Target Interacting Protein Information

Content Navigation (  All   None )                                      
Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T81240 Target Info
Target Name E3 ubiquitin protein ligase Itchy (ITCH)
Synonyms NFE2-associated polypeptide 1; NAPP1; Itch; HECT-type E3 ubiquitin transferase Itchy homolog; E3 ubiquitin-protein ligase Itchy homolog; Atrophin-1-interacting protein 4; AIP4
Target Type Literature-reported Target
Gene Name ITCH
Biochemical Class Acyltransferase
UniProt ID
ITCH_HUMAN 
Target Interacting Proteins  Top
Acyltransferases [+] 1 Acyltransferases +
Interacting Protein Name E3 ubiquitin-protein ligase DTX1 (DTX1) Interacting Protein Interacting Protein Info
UniProt ID
DTX1_HUMAN 
Synonyms hDx.1
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [1]
2 Co-localization [1]
3 Reconstituted Complex [2]
Adapter proteins [+] 1 Adapter proteins +
Interacting Protein Name Signal transducing adapter molecule 1 (STAM) Interacting Protein Interacting Protein Info
UniProt ID
STAM1_HUMAN 
Synonyms STAM.1; STAM1
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [4]
3 Reconstituted Complex [4]
G-protein-coupled receptors [+] 1 G-protein-coupled receptors +
Interacting Target Name C-X-C chemokine receptor type 4 (CXCR4) Successful Target Interacting Protein Info
UniProt ID
CXCR4_HUMAN 
Synonyms Stromal cell-derived factor 1 receptor; SDF-1 receptor; NPYRL; LPS-associated protein 3; Lipopolysaccharide-associated protein 3; Leukocyte-derived seven transmembrane domain receptor; LESTR; LCR1; LAP-3; HM89; Fusin; FB22; CXC-R4; CXCR-4; Chemokine receptor CXCR4; CD184 antigen; CD184
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [5]
2 Co-fractionation [4]
3 Fluorescence Resonance Energy Transfer [5]
4 Reconstituted Complex [5]
Kinases [+] 3 Kinases +
Interacting Protein Name Serine/threonine-protein kinase LATS1 (LATS1) Interacting Protein Interacting Protein Info
UniProt ID
LATS1_HUMAN 
Synonyms WARTS; wts
Evidence Score (E-score) 6 Experimental Evidences +
1 Affinity Capture-Western [6]
2 Affinity Capture-Western [7]
3 Affinity Capture-Western [8]
4 Biochemical Activity [9]
5 Reconstituted Complex [6]
6 Reconstituted Complex [9]
Interacting Target Name Erbb4 tyrosine kinase receptor (Erbb-4) Successful Target Interacting Protein Info
UniProt ID
ERBB4_HUMAN 
Synonyms Tyrosine kinase-type cell surface receptor HER4; Receptor tyrosine-protein kinase erbB-4; Proto-oncogene-like protein c-ErbB-4; P180erbB4; HER4
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [10]
2 Affinity Capture-Western [11]
3 Far Western [11]
4 Reconstituted Complex [10]
5 Reconstituted Complex [11]
Interacting Protein Name DNA-directed RNA polymerase II subunit RPB1 (POLR2A) Interacting Protein Interacting Protein Info
UniProt ID
RPB1_HUMAN 
Synonyms POLR2; POLRA; RPB1; RPBh1; RPO2; RPOL2; RpIILS; hRPB220; hsRPB1
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [12]
3 Reconstituted Complex [12]
Peptidases [+] 1 Peptidases +
Interacting Protein Name Probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) Interacting Protein Interacting Protein Info
UniProt ID
USP9X_HUMAN 
Synonyms DFFRX; FAF; FAM; MRX99
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [13]
3 Affinity Capture-Western [14]
4 Reconstituted Complex [13]
Transcription regulators [+] 5 Transcription regulators +
Interacting Protein Name Tumor protein 63 (TP63) Interacting Protein Interacting Protein Info
UniProt ID
P63_HUMAN 
Synonyms AIS; B(p51A); B(p51B); EEC3; KET; LMS; NBP; OFC8; RHS; SHFM4; TP53CP; TP53L; TP73L; p40; p51; p53CP; p63; p73H; p73L
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [15]
2 Co-crystal Structure [16]
3 Co-crystal Structure [17]
4 Reconstituted Complex [16]
5 Reconstituted Complex [17]
Interacting Protein Name Tumor protein p73 (TP73) Interacting Protein Interacting Protein Info
UniProt ID
P73_HUMAN 
Synonyms P73
