AiPD: Autoinhibited Protein Database

P51955

Gene name	NEK2 (NEK2A, NLK1)
Protein name	Serine/threonine-protein kinase Nek2
Names	HSPK 21, Never in mitosis A-related kinase 2, NimA-related protein kinase 2, NimA-like protein kinase 1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:4751
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	CAMK FAMILY PROTEIN KINASE (PTHR44899)

Descriptions

NEK2 is a NIMA-related kinase essential for proper mitotic progression. NEK2 contains a tyrosine motif that is also found in NEK6 and NEK7. The tyrosine motif is involved in autoinhibition in NEK6 and NEK7. However, the catalytic domain of NEK2 is not autoinhibited by the motif. The analysis of NEK2 structure discovered that its activation loop forms a crystal contact with a hydrophobic groove between the C-helix and β4/β5 strands of an adjacent molecule, which inhibits the activity of NEK2. The mutation in the activation loop (F172A and F176A) resulted in the increased kinase activity and stabilization of the autoinhibitied state of NEK2.

Autoinhibitory domains (AIDs)

Accessory elements

158-181 (Activation loop from InterPro)

Target domain	8-271 (Protein kinase domain)
Relief mechanism
Assay	Structural analysis, Mutagenesis experiment

References

Richards MW et al. (2009) "An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9", Molecular cell, 36, 560-70

Westwood I et al. (2009) "Insights into the conformational variability and regulation of human Nek2 kinase", Journal of molecular biology, 386, 476-85

Autoinhibited structure

Activated structure

31 structures for P51955

Entry ID	Method	Resolution	Chain	Position	Source
2JAV	X-ray	220 A	A	1-271	PDB
2W5A	X-ray	155 A	A	1-271	PDB
2W5B	X-ray	240 A	A	1-271	PDB
2W5H	X-ray	233 A	A	1-271	PDB
2WQO	X-ray	217 A	A	1-271	PDB
2XK3	X-ray	220 A	A	1-271	PDB
2XK4	X-ray	210 A	A	1-271	PDB
2XK6	X-ray	220 A	A	1-271	PDB
2XK7	X-ray	199 A	A	1-271	PDB
2XK8	X-ray	200 A	A	1-271	PDB
2XKC	X-ray	250 A	A	1-271	PDB
2XKD	X-ray	196 A	A	1-271	PDB
2XKE	X-ray	220 A	A	1-271	PDB
2XKF	X-ray	235 A	A	1-271	PDB
2XNM	X-ray	185 A	A	1-271	PDB
2XNN	X-ray	250 A	A	1-271	PDB
2XNO	X-ray	198 A	A	1-271	PDB
2XNP	X-ray	198 A	A	1-271	PDB
4A4X	X-ray	240 A	A	1-271	PDB
4AFE	X-ray	260 A	A	1-271	PDB
5M51	X-ray	190 A	A	1-271	PDB
5M53	X-ray	190 A	A	1-271	PDB
5M55	X-ray	240 A	A	1-271	PDB
5M57	X-ray	230 A	A	1-271	PDB
6SGD	X-ray	200 A	A	1-271	PDB
6SGH	X-ray	300 A	A	1-271	PDB
6SGI	X-ray	230 A	A	1-271	PDB
6SGK	X-ray	200 A	A	1-271	PDB
6SK9	X-ray	200 A	A	1-271	PDB
6TM5	EM	390 A	Q/S	1-445	PDB
AF-P51955-F1	Predicted				AlphaFoldDB

