AiPD: Autoinhibited Protein Database

Q9Y4K3

Gene name	TRAF6 (RNF85)
Protein name	TNF receptor-associated factor 6
Names	E3 ubiquitin-protein ligase TRAF6, Interleukin-1 signal transducer, RING finger protein 85, RING-type E3 ubiquitin transferase TRAF6
Species	Homo sapiens (Human)
KEGG Pathway	hsa:7189
EC number	2.3.2.27: Aminoacyltransferases
Protein Class	TNF RECEPTOR ASSOCIATED FACTOR (PTHR10131)

Descriptions

The Tumor Necrosis Factor (TNF) Receptor Associated Factor (TRAF) class of intracellular signal transducers is responsible for mediating many of the activation events initiated by TNF receptor (TNFR) and Toll-like/Interleukin-1, 17 and 18 receptor (TIR) families. These receptors can, both directly and indirectly, activate TRAF6 via specific binding of proteins containing TRAF Interacting Motif (TIM) peptides to a groove on the carboxyl-terminal MATH domain.
TRAF6 is autoinhibited by an intramolecular interaction between the RING-Zinc (RZ) region and MATH domain. The interaction renders TRAF6 inactive and structurally closed, as well as incapable of auto-ubiquitination. RING-Zinc fingers region and the MATH domain are targets for ubiquitination. TRAF autoubiquitination in trans is a means of sustaining an open conformation active in downstream signaling.

Autoinhibitory domains (AIDs)

Target domain	70-273 (RZ domain)
Relief mechanism	Partner binding
Assay	Deletion assay

AID

346-522 (MATH domain)

Target domain

70-273 (RZ domain)

Relief mechanism

Partner binding (Binding of TNFR or TIR to MATH domain)

Assay

Deletion assay

Accessory elements

No accessory elements

References

Wang KZ et al. (2010) "TRAF6 is autoinhibited by an intramolecular interaction which is counteracted by trans-ubiquitination", Journal of cellular biochemistry, 110, 763-71

Autoinhibited structure

Activated structure

14 structures for Q9Y4K3

Entry ID	Method	Resolution	Chain	Position	Source
1LB4	X-ray	240 A	A	348-504	PDB
1LB5	X-ray	240 A	A	347-504	PDB
1LB6	X-ray	180 A	A	347-504	PDB
2ECI	NMR	-	A	50-128	PDB
2JMD	NMR	-	A	67-124	PDB
3HCS	X-ray	220 A	A/B	50-211	PDB
3HCT	X-ray	210 A	A	50-159	PDB
3HCU	X-ray	260 A	A/C	50-159	PDB
4Z8M	X-ray	295 A	A/B	346-504	PDB
5ZUJ	X-ray	260 A	A	350-501	PDB
6A33	X-ray	210 A	A	350-501	PDB
7L3L	X-ray	280 A	B/D	52-158	PDB
8HZ2	X-ray	260 A	A/B	54-210	PDB
AF-Q9Y4K3-F1	Predicted				AlphaFoldDB

