AiPD: Autoinhibited Protein Database

P41743

Gene name	PRKCI (DXS1179E)
Protein name	Protein kinase C iota type
Names	Atypical protein kinase C-lambda/iota, PRKC-lambda/iota, aPKC-lambda/iota, nPKC-iota
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5584
EC number
Protein Class	RIBOSOMAL PROTEIN S6 KINASE (PTHR24351)

Descriptions

PRKCI, an atypical PKC (aPKC) isoform, is an important kinase in multiple cellular processes and regulated by the phosphatidylinositol 3-kinase product phosphatidylinositol 3,4,5-(PO4)3 (PIP3). In aPKC molecule, the arginine motif (123-140) in the pseudosubstrate region on the regulatory domain binds to acidic residues in the substrate-binding region on the catalytic domain, leading to the off state of aPKCs. The autoinhibition of aPKC is released by binding with the acidic ligand PIP3 and consequently exposing the substrate-binding site.

Autoinhibitory domains (AIDs)

Target domain	233-596 (Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota)
Relief mechanism	Ligand binding
Assay	Mutagenesis experiment, Deletion assay, Structural analysis

AID

123-140 (Pseudosubstrate region)

Target domain

233-596 (Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota)

Relief mechanism

Ligand binding (PIP3 binding to pseudosubstrate region)

Assay

Mutagenesis experiment, Deletion assay, Structural analysis

Accessory elements

395-418 (Activation loop from InterPro)

Target domain	233-596 (Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota)
Relief mechanism
Assay

References

Ivey RA et al. (2014) "Requirements for pseudosubstrate arginine residues during autoinhibition and phosphatidylinositol 3,4,5-(PO₄)₃-dependent activation of atypical PKC", The Journal of biological chemistry, 289, 25021-30

Huang X et al. (2003) "Crystal structure of an inactive Akt2 kinase domain", Structure (London, England : 1993), 11, 21-30

Truebestein L et al. (2021) "Structure of autoinhibited Akt1 reveals mechanism of PIP(3)-mediated activation", Proceedings of the National Academy of Sciences of the United States of America, 118,

Lučić I et al. (2018) "Conformational sampling of membranes by Akt controls its activation and inactivation", Proceedings of the National Academy of Sciences of the United States of America, 115, E3940-E3949

Autoinhibited structure

Activated structure

11 structures for P41743

Entry ID	Method	Resolution	Chain	Position	Source
1VD2	NMR	-	A	25-108	PDB
1WMH	X-ray	150 A	A	25-108	PDB
1ZRZ	X-ray	300 A	A	233-596	PDB
3A8W	X-ray	210 A	A/B	249-588	PDB
3A8X	X-ray	200 A	A/B	249-588	PDB
3ZH8	X-ray	274 A	A/B/C	248-594	PDB
5LI1	X-ray	200 A	A	248-596	PDB
5LI9	X-ray	179 A	A	248-596	PDB
5LIH	X-ray	325 A	A/B	248-596	PDB
6ILZ	X-ray	326 A	A/C/E/G	249-588	PDB
AF-P41743-F1	Predicted				AlphaFoldDB

