AiPD: Autoinhibited Protein Database

O14757

Gene name	CHEK1 (CHK1)
Protein name	Serine/threonine-protein kinase Chk1
Names	CHK1 checkpoint homolog, Cell cycle checkpoint kinase, Checkpoint kinase-1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1111
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	MAP/MICROTUBULE AFFINITY-REGULATING KINASE (PTHR24346)

Descriptions

CHEK1 is a serine/threonine protein kinase and is a key mediator that links the DNA stress responses to the cell cycle. Full-length CHEK1 has only low basal activity when expressed. Truncation of the C-terminal regulatory region activates CHEK1 even in the absence of stress.

Autoinhibitory domains (AIDs)

Target domain	9-265 (Protein kinase domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment

AID

391-476 (C-terminal autoinhibitory region)

Target domain

9-265 (Protein kinase domain)

Relief mechanism

Partner binding (Phosphorylated claspin to a phosphate-binding site in the kinase domain of CHEK1)

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

147-172 (Activation loop from InterPro)

Target domain	9-265 (Protein kinase domain)
Relief mechanism
Assay

References

Ng CP et al. (2004) "Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains", The Journal of biological chemistry, 279, 8808-19

Autoinhibited structure

Activated structure

160 structures for O14757

Entry ID	Method	Resolution	Chain	Position	Source
1IA8	X-ray	170 A	A	1-289	PDB
1NVQ	X-ray	200 A	A	1-289	PDB
1NVR	X-ray	180 A	A	1-289	PDB
1NVS	X-ray	180 A	A	1-289	PDB
1ZLT	X-ray	174 A	A	1-289	PDB
1ZYS	X-ray	170 A	A	1-273	PDB
2AYP	X-ray	290 A	A	1-269	PDB
2BR1	X-ray	200 A	A	1-289	PDB
2BRB	X-ray	210 A	A	1-289	PDB
2BRG	X-ray	210 A	A	1-289	PDB
2BRH	X-ray	210 A	A	1-289	PDB
2BRM	X-ray	220 A	A	1-289	PDB
2BRN	X-ray	280 A	A	1-289	PDB
2BRO	X-ray	220 A	A	1-289	PDB
2C3J	X-ray	210 A	A	1-289	PDB
2C3K	X-ray	260 A	A	1-289	PDB
2C3L	X-ray	235 A	A	1-289	PDB
2CGU	X-ray	250 A	A	1-289	PDB
2CGV	X-ray	260 A	A	1-289	PDB
2CGW	X-ray	220 A	A	1-289	PDB
2CGX	X-ray	220 A	A	1-289	PDB
2E9N	X-ray	250 A	A	2-270	PDB
2E9O	X-ray	210 A	A	2-270	PDB
2E9P	X-ray	260 A	A	2-270	PDB
2E9U	X-ray	200 A	A	2-270	PDB
2E9V	X-ray	200 A	A/B	2-269	PDB
2GDO	X-ray	300 A	A	1-289	PDB
2GHG	X-ray	350 A	A	2-270	PDB
2HOG	X-ray	190 A	A	2-307	PDB
2HXL	X-ray	180 A	A	2-307	PDB
2HXQ	X-ray	200 A	A	2-307	PDB
2HY0	X-ray	170 A	A	2-307	PDB
2QHM	X-ray	200 A	A	1-307	PDB
2QHN	X-ray	170 A	A	1-307	PDB
2R0U	X-ray	190 A	A	1-307	PDB
2WMQ	X-ray	248 A	A	1-289	PDB
2WMR	X-ray	243 A	A	1-289	PDB
2WMS	X-ray	270 A	A	1-289	PDB
2WMT	X-ray	255 A	A	1-289	PDB
2WMU	X-ray	260 A	A	1-289	PDB
2WMV	X-ray	201 A	A	1-289	PDB
2WMW	X-ray	243 A	A	1-289	PDB
2WMX	X-ray	245 A	A	1-289	PDB
2X8D	X-ray	190 A	A	1-289	PDB
2X8E	X-ray	250 A	A	1-276	PDB
2X8I	X-ray	192 A	A	1-289	PDB
2XEY	X-ray	270 A	A	1-289	PDB
2XEZ	X-ray	225 A	A	1-289	PDB
2XF0	X-ray	240 A	A	1-289	PDB
2YDI	X-ray	160 A	A	1-289	PDB
2YDJ	X-ray	185 A	A/B	1-276	PDB
2YDK	X-ray	190 A	A	1-276	PDB
2YER	X-ray	183 A	A	1-276	PDB
2YEX	X-ray	130 A	A	1-276	PDB
2YM3	X-ray	201 A	A	1-289	PDB
2YM4	X-ray	235 A	A	1-289	PDB