244 variants for Q9Y4K3

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA5949866 rs547082469	11	G>V		No	ClinGen 1000Genomes ExAC gnomAD
rs17852887 CA220595446	12	S>F		No	ClinGen Ensembl
rs748986045 CA5949865	12	S>P		No	ClinGen ExAC gnomAD
CA380149131 rs1418472079	13	S>R		No	ClinGen gnomAD
CA5949863 rs769322740	17	S>N		No	ClinGen ExAC gnomAD
rs1453088768 CA380149077	18	D>E		No	ClinGen TOPMed
CA380149049 rs1314159296	20	C>Y		No	ClinGen TOPMed
CA5949861 rs747559755	23	M>V		No	ClinGen ExAC gnomAD
CA220595424 rs765097739	28	S>R		No	ClinGen ExAC TOPMed gnomAD
CA5949857 rs370057355	29	A>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949858 rs370057355	29	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1357823611 CA380148914	29	A>V		No	ClinGen Ensembl
CA380148903 rs1379813834	30	V>A		No	ClinGen gnomAD
rs1418393714 CA380148911	30	V>I		No	ClinGen TOPMed gnomAD
rs1418393714 CA380148909	30	V>L		No	ClinGen TOPMed gnomAD
CA5949856 rs780618300	31	T>I		No	ClinGen ExAC gnomAD
CA380148887 rs1421138534	32	K>E		No	ClinGen gnomAD
CA220595406 rs76605445	33	D>A		No	ClinGen Ensembl
rs76605445 CA220595404	33	D>G		No	ClinGen Ensembl
rs758804620 CA5949855	35	S>N		No	ClinGen ExAC TOPMed gnomAD
rs750708011 CA5949854	36	V>M		No	ClinGen ExAC gnomAD
CA380148799 rs1259355702	38	G>R		No	ClinGen gnomAD
CA5949853 rs779230479	41	S>N		No	ClinGen ExAC gnomAD
rs759328711 CA220595397	42	T>M		No	ClinGen TOPMed gnomAD
rs753791639 CA5949851	43	G>R		No	ClinGen ExAC TOPMed gnomAD
CA220595386 rs1031359230	44	N>S		No	ClinGen TOPMed
CA5949849 rs759449231	45	L>F		No	ClinGen ExAC gnomAD
rs751488547 CA5949848	46	S>A		No	ClinGen ExAC
rs1294385877 CA380148698	46	S>F		No	ClinGen Ensembl
CA380148669 rs1311497253	49	F>L		No	ClinGen gnomAD
CA380148641 rs1373018587	50	M>I		No	ClinGen TOPMed
CA5949847 rs766198008	50	M>T		No	ClinGen ExAC TOPMed gnomAD
rs1590642478 CA380148630	51	E>G		No	ClinGen Ensembl
rs998647138 CA220595370	52	E>D		No	ClinGen TOPMed
rs904321355 CA220595367	53	I>N		No	ClinGen gnomAD
rs772870667 CA5949845	58	V>A		No	ClinGen ExAC gnomAD
CA380148536 rs1179758607	58	V>I		No	ClinGen gnomAD
rs1353605695 CA380148488	61	D>G		No	ClinGen Ensembl
CA380148352 rs1455356924	71	P>A		No	ClinGen gnomAD
rs199552714 COSM3769288 CA5949843	83	T>M	pancreas [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC
rs1564968169 CA380148190	84	P>L		No	ClinGen Ensembl
rs1263751287 CA380148119	91	K>R		No	ClinGen gnomAD
CA380148101 rs1590642358	94	I>V		No	ClinGen Ensembl
CA5949839 rs34320471	95	I>L		No	ClinGen ExAC TOPMed gnomAD
CA220595329 rs1019670034	97	S>*		No	ClinGen TOPMed
CA380148066 rs1325843053	99	R>K		No	ClinGen TOPMed
CA380148040 rs1169399583	101	A>S		No	ClinGen gnomAD
rs368077395 CA5949820	109	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs774914488 CA380147963	112	L>V		No	ClinGen ExAC gnomAD
rs552722556 CA5949817	116	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA5949818 rs771304757	116	Q>K		No	ClinGen ExAC TOPMed gnomAD
rs1564967420 CA380147914	119	P>R		No	ClinGen Ensembl
CA5949814 COSM1268460 rs748164490	121	N>S	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs945331121 CA220594203	125	R>C		No	ClinGen gnomAD
rs781247915 CA5949813	127	I>V		No	ClinGen ExAC gnomAD
rs1255863441 CA380147846	129	S>C		No	ClinGen gnomAD
rs758390119 CA380147838	131	M>L		No	ClinGen ExAC gnomAD
CA5949812 rs758390119	131	M>V		No	ClinGen ExAC gnomAD
CA5949811 rs750341857	133	K>I		No	ClinGen ExAC gnomAD
CA5949810 rs764984865	135	P>A		No	ClinGen ExAC gnomAD
rs757037041 CA5949809	140	L>F		No	ClinGen ExAC gnomAD
CA380147760 rs1448050815	141	H>Q		No	ClinGen TOPMed