312 variants for P41743

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA355095851 rs1305218534	2	P>L		No	ClinGen TOPMed gnomAD
CA355095849 rs1305218534	2	P>R		No	ClinGen TOPMed gnomAD
rs1082973 CA87676314	4	Q>H		No	ClinGen gnomAD
CA355095884 rs1238949875	5	R>W		No	ClinGen gnomAD
CA355095901 rs1309785216	6	D>G		No	ClinGen gnomAD
CA355095895 rs1444111261	6	D>N		No	ClinGen TOPMed
rs746473761 CA2700305	7	S>G		No	ClinGen ExAC gnomAD
rs1194363431 CA355095934	8	S>R		No	ClinGen gnomAD
CA87676329 rs979336423	9	T>N		No	ClinGen Ensembl
rs146517821 CA2700308	10	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700307 rs781622043	10	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1215675569 CA355095969	11	S>F		No	ClinGen TOPMed gnomAD
rs1180800394 CA355095978	12	H>R		No	ClinGen TOPMed gnomAD
CA87676347 rs935282042	13	T>A		No	ClinGen TOPMed gnomAD
rs770401419 CA2700309	14	V>I		No	ClinGen ExAC gnomAD
CA355096024 rs1179487149	16	G>C		No	ClinGen gnomAD
rs763427114 CA2700312	16	G>D		No	ClinGen ExAC gnomAD
rs1577333820 CA355096030	17	G>S		No	ClinGen Ensembl
CA355096045 rs1453580506	18	G>C		No	ClinGen TOPMed gnomAD
CA2700316 rs554225297	19	S>I		No	ClinGen 1000Genomes ExAC gnomAD
CA355096053 rs1182925435	19	S>R		No	ClinGen TOPMed
CA2700317 rs572493199	21	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1397484473 CA355096092	22	H>Y		No	ClinGen gnomAD
CA355096120 rs1445671164	24	H>Y		No	ClinGen gnomAD
rs1331532531 CA355096154	26	V>I		No	ClinGen TOPMed gnomAD
rs1337327825 CA355096167	27	R>Q		No	ClinGen gnomAD
rs1283562436 CA355096207	30	A>V		No	ClinGen gnomAD
CA2700319 rs765259096	31	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA355096237 rs1256310680	33	R>C		No	ClinGen TOPMed gnomAD
CA355096239 rs1256310680	33	R>G		No	ClinGen TOPMed gnomAD
rs1457319386 CA355096243	33	R>H		No	ClinGen gnomAD
CA355096254 rs1252865018	34	G>A		No	ClinGen gnomAD
CA355096251 rs1199520604	34	G>W		No	ClinGen gnomAD
CA355098398 rs1292998335	39	T>I		No	ClinGen TOPMed
CA2700342 rs751420634	40	H>P		No	ClinGen ExAC gnomAD
rs751420634 CA2700343	40	H>R		No	ClinGen ExAC gnomAD
rs766148364 CA2700341	40	H>Y		No	ClinGen ExAC gnomAD
rs961288557 CA87658270	43	P>T		No	ClinGen TOPMed
rs202068509 CA87658273	50	L>R		No	ClinGen Ensembl
rs1296298304 CA355098478	51	C>W		No	ClinGen gnomAD
CA2700344 rs767204074	52	N>H		No	ClinGen ExAC gnomAD
CA2700345 rs369333148	52	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700346 rs755677529	55	R>*		No	ClinGen ExAC gnomAD
rs1280748335 CA355098512	57	M>L		No	ClinGen TOPMed
rs1232817418 CA355098517	57	M>T		No	ClinGen gnomAD
CA87658291 rs1032101463	58	C>Y		No	ClinGen Ensembl
CA355098535 rs1256752939	60	F>I		No	ClinGen gnomAD
CA355098549 rs1403982825	61	D>E		No	ClinGen TOPMed
CA355098547 rs1350537092	61	D>G		No	ClinGen gnomAD
rs140807328 CA2700349	62	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1272447670 CA355098555	62	N>S		No	ClinGen gnomAD
rs757899632 CA2700350	63	E>K		No	ClinGen ExAC TOPMed gnomAD
CA2700351 rs757899632	63	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA2700353 rs772402293	64	Q>R		No	ClinGen ExAC gnomAD
CA2700354 rs775805215	65	L>R		No	ClinGen ExAC gnomAD
rs201089076 CA87658313	66	F>L		No	ClinGen 1000Genomes
CA355098578 rs1197750201	66	F>Y		No	ClinGen gnomAD
CA2700356 rs768794063	67	T>A		No	ClinGen ExAC gnomAD
rs776632465 CA2700357	71	I>V		No	ClinGen ExAC gnomAD
rs762941664 CA2700358	73	E>D		No	ClinGen ExAC gnomAD
CA355098645 COSM582652 rs1478749679	75	G>*	lung [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1321696346 CA355099342	75	G>E		No	ClinGen gnomAD
rs760374153 CA355099352	76	D>E		No	ClinGen ExAC gnomAD
CA2700384 rs763696294	77	P>L		No	ClinGen ExAC gnomAD
