Target Interacting Protein Information

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Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T15510 Target Info
Target Name Insulin receptor substrate-1 (IRS1)
Synonyms Insulin receptor substrate 1; IRS-1
Target Type Clinical trial Target
Gene Name IRS1
UniProt ID
IRS1_HUMAN 
Target Interacting Proteins  Top
Adapter proteins [+] 1 Adapter proteins +
Interacting Protein Name Growth factor receptor-bound protein 2 (GRB2) Interacting Protein Interacting Protein Info
UniProt ID
GRB2_HUMAN 
Synonyms SH2/SH3 adapter GRB2; Protein Ash; Growth factor receptor-bound protein 2; ASH; Adapter protein GRB2
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-MS [1]
2 Affinity Capture-Western [2]
3 Protein-peptide [3]
4 Reconstituted Complex [4]
Beta-transducin repeats [+] 1 Beta-transducin repeats +
Interacting Protein Name Regulatory-associated protein of mTOR (RPTOR) Interacting Protein Interacting Protein Info
UniProt ID
RPTOR_HUMAN 
Synonyms KOG1; Mip1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [5]
2 Reconstituted Complex [5]
Ester hydrolases [+] 1 Ester hydrolases +
Interacting Target Name Protein-tyrosine phosphatase SHP-2 (PTPN11) Clinical trial Target Interacting Protein Info
UniProt ID
PTN11_HUMAN 
Synonyms Tyrosine-protein phosphatase non-receptor type 11; SH-PTP3; SH-PTP2; SHPTP2; SHP-2; SHP2; PTP-2C; PTP2C; PTP-1D; Protein-tyrosine phosphatase SHP2; Protein-tyrosine phosphatase 2C; Protein-tyrosine phosphatase 1D
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [6]
2 Biochemical Activity [7]
3 Protein-peptide [3]
4 Reconstituted Complex [7]
Kinases [+] 10 Kinases +
Interacting Protein Name Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) Interacting Protein Interacting Protein Info
UniProt ID
P85A_HUMAN 
Synonyms AGM7; GRB1; IMD36; p85; p85.ALPHA
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-MS [8]
2 Affinity Capture-Western [2]
3 Far Western [9]
4 Protein-peptide [3]
5 Yeast two hybrid [10]
Interacting Target Name Insulin receptor (INSR) Successful Target Interacting Protein Info
UniProt ID
INSR_HUMAN 
Synonyms IR; CD220 antigen; CD220
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [11]
2 Biochemical Activity [7]
3 Reconstituted Complex [12]
4 Yeast two hybrid [13]
Interacting Target Name Stress-activated protein kinase JNK1 (JNK1) Clinical trial Target Interacting Protein Info
UniProt ID
MK08_HUMAN 
Synonyms Stress-activated protein kinase 1c; SAPK1c; SAPK1; PRKM8; Mitogen-activated protein kinase 8; MAPK 8; MAP kinase 8; JNK-46; C-Jun N-terminal kinase 1
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [14]
2 Reconstituted Complex [14]
3 Yeast two hybrid [13]
Interacting Target Name Janus kinase 2 (JAK-2) Successful Target Interacting Protein Info
UniProt ID
JAK2_HUMAN 
Synonyms Tyrosine-protein kinase JAK2
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [15]
2 Biochemical Activity [16]
Interacting Target Name Serine/threonine-protein kinase mTOR (mTOR) Successful Target Interacting Protein Info
UniProt ID
MTOR_HUMAN 
Synonyms TOR kinase; Target of rapamycin; RAPT1; Rapamycin target protein 1; Rapamycin target protein; Rapamycin and FKBP12 target 1; RAFT1; Mechanistic target of rapamycin; Mammalian target of rapamycin; FRAP2; FRAP1; FRAP; FKBP-rapamycin associated protein; FKBP12-rapamycin complex-associated protein; FK506-binding protein 12-rapamycin complex-associated protein 1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [17]
2 Biochemical Activity [17]
Interacting Target Name Insulin-like growth factor I receptor (IGF1R) Successful Target Interacting Protein Info
UniProt ID
IGF1R_HUMAN 
Synonyms Type 1 insulin-like growth factor receptor; Insulin-like growth factor 1 receptor; IGF-IR; IGF-I receptor; IGF-1R; IGF-1 receptor; CD221 antigen; CD221
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [18]
2 Yeast two hybrid [19]
Interacting Target Name Protein kinase C delta (PRKCD) Clinical trial Target Interacting Protein Info
UniProt ID
KPCD_HUMAN 
Synonyms Tyrosine-protein kinase PRKCD; SDK1; Protein kinase C delta type catalytic subunit; Protein kinase C delta type; Protein Kinase C delta; PKC-delta; nPKC-delta
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [20]
2 Biochemical Activity [21]
Interacting Target Name Ribosomal protein S6 kinase beta-1 (S6K1) Clinical trial Target Interacting Protein Info
UniProt ID
KS6B1_HUMAN 
Synonyms STK14A; Serine/threonine-protein kinase 14A; S6K-beta-1; S6K; Ribosomal protein S6 kinase I; P70S6K1; p70-S6K 1; P70-S6K; p70 S6K-alpha; p70 S6KA; p70 S6 kinase alpha; p70 ribosomal S6 kinase alpha; 70 kDa ribosomal protein S6 kinase 1
Evidence Score (E-score) 2 Experimental Evidences +
1 Biochemical Activity [22]
2 Reconstituted Complex [22]