rs915337241 CA220594191	144	E>K		No	ClinGen Ensembl
CA5949786 rs763790387	152	Q>E		No	ClinGen ExAC gnomAD
rs763790387 CA380147513	152	Q>K		No	ClinGen ExAC gnomAD
CA220593597 rs963936751	153	A>T		No	ClinGen Ensembl
rs1479680091 CA380147502	154	H>Y		No	ClinGen TOPMed
rs184872313 CA5949784	155	C>S		No	ClinGen 1000Genomes ExAC gnomAD
rs767175873 CA5949783	156	E>G		No	ClinGen ExAC gnomAD
CA380147467 rs1293716205	158	A>V		No	ClinGen gnomAD
rs759073172 CA5949782	159	L>F		No	ClinGen ExAC TOPMed gnomAD
rs145863131 CA5949781	160	M>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA220593563 rs950811873	161	D>N		No	ClinGen TOPMed gnomAD
rs1186118901 CA380147435	163	P>L		No	ClinGen TOPMed
CA380147436 rs1564966938	163	P>S		No	ClinGen Ensembl
CA380147412 rs1429532893	166	Q>R		No	ClinGen TOPMed
rs374431321 CA5949778	167	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs577802750 CA220593546	167	R>H		No	ClinGen TOPMed gnomAD
rs75433098 CA220593542	169	F>L		No	ClinGen Ensembl
CA220593535 rs74830764	170	Q>P		No	ClinGen Ensembl
rs1394703667 CA380147364	173	H>R		No	ClinGen gnomAD
rs762066204 CA5949776	174	I>V		No	ClinGen ExAC gnomAD
CA380147342 rs1324774737	176	I>S		No	ClinGen gnomAD
rs768746489 CA5949774	176	I>V		No	ClinGen ExAC TOPMed gnomAD
rs778722636 CA5949772	181	D>A		No	ClinGen ExAC gnomAD
rs777671341 CA5949769	186	Q>H		No	ClinGen ExAC gnomAD
CA220593518 rs202213842	187	V>A		No	ClinGen 1000Genomes
CA220593513 rs1047107972	188	S>Y		No	ClinGen TOPMed
CA380147247 rs1388994498	190	D>V		No	ClinGen gnomAD
CA380147242 rs1215343595	191	N>Y		No	ClinGen gnomAD
rs752427799 CA5949767	192	C>Y		No	ClinGen ExAC gnomAD
rs780939272 CA5949766	194	A>S		No	ClinGen ExAC gnomAD
rs780939272 CA380147223	194	A>T		No	ClinGen ExAC gnomAD
rs754545305 CA5949765	194	A>V		No	ClinGen ExAC gnomAD
CA380147217 rs1272594739	195	S>P		No	ClinGen gnomAD
CA5949763 rs765799965	196	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1466495606 CA380147201	197	A>E		No	ClinGen gnomAD
rs763566105 CA5949762	197	A>P		No	ClinGen ExAC TOPMed gnomAD
rs763566105 CA380147203	197	A>S		No	ClinGen ExAC TOPMed gnomAD
rs370394325 CA5949747	203	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA220592444 rs146832696	203	I>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949748 rs146832696	203	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1005252014 CA220592445	203	I>V		No	ClinGen gnomAD
rs145105758 CA5949746	206	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA380146965 rs1434629204	210	L>S		No	ClinGen gnomAD
CA380146949 rs1175565773	211	A>V		No	ClinGen gnomAD
rs148861693 COSM926727 CA5949744	212	N>S	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
COSM1507898 rs765675724 CA5949742	219	N>S	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA380146839 rs1325739918	221	I>T		No	ClinGen gnomAD
rs200882261 CA5949741	221	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA380146825 rs1210133922	223	I>V		No	ClinGen gnomAD
rs754269736 CA5949740	225	E>K		No	ClinGen ExAC TOPMed gnomAD
rs754269736 CA380146807	225	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA5949720 rs756392662	227	M>I		No	ClinGen ExAC gnomAD
rs752986438 CA5949719	228	P>S		No	ClinGen ExAC gnomAD
rs767573599 CA5949718	233	L>V		No	ClinGen ExAC TOPMed gnomAD
CA380146043 rs1291857212	234	D>V		No	ClinGen gnomAD
CA5949717 rs759661560	235	C>F		No	ClinGen ExAC gnomAD
rs1356662734 CA380146017	236	P>R		No	ClinGen gnomAD
CA380146005 rs1365384154	238	A>T		No	ClinGen TOPMed
rs1295724464 CA380145981	240	I>V		No	ClinGen gnomAD
rs774636689 CA5949716	241	P>L		No	ClinGen ExAC TOPMed gnomAD