298 variants for P51955

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000076909 rs398122961	206	L>missing	Retinitis pigmentosa 67 [ClinVar]	Yes	ClinVar dbSNP
rs528173241 CA1381785	2	P>L		No	ClinGen 1000Genomes ExAC gnomAD
CA344786949 rs1220958293	4	R>L		No	ClinGen gnomAD
rs200051849 CA1381783	4	R>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA36826674 rs1033497592	8	Y>S		No	ClinGen Ensembl
CA1381781 rs780341599	9	E>V		No	ClinGen ExAC TOPMed
rs1553299887 CA1381779	12	Y>H		No	ClinGen Ensembl
rs958689367 CA36826651	14	I>T		No	ClinGen TOPMed
rs1281408160 CA344786873	16	T>A		No	ClinGen gnomAD
rs371921288 CA1381777	17	G>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344786861 rs1571650345	18	S>P		No	ClinGen Ensembl
CA1381774 rs752684512	21	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1278518247 CA344786768	25	I>T		No	ClinGen TOPMed gnomAD
rs369153129 CA36826594	26	R>L		No	ClinGen ESP gnomAD
rs370861680 CA1381771	26	R>W		No	ClinGen ExAC gnomAD
rs766070250 CA1381770	27	R>K		No	ClinGen ExAC TOPMed gnomAD
CA36826592 rs765507869	28	K>R		No	ClinGen Ensembl
rs1571650251 CA344786711	29	S>R		No	ClinGen Ensembl
CA344786701 rs1169843035	30	D>V		No	ClinGen gnomAD
CA344786695 rs1478078285	31	G>S		No	ClinGen TOPMed gnomAD
rs1462907071 CA344786671	32	K>N		No	ClinGen TOPMed
rs765862166 CA1381753	33	I>M		No	ClinGen ExAC gnomAD
CA344785910 rs1459491017	33	I>T		No	ClinGen gnomAD
rs1315213752 CA344785779	39	L>H		No	ClinGen TOPMed gnomAD
rs1315213752 CA344785777	39	L>R		No	ClinGen TOPMed gnomAD
rs1330186820 CA344785746	41	Y>C		No	ClinGen TOPMed
rs753966596 CA344785694	44	M>L		No	ClinGen TOPMed gnomAD
rs753966596 CA36825921	44	M>V		No	ClinGen TOPMed gnomAD
CA344785659 rs1374113223	45	T>A		No	ClinGen gnomAD
CA344785656 rs1374113223	45	T>S		No	ClinGen gnomAD
COSM1663035 COSM1663036 CA1381747 rs774941061	51	M>I	kidney [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA344785546 rs762290467	51	M>K		No	ClinGen ExAC gnomAD
rs762290467 CA344785541	51	M>R		No	ClinGen ExAC gnomAD
CA1381748 rs762290467	51	M>T		No	ClinGen ExAC gnomAD
rs764701724 CA1381746	53	V>A		No	ClinGen ExAC gnomAD
CA36825903 rs970410564	53	V>I		No	ClinGen Ensembl
rs775627721 CA1381744	57	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1438076471 CA344785397	60	R>C		No	ClinGen gnomAD
CA1381743 rs769815273	60	R>H		No	ClinGen ExAC gnomAD
CA1381742 rs764749288	62	L>R		No	ClinGen ExAC gnomAD
rs771809019 CA1381740	65	P>S		No	ClinGen ExAC gnomAD
rs368396189 CA1381739	69	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA1381737 rs754907915	69	R>H		No	ClinGen ExAC gnomAD
rs368396189 CA1381738	69	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs375409578 CA36825857	71	Y>C		No	ClinGen ESP TOPMed gnomAD
CA1381736 rs749229852	72	D>H		No	ClinGen ExAC gnomAD
rs779581769 CA344785114	73	R>L		No	ClinGen ExAC TOPMed gnomAD
rs779581769 CA1381735	73	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs145931962 CA36825851	73	R>W		No	ClinGen ESP TOPMed gnomAD
rs985623901 CA36825842	75	I>T		No	ClinGen TOPMed
CA36825843 rs147996367	75	I>V		No	ClinGen ESP
rs755607037 CA1381734	76	D>G		No	ClinGen ExAC gnomAD
CA344785067 rs1214275935	76	D>N		No	ClinGen gnomAD
rs767290689 CA1381732	77	R>Q		No	ClinGen ExAC gnomAD
rs149282984 CA1381733	77	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1391282322 CA344785007	78	T>I		No	ClinGen TOPMed gnomAD
CA36825818 rs372274678	78	T>S		No	ClinGen ESP TOPMed
CA344785009 rs1391282322	78	T>S		No	ClinGen TOPMed gnomAD
rs1304744226 CA344784996	79	N>S		No	ClinGen gnomAD
CA1381731 rs757627703	82	L>V		No	ClinGen ExAC gnomAD
