AiPD: Autoinhibited Protein Database

Q8TDX7

Gene name	NEK7
Protein name	Serine/threonine-protein kinase Nek7
Names	Never in mitosis A-related kinase 7, NimA-related protein kinase 7
Species	Homo sapiens (Human)
KEGG Pathway	hsa:140609
EC number	2.7.11.34: Protein-serine/threonine kinases
Protein Class	MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 20-RELATED (PTHR43289)

Descriptions

Nek7 is a NIMA-related kinase essential for proper mitotic spindle assembly. Nek7 is subject to autoinhibition by a tyrosine motif, Tyr97, like Nek6 (Tyr108). This is because the Y97A mutation is more active than wild-type Nek7.

Autoinhibitory domains (AIDs)

Target domain	20-30 (N-terminal extension of kinase domain)
Relief mechanism	Partner binding
Assay	Structural analysis, Mutagenesis experiment

AID

97-103 (β4 sheet containing tyrosine motif)

Target domain

20-30 (N-terminal extension of kinase domain)

Relief mechanism

Partner binding (Interaction with C-terminal domain of Nek9)

Assay

Structural analysis, Mutagenesis experiment

Accessory elements

178-201 (Activation loop from InterPro)

Target domain	34-299 (Protein kinase domain)
Relief mechanism
Assay

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

Haq T et al. (2015) "Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization", Nature communications, 6, 8771

Autoinhibited structure

Activated structure

10 structures for Q8TDX7

Entry ID	Method	Resolution	Chain	Position	Source
2WQM	X-ray	210 A	A	1-302	PDB
2WQN	X-ray	230 A	A	1-302	PDB
5DE2	X-ray	278 A	A/B	1-302	PDB
6NPY	EM	380 A	B	1-302	PDB
6S73	X-ray	350 A	A/B/C/D	1-302	PDB
6S75	X-ray	330 A	A/B/C/D	1-302	PDB
6S76	X-ray	338 A	A/B/C/D	1-302	PDB
8EJ4	EM	340 A	K/L/M/N/O/P/Q/R/S/T	20-297	PDB
8SXN	EM	404 A	A/B	1-302	PDB
AF-Q8TDX7-F1	Predicted				AlphaFoldDB