rs377030527 CA5949715	245	S>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949714 rs376945338	247	F>S		No	ClinGen ESP ExAC gnomAD
rs1477427444 CA380145893	248	G>D		No	ClinGen gnomAD
CA5949713 rs776672755	248	G>R		No	ClinGen ExAC
CA380145860 rs1455564718	251	E>K		No	ClinGen gnomAD
CA380145850 rs1305709407	252	K>E		No	ClinGen TOPMed
rs1375802941 CA380145844	252	K>R		No	ClinGen TOPMed gnomAD
rs775208286 CA5949686	253	M>I		No	ClinGen ExAC gnomAD
rs760658124 CA5949687	253	M>V		No	ClinGen ExAC gnomAD
rs1255316683 CA380145633	259	A>S		No	ClinGen gnomAD
CA380145624 rs771879519	260	R>C		No	ClinGen ExAC TOPMed gnomAD
CA5949685 rs771879519	260	R>S		No	ClinGen ExAC TOPMed gnomAD
rs759228997 CA5949684	262	L>Q		No	ClinGen ExAC gnomAD
rs1590634108 CA380145522	269	H>N		No	ClinGen Ensembl
CA5949683 rs773951368	270	M>I		No	ClinGen ExAC gnomAD
CA220590001 rs963487647	273	L>F		No	ClinGen TOPMed
CA380145413 rs1441975568	278	H>D		No	ClinGen gnomAD
CA380145409 rs1441975568	278	H>N		No	ClinGen gnomAD
CA220589990 rs55840758	279	S>N		No	ClinGen Ensembl
rs1397134360 CA380145346	282	V>D		No	ClinGen gnomAD
CA5949680 rs376933557	282	V>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949679 rs376933557	282	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949678 rs748672638	283	I>M		No	ClinGen ExAC TOPMed gnomAD
rs1169635412 CA380145329	283	I>T		No	ClinGen gnomAD
CA380145305 rs1173673453	284	P>R		No	ClinGen gnomAD
CA5949677 rs781456089	284	P>T		No	ClinGen ExAC gnomAD
rs1158440319 CA380145290	285	D>G		No	ClinGen TOPMed
CA5949675 rs751855450	285	D>N		No	ClinGen ExAC gnomAD
CA5949674 rs147645716	286	S>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949673 rs758560289	287	G>E		No	ClinGen ExAC gnomAD
rs900697253 CA220589921	288	Y>C		No	ClinGen TOPMed
CA5949672 rs750597806	288	Y>H		No	ClinGen ExAC gnomAD
rs1207985971 COSM3700062 CA5949670	289	I>V	liver [Cosmic]	No	ClinGen cosmic curated gnomAD
CA380145197 COSM1507899 rs1279744976	292	V>F	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
CA5949668 rs78639425	293	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA220589887 rs776312804	293	R>W		No	ClinGen Ensembl
CA380145157 rs1277936375	294	N>H		No	ClinGen gnomAD
CA380145081 rs1165511778	298	T>S		No	ClinGen Ensembl
CA5949666 rs767244798	299	I>V		No	ClinGen ExAC gnomAD
rs759276140 CA5949665	300	H>Q		No	ClinGen ExAC gnomAD
CA380145025 rs1412886563	301	Q>R		No	ClinGen gnomAD
CA5949663 rs770500483	314	R>W		No	ClinGen ExAC gnomAD
rs762588981 CA5949662	321	E>Q		No	ClinGen ExAC gnomAD
rs1157696222 CA380144719	324	S>N		No	ClinGen TOPMed gnomAD
rs1157696222 CA380144717	324	S>T		No	ClinGen TOPMed gnomAD
rs145275891 CA5949660	325	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs145275891 CA5949659	325	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1470296867 CA380144709	325	M>V		No	ClinGen TOPMed gnomAD
rs1184735808 CA380144691	326	Y>C		No	ClinGen gnomAD
rs780561325 COSM1230215 CA5949655	332	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA5949654 rs535909443	333	T>N		No	ClinGen ExAC gnomAD
CA220589778 rs535909443	333	T>S		No	ClinGen ExAC gnomAD
CA5949652 rs778902552	334	I>V		No	ClinGen ExAC gnomAD
rs1351619329 COSM285912 CA380144598	335	R>*	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1351619329 CA380144600	335	R>G		No	ClinGen gnomAD
CA380144574 rs1231164368	337	L>F		No	ClinGen gnomAD
CA380144565 rs1354747764	338	E>K		No	ClinGen TOPMed gnomAD
CA380144536 rs1293903033	340	K>E		No	ClinGen TOPMed gnomAD
CA5949650 rs752595856	341	V>I		No	ClinGen ExAC gnomAD
rs1342978071 CA380144511	342	A>P		No	ClinGen gnomAD
rs1400964751 CA380144479	344	I>M		No	ClinGen TOPMed gnomAD
