AiPD: Autoinhibited Protein Database

Q8N7A1

Gene name	KLHDC1 (MSTP025)
Protein name	Kelch domain-containing protein 1
Names
Species	Homo sapiens (Human)
KEGG Pathway	hsa:122773
EC number
Protein Class

Descriptions

The ubiquitin-proteasome system (UPS) is a major pathway regulating eukaryotic protein levels. Selectivity for UPS protein substrates, containing terminal destabilizing motifs (degrons), is largely governed by E3 ligases, which modify proteins with ubiquitin (UB) to target them for degradation.<br>KLHDC2 is a substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation.<br>Autoinhibition of KLHDC2 involves the self-assembly of its C-terminal Gly-Ser motif, which mimics a C-degron and engages the substrate-binding domain of another protomer in the homotetramer. This autoinhibited state prevents the binding of diGly substrates, ensuring that only true substrates that can displace the C-degron mimic can bind and activate the E3 ligase for ubiquitylation.

Autoinhibitory domains (AIDs)

224-236 (C-terminal Gly-Ser motif) SS

Target domain	0-341 (Substrate binding domain)
Relief mechanism
Assay

AID

224-236 (C-terminal Gly-Ser motif)

Target domain

0-341 (Substrate binding domain)

Relief mechanism

Assay

Accessory elements

No accessory elements

References

Scott DC et al. (2023) "E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity", Molecular cell, 83, 770-786.e9

Autoinhibited structure

Activated structure

1 structures for Q8N7A1

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q8N7A1-F1	Predicted				AlphaFoldDB