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [18]
2 Biochemical Activity [18]
3 Reconstituted Complex [19]
4 Reconstituted Complex [18]
Interacting Protein Name POU class 5 homeobox 1 (POU5F1) Interacting Protein Interacting Protein Info
UniProt ID
PO5F1_HUMAN 
Synonyms OCT3; OCT4; OTF.3; OTF3; OTF4; Oct.3; Oct.4
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [20]
2 Biochemical Activity [20]
3 Biochemical Activity [21]
Interacting Protein Name Transcription factor NF-E2 45 kDa subunit (NFE2) Interacting Protein Interacting Protein Info
UniProt ID
NFE2_HUMAN 
Synonyms NF.E2; p45
Evidence Score (E-score) 3 Experimental Evidences +
1 Biochemical Activity [22]
2 Far Western [23]
3 Yeast two hybrid [23]
Interacting Target Name Mothers against decapentaplegic homolog 7 (SMAD7) Clinical trial Target Interacting Protein Info
UniProt ID
SMAD7_HUMAN 
Synonyms Smad7; SMAD family member 7; SMAD 7; Mothers against DPP homolog 8; Mothers against decapentaplegic homolog 8; MAD homolog 8; hSMAD7
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [24]
2 Affinity Capture-Western [25]
Ubiquitin related proteins [+] 2 Ubiquitin related proteins +
Interacting Protein Name Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) Interacting Protein Interacting Protein Info
UniProt ID
UB2L3_HUMAN 
Synonyms E2.F1; L.UBC; UBCH7; UbcM4
Evidence Score (E-score) 16 Experimental Evidences +
1 Affinity Capture-Western [13]
2 Affinity Capture-Western [26]
3 Affinity Capture-Western [27]
4 Reconstituted Complex [28]
5 Reconstituted Complex [29]
6 Reconstituted Complex [19]
7 Reconstituted Complex [30]
8 Reconstituted Complex [31]
9 Reconstituted Complex [18]
10 Reconstituted Complex [32]
11 Reconstituted Complex [33]
12 Reconstituted Complex [27]
13 Reconstituted Complex [34]
14 Reconstituted Complex [35]
15 Reconstituted Complex [36]
16 Reconstituted Complex [37]
Interacting Target Name Polyubiquitin-C (UBC) Patented-recorded Target Interacting Protein Info
UniProt ID
UBC_HUMAN 
Synonyms HMG20; ubiquitin C
Evidence Score (E-score) 4 Experimental Evidences +
1 Biochemical Activity [38]
2 Biochemical Activity [39]
3 Biochemical Activity [33]
4 Protein-peptide [40]
Other proteins [+] 10 Other proteins +
Interacting Target Name Vitamin D3 up-regulated protein 1 (VDUP1) Literature-reported Target Interacting Protein Info
UniProt ID
TXNIP_HUMAN 
Synonyms Vitamin D(3) up-regulating protein-1; Thioredoxin-interacting protein; Thioredoxin-binding protein 2
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [32]
2 Biochemical Activity [32]
3 Co-crystal Structure [41]
4 Proximity Label-MS [42]
5 Reconstituted Complex [41]
Interacting Protein Name Rho guanine nucleotide exchange factor 7 (ARHGEF7) Interacting Protein Interacting Protein Info
UniProt ID
ARHG7_HUMAN 
Synonyms BETA.PIX; COOL.1; COOL1; Nbla10314; P50; P50BP; P85; P85COOL1; P85SPR; PAK3; PIXB
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [43]
2 Co-crystal Structure [43]
3 Protein-peptide [44]
4 Reconstituted Complex [43]
5 Reconstituted Complex [45]
Interacting Protein Name Protein kinase C and casein kinase substrate in neurons protein 1 (PACSIN1) Interacting Protein Interacting Protein Info
UniProt ID
PACN1_HUMAN 
Synonyms SDPI
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [45]
2 Far Western [45]
3 Fluorescence Resonance Energy Transfer [45]
4 Protein-peptide [44]
5 Reconstituted Complex [45]
Interacting Protein Name Endophilin-A1 (SH3GL2) Interacting Protein Interacting Protein Info
UniProt ID
SH3G2_HUMAN 
Synonyms CNSA2; EEN.B1; SH3D2A; SH3P4
Evidence Score (E-score) 5 Experimental Evidences +
1 Affinity Capture-Western [45]
2 Far Western [45]
3 Fluorescence Resonance Energy Transfer [45]
4 Protein-peptide [44]
5 Reconstituted Complex [45]
Interacting Protein Name Myc box-dependent-interacting protein 1 (BIN1) Interacting Protein Interacting Protein Info
UniProt ID
BIN1_HUMAN 
Synonyms AMPH2; AMPHL; SH3P9