CA380144485 rs1440580411	344	I>N		No	ClinGen TOPMed
rs147417401 CA5949649	344	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949647 rs751422527	350	N>D		No	ClinGen ExAC gnomAD
CA5949646 rs766148455	350	N>S		No	ClinGen ExAC TOPMed gnomAD
CA5949645 rs762641979	353	Y>S		No	ClinGen ExAC gnomAD
CA380144294 rs1286505713	358	G>V		No	ClinGen gnomAD
rs761330797 CA5949642	359	N>S		No	ClinGen ExAC gnomAD
CA5949641 rs376266610	361	G>R		No	ClinGen ExAC TOPMed
rs747509379 CA5949638	362	M>I		No	ClinGen ExAC TOPMed gnomAD
rs148751232 CA5949639	362	M>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA380144233 rs1447813072	363	H>Y		No	ClinGen gnomAD
rs776049763 CA5949637	364	L>W		No	ClinGen ExAC gnomAD
CA5949635 rs746111041 COSM428952	369	E>K	kidney breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA380143990 rs1401987236	381	Y>H		No	ClinGen TOPMed
CA380143858 rs1564964638	391	M>L		No	ClinGen Ensembl
CA380143783 rs1183306064	396	Q>P		No	ClinGen Ensembl
rs1394252847 CA380143722	401	Q>R		No	ClinGen TOPMed gnomAD
rs548543739 CA5949628	402	R>C		No	ClinGen 1000Genomes ExAC gnomAD
rs199830912 CA5949627	402	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1417916854 CA380143648	406	Y>C		No	ClinGen gnomAD
rs1299539710 CA380143630	407	I>M		No	ClinGen gnomAD
rs1475820971 CA380143520	417	E>K		No	ClinGen TOPMed gnomAD
rs1475820971 CA380143518	417	E>Q		No	ClinGen TOPMed gnomAD
rs916447705 CA380143473	420	S>N		No	ClinGen TOPMed gnomAD
rs761368102 CA5949624	420	S>R		No	ClinGen ExAC TOPMed gnomAD
rs916447705 CA220589614	420	S>T		No	ClinGen TOPMed gnomAD
CA380143455 rs1413660417	422	L>I		No	ClinGen TOPMed
rs1223436642 CA380143447	422	L>P		No	ClinGen gnomAD
CA380143437 rs1564964595	423	P>S		No	ClinGen Ensembl
rs1162144803 CA380143380	427	Q>L		No	ClinGen TOPMed
CA5949623 rs776263136	430	I>V		No	ClinGen ExAC gnomAD
CA380143339 rs1343753001	431	R>C		No	ClinGen gnomAD
rs200661146 CA5949622	434	I>V		No	ClinGen 1000Genomes ExAC gnomAD
rs749812433 CA220589592	439	E>A		No	ClinGen Ensembl
rs1437970764 CA380143240	439	E>Q		No	ClinGen Ensembl
rs776102924 COSM1507900 CA5949620	442	V>L	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA380143186 rs1327006408	443	R>K		No	ClinGen gnomAD
CA380143101 rs1353116587	449	I>V		No	ClinGen gnomAD
CA5949618 rs746183280	452	A>T		No	ClinGen ExAC gnomAD
CA380143032 rs1410994328	454	P>A		No	ClinGen gnomAD
CA5949617 rs774438696	455	E>K		No	ClinGen ExAC gnomAD
CA5949615 rs749457723	461	R>Q		No	ClinGen ExAC gnomAD
CA220589540 rs773499691	463	T>A		No	ClinGen gnomAD
CA220589535 rs942112506	463	T>I		No	ClinGen TOPMed
CA380142906 rs1479576702	465	P>A		No	ClinGen gnomAD
rs1378303413 COSM73056 CA380142894	466	R>W	ovary [Cosmic]	No	ClinGen cosmic curated TOPMed
rs746978261 CA5949612	482	L>I		No	ClinGen ExAC TOPMed gnomAD
rs779910368 CA380141698	492	T>I		No	ClinGen ExAC gnomAD
rs779910368 CA5949611	492	T>K		No	ClinGen ExAC gnomAD
CA380141651 rs1249361694	496	R>H		No	ClinGen Ensembl
CA5949607 rs756987677	502	R>H		No	ClinGen ExAC TOPMed gnomAD
CA380141526 rs1211229906	505	M>I		No	ClinGen TOPMed
rs753514303 CA5949606	505	M>V		No	ClinGen ExAC gnomAD
CA380141515 rs1434112138	506	G>D		No	ClinGen gnomAD
rs58304191 CA5949605	507	S>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA220589483 rs950725856	518	T>S		No	ClinGen TOPMed gnomAD
CA5949602 rs138175660	519	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA5949603 rs372550520	519	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1030321317 CA220589441	521	G>R		No	ClinGen TOPMed
CA5949601 rs759952168	522	V>L		No	ClinGen ExAC TOPMed gnomAD
CA5949600 rs774832063	523	V>Q		No	ClinGen ExAC gnomAD