421 variants for Q8N7A1

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1278164134	2	A>S		No	gnomAD
rs1278164134	2	A>T		No	gnomAD
rs779074317	2	A>V		No	ExAC gnomAD
rs1887616692	3	D>N		No	TOPMed
rs1887617005	4	S>A		No	gnomAD
rs745913804	6	L>P		No	ExAC gnomAD
rs1272385892	7	F>I		No	TOPMed gnomAD
rs780303723	7	F>L		No	ExAC gnomAD
rs1272385892	7	F>L		No	TOPMed gnomAD
rs1307542823	8	C>F		No	TOPMed gnomAD
rs747480397	8	C>R		No	ExAC gnomAD
rs1307542823	8	C>S		No	TOPMed gnomAD
rs1232123037	9	V>A		No	gnomAD
rs1176473029	10	A>V		No	TOPMed
rs748526529	11	E>*		No	ExAC gnomAD
rs748526529	11	E>K		No	ExAC gnomAD
rs1354438108	12	E>D		No	TOPMed gnomAD
rs772785595	13	R>C		No	ExAC TOPMed gnomAD
rs772785595	13	R>G		No	ExAC TOPMed gnomAD
rs772785595	13	R>S		No	ExAC TOPMed gnomAD
rs1479538042	14	S>R		No	gnomAD
rs1175809597	15	G>R		No	gnomAD
rs770384211	16	H>N		No	ExAC TOPMed gnomAD
rs770384211	16	H>Y		No	ExAC TOPMed gnomAD
rs2139721457	17	C>Y		No	Ensembl
rs1327398197	18	A>T		No	TOPMed gnomAD
rs142607802	18	A>V		No	ESP ExAC TOPMed gnomAD
rs1006578111	19	V>A		No	TOPMed gnomAD
rs143381329	19	V>M		No	ESP ExAC TOPMed gnomAD
rs1027311355	20	V>M		No	TOPMed gnomAD
rs376398071	21	D>E		No	ESP ExAC TOPMed gnomAD
rs1179020899	21	D>H		No	gnomAD
rs1179020899	21	D>N		No	gnomAD
rs1476048075	22	G>E		No	TOPMed
rs765477815	23	N>K		No	ExAC gnomAD
TCGA novel	23	N>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1887620581	25	L>F		No	gnomAD
rs982596430	26	Y>C		No	gnomAD
rs982596430	26	Y>S		No	gnomAD
rs908391197	27	V>L		No	gnomAD
rs908391197	27	V>M		No	gnomAD
rs140549878	28	W>*		No	ESP ExAC gnomAD
rs151334470	28	W>*		No	1000Genomes ESP ExAC TOPMed gnomAD
rs140549878	28	W>C		No	ESP ExAC gnomAD
rs1887621219	28	W>G		No	Ensembl
rs151334470	28	W>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs151334470	28	W>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1273416418	29	G>E		No	TOPMed gnomAD
rs748519693	29	G>R		No	ExAC TOPMed gnomAD
rs1489926543	30	G>D		No	TOPMed gnomAD
rs200915752	30	G>R		No	1000Genomes ExAC gnomAD
rs200915752	30	G>S		No	1000Genomes ExAC gnomAD
rs1489926543	30	G>V		No	TOPMed gnomAD
rs1198914379	32	V>G		No	gnomAD
TCGA novel	33	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs756568351	34	I>V		No	ExAC TOPMed gnomAD
COSM1300632	35	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1242407202	35	E>D		No	TOPMed
rs150457462	36	D>H		No	ESP ExAC TOPMed gnomAD
rs1594654678	37	N>D		No	Ensembl
rs1479106720	38	E>A		No	TOPMed gnomAD
rs754175506	39	V>A		No	ExAC TOPMed gnomAD
rs779272484	40	Y>*		No	ExAC gnomAD
rs1034158442	40	Y>F		No	TOPMed
rs757671778	40	Y>H		No	ExAC gnomAD
rs1281485186	43	N>D		No	gnomAD
rs1228851306	44	D>G		No	TOPMed gnomAD
rs1311643070	44	D>N		No	TOPMed gnomAD
rs567635131	45	E>D		No	ExAC TOPMed gnomAD
rs1324933051	45	E>K		No	TOPMed gnomAD
rs1337931558	46	I>L		No	TOPMed gnomAD
rs760026024	50	D>G		No	Ensembl
rs1265062914	50	D>H		No	TOPMed gnomAD
TCGA novel	51	I>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1888136057	52	D>G		No	TOPMed
rs1251195651	52	D>N		No	Ensembl
rs1888136150	54	G>E		No	TOPMed
COSM698476	56	W>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1888148510	57	R>G		No	Ensembl
rs780876175	58	M>I		No	ExAC gnomAD
rs754487927	58	M>V		No	ExAC gnomAD
rs1888148877	59	H>R		No	Ensembl
rs1454446958	59	H>Y		No	gnomAD
rs748028176	60	L>F		No	ExAC TOPMed gnomAD
rs748028176	60	L>V		No	ExAC TOPMed gnomAD
rs1888149192	62	E>G		No	TOPMed
rs1888149389	63	G>R		No	gnomAD
rs777414375	64	E>D		No	ExAC gnomAD