CA2700388 rs750971070	86	L>*		No	ClinGen ExAC gnomAD
CA87669294 rs370916263	87	E>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs370916263 CA2700390	87	E>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700389 rs182924386	87	E>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA87669307 rs982119706	89	A>P		No	ClinGen TOPMed gnomAD
CA355099432 rs982119706	89	A>T		No	ClinGen TOPMed gnomAD
rs1170271274 CA355099455	92	L>P		No	ClinGen gnomAD
rs902957582 CA87669310	92	L>V		No	ClinGen Ensembl
CA87669320 rs111567328	95	L>P		No	ClinGen Ensembl
rs1444607173 CA355099497	98	D>G		No	ClinGen TOPMed gnomAD
CA355099498 rs1444607173	98	D>V		No	ClinGen TOPMed gnomAD
CA2700393 rs781289139	99	S>C		No	ClinGen ExAC gnomAD
CA2700394 rs748182793	102	L>V		No	ClinGen ExAC TOPMed gnomAD
CA355099542 rs1271977652	105	V>L		No	ClinGen TOPMed
CA355099784 rs1214977029	107	P>A		No	ClinGen gnomAD
rs768340835 CA2700418	109	V>A		No	ClinGen ExAC gnomAD
CA355099797 rs1202631310	109	V>I		No	ClinGen TOPMed
rs368704903 COSM1291649 CA2700423	112	R>C	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs980860031 CA87672265 COSM208049	112	R>H	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA2700422 rs368704903	112	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs762390072 CA2700424	115	M>I		No	ClinGen ExAC gnomAD
rs1224423994 CA355099832	115	M>V		No	ClinGen TOPMed
CA355099849 rs1379196093	117	C>S		No	ClinGen TOPMed
rs766866155 CA2700425	121	D>N		No	ClinGen ExAC gnomAD
CA355099905 rs1279890266	123	S>C		No	ClinGen gnomAD
CA87676413 rs946756475	124	I>V		No	ClinGen TOPMed gnomAD
rs567380681 CA2700443	126	R>H		No	ClinGen ExAC gnomAD
rs567380681 CA87676416	126	R>L		No	ClinGen ExAC gnomAD
rs146841636 CA87676426	127	R>K		No	ClinGen Ensembl
rs56154494 CA2700445 VAR_042323	130	R>C		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
CA2700446 rs369872734	130	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs775812965 CA355099950	131	R>H		No	ClinGen ExAC gnomAD
rs775812965 CA2700448	131	R>L		No	ClinGen ExAC gnomAD
rs1187831601 CA355100000	138	A>T		No	ClinGen TOPMed
rs373086682 CA2700450	139	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA355100031 rs1204274368	142	T>S		No	ClinGen TOPMed
CA2700453 rs765219909	146	K>R		No	ClinGen ExAC gnomAD
CA87676473 rs762292026	147	R>H		No	ClinGen TOPMed
rs750420887 CA2700472	151	R>H		No	ClinGen ExAC TOPMed gnomAD
rs763154483 CA2700473	155	A>T		No	ClinGen ExAC gnomAD
rs752691470 CA2700475	158	T>R		No	ClinGen ExAC gnomAD
rs1293622637 CA355100166	160	R>Q		No	ClinGen TOPMed
rs1289447991 CA355100193	164	L>F		No	ClinGen gnomAD
CA355100200 rs1361108822	165	G>E		No	ClinGen gnomAD
CA87678592 rs1030581930	166	R>H		No	ClinGen TOPMed
rs1259133115 CA355100211	167	Q>R		No	ClinGen gnomAD
rs185526558 CA87678602	169	Y>C		No	ClinGen 1000Genomes
CA87678596 rs1050315708	169	Y>H		No	ClinGen TOPMed
rs148843944 CA355100249	172	I>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA2700479 rs756841596	172	I>T		No	ClinGen ExAC gnomAD
CA2700482 rs771576001	173	N>S		No	ClinGen ExAC TOPMed gnomAD
CA355100275 rs1436578624	176	L>F		No	ClinGen TOPMed gnomAD
rs1436578624 CA355100274	176	L>V		No	ClinGen TOPMed gnomAD
CA87678724 rs750524485	178	V>I		No	ClinGen Ensembl
rs1382818070 CA355100328	183	H>R		No	ClinGen gnomAD
rs868417022 CA87678730	185	L>I		No	ClinGen Ensembl
CA355100344 COSM3945125 rs1329586167	186	V>I	lung [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA2700486 rs776837368	187	T>A		No	ClinGen ExAC gnomAD
rs147562215 CA2700488	188	I>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA2700487 rs376895151	188	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA355100367 rs1238680908	189	E>D		No	ClinGen TOPMed gnomAD
