AiPD: Autoinhibited Protein Database

Q96J02

Gene name	ITCH
Protein name	E3 ubiquitin-protein ligase Itchy homolog
Names	Itch, Atrophin-1-interacting protein 4, AIP4, HECT-type E3 ubiquitin transferase Itchy homolog, NFE2-associated polypeptide 1, NAPP1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:83737
EC number	2.3.2.26: Aminoacyltransferases
Protein Class	HECT DOMAIN UBIQUITIN-PROTEIN LIGASE (PTHR11254)

Descriptions

E3 ubiquitin-protein ligase Itchy homolog protein (ITCH) is a HECT domain E3 ubiquitin ligase, belonging to the NEDD4 family. It plays a crucial role in regulating proteolysis and various cellular processes by targeting specific proteins for ubiquitination and subsequent degradation. Similar with other NEDD4 families such as WWP2, ITCH is autoinhibited through interactions between the WW2-WW3 linker and the HECT domain, resulting in a closed and inactive conformation. Deletion of the WW2-WW3 linker from ITCH sharply increases autoubiquitination activity compared to full-length ITCH. Binding of PPxY motif-containing proteins, such as NDFIP1, to the WW domain disrupts the autoinhibited form of ITCH and enhances its catalytic activity.

Autoinhibitory domains (AIDs)

Target domain	548-903 (HECT domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment

AID

392-437 (WW2-WW3 linker region)

Target domain

548-903 (HECT domain)

Relief mechanism

Partner binding (PPxY motif-containing protein binding)

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Mund T et al. (2009) "Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins", EMBO reports, 10, 501-7

Wiesner S et al. (2007) "Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain", Cell, 130, 651-62

Tsunoda T et al. (2022) "ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer", EMBO reports, 23, e51182

Chen Z et al. (2017) "A Tunable Brake for HECT Ubiquitin Ligases", Molecular cell, 66, 345-357.e6

Autoinhibited structure

Activated structure

13 structures for Q96J02

Entry ID	Method	Resolution	Chain	Position	Source
2DMV	NMR	-	A	328-357	PDB
2KYK	NMR	-	A	359-392	PDB
2NQ3	X-ray	180 A	A	1-155	PDB
2P4R	X-ray	200 A	T	246-270	PDB
2YSF	NMR	-	A	480-512	PDB
3TUG	X-ray	227 A	A	524-903	PDB
4ROF	X-ray	203 A	A/B	436-474	PDB
5C7M	X-ray	303 A	A	524-899	PDB
5CQ2	X-ray	140 A	A	433-521	PDB
5DWS	X-ray	165 A	A/C/E/G	436-474	PDB
5DZD	X-ray	157 A	A/B	475-514	PDB
5SXP	X-ray	165 A	F/G	249-269	PDB
AF-Q96J02-F1	Predicted				AlphaFoldDB