133 variants for Q8TDX7

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs201583122 CA1313903	5	S>P		No	ClinGen 1000Genomes ExAC gnomAD
CA1313904 rs142697088	7	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA1313907 rs116746425	8	M>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1313906 COSM98996 rs115665134	8	M>L	stomach [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA344094871 rs1558069041	8	M>T		No	ClinGen Ensembl
rs1373108454 CA344094894	11	P>L		No	ClinGen gnomAD
CA344094914 rs1166034221	15	Q>E		No	ClinGen gnomAD
CA344094936 rs976585620	17	Q>H		No	ClinGen TOPMed gnomAD
rs1312565112 CA344094948	19	Q>H		No	ClinGen TOPMed gnomAD
CA1313910 rs145553219	19	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA1313933 rs116247582	21	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1313934 rs116247582	21	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1313935 rs779021260	23	R>*		No	ClinGen ExAC TOPMed gnomAD
CA344092686 rs779021260	23	R>G		No	ClinGen ExAC TOPMed gnomAD
CA36133993 rs1013083415 COSM901848	23	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs748447738 CA344092693	24	P>L		No	ClinGen ExAC TOPMed gnomAD
rs748447738 CA1313936	24	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs148385729 CA1313938	25	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA36133995 rs905482740	26	M>R		No	ClinGen TOPMed
rs1046604108 CA36133994	26	M>V		No	ClinGen TOPMed
rs1217875629 CA344092720	28	Y>*		No	ClinGen TOPMed gnomAD
CA1313940 rs745749027	28	Y>H		No	ClinGen ExAC TOPMed gnomAD
CA344092730 rs1395242257	30	T>A		No	ClinGen gnomAD
CA1313942 rs200781170	32	A>G		No	ClinGen ExAC gnomAD
CA344092749 rs1571576743	33	N>Y		No	ClinGen Ensembl
VAR_040924 rs55833332 CA1313944	35	R>G		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA344092765 rs773843922	35	R>L		No	ClinGen ExAC TOPMed gnomAD
rs773843922 CA1313945	35	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA1313946 rs761592281	37	E>G		No	ClinGen ExAC gnomAD
rs1226149201 CA344092773	37	E>K		No	ClinGen gnomAD
rs749960374 CA1313948	40	I>M		No	ClinGen ExAC gnomAD
rs761194915 CA1313949	42	R>C		No	ClinGen ExAC TOPMed gnomAD
CA1313950 rs367681965	42	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1571576814 CA344092820	44	Q>E		No	ClinGen Ensembl
CA1313953 rs779405056	49	Y>C		No	ClinGen ExAC gnomAD
rs752851460 CA1313954	50	R>G		No	ClinGen ExAC gnomAD
rs1163478306 CA344092870	51	A>P		No	ClinGen gnomAD
CA1313955 rs758663766	52	A>D		No	ClinGen ExAC gnomAD
rs758663766 CA344092879	52	A>V		No	ClinGen ExAC gnomAD
CA1313956 rs371752680	54	L>F		No	ClinGen ESP ExAC gnomAD
CA344092896 rs1407627980	55	L>S		No	ClinGen gnomAD
CA1313958 rs141651146	59	P>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA344092922 rs1294739821	59	P>S		No	ClinGen gnomAD
CA344092943 rs1310535706	62	L>F		No	ClinGen gnomAD
CA1313960 rs375421905	65	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs924775216 CA36134996	67	I>M		No	ClinGen TOPMed
CA344093620 rs1449802836	70	L>*		No	ClinGen TOPMed
CA36134997 rs977072973	71	M>I		No	ClinGen Ensembl
rs761317968 CA36134998	73	A>V		No	ClinGen Ensembl
CA1314015 rs750418872	76	R>C		No	ClinGen ExAC gnomAD
rs760781979 CA1314017	76	R>L		No	ClinGen ExAC gnomAD
CA1314016 rs760781979	76	R>P		No	ClinGen ExAC gnomAD
CA1314018 rs752669919	77	A>V		No	ClinGen ExAC gnomAD
rs777647381 CA1314020	78	D>A		No	ClinGen ExAC gnomAD
rs369569806 CA36134999	78	D>N		No	ClinGen ESP TOPMed
rs756922781 COSM901850 CA1314022	82	E>*	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1339204812 CA344093707	83	I>T		No	ClinGen gnomAD
CA344093714 rs1226623643	84	D>G		No	ClinGen gnomAD
rs780971977 CA1314023	85	L>H		No	ClinGen ExAC gnomAD
CA344093951 rs1264252717	88	Q>*		No	ClinGen TOPMed
CA1314036 rs372818218	89	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA1314037 rs753873003	90	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1224061536 CA344094017	92	P>S		No	ClinGen TOPMed