rs566883090	64	E>K		No	1000Genomes ExAC gnomAD
rs566883090	64	E>Q		No	1000Genomes ExAC gnomAD
rs1888149814	67	A>V		No	TOPMed gnomAD
rs749176313	68	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs138562032	69	M>I		No	ESP TOPMed gnomAD
rs775835797	70	S>L		No	ExAC gnomAD
rs539091727	70	S>T		No	1000Genomes ExAC TOPMed gnomAD
TCGA novel	71	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	72	S>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1322792338	73	C>Y		No	TOPMed gnomAD
rs768683110	74	G>D		No	ExAC gnomAD
rs768683110	74	G>V		No	ExAC gnomAD
rs762252525	75	A>T		No	ExAC gnomAD
rs1566599948	75	A>V		No	Ensembl
rs1464028490	76	C>S		No	TOPMed gnomAD
rs1464028490	76	C>Y		No	TOPMed gnomAD
rs1234863604	79	G>R		No	TOPMed
rs1204287500	80	K>E		No	TOPMed gnomAD
rs765832224	80	K>R		No	ExAC gnomAD
rs750721789	82	Y>*		No	1000Genomes ExAC TOPMed gnomAD
rs1566599966	82	Y>C		No	Ensembl
rs763422694	83	I>T		No	ExAC gnomAD
rs1305334703	83	I>V		No	TOPMed
TCGA novel	84	F>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1294424497	85	G>E		No	TOPMed gnomAD
rs1408329709	87	Y>C		No	TOPMed gnomAD
rs1161775323	91	G>R		No	gnomAD
COSM3782842	92	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1387026663	95	R>*		No	TOPMed gnomAD
rs1457189831	95	R>Q		No	TOPMed gnomAD
rs1888163186	96	L>F		No	TOPMed
rs770176279	98	F>C		No	ExAC TOPMed gnomAD
rs1384086430	98	F>V		No	TOPMed
rs141657598	102	R>*		No	ESP ExAC TOPMed gnomAD
rs1448862033	102	R>Q		No	TOPMed gnomAD
TCGA novel	103	T>M	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1175153091	104	R>G		No	TOPMed
rs766696187	105	D>G		No	ExAC TOPMed gnomAD
TCGA novel	106	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs773489254	108	Y>C		No	TOPMed gnomAD
COSM1677964 rs906732304	108	Y>D	ovary [Cosmic]	No	cosmic curated Ensembl
rs1308826808	109	I>S		No	gnomAD
rs1250687912	112	K>E		No	TOPMed gnomAD
rs373777909	113	I>M		No	ESP ExAC TOPMed gnomAD
TCGA novel	114	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs752227205	114	T>I		No	ExAC TOPMed gnomAD
rs752227205	114	T>N		No	ExAC TOPMed gnomAD
rs376879567	115	D>N		No	ESP ExAC TOPMed gnomAD
rs113906781	116	F>L		No	Ensembl
rs753773344	120	P>R		No	ExAC gnomAD
rs1566600352	120	P>T		No	Ensembl
rs778712771	122	T>I		No	ExAC gnomAD
rs778712771	122	T>K		No	ExAC gnomAD
rs879218192	123	P>S		No	Ensembl
rs142389848	124	R>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs781439325	124	R>H		No	ExAC TOPMed gnomAD
rs1888166885	127	L>F		No	Ensembl
rs1325674919	127	L>P		No	TOPMed gnomAD
rs1329219142	128	S>P		No	TOPMed gnomAD
rs1888167266	131	V>I		No	TOPMed gnomAD
rs1566600414	132	Y>C		No	Ensembl
rs1363435232	133	K>R		No	gnomAD
rs1363435232	133	K>T		No	gnomAD
rs1403896857	134	D>E		No	gnomAD
COSM698475 rs201623858	134	D>H	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated 1000Genomes ExAC NCI-TCGA TOPMed gnomAD
rs201623858	134	D>N		No	1000Genomes ExAC TOPMed gnomAD
rs749742059	134	D>V		No	ExAC gnomAD
rs376828030	135	R>G		No	ESP ExAC TOPMed gnomAD
rs371511029	137	I>K		No	ESP ExAC TOPMed gnomAD
rs1888600127	137	I>M		No	TOPMed gnomAD
rs1888600303	138	Y>C		No	gnomAD
rs1566609389	140	G>S		No	Ensembl
rs1888600595	141	G>D		No	Ensembl
rs1273047404	141	G>S		No	TOPMed
rs1888600784	143	G>E		No	Ensembl
rs772528464	144	C>R		No	ExAC gnomAD
rs776006467	144	C>Y		No	ExAC gnomAD
rs760317077	145	R>G		No	ExAC gnomAD
rs1566609415	148	S>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs922457629	148	S>I		No	Ensembl
rs1566609415	148	S>R		No	TOPMed gnomAD
rs922457629	148	S>T		No	Ensembl