Interacting Protein Name Phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) Interacting Protein Interacting Protein Info
UniProt ID
P55G_HUMAN 
Synonyms p55; p55.GAMMA
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [23]
2 Yeast two hybrid [10]
Interacting Protein Name Phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) Interacting Protein Interacting Protein Info
UniProt ID
P85B_HUMAN 
Synonyms MPPH; MPPH1; P85B; p85; p85.BETA
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [8]
2 Affinity Capture-Western [24]
Proteins 14-3-3 [+] 1 Proteins 14-3-3 +
Interacting Protein Name 14-3-3 protein epsilon (YWHAE) Interacting Protein Interacting Protein Info
UniProt ID
1433E_HUMAN 
Synonyms 14.3.3E; HEL2; KCIP.1; MDCR; MDS
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [8]
2 Yeast two hybrid [25]
Vesicle fusion pores [+] 1 Vesicle fusion pores +
Interacting Protein Name Tripartite motif-containing protein 72 (TRIM72) Interacting Protein Interacting Protein Info
UniProt ID
TRI72_HUMAN 
Synonyms MG53
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [26]
2 Co-localization [26]
3 Protein-Fragment Complementation Assay [26]
Other proteins [+] 1 Other proteins +
Interacting Protein Name F-box/WD repeat-containing protein 8 (FBXW8) Interacting Protein Interacting Protein Info
UniProt ID
FBXW8_HUMAN 
Synonyms FBW6; FBW8; FBX29; FBXO29; FBXW6
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [27]
2 Reconstituted Complex [22]
References  Top
REF 1 Selected reaction monitoring mass spectrometry reveals the dynamics of signaling through the GRB2 adaptor. Nat Biotechnol. 2011 Jun 26;29(7):653-8.
REF 2 ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation. Oncogene. 2002 Aug 22;21(37):5684-95.
REF 3 SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome. Cell Commun Signal. 2012 Sep 14;10(1):27.
REF 4 Involvement of Janus kinases in the insulin signaling pathway. Eur J Biochem. 1995 Dec 1;234(2):656-60.
REF 5 Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. J Biol Chem. 2009 Aug 21;284(34):22525-34.
REF 6 The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling. J Biol Chem. 1998 Oct 9;273(41):26908-14.
REF 7 The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta. Biochemistry. 2002 Jan 15;41(2):603-8.
REF 8 Serine Phosphorylation by mTORC1 Promotes IRS-1 Degradation through SCF-TRCP E3Ubiquitin Ligase. iScience. 2018 Jul 27;5:1-18.
REF 9 An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but pres... Diabetologia. 2002 May;45(5):657-67.
REF 10 Phospho-tyrosine dependent protein-protein interaction network. Mol Syst Biol. 2015 Mar 26;11(3):794.
REF 11 Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation. Biochim Biophys Acta. 2015 May;1853(5):1022-34.
REF 12 PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities. J Biol Chem. 1995 Nov 17;270(46):27407-10.
REF 13 Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem. 2002 Jan 11;277(2):1531-7.
REF 14 The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000 Mar 24;275(12):9047-54.
REF 15 Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation. J Exp Med. 2001 Jan 15;193(2):263-9.
REF 16 Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor. Endocrinology. 1998 Mar;139(3):884-93.
REF 17 Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol. 2006 Jan;26(1):63-76.
REF 18 Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Mol Cell Biol. 1999 Apr;19(4):3125-35.
REF 19 Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system. J Biol Chem. 1995 Oct 6;270(40):23456-60.
REF 20 Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling. Diabetes. 2002 Jun;51(6):1921-30.
REF 21 Retinoic acid mediates degradation of IRS-1 by the ubiquitin-proteasome pathway, via a PKC-dependant mechanism. Oncogene. 2004 Dec 9;23(57):9269-79.
REF 22 Identification of the degradation determinants of insulin receptor substrate 1 for signaling cullin-RING E3 ubiquitin ligase 7-mediated ubiquitination. J Biol Chem. 2012 Nov 23;287(48):40758-66.
REF 23 Multiple forms of p55PIK, a regulatory subunit of phosphoinositide 3-kinase, are generated by alternative initiation of translation. Biochem J. 1999 Aug 1;341 ( Pt 3):831-7.
REF 24 FBXL2- and PTPL1-mediated degradation of p110-free p85 regulatory subunit controls the PI(3)K signallingcascade. Nat Cell Biol. 2013 May;15(5):472-80.
REF 25 14-3-3 (epsilon) interacts with the insulin-like growth factor I receptor and insulin receptor substrate I in a phosphoserine-dependent manner. J Biol Chem. 1997 Apr 25;272(17):11663-9.
REF 26 MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) Interaction Disruptor Sensitizes Insulin Signaling in Skeletal Muscle. J Biol Chem. 2016 Dec 23;291(52):26627-26635.
REF 27 The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell. 2008 May 23;30(4):403-14.

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