2YM5	X-ray	203 A	A	1-289	PDB
2YM6	X-ray	201 A	A	1-289	PDB
2YM7	X-ray	181 A	A	1-289	PDB
2YM8	X-ray	207 A	A	1-289	PDB
2YWP	X-ray	290 A	A	2-270	PDB
3F9N	X-ray	190 A	A	2-307	PDB
3JVR	X-ray	176 A	A	2-272	PDB
3JVS	X-ray	190 A	A	2-272	PDB
3NLB	X-ray	190 A	A	1-289	PDB
3OT3	X-ray	144 A	A	2-274	PDB
3OT8	X-ray	165 A	A	2-274	PDB
3PA3	X-ray	140 A	A	2-274	PDB
3PA4	X-ray	159 A	A	2-274	PDB
3PA5	X-ray	170 A	A	2-274	PDB
3TKH	X-ray	179 A	A	1-307	PDB
3TKI	X-ray	160 A	A	1-307	PDB
3U9N	X-ray	185 A	A	2-274	PDB
4FSM	X-ray	230 A	A	2-280	PDB
4FSN	X-ray	210 A	A	4-280	PDB
4FSQ	X-ray	240 A	A	2-280	PDB
4FSR	X-ray	250 A	A	2-280	PDB
4FST	X-ray	190 A	A	2-270	PDB
4FSU	X-ray	210 A	A	2-280	PDB
4FSW	X-ray	230 A	A	2-280	PDB
4FSY	X-ray	230 A	A	2-280	PDB
4FSZ	X-ray	230 A	A	2-280	PDB
4FT0	X-ray	230 A	A	2-280	PDB
4FT3	X-ray	250 A	A	2-280	PDB
4FT5	X-ray	240 A	A	2-280	PDB
4FT7	X-ray	220 A	A	2-280	PDB
4FT9	X-ray	220 A	A	2-280	PDB
4FTA	X-ray	240 A	A	2-280	PDB
4FTC	X-ray	200 A	A	2-280	PDB
4FTI	X-ray	220 A	A	2-280	PDB
4FTJ	X-ray	220 A	A	2-280	PDB
4FTK	X-ray	230 A	A	2-280	PDB
4FTL	X-ray	250 A	A	2-280	PDB
4FTM	X-ray	190 A	A	2-280	PDB
4FTN	X-ray	202 A	A	2-280	PDB
4FTO	X-ray	210 A	A	2-280	PDB
4FTQ	X-ray	200 A	A	2-280	PDB
4FTR	X-ray	225 A	A	2-280	PDB
4FTT	X-ray	230 A	A	2-280	PDB
4FTU	X-ray	210 A	A	2-280	PDB
4GH2	X-ray	203 A	A	2-280	PDB
4HYH	X-ray	170 A	A	1-289	PDB
4HYI	X-ray	140 A	A	1-289	PDB
4JIK	X-ray	190 A	A	2-274	PDB
4QYE	X-ray	205 A	A	1-289	PDB
4QYF	X-ray	215 A	A	1-289	PDB
4QYG	X-ray	175 A	A/B	1-289	PDB
4QYH	X-ray	190 A	A/B	1-289	PDB
4RVK	X-ray	185 A	A	1-289	PDB
4RVL	X-ray	185 A	A	1-289	PDB
4RVM	X-ray	186 A	A	1-289	PDB
5DLS	X-ray	215 A	A	1-289	PDB
5F4N	X-ray	191 A	A	1-273	PDB
5OOP	X-ray	170 A	A	1-289	PDB
5OOR	X-ray	190 A	A	1-289	PDB
5OOT	X-ray	210 A	A	1-289	PDB
5OP2	X-ray	190 A	A	1-289	PDB
5OP4	X-ray	200 A	A	1-289	PDB
5OP5	X-ray	190 A	A	1-289	PDB
5OP7	X-ray	180 A	A	1-289	PDB
5OPB	X-ray	155 A	A	1-289	PDB
5OPR	X-ray	195 A	A	1-289	PDB
5OPS	X-ray	200 A	A	1-289	PDB
5OPU	X-ray	155 A	A	1-289	PDB
5OPV	X-ray	190 A	A	1-289	PDB
5OQ5	X-ray	140 A	A	1-289	PDB
5OQ6	X-ray	195 A	A	1-289	PDB
5OQ7	X-ray	210 A	A/B	1-289	PDB
5OQ8	X-ray	200 A	A	1-289	PDB
5WI2	X-ray	250 A	A/B	377-476	PDB
6FC8	X-ray	161 A	A	1-276	PDB
6FCF	X-ray	185 A	A	1-276	PDB
6FCK	X-ray	190 A	A	1-276	PDB
7AKM	X-ray	193 A	A/B	2-287	PDB
7AKO	X-ray	180 A	A/B	2-289	PDB
7BJD	X-ray	200 A	A	1-289	PDB
7BJE	X-ray	180 A	A	1-289	PDB
7BJH	X-ray	180 A	A	1-289	PDB
7BJJ	X-ray	180 A	A	1-289	PDB
7BJM	X-ray	230 A	A	1-289	PDB
7BJO	X-ray	230 A	A	1-289	PDB
7BJR	X-ray	190 A	A	1-289	PDB
7BJX	X-ray	240 A	A/B	1-289	PDB
7BK1	X-ray	200 A	A	1-289	PDB
7BK2	X-ray	200 A	A	1-289	PDB
7BK3	X-ray	200 A	A	1-289	PDB
7BKN	X-ray	274 A	A	1-289	PDB
7BKO	X-ray	230 A	A	1-289	PDB
7MCK	X-ray	165 A	A	1-289	PDB
7SUF	X-ray	148 A	A	1-289	PDB
7SUG	X-ray	148 A	A	1-289	PDB
7SUH	X-ray	246 A	A	1-289	PDB
7SUI	X-ray	212 A	A	1-289	PDB
7SUJ	X-ray	230 A	A/B	1-289	PDB
8E80	X-ray	149 A	A	1-289	PDB
8E81	X-ray	162 A	A	1-289	PDB
8SIV	X-ray	176 A	A	1-289	PDB
8SIW	X-ray	188 A	A/B	1-289	PDB
8SIX	X-ray	155 A	A	1-289	PDB
AF-O14757-F1	Predicted				AlphaFoldDB

