (Human).
Sequence Length	1382
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). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin..
Protein Sequence	MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHLQILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNEECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECLGNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQGCHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGCTVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQERNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQNVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWERQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQILKELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS

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	23302862
43	N-linked_Glycosylation	PGMDIRNNLTRLHEL CCCCCCCCHHHHHHH	32.70	23302862
52	N-linked_Glycosylation	TRLHELENCSVIEGH HHHHHHCCCEEEECE	35.67	23302862
52	N-linked_Glycosylation	TRLHELENCSVIEGH HHHHHHCCCEEEECE	35.67	7613486
68	Phosphorylation	QILLMFKTRPEDFRD EEEEEEECCHHHHHC	39.94	27251275
85	Phosphorylation	FPKLIMITDYLLLFR CCHHHHHHHHHHHHH	10.95	24719451
87	Phosphorylation	KLIMITDYLLLFRVY HHHHHHHHHHHHHHH	7.21	24719451
94	Phosphorylation	YLLLFRVYGLESLKD HHHHHHHHCHHHHHH	16.25	22461510
98	Phosphorylation	FRVYGLESLKDLFPN HHHHCHHHHHHHCCC	45.84	22461510
105	N-linked_Glycosylation	SLKDLFPNLTVIRGS HHHHHCCCCEEEECC	40.80	7613486
105	N-linked_Glycosylation	SLKDLFPNLTVIRGS HHHHHCCCCEEEECC	40.80	7613486
138	N-linked_Glycosylation	LGLYNLMNITRGSVR CCHHHHHCCCCCCEE	35.33	23302862
138	N-linked_Glycosylation	LGLYNLMNITRGSVR CCHHHHHCCCCCCEE	35.33	7613486
242	N-linked_Glycosylation	CHSECLGNCSQPDDP ECHHHHCCCCCCCCC	14.87	23302862
282	N-linked_Glycosylation	FQDWRCVNFSFCQDL CCCCEEEEEHHHHHH	30.39	16894147
322	N-linked_Glycosylation	CPSGYTMNSSNLLCT CCCCCEECCCCCEEC	34.19	UniProtKB CARBOHYD
361	Phosphorylation	AQELRGCTVINGSLI HHHHCCCEEECCEEE	27.52	-
364	N-linked_Glycosylation	LRGCTVINGSLIINI HCCCEEECCEEEEEE	29.66	16894147
366	Phosphorylation	GCTVINGSLIINIRG CCEEECCEEEEEECC	16.35	-
400	Phosphorylation	GYLKIRRSYALVSLS HHHHHCHHHHHHHHH	12.62	30576142
401	Phosphorylation	YLKIRRSYALVSLSF HHHHCHHHHHHHHHH	11.35	30576142
405	Phosphorylation	RRSYALVSLSFFRKL CHHHHHHHHHHHHHH	21.10	29083192
407	Phosphorylation	SYALVSLSFFRKLRL HHHHHHHHHHHHHCC	18.16	30576142
424	N-linked_Glycosylation	GETLEIGNYSFYALD CCEEEECCEEEEEEC	34.63	1993068
424	N-linked_Glycosylation	GETLEIGNYSFYALD CCEEEECCEEEEEEC	34.63	1993068
445	N-linked_Glycosylation	LWDWSKHNLTITQGK HHHHHHCCEEEECCE	42.49	8513978
445	N-linked_Glycosylation	LWDWSKHNLTITQGK HHHHHHCCEEEECCE	42.49	8513978
447	Phosphorylation	DWSKHNLTITQGKLF HHHHCCEEEECCEEE	27.56	24719451
457	Phosphorylation	QGKLFFHYNPKLCLS CCEEEEECCHHHHHH	28.18	24719451
464	Phosphorylation	YNPKLCLSEIHKMEE CCHHHHHHHHHHHHH	33.24	-
503	Phosphorylation	ENELLKFSYIRTSFD HHHHHHHHEEECCCH	20.33	24719451
541	N-linked_Glycosylation	YKEAPYQNVTEFDGQ CCCCCCCCCEEECCC	36.51	1472036
567	Phosphorylation	DIDPPLRSNDPKSQN ECCCCCCCCCCCCCC	53.95	28348404
572	Phosphorylation	LRSNDPKSQNHPGWL CCCCCCCCCCCCCHH	41.42	29978859