rs751965926 CA1381730	84	I>V		No	ClinGen ExAC gnomAD
rs763496344 CA1381728	88	Y>C		No	ClinGen ExAC gnomAD
rs1376025508 CA344784855	90	E>K		No	ClinGen gnomAD
rs775902118 CA1381727	91	G>E		No	ClinGen ExAC gnomAD
CA344784839 rs1240295488	91	G>R		No	ClinGen gnomAD
rs181925177 CA36825791	94	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs776779483 CA1381724	96	S>N		No	ClinGen ExAC gnomAD
rs1312492844 CA344784749	97	V>L		No	ClinGen gnomAD
rs747301231 CA1381722	99	T>I		No	ClinGen ExAC gnomAD
CA344784661 rs1253746864	104	E>K		No	ClinGen gnomAD
rs1477751580 CA344784465	109	D>H		No	ClinGen gnomAD
CA344784422 rs1377850573	111	E>A		No	ClinGen TOPMed
rs1253628601 CA344784390	113	V>I		No	ClinGen gnomAD
rs753913263 CA1381703	115	R>*		No	ClinGen ExAC TOPMed gnomAD
rs753913263 CA344784364	115	R>G		No	ClinGen ExAC TOPMed gnomAD
COSM94816 CA1381702 rs766507035 COSM903497	115	R>Q	endometrium breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs760853858 CA1381701	116	V>M		No	ClinGen ExAC gnomAD
CA36825423 rs949581579	117	M>T		No	ClinGen Ensembl
rs1317151113 CA344784303	119	Q>R		No	ClinGen TOPMed gnomAD
CA344784273 rs1558230519	121	T>S		No	ClinGen Ensembl
CA1381699 rs768444644	123	A>V		No	ClinGen ExAC gnomAD
rs918172930 CA36825408	126	E>*		No	ClinGen Ensembl
CA344784195 rs1333718925	126	E>V		No	ClinGen gnomAD
CA36825398 rs959309585	130	R>Q		No	ClinGen Ensembl
CA1381697 rs775431278	132	D>E		No	ClinGen ExAC gnomAD
CA344784115 rs1408416719	132	D>N		No	ClinGen gnomAD
CA1381696 rs146297864 COSM99090	134	G>D	stomach [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA1381695 rs745856837	135	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA344784073 rs1424895804	135	H>Y		No	ClinGen gnomAD
CA344784058 rs1571648240	136	T>P		No	ClinGen Ensembl
CA1381693 COSM1601618 COSM1601617 rs151049149	137	V>I	liver [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA1381692 rs746620317	139	H>R		No	ClinGen ExAC TOPMed gnomAD
rs1216643828 CA344784002	140	R>Q		No	ClinGen gnomAD
rs778979955 CA1381691	140	R>W		No	ClinGen ExAC TOPMed gnomAD
rs770318535 CA1381690	141	D>N		No	ClinGen ExAC gnomAD
CA36825318 rs955252425	142	L>M		No	ClinGen TOPMed
rs753012512 CA1381689	143	K>N		No	ClinGen ExAC gnomAD
CA1381688 rs779404718	144	P>L		No	ClinGen ExAC gnomAD
CA36825297 rs1028215324	146	N>S		No	ClinGen Ensembl
rs766402568 CA1381685	151	G>S		No	ClinGen ExAC gnomAD
CA1381684 rs377505890	152	K>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs750582260 CA1381683	153	Q>P		No	ClinGen ExAC TOPMed gnomAD
CA344783796 rs1183594225	154	N>T		No	ClinGen TOPMed
CA344783782 COSM3803799 rs1411448957 COSM3803798	155	V>I	breast [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1423040257 CA344783750	157	L>V		No	ClinGen TOPMed
rs1289056813 CA344783712	159	D>E		No	ClinGen gnomAD
CA344783464 rs1467409025	169	D>N		No	ClinGen TOPMed
rs759517583 CA1381678	170	T>K		No	ClinGen ExAC TOPMed gnomAD
CA344783431 rs759517583	170	T>M		No	ClinGen ExAC TOPMed gnomAD
rs759517583 CA344783437	170	T>R		No	ClinGen ExAC TOPMed gnomAD
rs776741757 CA1381677	171	S>N		No	ClinGen ExAC TOPMed gnomAD
rs770518324 CA1381676	172	F>S		No	ClinGen ExAC gnomAD
CA1381675 rs746532045	174	K>I		No	ClinGen ExAC gnomAD
CA1381674 rs777421680	175	T>I		No	ClinGen ExAC gnomAD
CA36825221 rs1006751197	176	F>L		No	ClinGen TOPMed
CA36825228 rs1006751197	176	F>L		No	ClinGen TOPMed
rs1377599830 CA344783240	177	V>I		No	ClinGen TOPMed
rs1322011011 CA344783219	178	G>S		No	ClinGen TOPMed gnomAD
rs771623184 CA1381673	179	T>I		No	ClinGen ExAC gnomAD