435 variants for Q96J02

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001196864 rs2038572425	9	G>R	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
RCV000704773 rs373940007 CA9821235	28	K>R	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1978516186 RCV001228814	69	L>F	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
rs587776592 RCV000004641	132	I>missing	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
rs149625278 CA9821308 RCV000648215	156	C>Y	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1983332740 RCV001255428	243	L>missing	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
CA9821414 rs773997755 RCV000648211	273	S>A	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA9821839 RCV000706454 rs139633287 COSM577047	680	I>V	lung Syndromic multisystem autoimmune disease due to ITCH deficiency [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV001194604 rs1988702062	693	E>*	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
rs1381447036 RCV001255429	710	E>missing	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
rs1568998827 CA408672571 RCV001329453	793	W>*	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA408673194 rs1234261647 RCV000697503	804	R>S	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs767087220 CA9821975 RCV000695190	859	V>I	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1978326856 RCV001240180	902	Q>*	Syndromic multisystem autoimmune disease due to ITCH deficiency [ClinVar]	Yes	ClinVar dbSNP
rs1245034082 CA408660595	2	S>F		No	ClinGen gnomAD
rs764016207 CA9821207	4	S>G		No	ClinGen ExAC TOPMed gnomAD
CA408660611 rs1194377363	5	G>R		No	ClinGen TOPMed gnomAD
rs751414549 CA9821208	6	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1262792868 CA408660624	7	Q>*		No	ClinGen gnomAD
rs11552867 CA313391122	8	L>P		No	ClinGen TOPMed
rs11552867 CA408660634	8	L>R		No	ClinGen TOPMed
COSM4136840 rs567180261 CA9821211	11	M>I	ovary [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
rs767198019 CA9821210	11	M>V		No	ClinGen ExAC TOPMed gnomAD
CA9821212 rs755675723	12	G>D		No	ClinGen ExAC TOPMed gnomAD
rs940585949 CA313391161	13	S>G		No	ClinGen TOPMed
CA313391167 rs775405660	13	S>T		No	ClinGen Ensembl
CA9821214 rs753254646	15	T>I		No	ClinGen ExAC gnomAD
CA9821215 rs377431173	16	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs930283902 CA313391184	18	S>L		No	ClinGen Ensembl
CA408661213 rs1282807075	33	K>N		No	ClinGen gnomAD
rs879924656 CA313403971	33	K>R		No	ClinGen TOPMed gnomAD
CA408661223 rs1453654131	35	N>D		No	ClinGen gnomAD
CA9821237 rs781351779	43	V>I		No	ClinGen ExAC gnomAD
CA16603315 RCV000439717 rs1057520172	44	E>G		No	ClinGen ClinVar Ensembl dbSNP
CA313403981 rs998219387	45	V>I		No	ClinGen Ensembl
rs756349757 CA9821239	46	T>A		No	ClinGen ExAC gnomAD
rs1273914575 CA408661312	48	D>A		No	ClinGen gnomAD
CA9821241 rs749409829	49	G>E		No	ClinGen ExAC TOPMed
rs144293716 CA9821245	58	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1384700874 CA408661435	65	W>R		No	ClinGen TOPMed
CA9821250 rs759144696	66	K>E		No	ClinGen ExAC gnomAD
CA408661457 rs1396703645	68	P>T		No	ClinGen gnomAD
rs1351295729 CA408661479	71	V>A		No	ClinGen gnomAD
CA9821270 rs746815909	72	I>V		No	ClinGen ExAC gnomAD
rs776445457 CA9821272	73	V>I		No	ClinGen ExAC TOPMed gnomAD
CA408661525 rs1484852077	77	S>N		No	ClinGen gnomAD
CA313407659 rs564964052	80	H>Y		No	ClinGen TOPMed gnomAD
rs532322331 CA9821276	82	R>C		No	ClinGen ExAC TOPMed gnomAD
rs532322331 CA9821275	82	R>G		No	ClinGen ExAC TOPMed gnomAD
CA9821277 rs767950508 COSM3693445	82	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA408661582 rs1396445816	85	S>N		No	ClinGen gnomAD
rs991608301 CA313407678	94	L>S		No	ClinGen TOPMed
CA408661704 rs1158412425	103	Y>C		No	ClinGen gnomAD
rs766676602 CA9821280	105	T>A		No	ClinGen ExAC gnomAD
rs754067595 CA9821281	108	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1159695069 CA408661745	109	N>S		No	ClinGen TOPMed gnomAD
rs201149238 CA9821283	110	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9821282 rs574578082	110	N>Y		No	ClinGen 1000Genomes ExAC gnomAD
CA9821285 COSM1411293 rs199947085	113	L>F	ovary large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA313408767 rs998704134	115	E>V		No	ClinGen TOPMed
CA408661808 rs1339798251	116	V>E		No	ClinGen gnomAD
CA408661815 rs1601841346	117	V>A		No	ClinGen Ensembl
rs1174175667 CA408661810	117	V>I		No	ClinGen TOPMed
CA408661818 rs1274482221	118	V>L		No	ClinGen gnomAD
CA9821293 rs769621140	124	G>S		No	ClinGen ExAC gnomAD
rs775254034 CA9821294	125	D>Y		No	ClinGen ExAC gnomAD
CA9821295 rs762402155	126	K>E		No	ClinGen ExAC gnomAD
CA9821297 rs183893157	129	T>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs150122428 CA313408806	131	T>A		No	ClinGen ESP TOPMed
CA408661910 rs1474507113	132	I>T		No	ClinGen gnomAD
COSM1177843 rs138451400 CA9821300	137	I>V	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs759868750 CA9821301	140	D>N		No	ClinGen ExAC gnomAD
CA408661980 rs1179469441	143	Q>*		No	ClinGen TOPMed
CA408661986 rs1486359203	144	L>I		No	ClinGen TOPMed
rs202036043 CA9821304	145	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA9821305 rs764175154	146	S>C		No	ClinGen ExAC TOPMed