633	N-linked_Glycosylation	LDPISVSNSSSQIIL CCCEECCCCCCEEEE	43.70	UniProtKB CARBOHYD
651	N-linked_Glycosylation	PPSDPNGNITHYLVF CCCCCCCCEEEEEEE	42.50	UniProtKB CARBOHYD
682	Phosphorylation	LKGLKLPSRTWSPPF HHCCCCCCCCCCCCC	53.42	20860994
684	Phosphorylation	GLKLPSRTWSPPFES CCCCCCCCCCCCCCC	34.33	26471730
686	Phosphorylation	KLPSRTWSPPFESED CCCCCCCCCCCCCHH	23.29	26471730
691	Phosphorylation	TWSPPFESEDSQKHN CCCCCCCCHHHHHCC	47.27	26471730
698	N-linked_Glycosylation	SEDSQKHNQSEYEDS CHHHHHCCHHHHCCC	54.85	UniProtKB CARBOHYD
715	Phosphorylation	ECCSCPKTDSQILKE CCCCCCCCHHHHHHH	26.48	-
717	Phosphorylation	CSCPKTDSQILKELE CCCCCCHHHHHHHHH	25.09	-
721	Ubiquitination	KTDSQILKELEESSF CCHHHHHHHHHHCCH	62.98	29967540
731	Phosphorylation	EESSFRKTFEDYLHN HHCCHHHHHHHHHCC	28.18	-
759 (in isoform 2)	O-linked_Glycosylation	-	38.90	OGP
769	N-linked_Glycosylation	RSLGDVGNVTVAVPT CCCCCCCCEEEEEEC	26.57	8027066
769	N-linked_Glycosylation	RSLGDVGNVTVAVPT CCCCCCCCEEEEEEC	26.57	8027066
771	Phosphorylation	LGDVGNVTVAVPTVA CCCCCCEEEEEECEE	13.52	28985074
782	N-linked_Glycosylation	PTVAAFPNTSSTSVP ECEECCCCCCCCCCC	46.25	8027066
782	N-linked_Glycosylation	PTVAAFPNTSSTSVP ECEECCCCCCCCCCC	46.25	8027066
786	O-linked_Glycosylation	AFPNTSSTSVPTSPE CCCCCCCCCCCCCCC	33.25	OGP
790	O-linked_Glycosylation	TSSTSVPTSPEEHRP CCCCCCCCCCCCCCC	55.55	OGP
791	O-linked_Glycosylation	SSTSVPTSPEEHRPF CCCCCCCCCCCCCCH	25.01	OGP
791	Phosphorylation	SSTSVPTSPEEHRPF CCCCCCCCCCCCCCH	25.01	28985074
810	Phosphorylation	NKESLVISGLRHFTG CHHHHEEECCCHHCC	25.05	24719451
816	Phosphorylation	ISGLRHFTGYRIELQ EECCCHHCCEEEEEE	27.46	24719451
818	Phosphorylation	GLRHFTGYRIELQAC CCCHHCCEEEEEEEC	12.83	21403953
835	Phosphorylation	DTPEERCSVAAYVSA CCHHHHHHHHHHHHH	22.47	29083192
839	Phosphorylation	ERCSVAAYVSARTMP HHHHHHHHHHHCCCC	5.79	29083192
841	Phosphorylation	CSVAAYVSARTMPEA HHHHHHHHHCCCCCH	10.19	29083192
844	Phosphorylation	AAYVSARTMPEAKAD HHHHHHCCCCCHHCC	36.47	29083192
917	Phosphorylation	GCRLRGLSPGNYSVR CCCCCCCCCCCEEEE	33.32	25072903
920	N-linked_Glycosylation	LRGLSPGNYSVRIRA CCCCCCCCEEEEEEE	29.32	8027066
920	N-linked_Glycosylation	LRGLSPGNYSVRIRA CCCCCCCCEEEEEEE	29.32	8027066
921	Phosphorylation	RGLSPGNYSVRIRAT CCCCCCCEEEEEEEE	17.92	25072903
922	Phosphorylation	GLSPGNYSVRIRATS CCCCCCEEEEEEEEE	14.66	25072903
929	Phosphorylation	SVRIRATSLAGNGSW EEEEEEEECCCCCCC	18.42	-
933	N-linked_Glycosylation	RATSLAGNGSWTEPT EEEECCCCCCCCCCE	35.40	8027066
933	N-linked_Glycosylation	RATSLAGNGSWTEPT EEEECCCCCCCCCCE	35.40	8027066
940	Phosphorylation	NGSWTEPTYFYVTDY CCCCCCCEEEEEEEC	21.74	-
992	Phosphorylation	DGPLGPLYASSNPEY CCCCCCCCCCCCCCC	13.94	1658004
999	Dephosphorylation	YASSNPEYLSASDVF CCCCCCCCCCHHHCC	13.76	15632081
999	Phosphorylation	YASSNPEYLSASDVF CCCCCCCCCCHHHCC	13.76	8496180
1001	Phosphorylation	SSNPEYLSASDVFPC CCCCCCCCHHHCCCC	25.48	-
1011	Phosphorylation	DVFPCSVYVPDEWEV HCCCCEEECCCCCEE	7.03	12707268
1022	Ubiquitination	EWEVSREKITLLREL CCEECHHHHHHHHHH	39.62	-
1033	Phosphorylation	LRELGQGSFGMVYEG HHHHCCCCCEEEEEC	15.67	22817900
1035	Ubiquitination	ELGQGSFGMVYEGNA HHCCCCCEEEEECCH	13.32	33845483
1035 (in isoform 2)	Ubiquitination	-	13.32	21906983