rs751598241 CA1314040	99	A>S		No	ClinGen ExAC gnomAD
rs757089870 CA1314041	102	I>T		No	ClinGen ExAC gnomAD
CA344094223 rs1456116271	104	D>G		No	ClinGen gnomAD
CA344094218 rs1387923697	104	D>H		No	ClinGen TOPMed gnomAD
rs1441149962 CA344094281	108	N>H		No	ClinGen TOPMed
CA344094354 rs1156591886	115	D>G		No	ClinGen gnomAD
CA344094352 rs1418928463	115	D>N		No	ClinGen gnomAD
CA36135155 rs867302189	118	D>N		No	ClinGen Ensembl
CA1314046 rs748779876	119	L>Q		No	ClinGen ExAC gnomAD
CA1314065 rs750187883	125	H>Y		No	ClinGen ExAC gnomAD
CA1314067 rs755751284	132	L>Q		No	ClinGen ExAC
CA344095190 rs1571598324	135	E>Q		No	ClinGen Ensembl
rs964825750 CA36136616	138	V>I		No	ClinGen TOPMed
rs1049392766 CA36136617	146	C>S		No	ClinGen gnomAD
rs367944492 CA1314068	147	S>G		No	ClinGen ExAC TOPMed gnomAD
rs1482135308 CA344095314	148	A>T		No	ClinGen gnomAD
CA1314069 rs372494155	152	M>T		No	ClinGen ESP ExAC TOPMed
CA1314070 rs754449598	154	S>P		No	ClinGen ExAC gnomAD
rs778458670 CA1314071	155	R>*		No	ClinGen ExAC gnomAD
CA344095366 rs1423760560	155	R>P		No	ClinGen gnomAD
CA1314072 rs748638300	158	M>L		No	ClinGen ExAC gnomAD
CA344095429 rs1301055508	162	I>T		No	ClinGen gnomAD
CA36136719 rs952495056 COSM901853	167	V>M	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA36136720 rs1026244811	169	I>V		No	ClinGen TOPMed
rs1403801905 CA344095487	171	A>D		No	ClinGen gnomAD
CA1314094 rs781729294	178	G>R		No	ClinGen ExAC gnomAD
rs1365096450 CA344095543	180	L>F		No	ClinGen TOPMed
CA344095559 rs1262531363	183	G>S		No	ClinGen gnomAD
CA344095567 rs1208590623	184	R>Q		No	ClinGen gnomAD
CA344095566 rs1465765236	184	R>W		No	ClinGen TOPMed gnomAD
CA36136721 rs775916237	188	S>*		No	ClinGen Ensembl
CA1314099 rs768828828	189	K>E		No	ClinGen ExAC gnomAD
rs927807022 CA36136722	189	K>N		No	ClinGen Ensembl
CA344095629 rs1391584004	193	A>V		No	ClinGen TOPMed
CA1314100 rs772989091	196	L>F		No	ClinGen ExAC gnomAD
CA36138182 rs889454410	218	D>N		No	ClinGen Ensembl
CA1314119 rs768610334	219	I>T		No	ClinGen ExAC gnomAD
rs1430628777 CA344095870	225	L>Q		No	ClinGen TOPMed
rs79288469 CA36138183	228	E>*		No	ClinGen Ensembl
CA1314145 rs781081703	231	A>S		No	ClinGen ExAC gnomAD
rs745875793 CA1314146	237	Y>C		No	ClinGen ExAC gnomAD
CA1314147 rs769564996	244	Y>C		No	ClinGen ExAC gnomAD
rs768387407 CA1314150	247	C>F		No	ClinGen ExAC gnomAD
rs1558100225 CA344096063	250	I>M		No	ClinGen Ensembl
CA344096075 rs1339259296	252	Q>P		No	ClinGen gnomAD
CA1314151 rs148698699	254	D>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs761363477 CA1314152	262	H>Q		No	ClinGen ExAC
rs774023349 CA1314170	267	L>F		No	ClinGen ExAC gnomAD
rs774023349 CA1314169	267	L>V		No	ClinGen ExAC gnomAD
CA1314172 rs142206404	268	R>Q		No	ClinGen ESP ExAC gnomAD
CA1314174 rs766937646	272	N>D		No	ClinGen ExAC gnomAD
rs777056225 CA1314175	273	M>T		No	ClinGen ExAC gnomAD
CA1314176 rs759916449	274	C>R		No	ClinGen ExAC gnomAD
CA344093045 rs1269141251	276	N>D		No	ClinGen gnomAD
rs1452424739 CA344093048	276	N>S		No	ClinGen gnomAD
CA344093072 rs1376063083	279	P>L		No	ClinGen TOPMed gnomAD
CA1314178 rs765591026	281	K>R		No	ClinGen ExAC gnomAD
CA344093089 rs1160601594	282	R>*		No	ClinGen gnomAD
COSM1217083 rs1426043858 CA344093092	282	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
CA1314181 rs114884409	285	V>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM98941 rs114884409 CA1314180	285	V>I	stomach [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs755998519 CA1314183	286	T>I		No	ClinGen ExAC
rs751670487 CA1314182	286	T>S		No	ClinGen ExAC TOPMed gnomAD
rs754797321 CA1314186	291	V>I		No	ClinGen ExAC TOPMed gnomAD
CA344093155 rs1487416368	292	A>V		No	ClinGen TOPMed
CA1314187 rs778626751	295	M>L		No	ClinGen ExAC gnomAD
CA344093183 rs1411097098	296	H>R		No	ClinGen gnomAD
CA344093180 rs1262787048	296	H>Y		No	ClinGen TOPMed
rs866375032 CA36141072	300	A>T		No	ClinGen Ensembl
rs369005222 CA1314189	301	S>G		No	ClinGen ESP ExAC gnomAD