CA344783182 rs1288881753	180	P>A		No	ClinGen gnomAD
rs747895630 CA344783176	180	P>H		No	ClinGen ExAC gnomAD
CA1381672 rs747895630	180	P>L		No	ClinGen ExAC gnomAD
CA344783156 rs1314606306	181	Y>H		No	ClinGen gnomAD
rs1279272576 CA344783151	181	Y>S		No	ClinGen TOPMed
CA1381670 rs755399046	183	M>I		No	ClinGen ExAC TOPMed gnomAD
rs375335162 CA1381671	183	M>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs566646481 CA1381655	187	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA36823970 rs755860084	188	M>R		No	ClinGen Ensembl
CA1381654 rs144260153	189	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA36823957 rs901790418	190	R>C		No	ClinGen TOPMed gnomAD
rs139313101 CA1381653	190	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA36823956 rs993989313	191	M>R		No	ClinGen Ensembl
CA1381652 rs774072704	194	N>D		No	ClinGen ExAC TOPMed gnomAD
CA344781156 rs1241595367	194	N>S		No	ClinGen TOPMed
CA344781112 rs1345355060	197	S>P		No	ClinGen gnomAD
rs1424424423 CA344781098	198	D>N		No	ClinGen gnomAD
rs1302716469 CA344781045	201	S>A		No	ClinGen gnomAD
rs1571646049 CA344780911	206	L>Q		No	ClinGen Ensembl
rs780462738 CA1381649	207	Y>*		No	ClinGen ExAC gnomAD
CA344780894 rs1213878447	207	Y>H		No	ClinGen TOPMed
rs756599576 CA1381648	208	E>D		No	ClinGen ExAC gnomAD
CA344780399 rs1162203681	213	M>I		No	ClinGen TOPMed
CA1381645 rs757390908	213	M>T		No	ClinGen ExAC gnomAD
rs369881336 CA1381622 COSM162871	215	P>A	NS [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed
rs1454110035 CA344780354	216	F>L		No	ClinGen gnomAD
CA344780287 rs1398071088	217	T>R		No	ClinGen gnomAD
rs377538977 CA36823505	218	A>G		No	ClinGen ESP TOPMed
CA1381620 rs779967834	220	S>N		No	ClinGen ExAC gnomAD
rs1356090201 CA344780095	224	L>V		No	ClinGen gnomAD
CA344780069 rs544218144	225	A>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1381617 rs544218144	225	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA36823469 rs545302925	228	I>M		No	ClinGen Ensembl
CA344779970 rs1386077899	228	I>S		No	ClinGen gnomAD
rs372477595 CA344779817	235	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs372477595 CA1381616	235	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA344779775 rs1238153644	237	P>L		No	ClinGen TOPMed gnomAD
rs1437873919 CA344779787	237	P>T		No	ClinGen gnomAD
rs1275708583 CA344779768	238	Y>H		No	ClinGen TOPMed
rs763642279 CA1381613	239	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1264058723 CA344779752	239	R>H		No	ClinGen gnomAD
rs763642279 CA1381614	239	R>S		No	ClinGen ExAC TOPMed gnomAD
rs148642058 CA1381611	242	D>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA1381609 rs759961131	244	L>S		No	ClinGen ExAC gnomAD
CA1381608 rs776935855	249	T>M		No	ClinGen ExAC TOPMed gnomAD
rs771466348 CA1381607	252	L>F		No	ClinGen ExAC gnomAD
rs1305618631 CA344779552	253	N>I		No	ClinGen gnomAD
rs1367385481 CA344779528	255	K>Q		No	ClinGen TOPMed
rs978868629 CA36822854	256	D>G		No	ClinGen TOPMed gnomAD
rs978868629 CA344779461	256	D>V		No	ClinGen TOPMed gnomAD
rs1477898965 CA344779447	257	Y>C		No	ClinGen TOPMed
CA1381587 rs761216195	259	R>*		No	ClinGen ExAC gnomAD
CA344779420 rs1177477304	259	R>Q		No	ClinGen TOPMed
CA1381585 rs772218924	260	P>L		No	ClinGen ExAC gnomAD
rs773890490 CA1381586	260	P>S		No	ClinGen ExAC gnomAD
CA36822815 rs938898081	266	L>V		No	ClinGen Ensembl
CA344779242 rs149647934	269	P>A		No	ClinGen ESP gnomAD
rs149647934 CA36822791	269	P>S		No	ClinGen ESP gnomAD
CA344779244 rs149647934	269	P>T		No	ClinGen ESP gnomAD
rs1260605461 CA344779196	271	I>V		No	ClinGen gnomAD