No associated diseases with Q9Y4K3

8 regional properties for Q9Y4K3

Type	Name	Position	InterPro Accession
domain	Zinc finger, TRAF-type	151 - 192	IPR001293-1
domain	Zinc finger, TRAF-type	204 - 261	IPR001293-2
domain	Zinc finger, RING-type	70 - 109	IPR001841
domain	MATH/TRAF domain	350 - 499	IPR002083
conserved_site	Zinc finger, RING-type, conserved site	85 - 94	IPR017907
domain	TNF receptor-associated factor 6, C3HC3D-type RING zinc finger	67 - 124	IPR027139
domain	TNF receptor-associated factor 6, MATH domain	351 - 500	IPR037309
domain	TNF receptor-associated factor 6, zinc finger 2	157 - 183	IPR041310

Functions

		Description
EC Number	2.3.2.27	Aminoacyltransferases
Subcellular Localization	Cytoplasm Cytoplasm, cell cortex Nucleus Lipid droplet	Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes Found in punctate nuclear body protein complexes Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus RSAD2/viperin recruits it to the lipid droplet (By similarity)
PANTHER Family	PTHR10131	TNF RECEPTOR ASSOCIATED FACTOR
PANTHER Subfamily	PTHR10131:SF131	TNF RECEPTOR-ASSOCIATED FACTOR 6
PANTHER Protein Class	scaffold/adaptor protein
PANTHER Pathway Category	CCKR signaling map TRAF6 p38 MAPK pathway TRAF6 Toll receptor signaling pathway TRAF6

11 GO annotations of cellular component

Name	Definition
CD40 receptor complex	A protein complex that contains at least CD40 (a cell surface receptor of the tumour necrosis factor receptor (TNFR) superfamily), and other signaling molecules.
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 side of plasma membrane	The leaflet the plasma membrane that faces the cytoplasm and any proteins embedded or anchored in it or attached to its surface.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endosome membrane	The lipid bilayer surrounding an endosome.
lipid droplet	An intracellular non-membrane-bounded organelle comprising a matrix of coalesced lipids surrounded by a phospholipid monolayer. May include associated proteins.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.
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.