rs1262815311 CA408662008	147	E>A		No	ClinGen TOPMed
CA9821306 rs751456152	151	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1295009852 CA408662086	159	N>D		No	ClinGen gnomAD
RCV000202683 rs864309573 CA248882	159	N>I		No	ClinGen ClinVar TOPMed dbSNP gnomAD
rs1346700990 CA408662107	160	G>E		No	ClinGen TOPMed
CA408662109 rs1346700990	160	G>V		No	ClinGen TOPMed
CA408662119 rs1363501401	162	S>L		No	ClinGen TOPMed gnomAD
CA408662124 rs1300101952	163	L>F		No	ClinGen gnomAD
CA313411530 rs146558867	165	L>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9821324 rs146558867	165	L>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA408662144 rs1236882947	166	P>H		No	ClinGen TOPMed gnomAD
CA408662145 rs1236882947	166	P>R		No	ClinGen TOPMed gnomAD
CA408662142 rs1394583571	166	P>S		No	ClinGen TOPMed
rs1353617995 CA408662155	168	L>V		No	ClinGen gnomAD
CA408662169 rs1601849348	170	C>G		No	ClinGen Ensembl
CA408662179 rs1243898641	171	N>S		No	ClinGen gnomAD
rs1486207844 CA408662184	172	S>G		No	ClinGen gnomAD
rs1411775976 CA408662193	173	A>T		No	ClinGen gnomAD
rs1007090684 CA313411532	173	A>V		No	ClinGen gnomAD
rs989735759 CA408662202	174	I>M		No	ClinGen TOPMed gnomAD
CA313411549 rs1018522800	175	S>L		No	ClinGen TOPMed gnomAD
CA313411560 rs962670147	177	H>Q		No	ClinGen TOPMed gnomAD
rs962670147 CA408662220	177	H>Q		No	ClinGen TOPMed gnomAD
rs1156892976 CA408662216	177	H>Y		No	ClinGen TOPMed gnomAD
rs1354122064 CA408662224	178	C>Y		No	ClinGen gnomAD
rs1337089619 CA408662239	180	L>F		No	ClinGen gnomAD
CA408662240 rs1235906715	180	L>H		No	ClinGen TOPMed
CA408662243 rs1324654549	181	C>R		No	ClinGen TOPMed gnomAD
CA408662252 rs1368322596	182	L>F		No	ClinGen gnomAD
CA9821326 rs765532777	183	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1350469813 CA408662267	184	G>A		No	ClinGen gnomAD
rs1222448344 CA408662271	185	L>S		No	ClinGen gnomAD
rs1270310844 CA408662287	187	D>G		No	ClinGen TOPMed gnomAD
rs1215761563 CA408662283	187	D>N		No	ClinGen gnomAD
rs536848052 CA313411574	188	S>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs536848052 CA9821327	188	S>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9821328 rs763167918	189	P>L		No	ClinGen ExAC TOPMed gnomAD
CA408662302 rs1203917762	190	I>F		No	ClinGen TOPMed gnomAD
CA408662304 rs1245341249	190	I>T		No	ClinGen TOPMed gnomAD
rs1405492270 CA408662313	192	A>T		No	ClinGen TOPMed
CA313411582 rs937191688	194	R>*		No	ClinGen TOPMed gnomAD
rs530510456 CA408662327	194	R>L		No	ClinGen ExAC TOPMed gnomAD
rs530510456 CA9821329	194	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA408662331 rs1391275406	195	V>A		No	ClinGen TOPMed gnomAD
CA313411592 rs555052742	195	V>I		No	ClinGen 1000Genomes TOPMed
CA408662342 rs1469384042	197	G>E		No	ClinGen TOPMed
CA408662345 rs1253368266	198	F>I		No	ClinGen TOPMed gnomAD
rs1469390584 CA408662352	198	F>L		No	ClinGen gnomAD
rs1175293033 CA408662358	199	T>I		No	ClinGen TOPMed gnomAD
rs1410003355 CA408662361	200	G>C		No	ClinGen gnomAD
rs771526786 CA9821342	205	D>G		No	ClinGen ExAC gnomAD
CA313417187 rs373751787	206	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA9821345 rs770147109	208	S>F		No	ClinGen ExAC gnomAD
rs775987482 CA408662461	212	D>E		No	ClinGen ExAC TOPMed gnomAD
CA408662458 rs1274835131	212	D>G		No	ClinGen TOPMed gnomAD
rs763214263 CA9821347	214	T>A		No	ClinGen ExAC gnomAD
rs996268129 CA313417229	214	T>I		No	ClinGen TOPMed
rs112357913 CA313417234	215	R>K		No	ClinGen Ensembl
rs539049941 CA9821369	216	V>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs773485992 CA9821370	219	N>D		No	ClinGen ExAC TOPMed gnomAD
CA9821371 rs760820172	219	N>S		No	ClinGen ExAC gnomAD
CA9821372 rs766383556	220	G>V		No	ClinGen ExAC gnomAD
rs200506310 CA9821373	222	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA408662551 COSM443685 rs775855652	225	E>K	breast [Cosmic]	No	ClinGen cosmic curated Ensembl
CA313377588 rs775855652	225	E>Q		No	ClinGen Ensembl
CA313377591 rs1014076570	227	A>G		No	ClinGen Ensembl
rs1193862113 CA408662581	229	A>G		No	ClinGen TOPMed
CA9821374 rs759393619	229	A>T		No	ClinGen ExAC gnomAD
rs368544131 CA313377595	230	G>V		No	ClinGen ESP TOPMed gnomAD
rs904147573 CA313377598	232	N>D		No	ClinGen TOPMed
CA408662606 rs1439066122	233	R>S		No	ClinGen gnomAD
CA313377601 rs200246240	233	R>W		No	ClinGen 1000Genomes
CA9821375 rs764880325	235	V>I		No	ClinGen ExAC gnomAD
CA9821376 rs752347603	236	S>G		No	ClinGen ExAC gnomAD
rs1202637298 CA408662630	237	G>E		No	ClinGen TOPMed
rs758111695 CA9821377	238	N>S		No	ClinGen ExAC gnomAD
rs758111695 CA408662636	238	N>T		No	ClinGen ExAC gnomAD
rs1320855096 CA408662643	239	N>T		No	ClinGen TOPMed
rs777388999 CA9821378	242	S>L		No	ClinGen ExAC gnomAD
CA408662678 rs1601902200	245	N>D		No	ClinGen Ensembl
CA408662688 rs1568940667	246	G>D		No	ClinGen Ensembl
rs751119730 CA9821379	251	S>C		No	ClinGen ExAC TOPMed
rs751119730 CA313377616	251	S>Y		No	ClinGen ExAC TOPMed
CA313377621 rs540203213	253	P>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9821380 rs540203213	253	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA408662731 rs1601902249	253	P>T		No	ClinGen Ensembl
CA408662740 rs1268272734	255	R>G		No	ClinGen TOPMed gnomAD
CA313377627 rs567519259	257	S>L		No	ClinGen Ensembl