276 variants for O14757

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA6349430 rs369248914 RCV000708693	160	R>C	Hereditary cancer-predisposing syndrome [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA351245 rs756054805 RCV000210167	379	R>*	Hereditary cancer-predisposing syndrome [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA6349285 rs757321404	2	A>G		No	ClinGen ExAC gnomAD
CA6349286 rs201459198	4	P>S		No	ClinGen ExAC TOPMed gnomAD
rs200520758 CA6349287	12	V>L		No	ClinGen ExAC TOPMed gnomAD
CA383189905 rs1395953036	18	G>D		No	ClinGen TOPMed
rs1350704599 CA383189936	20	Y>C		No	ClinGen gnomAD
rs751896993 CA6349290	21	G>R		No	ClinGen ExAC gnomAD
CA6349308 rs766554164	25	L>I		No	ClinGen ExAC gnomAD
rs1565361701 CA383190120	26	A>V		No	ClinGen Ensembl
CA6349310 rs755282936	28	N>S		No	ClinGen ExAC gnomAD
CA383190150 rs1555067411 RCV000586016	29	R>G		No	ClinGen ClinVar Ensembl dbSNP
CA6349311 rs781671034	30	V>I		No	ClinGen ExAC gnomAD
CA383190178 rs1191531722	31	T>N		No	ClinGen gnomAD
rs1269445439 CA383190213	34	A>T		No	ClinGen gnomAD
rs1380056031 CA383190227	35	V>L		No	ClinGen TOPMed
rs753180922 CA6349312	36	A>S		No	ClinGen ExAC gnomAD
rs753180922 CA6349313	36	A>T		No	ClinGen ExAC gnomAD
CA6349314 rs367942205	39	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs778668643 CA6349317	41	D>N		No	ClinGen ExAC TOPMed gnomAD
CA383190301 rs1458791146	42	M>V		No	ClinGen gnomAD
rs771939046 CA6349319	44	R>C		No	ClinGen ExAC gnomAD
rs537858020 CA6349320	44	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6349321 rs760734978	45	A>D		No	ClinGen ExAC gnomAD
rs1565361807 CA383190322	45	A>S		No	ClinGen Ensembl
rs768467449 CA6349322	46	V>I		No	ClinGen ExAC TOPMed gnomAD
rs1367390698 CA383190345	48	C>*		No	ClinGen gnomAD
CA383190365 rs1565361841	51	N>S		No	ClinGen Ensembl
rs779362881 CA230484454	55	E>D		No	ClinGen ExAC TOPMed gnomAD
rs762977718 CA6349324	55	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1266930698 CA383190407	57	C>G		No	ClinGen gnomAD
CA383190442 rs1248538225	61	M>I		No	ClinGen gnomAD
rs751719325 CA6349331	64	H>N		No	ClinGen ExAC gnomAD
CA383190471 rs554220572	65	E>D		No	ClinGen 1000Genomes ExAC
rs554220572 CA6349333	65	E>D		No	ClinGen 1000Genomes ExAC
CA6349335 rs767992502	67	V>I		No	ClinGen ExAC gnomAD
rs767992502 CA6349336	67	V>L		No	ClinGen ExAC gnomAD
rs375481689 CA6349339	69	K>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1386843282 CA383190495	69	K>N		No	ClinGen gnomAD
rs1356561612 CA383190499	70	F>V		No	ClinGen TOPMed
CA6349340 rs141665265	71	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA383190509 rs141665265	71	Y>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA383190519 rs1224598742	73	H>D		No	ClinGen TOPMed
CA383190535 rs1565362006	75	R>K		No	ClinGen Ensembl
rs758124077 CA6349343	77	G>V		No	ClinGen ExAC TOPMed gnomAD
