ITCH

Details:

UniProt Entry: Q96J02

Gene: ITCH

Class: HECT

Family: HECT1

Protein length: 903

Database confidence: 0.875

InterPro: InterPro Entry

Mode of Action: Standalone

AlphaFold Model: Link

PDB Structures: 2dmv, 2kyk, 2nq3, 2p4r, 2ysf, 3tug, 4rof, 5c7m, 5cq2, 5dws, 5dzd, 5sxp

Protein Sequence ▾

Domain Architecture (From InterPro) ▾

Protein functions ▾

Start	End	Type	Name	InterPro	Source
1	115	Domain	C2 domain	IPR000008	PS50004
6	359	Family	E3 ubiquitin-protein ligase, SMURF1 type	IPR024928	PIRSF001569
13	155	Homologous_superfamily	C2 domain superfamily	IPR035892	G3DSA:2.60.40.150
17	139	Homologous_superfamily	C2 domain superfamily	IPR035892	SSF49562
19	114	Domain	C2 domain	IPR000008	SM00239
19	109	Domain	C2 domain	IPR000008	PF00168
325	358	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
326	359	Domain	WW domain	IPR001202	PS50020
327	359	Domain	WW domain	IPR001202	SM00456
328	357	Domain	WW domain	IPR001202	PF00397
329	359	Domain	WW domain	IPR001202	cd00201
332	357	Domain	WW domain	IPR001202	PS01159
358	392	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
358	391	Domain	WW domain	IPR001202	PS50020
358	396	Family	E3 ubiquitin-protein ligase, SMURF1 type	IPR024928	PIRSF001569
360	389	Domain	WW domain	IPR001202	PF00397
360	391	Domain	WW domain	IPR001202	SM00456
361	391	Domain	WW domain	IPR001202	cd00201
364	389	Domain	WW domain	IPR001202	PS01159
390	903	Family	E3 ubiquitin-protein ligase, SMURF1 type	IPR024928	PIRSF001569
434	472	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
438	471	Domain	WW domain	IPR001202	PS50020
439	471	Domain	WW domain	IPR001202	SM00456
440	469	Domain	WW domain	IPR001202	PF00397
441	470	Domain	WW domain	IPR001202	cd00201
444	469	Domain	WW domain	IPR001202	PS01159
475	510	Homologous_superfamily	WW domain superfamily	IPR036020	SSF51045
478	511	Domain	WW domain	IPR001202	PS50020
479	511	Domain	WW domain	IPR001202	SM00456
481	510	Domain	WW domain	IPR001202	cd00201
484	509	Domain	WW domain	IPR001202	PS01159
530	897	Homologous_superfamily	HECT, E3 ligase catalytic domain	IPR035983	SSF56204
548	901	Domain	HECT domain	IPR000569	cd00078
567	903	Domain	HECT domain	IPR000569	SM00119
569	903	Domain	HECT domain	IPR000569	PS50237
599	901	Domain	HECT domain	IPR000569	PF00632