1038	Phosphorylation	QGSFGMVYEGNARDI CCCCEEEEECCHHHH	14.82	25884760
1044	Ubiquitination	VYEGNARDIIKGEAE EEECCHHHHHCCCCE	44.55	22505724
1045	Ubiquitination	YEGNARDIIKGEAET EECCHHHHHCCCCEE	2.67	32142685
1045 (in isoform 2)	Ubiquitination	-	2.67	21906983
1047	Ubiquitination	GNARDIIKGEAETRV CCHHHHHCCCCEEEE	51.54	21906983
1056	Ubiquitination	EAETRVAVKTVNESA CCEEEEEEEECCCCC	4.96	22505724
1057	Ubiquitination	AETRVAVKTVNESAS CEEEEEEEECCCCCC	36.70	21906983
1062	Phosphorylation	AVKTVNESASLRERI EEEECCCCCCHHHHH	20.25	7926007
1064	Phosphorylation	KTVNESASLRERIEF EECCCCCCHHHHHHH	36.92	7926007
1067 (in isoform 1)	Ubiquitination	-	64.40	21906983
1077 (in isoform 1)	Ubiquitination	-	6.23	21906983
1083	S-nitrosocysteine	SVMKGFTCHHVVRLL HHHCCCCHHHHHHHH	1.63	-
1083	S-nitrosylation	SVMKGFTCHHVVRLL HHHCCCCHHHHHHHH	1.63	22178444
1112	Acetylation	LMAHGDLKSYLRSLR HHHCCCHHHHHHHHC	41.62	19608861
1149	Phosphorylation	EIADGMAYLNAKKFV HHHHHHHHHCHHHHH	7.50	22817900
1162	Ubiquitination	FVHRDLAARNCMVAH HHCHHHHHCCCEEEE	15.54	32015554
1165	S-nitrosocysteine	RDLAARNCMVAHDFT HHHHHCCCEEEEEEE	1.61	-
1165	S-nitrosylation	RDLAARNCMVAHDFT HHHHHCCCEEEEEEE	1.61	22178444
1174	Ubiquitination	VAHDFTVKIGDFGMT EEEEEEEEECCCCCC	37.60	32015554
1177	Phosphorylation	DFTVKIGDFGMTRDI EEEEEECCCCCCCCE	40.16	32142685
1181	Phosphorylation	KIGDFGMTRDIYETD EECCCCCCCCEEECC	26.10	21945579
1182	Ubiquitination	IGDFGMTRDIYETDY ECCCCCCCCEEECCC	21.31	21987572
1183	Ubiquitination	GDFGMTRDIYETDYY CCCCCCCCEEECCCC	38.36	21987572
1185	Dephosphorylation	FGMTRDIYETDYYRK CCCCCCEEECCCCCC	19.64	1373652
1185	Phosphorylation	FGMTRDIYETDYYRK CCCCCCEEECCCCCC	19.64	21945579
1187	Phosphorylation	MTRDIYETDYYRKGG CCCCEEECCCCCCCC	16.60	21945579
1189	Dephosphorylation	RDIYETDYYRKGGKG CCEEECCCCCCCCCC	16.76	12612081
1189	Phosphorylation	RDIYETDYYRKGGKG CCEEECCCCCCCCCC	16.76	22322096
1190	Dephosphorylation	DIYETDYYRKGGKGL CEEECCCCCCCCCCC	14.52	12237455
1190	Phosphorylation	DIYETDYYRKGGKGL CEEECCCCCCCCCCC	14.52	21945579
1192	Ubiquitination	YETDYYRKGGKGLLP EECCCCCCCCCCCCC	56.76	-
1194	Ubiquitination	TDYYRKGGKGLLPVR CCCCCCCCCCCCCEE	24.72	21987572
1195	Ubiquitination	DYYRKGGKGLLPVRW CCCCCCCCCCCCEEE	55.86	21987572
1216	Phosphorylation	KDGVFTTSSDMWSFG CCCCEECCHHHHHHH	22.68	22817900
1217	Phosphorylation	DGVFTTSSDMWSFGV CCCEECCHHHHHHHH	29.41	22817900
1221	Phosphorylation	TTSSDMWSFGVVLWE ECCHHHHHHHHHHHH	12.89	22817900
1261	S-nitrosocysteine	YLDQPDNCPERVTDL CCCCCCCCHHHHHHH	4.89	-
1261	S-nitrosylation	YLDQPDNCPERVTDL CCCCCCCCHHHHHHH	4.89	22178444
1272	S-nitrosocysteine	VTDLMRMCWQFNPKM HHHHHHHHHHCCCCC	1.50	-
1272	S-nitrosylation	VTDLMRMCWQFNPKM HHHHHHHHHHCCCCC	1.50	22178444
1314	Phosphorylation	EENKAPESEELEMEF CCCCCCCCHHHCCHH	35.00	22817900
1332	Phosphorylation	ENVPLDRSSHCQREE HCCCCCCCCCCCCCC	24.89	22817900
1333	Phosphorylation	NVPLDRSSHCQREEA CCCCCCCCCCCCCCC	29.22	22817900
1339	Ubiquitination	SSHCQREEAGGRDGG CCCCCCCCCCCCCCC	55.60	21963094
1340	Ubiquitination	SHCQREEAGGRDGGS CCCCCCCCCCCCCCC	22.46	21963094
1340 (in isoform 2)	Ubiquitination	-	22.46	21906983
1347	Phosphorylation	AGGRDGGSSLGFKRS CCCCCCCCCCCCCCC	28.11	28348404