CA355100377 rs1260622724	191	G>R		No	ClinGen gnomAD
CA2700490 rs763066411	192	R>Q		No	ClinGen ExAC gnomAD
CA2700489 COSM1222039 rs141965722	192	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA2700492 rs766551522	197	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA355100416 rs1192616664	197	Q>R		No	ClinGen gnomAD
CA2700518 rs774546861	200	V>A		No	ClinGen ExAC TOPMed gnomAD
rs111317464 CA87680754	201	M>V		No	ClinGen Ensembl
rs763902996 CA355100467	203	M>L		No	ClinGen ExAC TOPMed gnomAD
rs763902996 CA2700521	203	M>V		No	ClinGen ExAC TOPMed gnomAD
rs71277168 CA2700522	204	D>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA2700524 rs374000097	205	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs750284734 CA2700525	208	M>I		No	ClinGen ExAC gnomAD
rs750284734 CA87680780	208	M>I		No	ClinGen ExAC gnomAD
CA2700526 rs758015497	209	H>N		No	ClinGen ExAC gnomAD
CA355100551 rs766040399	215	T>A		No	ClinGen ExAC gnomAD
rs763072369 CA355100554	215	T>I		No	ClinGen TOPMed gnomAD
CA87680798 rs763072369	215	T>R		No	ClinGen TOPMed gnomAD
rs766040399 CA2700527	215	T>S		No	ClinGen ExAC gnomAD
rs767045797 CA355100575	217	I>F		No	ClinGen ExAC TOPMed gnomAD
rs1435957709 CA355100579	217	I>M		No	ClinGen gnomAD
rs767045797 CA2700557	217	I>V		No	ClinGen ExAC TOPMed gnomAD
CA2700559 rs191938996	219	Y>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA2700560 rs370513574	222	S>*		No	ClinGen ESP ExAC
rs757703152 CA2700562	224	H>Q		No	ClinGen ExAC gnomAD
CA2700561 rs754218167	224	H>R		No	ClinGen ExAC TOPMed gnomAD
rs756263490 CA87682570	227	L>S		No	ClinGen Ensembl
rs147104137 CA2700564	229	Q>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA355100674 rs1301070129	231	G>V		No	ClinGen gnomAD
CA2700565 rs772250699	234	K>T		No	ClinGen ExAC gnomAD
rs199997573 CA2700583	236	A>S		No	ClinGen ExAC TOPMed gnomAD
CA355100728 rs1441299379	237	M>I		No	ClinGen TOPMed
rs747042200 CA2700584	237	M>V		No	ClinGen ExAC TOPMed gnomAD
rs768734145 CA2700585	239	T>A		No	ClinGen ExAC gnomAD
CA355100756 rs1560181245	241	E>G		No	ClinGen Ensembl
CA355100767 rs1178271455	243	G>C		No	ClinGen gnomAD
rs200726509 CA2700587	243	G>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs1458333589 CA355100797	247	S>F		No	ClinGen gnomAD
CA355100836 rs1393309823	253	D>G		No	ClinGen gnomAD
CA2700589 rs774168806	255	D>H		No	ClinGen ExAC TOPMed gnomAD
rs774168806 CA355100848	255	D>N		No	ClinGen ExAC TOPMed gnomAD
rs771711948 CA2700591	258	R>Q		No	ClinGen ExAC gnomAD
rs138560118 CA2700590	258	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs879138314 CA87686337	271	V>F		No	ClinGen Ensembl
CA355100956 rs1335738205	272	R>*		No	ClinGen TOPMed gnomAD
rs762380206 CA2700597	272	R>Q		No	ClinGen ExAC gnomAD
CA2700600 rs150239950	273	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700601 rs750752062	274	K>E		No	ClinGen ExAC gnomAD
CA355100979 rs1402498314	275	K>N		No	ClinGen Ensembl
CA87686401 rs867140849	276	T>A		No	ClinGen Ensembl
CA355100995 COSM284260 rs1428010723	278	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1254638218 CA355100998	278	R>H		No	ClinGen gnomAD
CA2700603 rs368607450	284	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs766563408 CA2700604	285	V>A		No	ClinGen ExAC TOPMed gnomAD
rs755258716 CA2700606	289	L>I		No	ClinGen ExAC gnomAD
rs973528502 CA87686466	291	N>D		No	ClinGen Ensembl
rs1329248941 CA355101093	292	D>G		No	ClinGen TOPMed gnomAD
CA2700608 rs748272532	293	D>E		No	ClinGen ExAC gnomAD
CA2700629 rs573160898	295	D>V		No	ClinGen 1000Genomes ExAC gnomAD
CA355101134 rs1425394515	296	I>V		No	ClinGen TOPMed
rs1228343200 CA355101143	297	D>G		No	ClinGen gnomAD
rs752731655 CA2700630	298	W>*		No	ClinGen ExAC gnomAD