GO term	Name	Ontology	Evidence	Reference
GO:0002376	immune system process	Biological Process	IEA	GO_REF:0000120
GO:0002683	negative regulation of immune system process	Biological Process	IEA	GO_REF:0000117
GO:0002684	positive regulation of immune system process	Biological Process	IEA	GO_REF:0000117
GO:0006511	ubiquitin-dependent protein catabolic process	Biological Process	IEA	GO_REF:0000117
GO:0006915	apoptotic process	Biological Process	IEA	GO_REF:0000043
GO:0009896	positive regulation of catabolic process	Biological Process	IEA	GO_REF:0000117
GO:0010468	regulation of gene expression	Biological Process	IEA	GO_REF:0000117
GO:0010604	positive regulation of macromolecule metabolic process	Biological Process	IEA	GO_REF:0000117
GO:0045087	innate immune response	Biological Process	IEA	GO_REF:0000043
GO:0046718	symbiont entry into host cell	Biological Process	IEA	GO_REF:0000117
GO:0050687	negative regulation of defense response to virus	Biological Process	IEA	GO_REF:0000117
GO:0051241	negative regulation of multicellular organismal process	Biological Process	IEA	GO_REF:0000117
GO:0051607	defense response to virus	Biological Process	IEA	GO_REF:0000043
GO:0070936	protein K48-linked ubiquitination	Biological Process	IEA	GO_REF:0000117
GO:1902532	negative regulation of intracellular signal transduction	Biological Process	IEA	GO_REF:0000117
GO:0016567	protein ubiquitination	Biological Process	IEA	GO_REF:0000041
GO:0002870	T cell anergy	Biological Process	IEA	GO_REF:0000107
GO:0030163	protein catabolic process	Biological Process	IEA	GO_REF:0000107
GO:0035739	CD4-positive, alpha-beta T cell proliferation	Biological Process	IEA	GO_REF:0000107
GO:0000209	protein polyubiquitination	Biological Process	IEA	GO_REF:0000107
GO:0002669	positive regulation of T cell anergy	Biological Process	IEA	GO_REF:0000107
GO:0002753	cytoplasmic pattern recognition receptor signaling pathway	Biological Process	IDA	PMID:16125763
GO:0006979	response to oxidative stress	Biological Process	IDA	PMID:17603038
GO:0038160	CXCL12-activated CXCR4 signaling pathway	Biological Process	IDA	PMID:28978524
GO:0045732	positive regulation of protein catabolic process	Biological Process	IEA	GO_REF:0000107
GO:2000562	negative regulation of CD4-positive, alpha-beta T cell proliferation	Biological Process	IEA	GO_REF:0000107
GO:0001558	regulation of cell growth	Biological Process	NAS	PMID:9462742
GO:0006513	protein monoubiquitination	Biological Process	IDA	PMID:34927784
GO:0006954	inflammatory response	Biological Process	NAS	PMID:9462742
GO:0031623	receptor internalization	Biological Process	IMP	PMID:34927784
GO:0032480	negative regulation of type I interferon production	Biological Process	TAS	Reactome:R-HSA-936440
GO:0035519	protein K29-linked ubiquitination	Biological Process	IDA	PMID:17028573
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	Biological Process	TAS	Reactome:R-HSA-168638
GO:0039532	negative regulation of cytoplasmic pattern recognition receptor signaling pathway	Biological Process	IDA	PMID:27736772
GO:0043066	negative regulation of apoptotic process	Biological Process	IMP	PMID:20068034
GO:0043124	negative regulation of canonical NF-kappaB signal transduction	Biological Process	ISS	GO_REF:0000024
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	Biological Process	IBA	GO_REF:0000033
GO:0046329	negative regulation of JNK cascade	Biological Process	ISS	GO_REF:0000024
GO:0051865	protein autoubiquitination	Biological Process	IMP	PMID:24790097
GO:0060544	regulation of necroptotic process	Biological Process	TAS	Reactome:R-HSA-5675482
GO:0070534	protein K63-linked ubiquitination	Biological Process	IDA	PMID:18718448
GO:0090085	regulation of protein deubiquitination	Biological Process	ISS	GO_REF:0000024
GO:0141198	protein branched polyubiquitination	Biological Process	IDA	PMID:29378950
GO:1902036	regulation of hematopoietic stem cell differentiation	Biological Process	TAS	Reactome:R-HSA-8939236
GO:2000646	positive regulation of receptor catabolic process	Biological Process	IMP	PMID:24790097
GO:0005634	nucleus	Cellular Component	IEA	GO_REF:0000117
GO:0005737	cytoplasm	Cellular Component	IEA	GO_REF:0000120
GO:0005768	endosome	Cellular Component	IEA	GO_REF:0000043
GO:0005829	cytosol	Cellular Component	IEA	GO_REF:0000117
GO:0005886	plasma membrane	Cellular Component	IEA	GO_REF:0000120
GO:0016020	membrane	Cellular Component	IEA	GO_REF:0000120
GO:0031410	cytoplasmic vesicle	Cellular Component	IEA	GO_REF:0000117
GO:0031901	early endosome membrane	Cellular Component	IEA	GO_REF:0000044
GO:0071944	cell periphery	Cellular Component	IEA	GO_REF:0000117
GO:0005654	nucleoplasm	Cellular Component	IDA	GO_REF:0000052
GO:0005769	early endosome	Cellular Component	IDA	PMID:24790097
GO:0005739	mitochondrion	Cellular Component	IC	PMID:27736772
GO:0005938	cell cortex	Cellular Component	IEA	GO_REF:0000107
GO:0010008	endosome membrane	Cellular Component	IEA	GO_REF:0000044
GO:0070062	extracellular exosome	Cellular Component	HDA	PMID:23533145
GO:0032991	protein-containing complex	Cellular Component	IDA	PMID:24790097
GO:0004842	ubiquitin-protein transferase activity	Molecular Function	IEA	GO_REF:0000002
GO:0016740	transferase activity	Molecular Function	IEA	GO_REF:0000043
GO:0061630	ubiquitin protein ligase activity	Molecular Function	IEA	GO_REF:0000117
GO:0005515	protein binding	Molecular Function	IPI	PMID:15051726
GO:0016874	ligase activity	Molecular Function	IEA	GO_REF:0000107
GO:0019787	ubiquitin-like protein transferase activity	Molecular Function	TAS	Reactome:R-HSA-688137
GO:0034450	ubiquitin-ubiquitin ligase activity	Molecular Function	IDA	PMID:29378950
GO:0043021	ribonucleoprotein complex binding	Molecular Function	IPI	PMID:19881509
GO:0044389	ubiquitin-like protein ligase binding	Molecular Function	IPI	PMID:24790097
GO:0045236	CXCR chemokine receptor binding	Molecular Function	IPI	PMID:19116316
GO:1990763	arrestin family protein binding	Molecular Function	IPI	PMID:23886940