14 GO annotations of molecular function

Name	Definition
histone deacetylase binding	Binding to histone deacetylase.
identical protein binding	Binding to an identical protein or proteins.
mitogen-activated protein kinase kinase kinase binding	Binding to a mitogen-activated protein kinase kinase kinase, a protein that can phosphorylate a MAP kinase kinase.
protein kinase B binding	Binding to protein kinase B, an intracellular kinase that is important in regulating glucose metabolism.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein N-terminus binding	Binding to a protein N-terminus, the end of any peptide chain at which the 2-amino (or 2-imino) function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
thioesterase binding	Binding to a thioesterase.
tumor necrosis factor receptor binding	Binding to a tumor necrosis factor receptor.
tumor necrosis factor receptor superfamily binding	Binding to a member of the tumor necrosis factor receptor superfamily.
ubiquitin conjugating enzyme binding	Binding to a ubiquitin conjugating enzyme, any of the E2 proteins.
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 protein ligase binding	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
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.
zinc ion binding	Binding to a zinc ion (Zn).

50 GO annotations of biological process

Name	Definition
activation of NF-kappaB-inducing kinase activity	The stimulation of the activity of NF-kappaB-inducing kinase through phosphorylation at specific residues.
activation of protein kinase activity	Any process that initiates the activity of an inactive protein kinase.
antigen processing and presentation of exogenous peptide antigen via MHC class II	The process in which an antigen-presenting cell expresses a peptide antigen of exogenous origin on its cell surface in association with an MHC class II protein complex. The peptide antigen is typically, but not always, processed from a whole protein.
bone resorption	The process in which specialized cells known as osteoclasts degrade the organic and inorganic portions of bone, and endocytose and transport the degradation products.
cell development	The process whose specific outcome is the progression of the cell over time, from its formation to the mature structure. Cell development does not include the steps involved in committing a cell to a specific fate.
cellular response to cytokine stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus.
cellular response to DNA damage stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to lipopolysaccharide	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cytoplasmic pattern recognition receptor signaling pathway	The series of molecular signals initiated by a ligand binding to a cytoplasmic pattern recognition receptor (PRR). PRRs bind pathogen-associated molecular pattern (PAMPs), structures conserved among microbial species.
Fc-epsilon receptor signaling pathway	The series of molecular signals initiated by the binding of the Fc portion of immunoglobulin E (IgE) to an Fc-epsilon receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. The Fc portion of an immunoglobulin is its C-terminal constant region.
I-kappaB kinase/NF-kappaB signaling	The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
in utero embryonic development	The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus.
interleukin-1-mediated signaling pathway	The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
interleukin-17-mediated signaling pathway	The series of molecular signals initiated by interleukin-17 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
MyD88-dependent toll-like receptor signaling pathway	A toll-like receptor signaling pathway in which the MyD88 adaptor molecule mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response.
myeloid dendritic cell differentiation	The process in which a monocyte acquires the specialized features of a dendritic cell, an immunocompetent cell of the lymphoid and hemopoietic systems and skin.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
negative regulation of transcription, DNA-templated	Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
neural tube closure	The last step in the formation of the neural tube, where the paired neural folds are brought together and fuse at the dorsal midline.
odontogenesis of dentin-containing tooth	The process whose specific outcome is the progression of a dentin-containing tooth over time, from its formation to the mature structure. A dentin-containing tooth is a hard, bony organ borne on the jaw or other bone of a vertebrate, and is composed mainly of dentin, a dense calcified substance, covered by a layer of enamel.
ossification	The formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance.
osteoclast differentiation	The process in which a relatively unspecialized monocyte acquires the specialized features of an osteoclast. An osteoclast is a specialized phagocytic cell associated with the absorption and removal of the mineralized matrix of bone tissue.
positive regulation of DNA-binding transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of I-kappaB kinase/NF-kappaB signaling	Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling.
positive regulation of interleukin-12 production	Any process that activates or increases the frequency, rate, or extent of interleukin-12 production.
positive regulation of interleukin-2 production	Any process that activates or increases the frequency, rate, or extent of interleukin-2 production.
positive regulation of interleukin-6 production	Any process that activates or increases the frequency, rate, or extent of interleukin-6 production.
positive regulation of JNK cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of JUN kinase activity	Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of leukocyte adhesion to vascular endothelial cell	Any process that activates or increases the frequency, rate or extent of leukocyte adhesion to vascular endothelial cell.
positive regulation of lipopolysaccharide-mediated signaling pathway	Any process that activates or increases the frequency, rate or extent of signaling in response to detection of lipopolysaccharide.
positive regulation of NF-kappaB transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB.
positive regulation of NIK/NF-kappaB signaling	Any process that activates or increases the frequency, rate or extent of NIK/NF-kappaB signaling.
positive regulation of osteoclast differentiation	Any process that activates or increases the frequency, rate or extent of osteoclast differentiation.
positive regulation of protein ubiquitination	Any process that activates or increases the frequency, rate or extent of the addition of ubiquitin groups to a protein.
positive regulation of T cell cytokine production	Any process that activates or increases the frequency, rate, or extent of T cell cytokine production.
positive regulation of T cell proliferation	Any process that activates or increases the rate or extent of T cell proliferation.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of transcription regulatory region DNA binding	Any process that activates or increases the frequency, rate or extent of transcription regulatory region DNA binding.
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 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.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of I-kappaB kinase/NF-kappaB signaling	Any process that modulates I-kappaB kinase/NF-kappaB signaling.
regulation of immunoglobulin production	Any process that modulates the frequency, rate, or extent of immunoglobulin production.
response to interleukin-1	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
stimulatory C-type lectin receptor signaling pathway	The series of molecular signals initiated by the binding of C-type lectin to its receptor on the surface of a target cell, and resulting in cellular activation.
T cell receptor signaling pathway	The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
T-helper 1 type immune response	An immune response which is associated with resistance to intracellular bacteria, fungi, and protozoa, and pathological conditions such as arthritis, and which is typically orchestrated by the production of particular cytokines by T-helper 1 cells, most notably interferon-gamma, IL-2, and lymphotoxin.
tumor necrosis factor-mediated signaling pathway	The series of molecular signals initiated by tumor necrosis factor binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.