CA355101161 rs1281629002	300	Q>*		No	ClinGen gnomAD
CA355101180 rs1379694217	302	E>G		No	ClinGen TOPMed
rs1234702783 CA355101223	308	Q>E		No	ClinGen TOPMed
CA2700632 rs778855961	308	Q>R		No	ClinGen ExAC gnomAD
rs745782136 CA2700633	310	S>A		No	ClinGen ExAC gnomAD
rs977008114 CA87687050	312	H>Y		No	ClinGen TOPMed gnomAD
CA2700635 rs779686819	319	H>Y		No	ClinGen ExAC gnomAD
rs1172744102 CA355101352	327	R>G		No	ClinGen gnomAD
rs777394724 CA355101374	328	L>F		No	ClinGen ExAC TOPMed gnomAD
CA87687542 rs950321169	329	F>L		No	ClinGen TOPMed
CA355101401 rs1232048013	332	I>T		No	ClinGen gnomAD
CA355101398 rs1370173894	332	I>V		No	ClinGen gnomAD
rs980725247 CA87687565	337	G>R		No	ClinGen TOPMed
rs1560181937 CA355101525	349	K>I		No	ClinGen Ensembl
CA355101557 rs1399769269	354	H>D		No	ClinGen TOPMed
CA355101573 rs1386397434	356	R>T		No	ClinGen TOPMed
rs927803592 CA87689386	358	Y>H		No	ClinGen TOPMed
CA2700678 rs752586080	359	S>A		No	ClinGen ExAC gnomAD
COSM125590 CA2700679 rs554687623	359	S>C	upper_aerodigestive_tract [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
CA355101634 rs1224995597	363	S>G		No	ClinGen gnomAD
CA2700680 rs200664120	364	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs770485461 CA2700682	365	A>G		No	ClinGen ExAC TOPMed gnomAD
rs778456196 CA2700683	369	L>I		No	ClinGen ExAC gnomAD
rs746373616 CA2700684	372	R>*		No	ClinGen ExAC gnomAD
rs772611163 CA2700685	372	R>Q		No	ClinGen ExAC gnomAD
CA2700687 rs761124312	376	Y>F		No	ClinGen ExAC gnomAD
CA355101771 rs1373137084	383	N>S		No	ClinGen gnomAD
CA87689421 rs201380049	392	I>V		No	ClinGen TOPMed gnomAD
rs773463648 COSM1222038 CA2700694	398	G>S	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA355101894 rs1230577514	401	K>E		No	ClinGen gnomAD
CA87695170 rs1008561303	405	R>L		No	ClinGen TOPMed gnomAD
rs1008561303 CA355102070	405	R>Q		No	ClinGen TOPMed gnomAD
CA2700714 rs763152419	405	R>W		No	ClinGen ExAC gnomAD
rs1332841310 CA355102074	406	P>A		No	ClinGen TOPMed
rs374177981 CA2700716	406	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs374177981 CA2700717	406	P>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1193411428 CA355102095	409	T>R		No	ClinGen gnomAD
rs900136662 CA87695213	410	T>A		No	ClinGen TOPMed
rs1560185295 CA355102102	411	S>G		No	ClinGen Ensembl
rs1560185295 CA355102101	411	S>R		No	ClinGen Ensembl
rs763947334 CA2700718	415	G>A		No	ClinGen ExAC gnomAD
rs1560185302 CA355102143	417	P>A		No	ClinGen Ensembl
CA355102205 rs1182254154	426	R>G		No	ClinGen TOPMed
rs756884894 CA2700720	426	R>S		No	ClinGen ExAC gnomAD
CA355102226 rs1458431350	429	D>H		No	ClinGen gnomAD
CA2700745 rs773224124	431	G>A		No	ClinGen ExAC TOPMed gnomAD
CA2700746 rs773224124 COSM4149659	431	G>V	ovary [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs201740893 CA87696503	432	F>L		No	ClinGen 1000Genomes
rs1483055491 CA355102263	432	F>L		No	ClinGen gnomAD
rs374883456 CA2700748	439	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700750 rs184216798	443	M>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA2700751 rs779029814	446	M>T		No	ClinGen ExAC gnomAD
rs1364845286 CA355102358	446	M>V		No	ClinGen TOPMed
rs745958617 CA2700752	447	M>V		No	ClinGen ExAC gnomAD
rs1388083127 CA355102385	450	R>G		No	ClinGen gnomAD
rs1577375356 CA355102394	451	S>A		No	ClinGen Ensembl
rs1161973892 CA355102416	454	D>G		No	ClinGen TOPMed
rs768597939 CA2700753	455	I>V		No	ClinGen ExAC TOPMed gnomAD
rs776558522 CA2700754	456	V>A		No	ClinGen ExAC TOPMed gnomAD
CA355102428 rs1372532118	456	V>I		No	ClinGen gnomAD
CA355102455 rs1450462772	460	D>G		No	ClinGen gnomAD
rs1341309666 CA355102451	460	D>N		No	ClinGen TOPMed gnomAD
rs1341870333 CA355102480	463	D>E		No	ClinGen gnomAD