CA1381583 rs534046984	273	D>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs766897728 CA1381584	273	D>N		No	ClinGen ExAC TOPMed gnomAD
rs143249148 CA1381581	277	D>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs757031845 CA1381579 COSM94815	278	E>K	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA344779009 rs1284977214	279	Q>*		No	ClinGen gnomAD
CA344778970 rs1326142454	281	R>G		No	ClinGen gnomAD
rs1319198009 CA344778960	281	R>I		No	ClinGen TOPMed gnomAD
rs948428346 CA36822759	282	N>S		No	ClinGen Ensembl
rs1352594832 CA344778848	287	G>R		No	ClinGen TOPMed
COSM903494 COSM1584010 rs533767848 CA1381577	288	R>*	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA1381576 rs181112920	288	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs764712596 CA1381574	292	E>D		No	ClinGen ExAC TOPMed gnomAD
rs1451436670 CA344778769	292	E>K		No	ClinGen TOPMed
rs754639923 CA1381573	293	P>T		No	ClinGen ExAC gnomAD
rs1433287246 CA344778696	295	K>I		No	ClinGen gnomAD
rs1372194983 COSM1584011 CA344778666 COSM903493	296	S>L	skin endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
CA36822664 rs924484677	296	S>P		No	ClinGen Ensembl
rs766728910 CA1381571	297	Q>E		No	ClinGen ExAC
CA344778649 rs1558228679	297	Q>R		No	ClinGen Ensembl
CA1381570 rs369354793	298	D>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1381568 rs762464147	303	L>V		No	ClinGen ExAC TOPMed gnomAD
CA344778441 rs1329307673	304	S>I		No	ClinGen Ensembl
rs1196575096 CA344778381	307	K>N		No	ClinGen gnomAD
rs774546841 CA1381566	309	K>N		No	ClinGen ExAC gnomAD
rs375540677 CA1381565	310	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs763917720 CA36822561	311	I>V		No	ClinGen gnomAD
rs1017541099 CA36822560	312	Q>R		No	ClinGen Ensembl
CA1381563 rs775595439	313	L>I		No	ClinGen ExAC gnomAD
CA344778245 rs746813208	314	Q>*		No	ClinGen ExAC gnomAD
rs746813208 CA1381561	314	Q>E		No	ClinGen ExAC gnomAD
CA1381560 rs777611391	315	E>*		No	ClinGen ExAC gnomAD
CA1381559 rs200225398	316	R>*		No	ClinGen ESP ExAC gnomAD
rs748133777 CA1381558	316	R>Q		No	ClinGen ExAC gnomAD
CA1381557 rs778457622	317	E>K		No	ClinGen ExAC gnomAD
CA1381556 rs146817802	318	R>*		No	ClinGen ESP ExAC TOPMed gnomAD
COSM259061 rs753485254 CA1381555	318	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs765948759 CA1381554	319	A>T		No	ClinGen ExAC TOPMed gnomAD
CA344778127 rs1444689671	321	K>Q		No	ClinGen gnomAD
rs1179610927 CA344778086	322	A>E		No	ClinGen gnomAD
rs1437089303 CA344778051	324	E>K		No	ClinGen gnomAD
CA344777943 rs1291273707	328	E>A		No	ClinGen gnomAD
CA1381548 rs140995957 COSM1584012 COSM903492	329	Q>*	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA1381549 rs140995957	329	Q>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs764512728 CA1381527	337	R>C		No	ClinGen ExAC gnomAD
rs763584429 CA1381526	337	R>H		No	ClinGen ExAC TOPMed gnomAD
rs763584429 CA344776395	337	R>P		No	ClinGen ExAC TOPMed gnomAD
rs1571642094 CA344776386	338	E>K		No	ClinGen Ensembl
CA36820792 rs1050943261	343	D>N		No	ClinGen TOPMed
CA344776110 rs1428343239	347	R>G		No	ClinGen gnomAD
CA1381522 rs776872046	347	R>K		No	ClinGen ExAC TOPMed gnomAD
rs776872046 CA1381523	347	R>T		No	ClinGen ExAC TOPMed gnomAD
CA344776083 rs1396598606	348	A>S		No	ClinGen TOPMed
rs1240576025 CA344776026	350	N>K		No	ClinGen gnomAD
CA1381519 rs774266098	351	L>V		No	ClinGen ExAC TOPMed gnomAD
rs768461134 CA1381518	352	L>F		No	ClinGen ExAC gnomAD
rs2230489 VAR_019990 CA1381517	354	N>S		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs779397609 CA1381516	356	S>N		No	ClinGen ExAC TOPMed gnomAD
rs988167642 CA36820706	360	E>K		No	ClinGen Ensembl