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [45]
2 Far Western [45]
3 Fluorescence Resonance Energy Transfer [45]
4 Protein-peptide [44]
Interacting Protein Name Protein numb homolog (NUMB) Interacting Protein Interacting Protein Info
UniProt ID
NUMB_HUMAN 
Synonyms C14orf41; S171; c14_5527
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [46]
2 Reconstituted Complex [46]
3 Reconstituted Complex [2]
4 Reconstituted Complex [47]
Interacting Protein Name WW domain-binding protein 2 (WBP2) Interacting Protein Interacting Protein Info
UniProt ID
WBP2_HUMAN 
Synonyms WBP.2
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [48]
3 Reconstituted Complex [12]
4 Reconstituted Complex [48]
Interacting Protein Name Apoptosis-stimulating of p53 protein 2 (TP53BP2) Interacting Protein Interacting Protein Info
UniProt ID
ASPP2_HUMAN 
Synonyms 53BP2; ASPP2; BBP; P53BP2; PPP1R13A
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [49]
2 Affinity Capture-Western [50]
3 Reconstituted Complex [49]
Interacting Protein Name Cleavage and polyadenylation specificity factor subunit 6 (CPSF6) Interacting Protein Interacting Protein Info
UniProt ID
CPSF6_HUMAN 
Synonyms CFIM; CFIM68; HPBRII.4; HPBRII.7
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-MS [3]
2 Affinity Capture-Western [12]
3 Reconstituted Complex [12]
Interacting Protein Name Segment polarity protein dishevelled homolog DVL-2 (DVL2) Interacting Protein Interacting Protein Info
UniProt ID
DVL2_HUMAN 
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [51]
2 Affinity Capture-Western [52]
3 Biochemical Activity [51]
References  Top
REF 1 Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains. EMBO Rep. 2006 Nov;7(11):1147-53.
REF 2 AIP4/Itch regulates Notch receptor degradation in the absence of ligand. PLoS One. 2008 Jul 16;3(7):e2735.
REF 3 Ubiquitin-Activated Interaction Traps (UBAITs) identify E3 ligase binding partners. EMBO Rep. 2015 Dec;16(12):1699-712.
REF 4 Novel roles for the E3 ubiquitin ligase atrophin-interacting protein 4 and signal transduction adaptor molecule 1 in G protein-coupled receptor signaling. J Biol Chem. 2012 Mar 16;287(12):9013-27.
REF 5 The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. Mol Biol Cell. 2009 Mar;20(5):1324-39.
REF 6 Negative regulation of the Hippo pathway by E3 ubiquitin ligase ITCH is sufficient to promote tumorigenicity. Cancer Res. 2011 Mar 1;71(5):2010-20.
REF 7 Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth. J Biol Chem. 2013 May 24;288(21):15181-93.
REF 8 Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability. Proc Natl Acad Sci U S A. 2017 May 2;114(18):4691-4696.
REF 9 Itch E3 ubiquitin ligase regulates large tumor suppressor 1 stability [corrected]. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4870-5.
REF 10 Isoform-specific monoubiquitination, endocytosis, and degradation of alternatively spliced ErbB4 isoforms. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4162-7.
REF 11 The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation. FASEB J. 2007 Sep;21(11):2849-62.
REF 12 WW domains provide a platform for the assembly of multiprotein networks. Mol Cell Biol. 2005 Aug;25(16):7092-106.
REF 13 The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. J Biol Chem. 2006 Dec 15;281(50):38738-47.
REF 14 Reciprocal regulation of the ubiquitin ligase Itch and the epidermal growth factor receptor signaling. Cell Signal. 2009 Aug;21(8):1326-36.
REF 15 The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12753-8.
REF 16 Recognition of p63 by the E3 ligase ITCH: Effect of an ectodermal dysplasia mutant. Cell Cycle. 2010 Sep 15;9(18):3730-9.
REF 17 Recognition mechanism of p63 by the E3 ligase Itch: novel strategy in the study and inhibition of this interaction. Cell Cycle. 2012 Oct 1;11(19):3638-48.
REF 18 The ubiquitin-protein ligase Itch regulates p73 stability. EMBO J. 2005 Feb 23;24(4):836-48.