rs554559908 CA2700758	464	Q>R		No	ClinGen ExAC gnomAD
rs765967034 CA2700759	466	T>I		No	ClinGen ExAC
rs751036713 CA2700760	470	L>V		No	ClinGen ExAC gnomAD
rs1485937829 CA355102534	471	F>S		No	ClinGen TOPMed
rs1378322375 CA355098661	474	I>F		No	ClinGen gnomAD
rs761243863 CA2700782	475	L>S		No	ClinGen ExAC gnomAD
rs1388201066 COSM78349 CA355098706	480	R>C	ovary pancreas large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs754216126 CA2700785	483	R>C		No	ClinGen ExAC gnomAD
COSM1420563 CA355098725 rs1389006052	483	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA87662365 rs17855494	485	L>M		No	ClinGen Ensembl
rs1302542745 CA355098771	491	S>G		No	ClinGen gnomAD
CA2700787 rs757566946	493	L>M		No	ClinGen ExAC gnomAD
CA87663224 rs373682853	500	D>E		No	ClinGen ESP TOPMed gnomAD
rs1577377456 CA355098858	501	P>L		No	ClinGen Ensembl
rs1469931815 CA355098855	501	P>S		No	ClinGen gnomAD
rs762444412 CA2700808	504	R>*		No	ClinGen ExAC gnomAD
rs17856646 CA87663245	508	H>L		No	ClinGen Ensembl
rs1319504292 CA355098949	515	D>N		No	ClinGen gnomAD
rs974333981 CA87663249	516	I>T		No	ClinGen TOPMed gnomAD
CA355098956 rs1282299429	516	I>V		No	ClinGen TOPMed
CA355098975 rs1577377491	519	H>N		No	ClinGen Ensembl
rs770998502 CA2700811	520	P>L		No	ClinGen ExAC TOPMed gnomAD
CA87663269 rs866058843	523	R>*		No	ClinGen gnomAD
rs368665283 CA87663273 COSM1041063	523	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated ESP gnomAD
CA355099038 rs1423404616	528	D>N		No	ClinGen gnomAD
CA355099043 rs1165933429	528	D>V		No	ClinGen gnomAD
CA355099051 rs1560187209	529	M>I		No	ClinGen Ensembl
CA2700815 rs781306402	529	M>V		No	ClinGen ExAC
CA2700834 rs752869987	530	M>L		No	ClinGen ExAC gnomAD
CA355099081 rs1296524027	531	E>D		No	ClinGen TOPMed gnomAD
rs199683302 CA87664538	532	Q>R		No	ClinGen Ensembl
CA355099097 rs1330922659	534	Q>*		No	ClinGen TOPMed
CA2700836 rs142234162	535	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA2700835 rs142234162	535	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA355099117 rs1216250049	537	P>S		No	ClinGen gnomAD
rs750120400 CA2700837	539	F>L		No	ClinGen ExAC TOPMed gnomAD
CA355099141 rs1311650226	540	K>N		No	ClinGen gnomAD
CA2700838 rs369277385	542	N>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs780053668 CA2700839	542	N>S		No	ClinGen ExAC gnomAD
rs780053668 CA2700840	542	N>T		No	ClinGen ExAC gnomAD
CA2700841 rs768466580	543	I>V		No	ClinGen ExAC TOPMed gnomAD
CA355099166 rs1208504932	545	G>R		No	ClinGen gnomAD
CA355099170 rs1458271182	545	G>V		No	ClinGen TOPMed
rs1249036295 CA355099191	548	G>D		No	ClinGen gnomAD
rs1189963071 CA355099229	553	D>G		No	ClinGen gnomAD
rs1414651390 CA355099279	560	P>A		No	ClinGen TOPMed
rs17851954 CA2700844	560	P>L		No	ClinGen ExAC gnomAD
rs17851954 CA87664624	560	P>R		No	ClinGen ExAC gnomAD
rs139167704 CA2700846	563	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700847 rs771277289	565	P>R		No	ClinGen ExAC gnomAD
CA355099326 rs371799261	567	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs145084763 CA2700849	568	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA2700869 rs777211672	570	I>L		No	ClinGen ExAC gnomAD
CA355099572 rs1305100978	571	V>M		No	ClinGen gnomAD
rs749763295 CA2700870	572	R>G		No	ClinGen ExAC gnomAD
rs1228061878 CA355099588	573	K>R		No	ClinGen gnomAD
CA355099596 rs1280082949	574	I>T		No	ClinGen TOPMed
rs1353052159 CA355099623	578	E>*		No	ClinGen gnomAD
rs1475798615 CA355099650	581	G>V		No	ClinGen TOPMed gnomAD
CA2700871 rs374370739	585	I>V		No	ClinGen ESP ExAC gnomAD
CA355099685 rs1225351390	586	N>S		No	ClinGen TOPMed gnomAD
CA355099689 rs1309853880	587	P>T		No	ClinGen TOPMed
CA2700875 rs775797042	594	E>K		No	ClinGen ExAC TOPMed