CA1381514 rs745466887	361	R>Q		No	ClinGen ExAC gnomAD
CA36820688 rs542160394	361	R>W		No	ClinGen gnomAD
rs973068064 CA36820668	362	K>T		No	ClinGen Ensembl
rs963100659 CA36820663	363	F>Y		No	ClinGen Ensembl
rs148490084 CA36820650	365	S>F		No	ClinGen ESP
CA1381491 rs748557421	372	L>R		No	ClinGen ExAC gnomAD
rs1369684505 CA344774112	373	L>F		No	ClinGen TOPMed
CA344774109 rs1358139566	373	L>R		No	ClinGen gnomAD
CA344774098 rs1397722593	375	L>F		No	ClinGen TOPMed gnomAD
rs1297455567 CA344774090	376	P>L		No	ClinGen TOPMed gnomAD
CA1381489 rs754988537	376	P>S		No	ClinGen ExAC gnomAD
rs753898563 CA1381488	381	K>N		No	ClinGen ExAC gnomAD
CA1381487 rs766490784	383	K>Q		No	ClinGen ExAC gnomAD
rs1385946017 CA344774031	385	H>L		No	ClinGen gnomAD
rs1165486612 CA344774019	387	S>G		No	ClinGen gnomAD
CA1381486 rs756257362	387	S>I		No	ClinGen ExAC TOPMed gnomAD
rs756257362 CA344774017	387	S>N		No	ClinGen ExAC TOPMed gnomAD
rs750686531 CA1381485	390	S>N		No	ClinGen ExAC gnomAD
rs1481812262 CA344773967	394	I>V		No	ClinGen gnomAD
rs544555116 CA344773954	395	M>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1381484 rs544555116	395	M>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA344773960 rs1313591921	395	M>V		No	ClinGen TOPMed
CA1381483 rs762818619	397	S>C		No	ClinGen ExAC TOPMed gnomAD
rs758512270 CA1381482	397	S>N		No	ClinGen ExAC gnomAD
CA1381481 rs765260024	399	N>K		No	ClinGen ExAC gnomAD
CA344773918 rs1246341978	401	E>Q		No	ClinGen gnomAD
CA1381479 rs759605651	405	T>I		No	ClinGen ExAC gnomAD
CA344773863 rs1306172346	405	T>S		No	ClinGen gnomAD
rs770516208 CA1381477	406	S>P		No	ClinGen ExAC gnomAD
rs746603282 CA1381476	408	S>Y		No	ClinGen ExAC gnomAD
CA1381475 rs576980203	409	K>R		No	ClinGen 1000Genomes ExAC gnomAD
CA1381474 VAR_040907 rs56102977	410	C>Y		No	ClinGen UniProt ExAC dbSNP gnomAD
rs748521808 CA1381473	412	D>N		No	ClinGen ExAC gnomAD
rs200747370 CA36818072	416	R>S		No	ClinGen TOPMed
CA1381471 rs755452613	419	A>G		No	ClinGen ExAC TOPMed gnomAD
CA344773655 rs1382502737	419	A>T		No	ClinGen gnomAD
rs1490097184 CA344773627	422	L>M		No	ClinGen gnomAD
CA344773613 rs1211179624	423	R>Q		No	ClinGen TOPMed gnomAD
CA1381468 rs756236866	423	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1484616327 CA344773605	424	A>P		No	ClinGen TOPMed gnomAD
rs1484616327 CA344773607	424	A>T		No	ClinGen TOPMed gnomAD
rs767783429 CA1381466	426	A>G		No	ClinGen ExAC TOPMed gnomAD
CA1381467 rs750553031	426	A>T		No	ClinGen ExAC gnomAD
rs767783429 CA344773544	426	A>V		No	ClinGen ExAC TOPMed gnomAD
rs757488320 CA344773536	427	L>V		No	ClinGen ExAC gnomAD
CA1381464 rs752525969	428	S>P		No	ClinGen ExAC gnomAD
CA1381463 rs765172198	430	I>V		No	ClinGen ExAC TOPMed
CA36817978 rs753859332	434	Y>D		No	ClinGen ExAC gnomAD
CA1381461 rs753859332	434	Y>H		No	ClinGen ExAC gnomAD
rs202099146 CA1381459	436	L>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1338508994 CA344773279	437	K>E		No	ClinGen Ensembl
rs554798094 CA1381458	437	K>N		No	ClinGen 1000Genomes ExAC gnomAD
CA344773208 rs1286575982	439	R>G		No	ClinGen TOPMed gnomAD
CA344773188 rs12031285	439	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA344773134 rs141984487	440	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs141984487 CA1381456	440	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs774663788 CA1381455	441	I>N		No	ClinGen ExAC gnomAD
rs936683592 CA36817923	444	M>I		No	ClinGen TOPMed
CA344773056 rs1200556151	444	M>V		No	ClinGen gnomAD
CA1381452 rs780623362	445	R>C		No	ClinGen ExAC gnomAD
rs769694500 CA1381451	445	R>H		No	ClinGen ExAC TOPMed gnomAD