rs1191416990 CA408662760	258	R>Q		No	ClinGen TOPMed gnomAD
CA9821382 rs749700881	260	P>A		No	ClinGen ExAC gnomAD
rs769071760 CA9821383	260	P>L		No	ClinGen ExAC gnomAD
CA9821384 rs371486505	261	P>T		No	ClinGen ESP ExAC gnomAD
CA408662784 rs1284234404	263	T>P		No	ClinGen gnomAD
CA408662788 rs1362508663	263	T>S		No	ClinGen gnomAD
rs1391038915 CA408662794	264	P>R		No	ClinGen TOPMed
rs1468406753 CA408662792	264	P>T		No	ClinGen TOPMed
rs200896809 CA9821385	265	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9821386 rs772473360	265	R>H		No	ClinGen ExAC TOPMed gnomAD
rs1032936752 CA313377641	266	R>K		No	ClinGen TOPMed gnomAD
CA9821387 rs561908911	267	P>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs776638717 CA9821408	268	A>V		No	ClinGen ExAC gnomAD
rs769770717 CA9821410	269	S>P		No	ClinGen ExAC gnomAD
rs1294659184 CA408662875	270	V>A		No	ClinGen gnomAD
CA408662869 rs907332969	270	V>I		No	ClinGen gnomAD
CA313378279 rs907332969	270	V>L		No	ClinGen gnomAD
rs371132495 CA9821412	271	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9821413 rs763819793	272	G>R		No	ClinGen ExAC gnomAD
CA9821415 rs761441607	274	P>S		No	ClinGen ExAC gnomAD
CA313378309 rs752529180	275	S>C		No	ClinGen Ensembl
CA408662923 rs1190135864	275	S>P		No	ClinGen gnomAD
rs1190135864 CA408662922	275	S>T		No	ClinGen gnomAD
CA9821418 rs755622231	276	A>V		No	ClinGen ExAC gnomAD
rs532039837 CA313378316	277	T>A		No	ClinGen 1000Genomes
CA9821419 rs765880341	277	T>I		No	ClinGen ExAC gnomAD
rs145113977 CA9821420	280	S>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs758843309 CA9821421	281	D>V		No	ClinGen ExAC gnomAD
CA408662986 rs1375036470	281	D>Y		No	ClinGen gnomAD
CA9821422 rs372508275	284	S>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs1360707678 CA408663019	284	S>N		No	ClinGen TOPMed gnomAD
CA408663038 rs1412931492	285	T>I		No	ClinGen gnomAD
rs757476200 CA9821424	286	G>S		No	ClinGen ExAC gnomAD
CA408663059 rs1217397730	287	S>C		No	ClinGen TOPMed
rs781452901 CA9821425	288	L>M		No	ClinGen ExAC gnomAD
rs368353835 CA9821426	289	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9821427 rs368353835	289	P>R		No	ClinGen ExAC TOPMed gnomAD
rs370394645 CA9821429	290	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA408663100 rs1402966218	292	N>D		No	ClinGen TOPMed
rs774074894 CA9821433	295	T>I		No	ClinGen ExAC gnomAD
rs761649622 CA9821434	296	N>S		No	ClinGen ExAC TOPMed gnomAD
rs772884585 CA9821436	298	S>C		No	ClinGen ExAC gnomAD
CA408663169 rs1158381249	298	S>P		No	ClinGen TOPMed
rs1438164821 CA408663198	300	G>E		No	ClinGen TOPMed
rs1450388697 CA408663199	301	A>T		No	ClinGen gnomAD
rs1188964083 CA408663214	303	S>Y		No	ClinGen gnomAD
CA408663226 rs1432762671	305	L>S		No	ClinGen gnomAD
CA408663236 rs1178081069	306	I>M		No	ClinGen gnomAD
CA408663238 rs1568942945	307	I>V		No	ClinGen Ensembl
rs1359700819 CA408663250	309	L>F		No	ClinGen gnomAD
CA408663267 rs1286623983	311	I>M		No	ClinGen TOPMed gnomAD
CA9821438 rs765925331	311	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1217962253 CA408663269	312	S>P		No	ClinGen TOPMed
CA408663292 rs1600337834	316	G>S		No	ClinGen Ensembl
CA9821440 rs763618197	317	P>L		No	ClinGen ExAC gnomAD
rs753257483 CA9821439	317	P>T		No	ClinGen ExAC gnomAD
CA408663302 rs1237001990	318	R>G		No	ClinGen gnomAD
CA408663326 rs1436322882	321	N>S		No	ClinGen TOPMed gnomAD
CA9821444 rs200085579	322	P>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA313378408 rs1039152066	323	V>I		No	ClinGen TOPMed gnomAD
rs750609503 CA9821445	326	A>S		No	ClinGen ExAC gnomAD
rs866476099 CA313378434	329	P>S		No	ClinGen Ensembl
rs532597401 CA9821447	331	G>S		No	ClinGen 1000Genomes ExAC gnomAD
rs755013435 CA313379347	340	G>R		No	ClinGen ExAC TOPMed gnomAD
CA9821468 rs755013435	340	G>R		No	ClinGen ExAC TOPMed gnomAD
rs755013435 CA9821469	340	G>W		No	ClinGen ExAC TOPMed gnomAD
rs1398131570 CA408663466	341	R>*		No	ClinGen gnomAD
CA9821470 rs748065611	341	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs771764384 CA9821471	344	Y>C		No	ClinGen ExAC gnomAD
CA9821472 rs534969276	346	D>G		No	ClinGen 1000Genomes ExAC gnomAD
rs201610952 CA9821473	347	H>R		No	ClinGen 1000Genomes ExAC
CA408663510 rs1291575831	348	V>I		No	ClinGen TOPMed gnomAD
rs776390329 CA9821475	353	T>A		No	ClinGen ExAC gnomAD
CA408663587 rs1600344179	358	E>D		No	ClinGen Ensembl
rs888291691 CA313379392	359	P>R		No	ClinGen TOPMed gnomAD
rs1421783983 CA408663610	363	G>S		No	ClinGen TOPMed
rs1276445617 CA408663888	366	R>W		No	ClinGen gnomAD
CA408663893 rs1443603080	367	R>W		No	ClinGen gnomAD
CA9821540 rs765360878	368	V>A		No	ClinGen ExAC gnomAD
CA9821539 rs765360878	368	V>G		No	ClinGen ExAC gnomAD
CA9821541 rs758376235	370	N>D		No	ClinGen ExAC gnomAD
CA408663909 rs758376235	370	N>H		No	ClinGen ExAC gnomAD
CA9821542 rs375212186	371	M>R		No	ClinGen ESP ExAC gnomAD
CA9821543 rs368511233	372	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1391208087 CA408663931	373	R>C		No	ClinGen TOPMed gnomAD
rs1473065586 CA408663932	373	R>H		No	ClinGen TOPMed
CA408663937 rs1600353983	374	I>F		No	ClinGen Ensembl
rs1600354011 CA408663946	375	Y>F		No	ClinGen Ensembl
rs1017701577 CA313380838	376	Y>*		No	ClinGen TOPMed
CA408663965 rs1600354053	378	D>Y		No	ClinGen Ensembl