7 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q3ZCC3	TRAF6	TNF receptor-associated factor 6	Bos taurus (Bovine)	SS
P70196	Traf6	TNF receptor-associated factor 6	Mus musculus (Mouse)	SS
A7XUJ6	TRAF6	TNF receptor-associated factor 6	Sus scrofa (Pig)	SS
B5DF45	Traf6	TNF receptor-associated factor 6	Rattus norvegicus (Rat)	SS
B6CJY5	TRAF6	TNF receptor-associated factor 6	Macaca mulatta (Rhesus macaque)	SS
Q28DL4	traf6	TNF receptor-associated factor 6	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q6IWL4	traf6	TNF receptor-associated factor 6	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MSLLNCENSC	GSSQSESDCC	VAMASSCSAV	TKDDSVGGTA	STGNLSSSFM	EEIQGYDVEF
70	80	90	100	110	120
DPPLESKYEC	PICLMALREA	VQTPCGHRFC	KACIIKSIRD	AGHKCPVDNE	ILLENQLFPD
130	140	150	160	170	180
NFAKREILSL	MVKCPNEGCL	HKMELRHLED	HQAHCEFALM	DCPQCQRPFQ	KFHINIHILK
190	200	210	220	230	240
DCPRRQVSCD	NCAASMAFED	KEIHDQNCPL	ANVICEYCNT	ILIREQMPNH	YDLDCPTAPI
250	260	270	280	290	300
PCTFSTFGCH	EKMQRNHLAR	HLQENTQSHM	RMLAQAVHSL	SVIPDSGYIS	EVRNFQETIH
310	320	330	340	350	360
QLEGRLVRQD	HQIRELTAKM	ETQSMYVSEL	KRTIRTLEDK	VAEIEAQQCN	GIYIWKIGNF
370	380	390	400	410	420
GMHLKCQEEE	KPVVIHSPGF	YTGKPGYKLC	MRLHLQLPTA	QRCANYISLF	VHTMQGEYDS
430	440	450	460	470	480
HLPWPFQGTI	RLTILDQSEA	PVRQNHEEIM	DAKPELLAFQ	RPTIPRNPKG	FGYVTFMHLE
490	500	510	520
ALRQRTFIKD	DTLLVRCEVS	TRFDMGSLRR	EGFQPRSTDA	GV