No associated diseases with Q8TDX7

4 regional properties for Q8TDX7

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	297 - 552	IPR000719
active_site	Serine/threonine-protein kinase, active site	414 - 426	IPR008271
binding_site	Protein kinase, ATP binding site	303 - 330	IPR017441
domain	Myosin light chain kinase 2, catalytic domain	292 - 552	IPR042717

Functions

		Description
EC Number	2.7.11.34	Protein-serine/threonine kinases
Subcellular Localization	Nucleus Cytoplasm Cytoplasm, cytoskeleton, spindle pole Cytoplasm, cytoskeleton, microtubule organizing center, centrosome	Present at centrosome throughout the cell cycle (PubMed:17586473) Also detected at spindle midzone of the anaphase cells and eventually concentrates at the midbody (PubMed:17586473) Interaction with ANKS3 prevents its translocation to the nucleus (By similarity)
PANTHER Family	PTHR43289	MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 20-RELATED
PANTHER Subfamily	PTHR43289:SF2	SERINE_THREONINE-PROTEIN KINASE NEK7
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.
microtubule organizing center	An intracellular structure that can catalyze gamma-tubulin-dependent microtubule nucleation and that can anchor microtubules by interacting with their minus ends, plus ends or sides.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
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.

5 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 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.

8 GO annotations of biological process

Name	Definition
cellular response to potassium ion	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 potassium ion stimulus.
positive regulation of NLRP3 inflammasome complex assembly	Any process that activates or increases the frequency, rate or extent of NLRP3 inflammasome complex assembly.
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 phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of mitotic cell cycle	Any process that modulates the rate or extent of progress through the mitotic cell cycle.
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
Q9HC98	NEK6	Serine/threonine-protein kinase Nek6	Homo sapiens (Human)	EV
Q9ES70	Nek6	Serine/threonine-protein kinase Nek6	Mus musculus (Mouse)	SS
Q9ES74	Nek7	Serine/threonine-protein kinase Nek7	Mus musculus (Mouse)	SS
A2BD05	NEK6	Serine/threonine-protein kinase Nek6	Sus scrofa (Pig)	SS
P59895	Nek6	Serine/threonine-protein kinase Nek6	Rattus norvegicus (Rat)	SS
D3ZBE5	Nek7	Serine/threonine-protein kinase Nek7	Rattus norvegicus (Rat)	SS
G5EFM9	nekl-3	Serine/threonine-protein kinase nekl-3	Caenorhabditis elegans	PR
Q9LVL5	WNK4	Probable serine/threonine-protein kinase WNK4	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9STK6	WNK3	Probable serine/threonine-protein kinase WNK3	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MDEQSQGMQG	PPVPQFQPQK	ALRPDMGYNT	LANFRIEKKI	GRGQFSEVYR	AACLLDGVPV
70	80	90	100	110	120
ALKKVQIFDL	MDAKARADCI	KEIDLLKQLN	HPNVIKYYAS	FIEDNELNIV	LELADAGDLS
130	140	150	160	170	180
RMIKHFKKQK	RLIPERTVWK	YFVQLCSALE	HMHSRRVMHR	DIKPANVFIT	ATGVVKLGDL
190	200	210	220	230	240
GLGRFFSSKT	TAAHSLVGTP	YYMSPERIHE	NGYNFKSDIW	SLGCLLYEMA	ALQSPFYGDK
250	260	270	280	290	300
MNLYSLCKKI	EQCDYPPLPS	DHYSEELRQL	VNMCINPDPE	KRPDVTYVYD	VAKRMHACTA

SS