REF 19 The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11280-5.
REF 20 Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction. J Cell Physiol. 2013 Jul;228(7):1443-51.
REF 21 Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner. Cell Res. 2010 Mar;20(3):332-44.
REF 22 Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination. Biochem Biophys Res Commun. 2008 Oct 24;375(3):326-30.
REF 23 Human ITCH is a coregulator of the hematopoietic transcription factor NF-E2. Genomics. 2001 Apr 15;73(2):238-41.
REF 24 USP11 augments TGF signalling by deubiquitylating ALK5. Open Biol. 2012 Jun;2(6):120063.
REF 25 AIP4 restricts transforming growth factor-beta signaling through a ubiquitination-independent mechanism. J Biol Chem. 2005 Jul 29;280(30):27645-53.
REF 26 Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7. J Immunol. 2015 Mar 1;194(5):2160-7.
REF 27 Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its cognate E2 ubiquitin ligase. J Biol Chem. 2018 Jan 19;293(3):1100-1105.
REF 28 Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell. 2007 Aug 24;130(4):651-62.
REF 29 Itch self-polyubiquitylation occurs through lysine-63 linkages. Biochem Pharmacol. 2008 Dec 1;76(11):1515-21.
REF 30 Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell. 2007 Nov 9;28(3):386-97.
REF 31 System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes. Mol Cell. 2016 Apr 7;62(1):121-36.
REF 32 The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. J Biol Chem. 2010 Mar 19;285(12):8869-79.
REF 33 Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations. Biochem J. 2015 Apr 15;467(2):345-52.
REF 34 HECT-type ubiquitin ligase ITCH targets lysosomal-associated protein multispanning transmembrane 5 (LAPTM5) and prevents LAPTM5-mediated cell death. J Biol Chem. 2011 Dec 23;286(51):44086-94.
REF 35 Itch E3 ligase-mediated regulation of TGF-beta signaling by modulating smad2 phosphorylation. Mol Cell. 2004 Sep 10;15(5):825-31.
REF 36 Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation. J Biol Chem. 2015 Sep 25;290(39):23875-87.
REF 37 Itch/-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis. Nat Commun. 2018 Mar 7;9(1):976.
REF 38 A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Mol Cell Proteomics. 2012 Aug;11(8):329-41.
REF 39 Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming. Nat Struct Mol Biol. 2013 Jun;20(6):696-701.
REF 40 A strategy for modulation of enzymes in the ubiquitin system. Science. 2013 Feb 1;339(6119):590-5.
REF 41 Structural basis for the regulatory role of the PPxY motifs in the thioredoxin-interacting protein TXNIP. Biochem J. 2016 Jan 15;473(2):179-87.
REF 42 Identification of Redox and Glucose-Dependent Txnip Protein Interactions. Oxid Med Cell Longev. 2016;2016:5829063.
REF 43 A novel interaction between atrophin-interacting protein 4 and beta-p21-activated kinase-interactive exchange factor is mediated by an SH3 domain. J Biol Chem. 2007 Sep 28;282(39):28893-903.
REF 44 Molecular basis of interactions between SH3 domain-containing proteins and the proline-rich region of the ubiquitin ligase Itch. J Biol Chem. 2017 Apr 14;292(15):6325-6338.
REF 45 Multiple Src Homology 3 Binding to the Ubiquitin Ligase Itch Conserved Proline-Rich Region. Biochemistry. 2015 Dec 22;54(50):7345-54.
REF 46 Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J Biol Chem. 2003 Jun 20;278(25):23196-203.
REF 47 Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal. Oncogene. 2011 Jan 6;30(1):65-76.
REF 48 Wnt Signaling Promotes Breast Cancer by Blocking ITCH-Mediated Degradation of YAP/TAZ Transcriptional Coactivator WBP2. Cancer Res. 2016 Nov 1;76(21):6278-6289.
REF 49 The E3 ubiquitin ligase Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability. FEBS Lett. 2015 Jan 2;589(1):94-101.
REF 50 ASPP2 suppresses invasion and TGF-1-induced epithelial-mesenchymal transition by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric cancer. Cancer Lett. 2017 Jul 10;398:52-61.
REF 51 The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled protein. Mol Cell Biol. 2012 Oct;32(19):3903-12.
REF 52 Disinhibition of the HECT E3 ubiquitin ligase WWP2 by polymerized Dishevelled. Open Biol. 2015 Dec;5(12):150185.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.