1 associated diseases with P51955

[MIM: 615565]: Retinitis pigmentosa 67 (RP67)

A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:24043777}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:24043777}. Note=The disease is caused by variants affecting the gene represented in this entry.

2 regional properties for P51955

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	8 - 271	IPR000719
active_site	Serine/threonine-protein kinase, active site	137 - 149	IPR008271

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	[Isoform 1]: Nucleus Nucleus, nucleolus Cytoplasm Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cytoskeleton, spindle pole Chromosome, centromere, kinetochore Chromosome, centromere	STK3/MST2 and SAV1 are required for its targeting to the centrosome Colocalizes with SGO1 and MAD1L1 at the kinetochore Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end
PANTHER Family	PTHR44899	CAMK FAMILY PROTEIN KINASE
PANTHER Subfamily	PTHR44899:SF9	NIMA-RELATED KINASE 2
PANTHER Protein Class	non-receptor serine/threonine protein kinase
PANTHER Pathway Category	No pathway information available

12 GO annotations of cellular component

Name	Definition
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
condensed nuclear chromosome	A highly compacted molecule of DNA and associated proteins resulting in a cytologically distinct nuclear chromosome.
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.
kinetochore	A multisubunit complex that is located at the centromeric region of DNA and provides an attachment point for the spindle microtubules.
microtubule	Any of the long, generally straight, hollow tubes of internal diameter 12-15 nm and external diameter 24 nm found in a wide variety of eukaryotic cells; each consists (usually) of 13 protofilaments of polymeric tubulin, staggered in such a manner that the tubulin monomers are arranged in a helical pattern on the microtubular surface, and with the alpha/beta axes of the tubulin subunits parallel to the long axis of the tubule; exist in equilibrium with pool of tubulin monomers and can be rapidly assembled or disassembled in response to physiological stimuli; concerned with force generation, e.g. in the spindle.
midbody	A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis.
nucleolus	A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
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.
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.
spindle pole	Either of the ends of a spindle, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules.

7 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding	Binding to a metal ion.
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 phosphatase binding	Binding to a protein phosphatase.
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.