1348	Phosphorylation	GGRDGGSSLGFKRSY CCCCCCCCCCCCCCH	35.47	30108239
1351	Ubiquitination	DGGSSLGFKRSYEEH CCCCCCCCCCCHHHC	7.83	21963094
1352	Methylation	GGSSLGFKRSYEEHI CCCCCCCCCCHHHCC	38.34	-
1352	Ubiquitination	GGSSLGFKRSYEEHI CCCCCCCCCCHHHCC	38.34	21963094
1354	Phosphorylation	SSLGFKRSYEEHIPY CCCCCCCCHHHCCCC	37.17	22322096
1355	Phosphorylation	SLGFKRSYEEHIPYT CCCCCCCHHHCCCCC	29.39	22322096
1361	Phosphorylation	SYEEHIPYTHMNGGK CHHHCCCCCCCCCCC	14.52	22322096
1362	Phosphorylation	YEEHIPYTHMNGGKK HHHCCCCCCCCCCCC	14.86	22322096
1372 (in isoform 1)	Ubiquitination	-	30.09	21906983
1375	Phosphorylation	KKNGRILTLPRSNPS CCCCEEEECCCCCCC	32.14	2110001
1379	Phosphorylation	RILTLPRSNPS---- EEEECCCCCCC----	51.67	19369195

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
992	Y	Phosphorylation	Kinase	INSR	P06213	PSP
999	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1011	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1062	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
1064	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
1173	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1177	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1178	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1185	Y	Phosphorylation	Kinase	MET	P08581	PSP
1185	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1189	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1190	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1302	S	Phosphorylation	Kinase	INSR	P06213	PSP
1314	S	Phosphorylation	Kinase	INSR	P06213	PSP
1336	S	Phosphorylation	Kinase	INSR	P06213	PSP
1343	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1348	S	Phosphorylation	Kinase	INSR	P06213	PSP
1349	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1355	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1361	Y	Phosphorylation	Kinase	INSR	P06213	PSP
1363	T	Phosphorylation	Kinase	PRKCA	P05696	GPS
1375	T	Phosphorylation	Kinase	PRKCA	P04409	GPS
1375	T	Phosphorylation	Kinase	KPCA	P17252	PhosphoELM
1375	T	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
1375	T	Phosphorylation	Kinase	PKC_GROUP	-	PhosphoELM

Functions of PTM Sites

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

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IRS1_HUMAN	IRS1	physical	11606564
FRS2_HUMAN	FRS2	physical	10650943
SOCS3_HUMAN	SOCS3	physical	12560330
IRS2_HUMAN	IRS2	physical	8626379
IRS1_HUMAN	IRS1	physical	8626379
FETUA_HUMAN	AHSG	physical	7906861
KHDR1_HUMAN	KHDRBS1	physical	11604231
PTN11_HUMAN	PTPN11	physical	8135823
GRB10_HUMAN	GRB10	physical	8621530
ENPP1_HUMAN	ENPP1	physical	10615944
GRB10_HUMAN	GRB10	physical	7479769
GRB14_RAT	Grb14	physical	9748281
CAV1_HUMAN	CAV1	physical	10598578
GRB2_HUMAN	GRB2	physical	9083103
KPCD_HUMAN	PRKCD	physical	11266508
VAV3_HUMAN	VAV3	physical	11094073
INSRR_HUMAN	INSRR	physical	8916919
SH2B1_HUMAN	SH2B1	physical	9742218
GRB10_HUMAN	GRB10	physical	9506989
SHIP2_HUMAN	INPPL1	physical	12504111
RASA1_HUMAN	RASA1	physical	1331107
JAK2_HUMAN	JAK2	physical	8912646
PTN11_HUMAN	PTPN11	physical	7493946
GRB7_HUMAN	GRB7	physical	10803466
