Overview
| Uniprot ID | Q96J02 |
|---|
| Protein Name | E3 ubiquitin-protein ligase Itchy homolog |
|---|
| Gene Name | ITCH |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 721 |
EIKSHDLKPNGGNIL |
Function
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)
Protein Sequence
10
MSDSGSQLGS
20
MGSLTMKSQL
30
QITVISAKLK
40
ENKKNWFGPS
50
PYVEVTVDGQ
60
SKKTEKCNNT
70
NSPKWKQPLT
80
VIVTPVSKLH
90
FRVWSHQTLK
100
SDVLLGTAAL
110
DIYETLKSNN
120
MKLEEVVVTL
130
QLGGDKEPTE
140
TIGDLSICLD
150
GLQLESEVVT
160
NGETTCSENG
170
VSLCLPRLEC
180
NSAISAHCNL
190
CLPGLSDSPI
200
SASRVAGFTG
210
ASQNDDGSRS
220
KDETRVSTNG
230
SDDPEDAGAG
240
ENRRVSGNNS
250
PSLSNGGFKP
260
SRPPRPSRPP
270
PPTPRRPASV
280
NGSPSATSES
290
DGSSTGSLPP
300
TNTNTNTSEG
310
ATSGLIIPLT
320
ISGGSGPRPL
330
NPVTQAPLPP
340
GWEQRVDQHG
350
RVYYVDHVEK
360
RTTWDRPEPL
370
PPGWERRVDN
380
MGRIYYVDHF
390
TRTTTWQRPT
400
LESVRNYEQW
410
QLQRSQLQGA
420
MQQFNQRFIY
430
GNQDLFATSQ
440
SKEFDPLGPL
450
PPGWEKRTDS
460
NGRVYFVNHN
470
TRITQWEDPR
480
SQGQLNEKPL
490
PEGWEMRFTV
500
DGIPYFVDHN
510
RRTTTYIDPR
520
TGKSALDNGP
530
QIAYVRDFKA
540
KVQYFRFWCQ
550
QLAMPQHIKI
560
TVTRKTLFED
570
SFQQIMSFSP
580
QDLRRRLWVI
590
FPGEEGLDYG
600
GVAREWFFLL
610
SHEVLNPMYC
620
LFEYAGKDNY
630
CLQINPASYI
640
NPDHLKYFRF
650
IGRFIAMALF
660
HGKFIDTGFS
670
LPFYKRILNK
680
PVGLKDLESI
690
DPEFYNSLIW
700
VKENNIEECD
710
LEMYFSVDKE
720
ILGEIKSHDL
730
KPNGGNILVT
740
EENKEEYIRM
750
VAEWRLSRGV
760
EEQTQAFFEG
770
FNEILPQQYL
780
QYFDAKELEV
790
LLCGMQEIDL
800
NDWQRHAIYR
810
HYARTSKQIM
820
WFWQFVKEID
830
NEKRMRLLQF
840
VTGTCRLPVG
850
GFADLMGSNG
860
PQKFCIEKVG
870
KENWLPRSHT
880
CFNRLDLPPY
890
KSYEQLKEKL
900
LFAIEETEGF
GQE
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005938 |
cell cortex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0031410 |
cytoplasmic vesicle |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0031901 |
early endosome membrane |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0032991 |
protein-containing complex |
| Molecular Function |
GO:1990763 |
arrestin family protein binding |
| Molecular Function |
GO:0045236 |
CXCR chemokine receptor binding |
| Molecular Function |
GO:0016874 |
ligase activity |
| Molecular Function |
GO:0043021 |
ribonucleoprotein complex binding |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0044389 |
ubiquitin-like protein ligase binding |
| Molecular Function |
GO:0019787 |
ubiquitin-like protein transferase activity |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Molecular Function |
GO:0034450 |
ubiquitin-ubiquitin ligase activity |
| Biological Process |
GO:0006915 |
apoptotic process |
| Biological Process |
GO:0051607 |
defense response to virus |
| Biological Process |
GO:0006954 |
inflammatory response |
| Biological Process |
GO:0045087 |
innate immune response |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:0043124 |
negative regulation of canonical NF-kappaB signal transduction |
| Biological Process |
GO:0039532 |
negative regulation of cytoplasmic pattern recognition receptor signaling pathway |
| Biological Process |
GO:0050687 |
negative regulation of defense response to virus |
| Biological Process |
GO:0046329 |
negative regulation of JNK cascade |
| Biological Process |
GO:0032480 |
negative regulation of type I interferon production |
| Biological Process |
GO:0035872 |
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway |
| Biological Process |
GO:2000646 |
positive regulation of receptor catabolic process |
| Biological Process |
GO:0043161 |
proteasome-mediated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0051865 |
protein autoubiquitination |
| Biological Process |
GO:0141198 |
protein branched polyubiquitination |
| Biological Process |
GO:0035519 |
protein K29-linked ubiquitination |
| Biological Process |
GO:0070936 |
protein K48-linked ubiquitination |
| Biological Process |
GO:0070534 |
protein K63-linked ubiquitination |
| Biological Process |
GO:0006513 |
protein monoubiquitination |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0031623 |
receptor internalization |
| Biological Process |
GO:0001558 |
regulation of cell growth |
| Biological Process |
GO:1902036 |
regulation of hematopoietic stem cell differentiation |
| Biological Process |
GO:0060544 |
regulation of necroptotic process |
| Biological Process |
GO:0090085 |
regulation of protein deubiquitination |
| Biological Process |
GO:0046718 |
symbiont entry into host cell |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
PMID: N/A