No associated diseases with P41743

5 regional properties for P41743

Type	Name	Position	InterPro Accession
domain	HECT domain	554 - 909	IPR000569
repeat	Ankyrin repeat	37 - 129	IPR002110-1
repeat	Ankyrin repeat	130 - 162	IPR002110-2
repeat	Ankyrin repeat	163 - 227	IPR002110-3
repeat	Ankyrin repeat	228 - 257	IPR002110-4

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Membrane Endosome Nucleus	Transported into the endosome through interaction with SQSTM1/p62 After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1 Colocalizes with CDK7 in the cytoplasm and nucleus Transported to vesicular tubular clusters (VTCs) through interaction with RAB2A
PANTHER Family	PTHR24351	RIBOSOMAL PROTEIN S6 KINASE
PANTHER Subfamily	PTHR24351:SF236	PROTEIN KINASE C IOTA TYPE
PANTHER Protein Class	protein modifying enzyme
PANTHER Pathway Category	No pathway information available

16 GO annotations of cellular component

Name	Definition
apical plasma membrane	The region of the plasma membrane located at the apical end of the cell.
bicellular tight junction	An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes.
cell leading edge	The area of a motile cell closest to the direction of movement.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endosome	A vacuole to which materials ingested by endocytosis are delivered.
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.
glutamatergic synapse	A synapse that uses glutamate as a neurotransmitter.
Golgi membrane	The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
intercellular bridge	A direct connection between the cytoplasm of two cells that is formed following the completion of cleavage furrow ingression during cell division. They are usually present only briefly prior to completion of cytokinesis. However, in some cases, such as the bridges between germ cells during their development, they become stabilised.
microtubule cytoskeleton	The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
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.
PAR polarity complex	A protein kinase complex that is required for the establishment of a cell polarity axis during the cell division cycle. Binds directly to activated CDC42 GTPase and is required for orchestrating a cellular gradient of CDC42. In S. cerevisiae components are: BEM1, CDC24 and CLA4; from worms to vertebrates it contains a PAR6 protein, PAR3 protein and an atypical PKC.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
Schaffer collateral - CA1 synapse	A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.
Schmidt-Lanterman incisure	Regions within compact myelin in which the cytoplasmic faces of the enveloping myelin sheath are not tightly juxtaposed, and include cytoplasm from the cell responsible for making the myelin. Schmidt-Lanterman incisures occur in the compact myelin internode, while lateral loops are analogous structures found in the paranodal region adjacent to the nodes of Ranvier.

9 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calcium-dependent protein kinase C activity	Calcium-dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein.
metal ion binding	Binding to a metal ion.
phospholipid binding	Binding to a phospholipid, a class of lipids containing phosphoric acid as a mono- or diester.
protein kinase activity	Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein kinase C activity	Catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein. This reaction requires diacylglycerol.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

28 GO annotations of biological process

Name	Definition
actin filament organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
cell migration	The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cell-cell junction organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a cell-cell junction. A cell-cell junction is a specialized region of connection between two cells.
cellular response to insulin 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 an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures.
establishment of apical/basal cell polarity	The specification and formation of the polarity of a cell along its apical/basal axis.
establishment or maintenance of epithelial cell apical/basal polarity	Any cellular process that results in the specification, formation or maintenance of the apicobasal polarity of an epithelial cell.
eye photoreceptor cell development	Development of a photoreceptor, a sensory cell in the eye that reacts to the presence of light. They usually contain a pigment that undergoes a chemical change when light is absorbed, thus stimulating a nerve.
Golgi vesicle budding	The evagination of the Golgi membrane, resulting in formation of a vesicle.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
membrane organization	A process which results in the assembly, arrangement of constituent parts, or disassembly of a membrane. A membrane is a double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins.
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 glial cell apoptotic process	Any process that stops, prevents, or reduces the frequency, rate, or extent of glial cell apoptotic process.
negative regulation of neuron apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of endothelial cell apoptotic process	Any process that activates or increases the frequency, rate or extent of endothelial cell apoptotic process.
positive regulation of glial cell proliferation	Any process that activates or increases the rate or extent of glial cell proliferation.
positive regulation of glucose import	Any process that activates or increases the frequency, rate or extent of the import of the hexose monosaccharide glucose into a cell or organelle.
positive regulation of neuron projection development	Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
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 Notch signaling pathway	Any process that activates or increases the frequency, rate or extent of the Notch signaling pathway.
positive regulation of protein localization to plasma membrane	Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
protein targeting to membrane	The process of directing proteins towards a membrane, usually using signals contained within the protein.
regulation of postsynaptic membrane neurotransmitter receptor levels	Any process that regulates the the local concentration of neurotransmitter receptor at the postsynaptic membrane.
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.
secretion	The controlled release of a substance by a cell or a tissue.
vesicle-mediated transport	A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.