CA9821545 rs781067911	380	F>L		No	ClinGen ExAC gnomAD
CA9821547 rs557788946	384	T>A		No	ClinGen 1000Genomes ExAC gnomAD
CA408664012 rs1484279693	385	T>A		No	ClinGen TOPMed
rs1324908711 CA408664015	385	T>M		No	ClinGen gnomAD
rs1568949531 CA408664024	386	W>C		No	ClinGen Ensembl
rs1299519505 CA408664035	388	R>K		No	ClinGen gnomAD
CA9821551 rs778268568	391	L>P		No	ClinGen ExAC gnomAD
CA9821552 rs747452758	394	V>I		No	ClinGen ExAC TOPMed gnomAD
CA9821554 rs763307837	395	R>Q		No	ClinGen ExAC gnomAD
CA9821556 rs770092708	396	N>K		No	ClinGen ExAC gnomAD
rs1248279016 CA408664090	397	Y>C		No	ClinGen gnomAD
CA408664106 rs1261063793	399	Q>R		No	ClinGen TOPMed
rs1460138625 CA408664120	401	Q>E		No	ClinGen gnomAD
CA408664128 rs1600354449	402	L>V		No	ClinGen Ensembl
rs146383612 CA9821559	403	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs764257608 CA9821560	404	R>H		No	ClinGen ExAC gnomAD
rs767540080 CA408664225	415	N>K		No	ClinGen ExAC TOPMed gnomAD
rs767540080 CA9821562	415	N>K		No	ClinGen ExAC TOPMed gnomAD
CA408664266 rs1568949777	421	G>W		No	ClinGen Ensembl
rs750277686 CA9821584	425	L>V		No	ClinGen ExAC gnomAD
CA9821585 rs760529689	428	T>A		No	ClinGen ExAC gnomAD
CA9821586 rs766018655	429	S>P		No	ClinGen ExAC gnomAD
rs577228627 CA9821587	430	Q>H		No	ClinGen ExAC gnomAD
rs1424511962 CA408664589	430	Q>R		No	ClinGen TOPMed
rs1193052291 CA408664624	435	D>N		No	ClinGen TOPMed
rs1568953807 CA408664636	436	P>H		No	ClinGen Ensembl
CA9821588 rs754679059	437	L>F		No	ClinGen ExAC
CA313382604 rs146021135	439	P>L		No	ClinGen 1000Genomes
CA408664688 rs1422261364	445	E>K		No	ClinGen gnomAD
CA9821606 rs776343448	448	T>I		No	ClinGen ExAC gnomAD
CA408665665 rs1568963705	451	N>Y		No	ClinGen Ensembl
CA9821611 rs373086001	457	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1229642621 CA408665716	458	N>S		No	ClinGen TOPMed gnomAD
CA408665728 rs1303227309	460	N>H		No	ClinGen gnomAD
rs756637836 CA9821613	460	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1381771083 CA408665742	462	R>*		No	ClinGen TOPMed
rs780578824 CA9821614	462	R>Q		No	ClinGen ExAC gnomAD
rs1052275 CA313386733	464	T>I		No	ClinGen Ensembl
CA408665794 rs1207005752	469	P>L		No	ClinGen gnomAD
rs925126854 CA313386753	470	R>T		No	ClinGen Ensembl
CA408665828 rs1205282746	473	G>S		No	ClinGen TOPMed gnomAD
CA9821645 rs372589721	474	Q>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs770996522 CA9821646	478	K>E		No	ClinGen ExAC gnomAD
rs76412574 CA313389628	478	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA9821648 rs745740703	479	P>T		No	ClinGen ExAC gnomAD
rs1399431957 CA408666378	483	G>V		No	ClinGen gnomAD
rs150653226 CA9821651	486	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA9821652 rs768224067	492	G>R		No	ClinGen ExAC gnomAD
CA9821654 rs761241388	498	D>N		No	ClinGen ExAC TOPMed gnomAD
CA313389738 rs75849635	499	H>Q		No	ClinGen Ensembl
rs201066823 CA9821657	510	R>C		No	ClinGen ExAC gnomAD
COSM2758045 CA9821658 rs765813305	510	R>H	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1381633045 CA408666641	513	K>I		No	ClinGen TOPMed gnomAD
rs1229807297 CA408666670	516	L>Q		No	ClinGen gnomAD
rs1229807297 CA408666674	516	L>R		No	ClinGen gnomAD
CA408667927 rs1368117033	518	N>D		No	ClinGen gnomAD
rs754988422 CA9821708	518	N>S		No	ClinGen ExAC gnomAD
rs1161299955 CA408667975	525	V>I		No	ClinGen gnomAD
rs748002342 CA9821710	531	K>R		No	ClinGen ExAC gnomAD
rs1419626764 CA408668021	532	V>I		No	ClinGen gnomAD
rs1437229274 CA408668028	533	Q>E		No	ClinGen TOPMed
rs777586026 CA9821712	533	Q>L		No	ClinGen ExAC gnomAD
rs746597590 CA9821713	535	F>L		No	ClinGen ExAC TOPMed gnomAD
CA9821714 rs770706516 COSM3389695	536	R>Q	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA408668123 rs1244008169	544	M>I		No	ClinGen gnomAD
CA9821739 rs748720455	548	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1388247412 CA408668198	555	K>R		No	ClinGen gnomAD
rs201871783 CA313396641	556	T>A		No	ClinGen 1000Genomes
rs200841333 CA313396650	558	F>L		No	ClinGen 1000Genomes
CA313396667 rs200239748	562	F>L		No	ClinGen 1000Genomes
CA313396670 rs199703668	562	F>S		No	ClinGen 1000Genomes
rs1270291556 CA408669060	566	M>I		No	ClinGen gnomAD
CA408669066 rs1318436647	567	S>N		No	ClinGen gnomAD
rs746147850 CA9821767 COSM373050	569	S>C	lung [Cosmic]	No	ClinGen cosmic curated ExAC
rs1568987061 CA408669081	569	S>N		No	ClinGen Ensembl
CA9821768 rs770045595	570	P>S		No	ClinGen ExAC gnomAD
CA9821771 rs764160233	576	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9821772 rs774383028	576	R>H		No	ClinGen ExAC TOPMed gnomAD
rs553442220 CA313402459	578	W>*		No	ClinGen Ensembl
rs761682470 CA9821773	589	Y>C		No	ClinGen ExAC gnomAD
CA9821774 rs767281431	593	A>T		No	ClinGen ExAC gnomAD
CA313403818 rs113468730	601	S>P		No	ClinGen Ensembl
rs1202424060 CA408669457	604	V>L		No	ClinGen gnomAD
CA408669495 rs1470332162	609	Y>D		No	ClinGen gnomAD
rs1017017378 CA313403833	615	A>S		No	ClinGen TOPMed
CA408669545 rs1412015966	616	G>W		No	ClinGen gnomAD
rs778741830 CA313403835	617	K>N		No	ClinGen Ensembl
rs1164703162 CA408669560	618	D>G		No	ClinGen gnomAD
CA408669556 rs1446855829	618	D>N		No	ClinGen gnomAD
CA408669568 rs1372710627	619	N>I		No	ClinGen TOPMed
rs766038122 CA9821796	623	Q>*		No	ClinGen ExAC gnomAD