rs1331757236	149	E>Q		No	gnomAD
rs1339542291	151	Q>K		No	gnomAD
rs778843990	151	Q>P		No	Ensembl
rs1888601835	152	D>G		No	TOPMed gnomAD
rs1394497770	153	C>R		No	TOPMed gnomAD
rs933700519	154	F>L		No	TOPMed
rs1280520805	154	F>S		No	TOPMed gnomAD
rs1227089435	155	D>V		No	TOPMed gnomAD
rs148702690	156	V>I		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1461808476	157	H>P		No	gnomAD
rs1461808476	157	H>R		No	gnomAD
rs866903862	159	A>T		No	Ensembl
rs1566610505	162	E>G		No	TOPMed gnomAD
rs141231808	163	E>Q		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1038144920	165	I>T		No	Ensembl
rs866077482	168	G>E		No	TOPMed gnomAD
rs1888654575	168	G>R		No	TOPMed
rs866077482	168	G>V		No	TOPMed gnomAD
rs1888654760	170	H>R		No	TOPMed
rs768325791	171	N>S		No	ExAC gnomAD
rs776096262	172	D>Y		No	ExAC gnomAD
rs1888655141	173	V>G		No	gnomAD
rs1888655079	173	V>I		No	TOPMed
TCGA novel	175	I>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs761557466	175	I>V		No	ExAC TOPMed gnomAD
rs762860968	178	T>I		No	ExAC TOPMed gnomAD
rs762860968	178	T>K		No	ExAC TOPMed gnomAD
rs762860968	178	T>R		No	ExAC TOPMed gnomAD
rs766367479	180	T>A		No	ExAC gnomAD
rs931252477	182	T>S		No	TOPMed
rs1024417252	186	P>L		No	TOPMed gnomAD
rs759296029	187	E>G		No	ExAC gnomAD
rs767368976	188	I>L		No	ExAC TOPMed gnomAD
rs139937511	190	G>D		No	ESP TOPMed gnomAD
rs142315153	190	G>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs774105559	191	G>R		No	ExAC TOPMed gnomAD
rs2139756693	193	P>A		No	Ensembl
rs1594672339	193	P>L		No	Ensembl
rs759552766	194	P>L		No	ExAC gnomAD
rs1594672358	195	Q>R		No	Ensembl
rs767154456	197	R>*		No	ExAC TOPMed gnomAD
rs1264753125	197	R>Q		No	TOPMed gnomAD
rs145471132	199	A>P		No	ESP ExAC TOPMed gnomAD
rs145471132	199	A>T		No	ESP ExAC TOPMed gnomAD
rs200431928 COSM4050989	199	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs766510107	200	H>Q		No	ExAC gnomAD
rs758602010	200	H>Y		No	ExAC gnomAD
TCGA novel	201	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs556911068	201	T>I		No	1000Genomes ExAC TOPMed gnomAD
rs1594672420	202	C>F		No	Ensembl
rs1471965697	202	C>S		No	TOPMed gnomAD
rs1368344736	203	A>S		No	gnomAD
rs931876548	204	V>A		No	Ensembl
rs376692639	204	V>F		No	ESP ExAC TOPMed gnomAD
rs376692639	204	V>I		No	ESP ExAC TOPMed gnomAD
rs376692639	204	V>L		No	ESP ExAC TOPMed gnomAD
rs2139756779	207	N>S		No	Ensembl
rs777447811	207	N>Y		No	ExAC gnomAD
rs1434530081	209	G>C		No	TOPMed gnomAD
rs1434530081	209	G>S		No	TOPMed gnomAD
rs1256056248	209	G>V		No	Ensembl
rs761557465	210	Y>C		No	gnomAD
rs772110151	214	G>R		No	ExAC TOPMed gnomAD
rs775143280	215	R>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed
rs775143280	215	R>G		No	ExAC TOPMed
rs555237025	215	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	1000Genomes NCI-TCGA TOPMed gnomAD
rs1230145454	216	V>I		No	TOPMed gnomAD
rs368449874	217	L>M		No	ESP ExAC TOPMed gnomAD
rs773520855	217	L>P		No	ExAC TOPMed gnomAD
rs1888750152	219	T>S		No	Ensembl
rs759710205	220	R>G		No	ExAC gnomAD
rs1566612828	221	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	Ensembl NCI-TCGA
rs753160913	224	L>F		No	ExAC TOPMed gnomAD
rs1197557405	224	L>M		No	Ensembl
rs1191774002	225	H>Y		No	gnomAD
rs1888751061	226	Y>*		No	gnomAD
rs150211112	226	Y>C		No	1000Genomes ESP ExAC TOPMed gnomAD
rs764386503	227	L>R		No	ExAC gnomAD
rs999123883	227	L>V		No	Ensembl
rs1217291436	228	N>I		No	gnomAD
rs1217291436	228	N>S		No	gnomAD
rs772434400	228	N>Y		No	gnomAD
rs1031822733	229	L>P		No	Ensembl
rs1888751693	231	T>A		No	Ensembl