30 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P24583	PKC1	Protein kinase C-like 1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
A1Z9X0	aPKC	Atypical protein kinase C	Drosophila melanogaster (Fruit fly)	SS
O15530	PDPK1	3-phosphoinositide-dependent protein kinase 1	Homo sapiens (Human)	EV
Q05513	PRKCZ	Protein kinase C zeta type	Homo sapiens (Human)	SS
Q16512	PKN1	Serine/threonine-protein kinase N1	Homo sapiens (Human)	EV
Q6P5Z2	PKN3	Serine/threonine-protein kinase N3	Homo sapiens (Human)	SS
Q16513	PKN2	Serine/threonine-protein kinase N2	Homo sapiens (Human)	EV
P24723	PRKCH	Protein kinase C eta type	Homo sapiens (Human)	SS
Q02156	PRKCE	Protein kinase C epsilon type	Homo sapiens (Human)	SS
Q04759	PRKCQ	Protein kinase C theta type	Homo sapiens (Human)	PR
Q05655	PRKCD	Protein kinase C delta type	Homo sapiens (Human)	SS
P17252	PRKCA	Protein kinase C alpha type	Homo sapiens (Human)	EV
P05129	PRKCG	Protein kinase C gamma type	Homo sapiens (Human)	SS
P05771	PRKCB	Protein kinase C beta type	Homo sapiens (Human)	SS
P31751	AKT2	RAC-beta serine/threonine-protein kinase	Homo sapiens (Human)	EV SS
P31749	AKT1	RAC-alpha serine/threonine-protein kinase	Homo sapiens (Human)	EV
Q9Y243	AKT3	RAC-gamma serine/threonine-protein kinase	Homo sapiens (Human)	SS
Q96BR1	SGK3	Serine/threonine-protein kinase Sgk3	Homo sapiens (Human)	SS
Q9HBY8	SGK2	Serine/threonine-protein kinase Sgk2	Homo sapiens (Human)	SS
O00141	SGK1	Serine/threonine-protein kinase Sgk1	Homo sapiens (Human)	PR
Q15208	STK38	Serine/threonine-protein kinase 38	Homo sapiens (Human)	EV
Q9Y2H1	STK38L	Serine/threonine-protein kinase 38-like	Homo sapiens (Human)	EV
Q6A1A2	PDPK2P	Putative 3-phosphoinositide-dependent protein kinase 2	Homo sapiens (Human)	PR
Q02956	Prkcz	Protein kinase C zeta type	Mus musculus (Mouse)	SS
Q62074	Prkci	Protein kinase C iota type	Mus musculus (Mouse)	SS
P09217	Prkcz	Protein kinase C zeta type	Rattus norvegicus (Rat)	SS
F1M7Y5	Prkci	Protein kinase C iota type	Rattus norvegicus (Rat)	SS
Q19266	pkc-3	Protein kinase C-like 3	Caenorhabditis elegans	SS
Q9SUA3	D6PKL1	Serine/threonine-protein kinase D6PKL1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q90XF2	prkci	Protein kinase C iota type	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MPTQRDSSTM	SHTVAGGGSG	DHSHQVRVKA	YYRGDIMITH	FEPSISFEGL	CNEVRDMCSF
70	80	90	100	110	120
DNEQLFTMKW	IDEEGDPCTV	SSQLELEEAF	RLYELNKDSE	LLIHVFPCVP	ERPGMPCPGE
130	140	150	160	170	180
DKSIYRRGAR	RWRKLYCANG	HTFQAKRFNR	RAHCAICTDR	IWGLGRQGYK	CINCKLLVHK
190	200	210	220	230	240
KCHKLVTIEC	GRHSLPQEPV	MPMDQSSMHS	DHAQTVIPYN	PSSHESLDQV	GEEKEAMNTR
250	260	270	280	290	300
ESGKASSSLG	LQDFDLLRVI	GRGSYAKVLL	VRLKKTDRIY	AMKVVKKELV	NDDEDIDWVQ
310	320	330	340	350	360
TEKHVFEQAS	NHPFLVGLHS	CFQTESRLFF	VIEYVNGGDL	MFHMQRQRKL	PEEHARFYSA
370	380	390	400	410	420
EISLALNYLH	ERGIIYRDLK	LDNVLLDSEG	HIKLTDYGMC	KEGLRPGDTT	STFCGTPNYI
430	440	450	460	470	480
APEILRGEDY	GFSVDWWALG	VLMFEMMAGR	SPFDIVGSSD	NPDQNTEDYL	FQVILEKQIR
490	500	510	520	530	540
IPRSLSVKAA	SVLKSFLNKD	PKERLGCHPQ	TGFADIQGHP	FFRNVDWDMM	EQKQVVPPFK
550	560	570	580	590
PNISGEFGLD	NFDSQFTNEP	VQLTPDDDDI	VRKIDQSEFE	GFEYINPLLM	SAEECV