rs541577551 CA313403852	623	Q>P		No	ClinGen Ensembl
CA408669617 rs1303782556	626	P>A		No	ClinGen TOPMed
CA9821797 rs753429065	627	A>T		No	ClinGen ExAC TOPMed gnomAD
COSM94528 rs1600455770 CA408669642	630	I>V	lung [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1035218399 CA313403874	631	N>S		No	ClinGen TOPMed
CA313403883 rs899430276	633	D>H		No	ClinGen TOPMed
rs899430276 CA313403880	633	D>N		No	ClinGen TOPMed
rs752240722 CA9821800	634	H>N		No	ClinGen ExAC gnomAD
CA9821801 rs757758667	639	R>C		No	ClinGen ExAC gnomAD
COSM1210955 CA9821802 rs781704531	639	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs746251467 CA9821803	644	F>L		No	ClinGen ExAC TOPMed gnomAD
rs80241710 CA313403931	646	A>S		No	ClinGen Ensembl
rs755290439 CA9821824	651	H>R		No	ClinGen ExAC
rs7268389 CA313404782	656	D>V		No	ClinGen Ensembl
CA408669842 rs1445655265	657	T>M		No	ClinGen TOPMed gnomAD
rs777573141 CA9821829	663	F>L		No	ClinGen ExAC gnomAD
CA408669888 rs1431712264	664	Y>C		No	ClinGen gnomAD
rs1470454047 CA408669895	665	K>R		No	ClinGen gnomAD
rs770844266 CA9821830	666	R>C		No	ClinGen ExAC TOPMed gnomAD
rs776461109 CA9821831	666	R>H		No	ClinGen ExAC gnomAD
CA9821834 rs759300326	671	P>R		No	ClinGen ExAC TOPMed gnomAD
rs1346977440 CA408669942	672	V>A		No	ClinGen gnomAD
rs1199004609 CA408669940	672	V>F		No	ClinGen Ensembl
rs762383802 CA9821838	677	L>V		No	ClinGen ExAC gnomAD
CA9821840 rs754843646	682	P>T		No	ClinGen ExAC gnomAD
CA408670012 rs1388555664	683	E>Q		No	ClinGen TOPMed
rs1600458725 CA408670030	685	Y>S		No	ClinGen Ensembl
rs766959569 CA9821842	686	N>S		No	ClinGen ExAC TOPMed gnomAD
CA408670070 rs1480822794	691	V>I		No	ClinGen gnomAD
rs1269748222 CA408670121	696	I>V		No	ClinGen TOPMed
rs757281730 CA9821869	697	E>K		No	ClinGen ExAC gnomAD
rs756003451 CA9821872	703	M>I		No	ClinGen ExAC gnomAD
CA313405242 rs867531441	706	S>F		No	ClinGen Ensembl
rs544554436 CA9821873	707	V>I		No	ClinGen 1000Genomes ExAC gnomAD
rs1568990577 CA408670256	709	K>R		No	ClinGen Ensembl
CA9821877 rs747674768	712	L>V		No	ClinGen ExAC gnomAD
CA9821879 rs772840953	716	K>E		No	ClinGen ExAC gnomAD
CA313405321 rs1050912826	717	S>G		No	ClinGen Ensembl
CA9821880 rs760143427	723	N>D		No	ClinGen ExAC TOPMed gnomAD
rs760143427 CA408670454	723	N>H		No	ClinGen ExAC TOPMed gnomAD
CA408670492 rs1380919325	726	N>D		No	ClinGen TOPMed
rs1322957108 CA408670498	726	N>S		No	ClinGen TOPMed
CA408670519 rs1384159436	727	I>M		No	ClinGen TOPMed gnomAD
CA9821882 rs775965039	733	N>S		No	ClinGen ExAC
CA9821884 rs377380158	735	E>D		No	ClinGen ESP ExAC gnomAD
rs754583869 CA9821883	737	Y>*		No	ClinGen ExAC gnomAD
CA313405390 rs890924646	738	I>V		No	ClinGen gnomAD
rs6059862 CA313405392	739	R>K		No	ClinGen Ensembl
rs1423130941 CA408672107	745	R>S		No	ClinGen gnomAD
CA408672114 rs1600481512	746	L>V		No	ClinGen Ensembl
rs1202471507 CA408672148	747	S>C		No	ClinGen TOPMed
CA408672182 rs1264024151	752	E>D		No	ClinGen gnomAD
CA313411861 rs574083139	758	F>L		No	ClinGen 1000Genomes ExAC gnomAD
rs761198501 CA313411855	758	F>S		No	ClinGen TOPMed
CA9821910 rs750545876	761	F>L		No	ClinGen ExAC gnomAD
CA408672272 rs1205179942	765	L>I		No	ClinGen gnomAD
CA313411905 rs1020647092	770	L>F		No	ClinGen TOPMed gnomAD
CA408672318 rs1479186036	771	Q>R		No	ClinGen gnomAD
CA9821914 rs754934939	776	K>N		No	ClinGen ExAC gnomAD
rs1347434826 CA408672352	776	K>Q		No	ClinGen gnomAD
CA408672429 rs1354134511	785	M>V		No	ClinGen gnomAD
CA408672498 rs1300141397	789	D>G		No	ClinGen gnomAD
rs1398695748 CA408672491	789	D>N		No	ClinGen TOPMed
rs760812822 CA9821929	797	A>V		No	ClinGen ExAC gnomAD
rs766431630 CA9821930	798	I>T		No	ClinGen ExAC gnomAD
rs759593203 CA9821932 COSM1026033	800	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs762270452 CA313412418	801	H>Q		No	ClinGen Ensembl
rs752572940 CA9821934	803	A>G		No	ClinGen ExAC gnomAD
CA408673457 rs1569001011	815	F>L		No	ClinGen Ensembl
CA408673473 rs1242054294	817	K>E		No	ClinGen gnomAD
rs1474462069 CA408673478	817	K>T		No	ClinGen gnomAD
CA408673493 rs1569001040 COSM1026034	818	E>*	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1420460046 CA408673577	823	K>R		No	ClinGen gnomAD
CA408673723 rs1403585134	834	T>P		No	ClinGen gnomAD
rs368005062 CA9821950 COSM1641328	836	R>*	stomach [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
CA408673760 rs1428002854	836	R>L		No	ClinGen gnomAD
CA408673796 rs1480881406	839	V>L		No	ClinGen gnomAD
CA9821953 rs763866443	845	L>I		No	ClinGen ExAC gnomAD
rs1201953901 CA408673885	846	M>L		No	ClinGen gnomAD
CA9821972 rs575380764	849	N>S		No	ClinGen 1000Genomes ExAC gnomAD
CA9821973 rs374226560	856	I>V		No	ClinGen ESP ExAC gnomAD
CA9821974 rs761631321	858	K>N		No	ClinGen ExAC TOPMed gnomAD
CA9821976 rs750008016	864	W>R		No	ClinGen ExAC gnomAD
rs760312401 CA9821977	867	R>K		No	ClinGen ExAC gnomAD
rs1569013598 CA408663148	869	H>R		No	ClinGen Ensembl
rs1369656426 CA408663648 COSM214197	874	R>C	skin breast [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1457975002 COSM185702 CA408663649	874	R>H	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
CA408663656 rs1393954588	875	L>P		No	ClinGen gnomAD
rs1437705287 CA408663687	880	Y>F		No	ClinGen TOPMed
rs774298764 CA9821993	894	I>M		No	ClinGen ExAC gnomAD