rs372468275	231	T>I		No	ESP ExAC TOPMed gnomAD
rs372468275	231	T>N		No	ESP ExAC TOPMed gnomAD
rs372468275	231	T>S		No	ESP ExAC TOPMed gnomAD
COSM3987657	233	T>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs866787485	234	W>*		No	Ensembl
rs998397107	234	W>C		No	Ensembl
rs1437108707	236	G>A		No	gnomAD
rs749882033	236	G>R		No	ExAC TOPMed gnomAD
rs1364848602	237	R>K		No	TOPMed gnomAD
rs757879867	237	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
TCGA novel	238	I>Q	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1389826709	238	I>T		No	gnomAD
rs748056716	239	T>A		No	ExAC TOPMed gnomAD
rs755897231	239	T>I		No	ExAC gnomAD
rs777432901	240	I>V		No	ExAC TOPMed gnomAD
rs746045880	242	G>E		No	ExAC gnomAD
rs772340102	243	E>D		No	ExAC gnomAD
rs375091818	244	S>G		No	ESP ExAC TOPMed gnomAD
rs747131729	244	S>R		No	ExAC TOPMed gnomAD
rs1432317935	244	S>T		No	gnomAD
rs1340727503	245	P>A		No	gnomAD
COSM955953	245	P>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs957571309	247	H>L		No	TOPMed gnomAD
rs1888843582	247	H>Y		No	1000Genomes TOPMed
rs1286329576	248	R>L		No	gnomAD
rs369123389	248	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs2139759858	251	H>Y		No	Ensembl
rs1046448054	255	P>R		No	Ensembl
rs1233201782	256	I>V		No	TOPMed gnomAD
rs762261269	257	A>G		No	ExAC gnomAD
rs765574014	258	D>E		No	ExAC gnomAD
rs200812928	259	D>N		No	1000Genomes ExAC TOPMed gnomAD
rs762686700	259	D>V		No	ExAC TOPMed gnomAD
rs1189280530	260	K>N		No	gnomAD
rs1566614620	261	L>F		No	Ensembl
rs1888845233	262	F>L		No	Ensembl
rs1888845435	264	C>Y		No	Ensembl
rs751086992	267	L>V		No	ExAC gnomAD
rs767166007	269	A>V		No	ExAC
rs1888845994	270	D>A		No	TOPMed
COSM955954	270	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1455148570	271	N>D		No	TOPMed gnomAD
rs752612471	272	I>V		No	ExAC gnomAD
rs777612491	273	P>S		No	ExAC gnomAD
rs752209267	275	S>N		No	ExAC TOPMed gnomAD
rs752209267	275	S>T		No	ExAC TOPMed gnomAD
COSM698474	276	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1888889907	278	W>*		No	TOPMed
rs191657026	279	I>L		No	1000Genomes ExAC TOPMed gnomAD
rs1417627057	279	I>T		No	TOPMed gnomAD
rs1186078439	281	N>I		No	TOPMed
rs753609461	284	T>I		No	ExAC gnomAD
rs1888890646	285	N>T		No	TOPMed
rs757001415	286	C>F		No	ExAC gnomAD
rs1888890878	287	W>R		No	Ensembl
rs1888890949	291	T>I		No	Ensembl
rs751717112	292	H>Q		No	ExAC TOPMed gnomAD
rs1208516620	292	H>R		No	TOPMed
rs1268024823	293	L>V		No	gnomAD
rs1888891387	294	P>R		No	Ensembl
rs2139761218	296	T>I		No	Ensembl
rs370596217	297	R>I		No	ESP ExAC TOPMed gnomAD
TCGA novel	297	R>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs770309301	298	P>L		No	ExAC TOPMed
rs770309301	298	P>R		No	ExAC TOPMed
rs781324311	298	P>S		No	ExAC gnomAD
rs781324311	298	P>T		No	ExAC gnomAD
rs1459900151	299	R>S		No	gnomAD
rs1229951170	301	W>*		No	Ensembl
rs1393806816	304	A>G		No	TOPMed gnomAD
rs1393806816	304	A>V		No	TOPMed gnomAD
rs367848070	305	C>S		No	ESP ExAC TOPMed gnomAD
rs367848070	305	C>Y		No	ESP ExAC TOPMed gnomAD
rs752982626	306	L>V		No	ExAC gnomAD
rs1287655753	308	K>R		No	TOPMed
rs756106364	312	I>L		No	ExAC gnomAD
rs1409847564	312	I>M		No	TOPMed gnomAD
rs1381385721	312	I>T		No	gnomAD
rs756106364	312	I>V		No	ExAC gnomAD
rs749753363 COSM1369926	314	V>A	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs777913644	314	V>L		No	ExAC gnomAD
rs771622350	315	F>L		No	ExAC gnomAD
rs945470189	316	G>C		No	Ensembl
rs1272522214	317	G>E		No	gnomAD
rs370328450	317	G>R		No	ESP TOPMed
rs1889025550	318	S>N		No	TOPMed