19 GO annotations of biological process

Name	Definition
blastocyst development	The process whose specific outcome is the progression of the blastocyst over time, from its formation to the mature structure. The mammalian blastocyst is a hollow ball of cells containing two cell types, the inner cell mass and the trophectoderm.
cell division	The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
centrosome separation	The process in which duplicated centrosome components move away from each other. The centriole pair within each centrosome becomes part of a separate microtubule organizing center that nucleates a radial array of microtubules called an aster. The two asters move to opposite sides of the nucleus to form the two poles of the mitotic spindle.
chromosome segregation	The process in which genetic material, in the form of chromosomes, is organized into specific structures and then physically separated and apportioned to two or more sets. In eukaryotes, chromosome segregation begins with the condensation of chromosomes, includes chromosome separation, and ends when chromosomes have completed movement to the spindle poles.
meiotic cell cycle	Progression through the phases of the meiotic cell cycle, in which canonically a cell replicates to produce four offspring with half the chromosomal content of the progenitor cell via two nuclear divisions.
mitotic cell cycle	Progression through the phases of the mitotic cell cycle, the most common eukaryotic cell cycle, which canonically comprises four successive phases called G1, S, G2, and M and includes replication of the genome and the subsequent segregation of chromosomes into daughter cells. In some variant cell cycles nuclear replication or nuclear division may not be followed by cell division, or G1 and G2 phases may be absent.
mitotic sister chromatid segregation	The cell cycle process in which replicated homologous chromosomes are organized and then physically separated and apportioned to two sets during the mitotic cell cycle. Each replicated chromosome, composed of two sister chromatids, aligns at the cell equator, paired with its homologous partner. One homolog of each morphologic type goes into each of the resulting chromosome sets.
mitotic spindle assembly	Mitotic bipolar spindle assembly begins with spindle microtubule nucleation from the separated spindle pole body, includes spindle elongation during prometaphase, and is complete when all kinetochores are stably attached the spindle, and the spindle assembly checkpoint is satisfied.
negative regulation of centriole-centriole cohesion	Any process that stops, prevents or reduces the frequency, rate or extent of centriole-centriole cohesion.
negative regulation of DNA binding	Any process that stops or reduces the frequency, rate or extent of DNA binding. DNA binding is any process in which a gene product interacts selectively with DNA (deoxyribonucleic acid).
positive regulation of telomerase activity	Any process that activates or increases the frequency, rate or extent of telomerase activity, the catalysis of the reaction: deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
positive regulation of telomere capping	Any process that activates or increases the frequency, rate or extent of telomere capping.
positive regulation of telomere maintenance via telomerase	Any process that activates or increases the frequency, rate or extent of the addition of telomeric repeats by telomerase.
protein autophosphorylation	The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of attachment of spindle microtubules to kinetochore	Any process that modulates the frequency, rate or extent of the attachment of spindle microtubules to the kinetochore.
regulation of mitotic centrosome separation	Any process that modulates the frequency, rate or extent of the separation of duplicated centrosome components at the beginning of mitosis.
regulation of mitotic nuclear division	Any process that modulates the frequency, rate or extent of mitosis.
spindle assembly	The aggregation, arrangement and bonding together of a set of components to form the spindle, the array of microtubules and associated molecules that serves to move duplicated chromosomes apart.

9 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P22209	KIN3	Serine/threonine-protein kinase KIN3	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
P21359	NF1	Neurofibromin	Homo sapiens (Human)	PR
Q04690	Nf1	Neurofibromin	Mus musculus (Mouse)	PR
O35942	Nek2	Serine/threonine-protein kinase Nek2	Mus musculus (Mouse)	PR
Q6ZEZ5	NEK3	Serine/threonine-protein kinase Nek3	Oryza sativa subsp japonica (Rice)	PR
Q10GB1	NEK1	Serine/threonine-protein kinase Nek1	Oryza sativa subsp japonica (Rice)	PR
Q9SLI2	NEK1	Serine/threonine-protein kinase Nek1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q8RXT4	NEK4	Serine/threonine-protein kinase Nek4	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9LT35	NEK6	Serine/threonine-protein kinase Nek6	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MPSRAEDYEV	LYTIGTGSYG	RCQKIRRKSD	GKILVWKELD	YGSMTEAEKQ	MLVSEVNLLR
70	80	90	100	110	120
ELKHPNIVRY	YDRIIDRTNT	TLYIVMEYCE	GGDLASVITK	GTKERQYLDE	EFVLRVMTQL
130	140	150	160	170	180
TLALKECHRR	SDGGHTVLHR	DLKPANVFLD	GKQNVKLGDF	GLARILNHDT	SFAKTFVGTP
190	200	210	220	230	240
YYMSPEQMNR	MSYNEKSDIW	SLGCLLYELC	ALMPPFTAFS	QKELAGKIRE	GKFRRIPYRY
250	260	270	280	290	300
SDELNEIITR	MLNLKDYHRP	SVEEILENPL	IADLVADEQR	RNLERRGRQL	GEPEKSQDSS
310	320	330	340	350	360
PVLSELKLKE	IQLQERERAL	KAREERLEQK	EQELCVRERL	AEDKLARAEN	LLKNYSLLKE
370	380	390	400	410	420
RKFLSLASNP	ELLNLPSSVI	KKKVHFSGES	KENIMRSENS	ESQLTSKSKC	KDLKKRLHAA
430	440
QLRAQALSDI	EKNYQLKSRQ	ILGMR