SHC1_HUMAN	SHC1	physical	10803466
HNRPQ_HUMAN	SYNCRIP	physical	11994298
GRB14_HUMAN	GRB14	physical	11726652
SRBS1_HUMAN	SORBS1	physical	11374898
SH2B1_HUMAN	SH2B1	physical	10594240
SHIP2_HUMAN	INPPL1	physical	17620296
SH2B2_HUMAN	SH2B2	physical	17620296
SH2B2_HUMAN	SH2B2	physical	15031295
SOCS1_HUMAN	SOCS1	physical	11342531
SOCS6_HUMAN	SOCS6	physical	11342531
IRS1_RAT	Irs1	physical	11342531
SOCS3_HUMAN	SOCS3	physical	15514089
PLCG1_HUMAN	PLCG1	physical	22974441
IRS1_HUMAN	IRS1	physical	11781100
STA5A_HUMAN	STAT5A	physical	12456798
STA5B_HUMAN	STAT5B	physical	12456798
JAK1_HUMAN	JAK1	physical	12456798
JAK2_HUMAN	JAK2	physical	12456798
STA5B_MOUSE	Stat5b	physical	12456798
DOK1_HUMAN	DOK1	physical	11551902
IRF7_HUMAN	IRF7	physical	21988832
TEAD1_HUMAN	TEAD1	physical	21988832
GRB2_RAT	Grb2	physical	7953556
HGF_RAT	Hgf	physical	7953556
ARRB2_HUMAN	ARRB2	physical	19122674
K1H1_HUMAN	KRT31	physical	25416956
SQSTM_HUMAN	SQSTM1	physical	9564850
PUR9_HUMAN	ATIC	physical	25687571
HACD3_HUMAN	PTPLAD1	physical	25687571
AAPK1_HUMAN	PRKAA1	physical	25687571
AAPK2_HUMAN	PRKAA2	physical	25687571
KIF5A_HUMAN	KIF5A	physical	25687571
MARH1_HUMAN	MARCH1	physical	27577745
PPM1A_HUMAN	PPM1A	physical	28065597
PPM1F_HUMAN	PPM1F	physical	28065597
PTPRR_HUMAN	PTPRR	physical	28065597
DUS18_HUMAN	DUSP18	physical	28065597
MPZL2_HUMAN	MPZL2	physical	28065597
SSH1_HUMAN	SSH1	physical	28065597
DUS19_HUMAN	DUSP19	physical	28065597
STYX_HUMAN	STYX	physical	28065597
INSR_HUMAN	INSR	physical	2033070
PPAC_HUMAN	ACP1	physical	9299573
CAV2_RAT	Cav2	physical	25667086
IRS1_HUMAN	IRS1	physical	25667086

Drug and Disease Associations

Kegg Disease
H00719	Leprechaunism; Donohue syndrome
H00942	Rabson-Mendenhall syndrome
H01228	Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN); Type A insulin resistance
H01267	Familial hyperinsulinemic hypoglycemia (HHF)
OMIM Disease
262190	Rabson-Mendenhall syndrome (RMS)
246200	Leprechaunism (LEPRCH)
125853	Diabetes mellitus, non-insulin-dependent (NIDDM)
609968	Familial hyperinsulinemic hypoglycemia 5 (HHF5)
256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. {ECO
Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [	DISEASE
Kegg Drug
D00085	Insulin (JAN/USP)
D03230	Insulin human (genetical recombination) (JP16); Insulin human (biosynthesis) (JAN); Insulin human (s
D03250	Insulin glargine (genetical recombination) (JAN); Insulin glargine (USAN/INN); Lantus (TN)
D04475	Insulin aspart (genetical recombination) (JAN); Insulin aspart (USAN/INN); Insulin X 14; NovoRapid (
D04477	Insulin lispro (genetical recombination) (JAN); Insulin lispro (USP/INN); Humalog (TN)
D04539	Insulin detemir (genetical recombination) (JAN); Insulin detemir (USAN/INN); Levemir (TN)
D04540	Insulin glulisine (genetical recombination) (JAN); Insulin glulisine (USAN/INN); Apidra (TN)
D04541	Insulin human, isophane (USP)
D04542	Insulin human zinc (USP)
D04543	Insulin human zinc, extended (USP)
D04544	Insulin I 125 (USAN); Imusay-125 (TN)
D04545	Insulin I 131 (USAN); Imusay-131 (TN)
D04546	Insulin, dalanated (USAN)