1 associated diseases with Q96J02

[MIM: 613385]: Autoimmune disease, multisystem, with facial dysmorphism (ADMFD)

A disorder characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut. {ECO:0000269|PubMed:20170897}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A disorder characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut. {ECO:0000269|PubMed:20170897}. Note=The disease is caused by variants affecting the gene represented in this entry.

6 regional properties for Q96J02

Type	Name	Position	InterPro Accession
domain	C2 domain	1 - 115	IPR000008
domain	HECT domain	548 - 903	IPR000569
domain	WW domain	326 - 359	IPR001202-1
domain	WW domain	358 - 391	IPR001202-2
domain	WW domain	438 - 471	IPR001202-3
domain	WW domain	478 - 511	IPR001202-4

Functions

		Description
EC Number	2.3.2.26	Aminoacyltransferases
Subcellular Localization	Cell membrane ; Peripheral membrane protein ; Cytoplasmic side Cytoplasm Nucleus Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side Endosome membrane ; Peripheral membrane protein ; Cytoplasmic side	May be recruited to exosomes by NDFIP1 (PubMed:18819914) Localizes to plasma membrane upon CXCL12 stimulation where it co-localizes with CXCL4 (PubMed:14602072) Localization to early endosomes is increased upon CXCL12 stimulation where it co-localizes with DTX3L and CXCL4 (PubMed:24790097)
PANTHER Family	PTHR11254	HECT DOMAIN UBIQUITIN-PROTEIN LIGASE
PANTHER Subfamily	PTHR11254:SF66	E3 UBIQUITIN-PROTEIN LIGASE ITCHY HOMOLOG
PANTHER Protein Class	ubiquitin-protein ligase
PANTHER Pathway Category	Ubiquitin proteasome pathway E3

11 GO annotations of cellular component

Name	Definition
cell cortex	The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle	A vesicle found in the cytoplasm of a cell.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
early endosome membrane	The lipid bilayer surrounding an early endosome.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
intracellular membrane-bounded organelle	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

8 GO annotations of molecular function

Name	Definition
arrestin family protein binding	Binding to a member of the arrestin family, proteins involved in agonist-mediated desensitization of G protein-coupled receptors.
CXCR chemokine receptor binding	Binding to a chemokine receptor in the CXCR family.
ligase activity	Catalysis of the joining of two molecules, or two groups within a single molecule, using the energy from the hydrolysis of ATP, a similar triphosphate, or a pH gradient.
ribonucleoprotein complex binding	Binding to a complex of RNA and protein.
ubiquitin protein ligase activity	Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
ubiquitin-like protein ligase binding	Binding to a ubiquitin-like protein ligase, such as ubiquitin-ligase.
ubiquitin-like protein transferase activity	Catalysis of the transfer of a ubiquitin-like from one protein to another via the reaction X-ULP + Y --> Y-ULP + X, where both X-ULP and Y-ULP are covalent linkages. ULP represents a ubiquitin-like protein.
ubiquitin-protein transferase activity	Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.

26 GO annotations of biological process

Name	Definition
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
defense response to virus	Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
inflammatory response	The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
innate immune response	Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
negative regulation of alpha-beta T cell proliferation	Any process that stops, prevents, or reduces the frequency, rate or extent of alpha-beta T cell proliferation.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of defense response to virus	Any process that stops, prevents or reduces the rate or extent of antiviral mechanisms, thereby facilitating viral replication.
negative regulation of JNK cascade	Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the JNK cascade.
negative regulation of NF-kappaB transcription factor activity	Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of the transcription factor NF-kappaB.
negative regulation of type I interferon production	Any process that stops, prevents, or reduces the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
nucleotide-binding oligomerization domain containing signaling pathway	The series of molecular signals initiated by the binding of a ligand (such as a bacterial peptidoglycan) to a cytoplasmic nucleotide-binding oligomerization domain containing (NOD) protein receptor, and ending with regulation of a downstream cellular process.
positive regulation of protein catabolic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
positive regulation of receptor catabolic process	Any process that activates or increases the frequency, rate or extent of receptor catabolic process.
positive regulation of T cell anergy	Any process that activates or increases the frequency, rate, or extent of T cell anergy.
proteasome-mediated ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein autoubiquitination	The ubiquitination by a protein of one or more of its own amino acid residues, or residues on an identical protein. Ubiquitination occurs on the lysine residue by formation of an isopeptide crosslink.
protein K29-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 29 of the ubiquitin monomers, is added to a protein. K29-linked ubiquitination targets the substrate protein for degradation.
protein K48-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation.
protein K63-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair.
protein polyubiquitination	Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
regulation of cell growth	Any process that modulates the frequency, rate, extent or direction of cell growth.
regulation of hematopoietic stem cell differentiation	Any process that modulates the frequency, rate or extent of hematopoietic stem cell differentiation.
regulation of protein deubiquitination	Any process that modulates the frequency, rate or extent of protein deubiquitination. Protein deubiquitination is the removal of one or more ubiquitin groups from a protein.
ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.
viral entry into host cell	The process that occurs after viral attachment by which a virus, or viral nucleic acid, breaches the plasma membrane or cell envelope and enters the host cell. The process ends when the viral nucleic acid is released into the host cell cytoplasm.

