E3 ubiquitin-protein ligase Itchy homolog (Itch) (EC 2.3.2.26) (Atrophin-1-interacting protein 4) (AIP4) (HECT-type E3 ubiquitin transferase Itchy homolog) (NFE2-associated polypeptide 1) (NAPP1)
1_MSDSG 6_ SQLGS 11_ MGSLT 16_ MKSQL 21_ QITVI 26_ SAKLK 31_ ENKKN 36_ WFGPS 41_ PYVEV 46_ TVDGQ 51_ SKKTE 56_ KCNNT 61_ NSPKW 66_ KQPLT 71_ VIVTP 76_ VSKLH 81_ FRVWS 86_ HQTLK 91_ SDVLL 96_ GTAAL 101_ DIYET 106_ LKSNN 111_ MKLEE 116_ VVVTL 121_ QLGGD 126_ KEPTE 131_ TIGDL 136_ SICLD 141_ GLQLE 146_ SEVVT 151_ NGETT 156_ CSENG 161_ VSLCL 166_ PRLEC 171_ NSAIS 176_ AHCNL 181_ CLPGL 186_ SDSPI 191_ SASRV 196_ AGFTG 201_ ASQND 206_ DGSRS 211_ KDETR 216_ VSTNG 221_ SDDPE 226_ DAGAG 231_ ENRRV 236_ SGNNS 241_ PSLSN 246_ GGFKP 251_ SRPPR 256_ PSRPP 261_ PPTPR 266_ RPASV 271_ NGSPS 276_ ATSES 281_ DGSST 286_ GSLPP 291_ TNTNT 296_ NTSEG 301_ ATSGL 306_ IIPLT 311_ ISGGS 316_ GPRPL 321_ NPVTQ 326_ APLPP 331_ GWEQR 336_ VDQHG 341_ RVYYV 346_ DHVEK 351_ RTTWD 356_ RPEPL 361_ PPGWE 366_ RRVDN 371_ MGRIY 376_ YVDHF 381_ TRTTT 386_ WQRPT 391_ LESVR 396_ NYEQW 401_ QLQRS 406_ QLQGA 411_ MQQFN 416_ QRFIY 421_ GNQDL 426_ FATSQ 431_ SKEFD 436_ PLGPL 441_ PPGWE 446_ KRTDS 451_ NGRVY 456_ FVNHN 461_ TRITQ 466_ WEDPR 471_ SQGQL 476_ NEKPL 481_ PEGWE 486_ MRFTV 491_ DGIPY 496_ FVDHN 501_ RRTTT 506_ YIDPR 511_ TGKSA 516_ LDNGP 521_ QIAYV 526_ RDFKA 531_ KVQYF 536_ RFWCQ 541_ QLAMP 546_ QHIKI 551_ TVTRK 556_ TLFED 561_ SFQQI 566_ MSFSP 571_ QDLRR 576_ RLWVI 581_ FPGEE 586_ GLDYG 591_ GVARE 596_ WFFLL 601_ SHEVL 606_ NPMYC 611_ LFEYA 616_ GKDNY 621_ CLQIN 626_ PASYI 631_ NPDHL 636_ KYFRF 641_ IGRFI 646_ AMALF 651_ HGKFI 656_ DTGFS 661_ LPFYK 666_ RILNK 671_ PVGLK 676_ DLESI 681_ DPEFY 686_ NSLIW 691_ VKENN 696_ IEECD 701_ LEMYF 706_ SVDKE 711_ ILGEI 716_ KSHDL 721_ KPNGG 726_ NILVT 731_ EENKE 736_ EYIRM 741_ VAEWR 746_ LSRGV 751_ EEQTQ 756_ AFFEG 761_ FNEIL 766_ PQQYL 771_ QYFDA 776_ KELEV 781_ LLCGM 786_ QEIDL 791_ NDWQR 796_ HAIYR 801_ HYART 806_ SKQIM 811_ WFWQF 816_ VKEID 821_ NEKRM 826_ RLLQF 831_ VTGTC 836_ RLPVG 841_ GFADL 846_ MGSNG 851_ PQKFC 856_ IEKVG 861_ KENWL 866_ PRSHT 871_ CFNRL 876_ DLPPY 881_ KSYEQ 886_ LKEKL 891_ LFAIE 896_ETEGF
1: Acts as an Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11046148, PubMed:14602072, PubMed:15051726, PubMed:16387660, PubMed:17028573, PubMed:18718448, PubMed:18718449, PubMed:19116316, PubMed:19592251, PubMed:19881509, PubMed:20068034, PubMed:20392206, PubMed:20491914, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885, PubMed:34927784). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Together with UBR5, involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP: catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP (PubMed:20068034, PubMed:29378950). ITCH synthesizes 'Lys-63'-linked chains, while UBR5 is branching multiple 'Lys-48'-linked chains of substrate initially modified (PubMed:29378950). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013). Ubiquitinates NEDD9/HEF1, resulting in proteasomal degradation of NEDD9/HEF1 (PubMed:15051726)