D04547	Isophane insulin injection (aqueous suspension) (JAN); Insulin, isophane (USP); Humalog PEN (TN)
D04548	Insulin, neutral (USAN); Neutral insulin injection (INN)
D04549	Insulin zinc, extended (USP); Ultralente iletin (TN)
D04550	Insulin zinc, prompt (USP); Semilente iletin (TN)
D04551	Insulin zinc (USP); Lente iletin (TN)
D05622	Proinsulin human (USAN)
D08080	Insulin injection, biphasic isophane (BAN); Insulin Humacart (TN)
D09727	Insulin degludec (genetical recombination) (JAN); Insulin degludec (USAN/INN); Tresiba (TN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of INSR_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1112, AND MASS SPECTROMETRY.	19608861 [Abstract]
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 ASN-920, AND MASSSPECTROMETRY.	19349973 [Abstract]
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry."; Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; J. Proteome Res. 8:651-661(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242 AND ASN-541, AND MASSSPECTROMETRY.	19159218 [Abstract]
"Identification of a disulfide bridge connecting the alpha-subunits ofthe extracellular domain of the insulin receptor."; Schaeffer L., Ljungqvist L.; Biochem. Biophys. Res. Commun. 189:650-653(1992). Cited for: DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-541.	1472036 [Abstract]
"Human insulin receptor and its relationship to the tyrosine kinasefamily of oncogenes."; Ullrich A., Bell J.R., Chen E.Y., Herrera R., Petruzzelli L.M.,Dull T.J., Gray A., Coussens L., Liao Y.-C., Tsubokawa M., Mason A.,Seeburg P.H., Grunfeld C., Rosen O.M., Ramachandran J.; Nature 313:756-761(1985). Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), PROTEIN SEQUENCE OF 28-49AND 763-782, GLYCOSYLATION AT ASN-43 AND ASN-769, AND VARIANT GLY-2.	2983222 [Abstract]
Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1064; SER-1348 ANDSER-1379, AND MASS SPECTROMETRY.	19369195 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400; TYR-401 ANDSER-407, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1354, AND MASSSPECTROMETRY.	18691976 [Abstract]
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks."; Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.; Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1189, AND MASSSPECTROMETRY.	17389395 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1185; TYR-1189 ANDTYR-1190, AND MASS SPECTROMETRY.	18083107 [Abstract]
"Time-resolved mass spectrometry of tyrosine phosphorylation sites inthe epidermal growth factor receptor signaling network reveals dynamicmodules."; Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J.,Lauffenburger D.A., White F.M.; Mol. Cell. Proteomics 4:1240-1250(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1189, AND MASSSPECTROMETRY.	15951569 [Abstract]
"Studies on the autophosphorylation of the insulin receptor from humanplacenta. Analysis of the sites phosphorylated by two-dimensionalpeptide mapping."; Tavare J.M., Denton R.M.; Biochem. J. 252:607-615(1988). Cited for: PROTEIN SEQUENCE OF 927-956; 981-1019; 1182-1194 AND 1352-1369, ANDAUTOPHOSPHORYLATION.	3166375 [Abstract]