23 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P39940	RSP5	E3 ubiquitin-protein ligase RSP5	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q9V853	Smurf	E3 ubiquitin-protein ligase Smurf1	Drosophila melanogaster (Fruit fly)	SS
Q9Y0H4	Su(dx)	E3 ubiquitin-protein ligase Su	Drosophila melanogaster (Fruit fly)	SS
O95817	BAG3	BAG family molecular chaperone regulator 3	Homo sapiens (Human)	PR
O60861	GAS7	Growth arrest-specific protein 7	Homo sapiens (Human)	PR
Q9HCE7	SMURF1	E3 ubiquitin-protein ligase SMURF1	Homo sapiens (Human)	PR
Q9HAU4	SMURF2	E3 ubiquitin-protein ligase SMURF2	Homo sapiens (Human)	EV
Q9H0M0	WWP1	NEDD4-like E3 ubiquitin-protein ligase WWP1	Homo sapiens (Human)	EV
O00308	WWP2	NEDD4-like E3 ubiquitin-protein ligase WWP2	Homo sapiens (Human)	EV
Q96PU5	NEDD4L	E3 ubiquitin-protein ligase NEDD4-like	Homo sapiens (Human)	PR
P46934	NEDD4	E3 ubiquitin-protein ligase NEDD4	Homo sapiens (Human)	EV
Q8IYU2	HACE1	E3 ubiquitin-protein ligase HACE1	Homo sapiens (Human)	EV
P46935	Nedd4	E3 ubiquitin-protein ligase NEDD4	Mus musculus (Mouse)	PR
Q9CUN6	Smurf1	E3 ubiquitin-protein ligase SMURF1	Mus musculus (Mouse)	PR
A2A5Z6	Smurf2	E3 ubiquitin-protein ligase SMURF2	Mus musculus (Mouse)	SS
Q8BZZ3	Wwp1	NEDD4-like E3 ubiquitin-protein ligase WWP1	Mus musculus (Mouse)	SS
Q60780	Gas7	Growth arrest-specific protein 7	Mus musculus (Mouse)	PR
Q9DBH0	Wwp2	NEDD4-like E3 ubiquitin-protein ligase WWP2	Mus musculus (Mouse)	SS
Q8CFI0	Nedd4l	E3 ubiquitin-protein ligase NEDD4-like	Mus musculus (Mouse)	PR
Q8C863	Itch	E3 ubiquitin-protein ligase Itchy	Mus musculus (Mouse)	EV
Q62940	Nedd4	E3 ubiquitin-protein ligase NEDD4	Rattus norvegicus (Rat)	PR
Q9N2Z7	wwp-1	E3 ubiquitin-protein ligase wwp-1	Caenorhabditis elegans	SS
A9JRZ0	smurf2	E3 ubiquitin-protein ligase SMURF2	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MSDSGSQLGS	MGSLTMKSQL	QITVISAKLK	ENKKNWFGPS	PYVEVTVDGQ	SKKTEKCNNT
70	80	90	100	110	120
NSPKWKQPLT	VIVTPVSKLH	FRVWSHQTLK	SDVLLGTAAL	DIYETLKSNN	MKLEEVVVTL
130	140	150	160	170	180
QLGGDKEPTE	TIGDLSICLD	GLQLESEVVT	NGETTCSENG	VSLCLPRLEC	NSAISAHCNL
190	200	210	220	230	240
CLPGLSDSPI	SASRVAGFTG	ASQNDDGSRS	KDETRVSTNG	SDDPEDAGAG	ENRRVSGNNS
250	260	270	280	290	300
PSLSNGGFKP	SRPPRPSRPP	PPTPRRPASV	NGSPSATSES	DGSSTGSLPP	TNTNTNTSEG
310	320	330	340	350	360
ATSGLIIPLT	ISGGSGPRPL	NPVTQAPLPP	GWEQRVDQHG	RVYYVDHVEK	RTTWDRPEPL
370	380	390	400	410	420
PPGWERRVDN	MGRIYYVDHF	TRTTTWQRPT	LESVRNYEQW	QLQRSQLQGA	MQQFNQRFIY
430	440	450	460	470	480
GNQDLFATSQ	SKEFDPLGPL	PPGWEKRTDS	NGRVYFVNHN	TRITQWEDPR	SQGQLNEKPL
490	500	510	520	530	540
PEGWEMRFTV	DGIPYFVDHN	RRTTTYIDPR	TGKSALDNGP	QIAYVRDFKA	KVQYFRFWCQ
550	560	570	580	590	600
QLAMPQHIKI	TVTRKTLFED	SFQQIMSFSP	QDLRRRLWVI	FPGEEGLDYG	GVAREWFFLL
610	620	630	640	650	660
SHEVLNPMYC	LFEYAGKDNY	CLQINPASYI	NPDHLKYFRF	IGRFIAMALF	HGKFIDTGFS
670	680	690	700	710	720
LPFYKRILNK	PVGLKDLESI	DPEFYNSLIW	VKENNIEECD	LEMYFSVDKE	ILGEIKSHDL
730	740	750	760	770	780
KPNGGNILVT	EENKEEYIRM	VAEWRLSRGV	EEQTQAFFEG	FNEILPQQYL	QYFDAKELEV
790	800	810	820	830	840
LLCGMQEIDL	NDWQRHAIYR	HYARTSKQIM	WFWQFVKEID	NEKRMRLLQF	VTGTCRLPVG
850	860	870	880	890	900
GFADLMGSNG	PQKFCIEKVG	KENWLPRSHT	CFNRLDLPPY	KSYEQLKEKL	LFAIEETEGF

GQE