Enzyme–Substrate Interactions ▾

Substrate	Name	Known ESI (UbiBrowser)	Known ESI (UbiNet)	PPI (IntAct direct) PSI-MI score ≥ 0.5	PPI (IntAct indirect) PSI-MI scores ≥ 0.5 for both PPIs	PubMed Ref.	IntAct Ref.	Substrate Specificity
P55957	BID	Yes	Yes	No	No	—	No	E3-specific
Q8NEA6	GLIS3	Yes	Yes	No	No	—	No	E3-specific
Q99541	PLIN2	Yes	Yes	No	No	—	No	E3-specific
Q16655	MAR1	Yes	Yes	Yes	No	37219487, 20491914	EBI-42493617	Cluster-specific
P22681	CBL	Yes	Yes	No	No	12226085	EBI-8529158	E3-specific
Q9UBN4	TRPC4	Yes	Yes	No	No	—	No	E3-specific
O60240	PLIN1	Yes	Yes	No	No	—	No	E3-specific
Q3T906	GNPTA	Yes	No	No	No	—	No	E3-specific
Q4VCS5	AMOT	Yes	Yes	No	No	—	No	Cluster-specific
Q9Y371	SHLB1	Yes	Yes	No	No	—	No	E3-specific
Q01860	PO5F1	Yes	Yes	No	No	—	No	Cluster-specific
Q9Y5X1	SNX9	Yes	Yes	Yes	No	20491914	EBI-7985303	E3-specific
Q15583	TGIF1	Yes	Yes	No	No	—	No	E3-specific
Q13571	LAPM5	Yes	Yes	No	No	—	No	Cluster-specific
P45985	MP2K4	Yes	Yes	No	No	—	No	E3-specific
P17275	JUNB	Yes	Yes	No	No	—	No	E3-specific
P16403	H12	Yes	Yes	No	No	—	No	E3-specific
Q14511	CASL	Yes	Yes	Yes	No	15051726	EBI-7161552	E3-specific
Q16630	CPSF6	Yes	Yes	No	No	28514442	EBI-21762353	E3-specific
Q16625	OCLN	Yes	Yes	No	No	—	No	Cluster-specific
O15357	SHIP2	Yes	Yes	No	No	—	No	E3-specific
Q8WWW0	RASF5	Yes	Yes	No	No	—	No	E3-specific
O15519	CFLAR	Yes	Yes	No	No	—	No	E3-specific
Q9HBA0	TRPV4	Yes	Yes	No	No	—	No	E3-specific
Q6PJG6	BRAT1	Yes	Yes	No	No	—	No	Cluster-specific
Q13635	PTC1	Yes	Yes	No	No	—	No	E3-specific
O75581	LRP6	Yes	Yes	No	No	—	No	E3-specific
Q9H3M7	TXNIP	Yes	Yes	No	No	—	No	E3-specific
Q9UM47	NOTC3	Yes	Yes	No	No	—	No	Cluster-specific
Q15750	TAB1	Yes	Yes	No	No	—	No	Cluster-specific
O95835	LATS1	Yes	Yes	No	No	—	No	Cluster-specific
Q16621	NFE2	Yes	Yes	No	No	—	No	E3-specific
O43294	TGFI1	Yes	No	No	No	37219487	EBI-42493585	E3-specific
Q15811	ITSN1	Yes	Yes	No	No	—	No	E3-specific
P17844	DDX5	Yes	Yes	No	No	—	No	E3-specific
Q9BTU6	P4K2A	Yes	Yes	Yes	No	23146885	EBI-8159264	E3-specific

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