rs1329201237	319	K>E		No	TOPMed gnomAD
rs1174547921	319	K>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs779417378	320	D>G		No	ExAC TOPMed gnomAD
COSM955955	320	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	321	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs201507697	322	L>*		No	TOPMed gnomAD
rs201507697	322	L>S		No	TOPMed gnomAD
rs1889026079	323	L>F		No	Ensembl
rs746276851	323	L>P		No	ExAC gnomAD
TCGA novel	323	L>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
COSM469990	324	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	324	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs771734199	325	L>V		No	ExAC TOPMed gnomAD
rs774957293	327	T>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs1411581112	328	G>C		No	gnomAD
rs1001891645	332	D>G		No	TOPMed gnomAD
rs1889125803	335	I>V		No	Ensembl
rs1594683535 COSM3886070	337	Q>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
rs758651900	338	T>A		No	ExAC gnomAD
rs780476157	340	P>S		No	ExAC gnomAD
rs1889126270	341	Y>F		No	Ensembl
rs1037648795	342	S>L		No	TOPMed gnomAD
rs2139768286	342	S>P		No	Ensembl
rs1209093550	345	R>G		No	gnomAD
rs1231110156	346	S>*		No	gnomAD
rs1889321261	349	D>V		No	Ensembl
rs1889321322	351	I>T		No	Ensembl
rs753947687	353	K>N		No	ExAC gnomAD
rs906808107	355	S>P		No	TOPMed gnomAD
rs906808107	355	S>T		No	TOPMed gnomAD
TCGA novel	355	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2139774364	356	I>V		No	Ensembl
rs1467241719	357	M>I		No	gnomAD
rs765439316	359	E>Q		No	ExAC TOPMed gnomAD
rs192469242	360	S>N		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1451048062	361	Q>*		No	gnomAD
rs1889322146	362	I>V		No	TOPMed
rs758961835	363	S>C		No	ExAC gnomAD
rs758961835 COSM5382287	363	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs1889322204	363	S>T		No	gnomAD
rs1418622708	364	L>S		No	gnomAD
rs1457453663	366	P>L		No	gnomAD
rs1566624682	367	P>A		No	Ensembl
rs1566624682	367	P>S		No	Ensembl
rs141365888	368	K>E		No	1000Genomes ESP ExAC TOPMed gnomAD
rs780771353	371	Q>*		No	ExAC gnomAD
rs780771353	371	Q>K		No	ExAC gnomAD
rs769224507	372	Q>*		No	ExAC TOPMed gnomAD
rs772790690	373	V>I		No	ExAC gnomAD
rs368273047	376	K>T		No	ESP ExAC TOPMed gnomAD
TCGA novel	377	I>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs940607888	377	I>L		No	Ensembl
rs770965841	379	F>L		No	ExAC gnomAD
rs770965841	379	F>V		No	ExAC gnomAD
rs1367507932	379	F>Y		No	Ensembl
rs1889323665	380	W>G		No	TOPMed
rs1889323732	381	A>T		No	TOPMed
rs1045657439	383	A>V		No	TOPMed
rs759426192	386	R>*		No	ExAC gnomAD
rs145332362	386	R>Q		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1248817726	387	E>K		No	gnomAD
rs1889324496	388	E>K		No	TOPMed
rs1191394241	389	Q>*		No	gnomAD
COSM4843197	390	R>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1889324777	392	Q>P		No	Ensembl
rs1408449065	394	E>G		No	TOPMed gnomAD
rs765353990	398	N>K		No	ExAC gnomAD
rs1377070223	398	N>T		No	TOPMed gnomAD
TCGA novel	399	K>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1889325405	400	Y>C		No	TOPMed
rs763368095	400	Y>H		No	ExAC TOPMed gnomAD
rs565752813	401	Q>R		No	1000Genomes ExAC gnomAD
rs141628700	402	W>*		No	ESP ExAC TOPMed gnomAD
rs1317271716	402	W>*		No	TOPMed gnomAD
rs141628700	402	W>C		No	ESP ExAC TOPMed gnomAD
rs1889325861	404	S>G		No	gnomAD
rs1011770830	405	S>R		No	Ensembl
rs755293371	406	N>I		No	ExAC TOPMed gnomAD
rs755293371	406	N>S		No	ExAC TOPMed gnomAD
rs1889326206	407	N>K		No	Ensembl
COSM955956	407	N>Y	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic

No associated diseases with Q8N7A1

No regional properties for Q8N7A1

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for Q8N7A1

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm, cytosol
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

3 GO annotations of cellular component

Name	Definition
Cul5-RING ubiquitin ligase complex	A ubiquitin ligase complex in which a cullin from the Cul5 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by an elongin-BC adaptor and a SOCS/BC box protein.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.

1 GO annotations of molecular function

Name	Definition
ubiquitin ligase-substrate adaptor activity	The binding activity of a molecule that brings together a ubiquitin ligase and its substrate. Usually mediated by F-box BTB/POZ domain proteins.

2 GO annotations of biological process

Name	Definition
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
ubiquitin-dependent protein catabolic process via the C-end degron rule pathway	The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the DesCEND (destruction via C-end degron) pathway. In the DesCEND pathway, C-terminal residues (C-end degrons) in substrates are recognized by Cul2-RING and Cul4-RING E3 ligases, whereupon the substrates are linked to ubiquitin and then delivered to the proteasome for degradation. C-end degrons can be present in full-length proteins, truncated proteins or proteolytically cleaved forms.

6 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q5E9A7	KLHDC2	Kelch domain-containing protein 2	Bos taurus (Bovine)	SS
Q9Y2U9	KLHDC2	Kelch domain-containing protein 2	Homo sapiens (Human)	EV
Q8N653	LZTR1	Leucine-zipper-like transcriptional regulator 1	Homo sapiens (Human)	PR
Q4G5Y1	Klhdc2	Kelch domain-containing protein 2	Mus musculus (Mouse)	SS
Q80YG3	Klhdc1	Kelch domain-containing protein 1	Mus musculus (Mouse)	SS
Q3KRE6	Klhdc2	Kelch domain-containing protein 2	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MADSQLFCVA	EERSGHCAVV	DGNFLYVWGG	YVSIEDNEVY	LPNDEIWTYD	IDSGLWRMHL
70	80	90	100	110	120
MEGELPASMS	GSCGACINGK	LYIFGGYDDK	GYSNRLYFVN	LRTRDETYIW	EKITDFEGQP
130	140	150	160	170	180
PTPRDKLSCW	VYKDRLIYFG	GYGCRRHSEL	QDCFDVHDAS	WEEQIFWGWH	NDVHIFDTKT
190	200	210	220	230	240
QTWFQPEIKG	GVPPQPRAAH	TCAVLGNKGY	IFGGRVLQTR	MNDLHYLNLD	TWTWSGRITI
250	260	270	280	290	300
NGESPKHRSW	HTLTPIADDK	LFLCGGLSAD	NIPLSDGWIH	NVTTNCWKQL	THLPKTRPRL
310	320	330	340	350	360
WHTACLGKEN	EIMVFGGSKD	DLLALDTGHC	NDLLIFQTQP	YSLLRSCLDC	IGKNSIMLES
370	380	390	400
QISLLPPKLL	QQVLKKITFW	AAANHREEQR	VQKEETENKY	QWISSN