CA6349345 rs746760826	79	I>M		No	ClinGen ExAC gnomAD
rs768667116 CA6349346	80	Q>R		No	ClinGen ExAC gnomAD
rs1227533180 CA383190593	83	F>Y		No	ClinGen TOPMed gnomAD
rs1207424665 CA383190602	85	E>K		No	ClinGen gnomAD
CA6349352 rs767610516	87	C>Y		No	ClinGen ExAC gnomAD
CA6349353 rs775964760	92	L>F		No	ClinGen ExAC gnomAD
rs764684778 CA6349355	96	I>V		No	ClinGen ExAC TOPMed gnomAD
rs754338984 CA6349356	97	E>*		No	ClinGen ExAC gnomAD
CA383190728 rs1426460534	101	G>C		No	ClinGen TOPMed gnomAD
CA383190726 rs1426460534	101	G>S		No	ClinGen TOPMed gnomAD
rs764300223 CA6349374	106	D>H		No	ClinGen ExAC gnomAD
rs764300223 CA6349375	106	D>N		No	ClinGen ExAC gnomAD
rs762470361 CA6349376	107	A>V		No	ClinGen ExAC TOPMed gnomAD
rs563722813 CA6349377	111	F>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1383121355 CA383190804	112	H>Y		No	ClinGen TOPMed gnomAD
CA383190824 rs1197536561	115	M>V		No	ClinGen TOPMed
CA230484942 rs1048249612	117	G>R		No	ClinGen Ensembl
rs749996823 CA6349378	118	V>G		No	ClinGen ExAC gnomAD
rs1207337706 CA383190893	124	I>V		No	ClinGen gnomAD
rs112275638 CA230485003	126	I>V		No	ClinGen Ensembl
rs867675787 CA230485006	129	R>G		No	ClinGen Ensembl
CA6349400 rs759158547	137	L>M		No	ClinGen ExAC gnomAD
CA6349401 rs752519129	137	L>P		No	ClinGen ExAC TOPMed gnomAD
CA6349402 rs371765740	139	D>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1391121414 CA383191009	141	R>K		No	ClinGen gnomAD
COSM541508 CA383191012 rs777701208	141	R>S	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1279298605 CA383191271	144	L>R		No	ClinGen TOPMed
CA6349420 rs775066373	145	K>I		No	ClinGen ExAC TOPMed gnomAD
rs760469704 CA6349421	145	K>N		No	ClinGen ExAC TOPMed gnomAD
CA6349422 rs763944664	149	F>V		No	ClinGen ExAC gnomAD
CA6349424 rs757193229	153	T>K		No	ClinGen ExAC gnomAD
CA6349423 rs753657060	153	T>S		No	ClinGen ExAC gnomAD
rs3731410 CA6349427 VAR_021123	156	R>Q		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
COSM3415648 rs140276570 CA6349426	156	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA383191367 rs1591395808	157	Y>D		No	ClinGen Ensembl
CA6349429 rs748445411	157	Y>F		No	ClinGen ExAC gnomAD
CA383191381 rs1161248510	159	N>D		No	ClinGen gnomAD
CA230486291 rs907672030	159	N>I		No	ClinGen gnomAD
rs907672030 CA230486289	159	N>S		No	ClinGen gnomAD
COSM35410 CA6349431 rs778046191	160	R>H	large_intestine central_nervous_system endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA6349432 rs749631457	162	R>C		No	ClinGen ExAC gnomAD
rs1427360758 CA383191415	162	R>H		No	ClinGen gnomAD
rs771372037 CA6349433	164	L>F		No	ClinGen ExAC gnomAD
CA6349434 rs373714183 COSM924552	166	K>N	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs1299890343 CA383191511	167	M>I		No	ClinGen gnomAD
rs1393469843 CA383191500	167	M>L		No	ClinGen gnomAD
rs1393469843 CA383191496	167	M>L		No	ClinGen gnomAD
CA6349435 rs745384189	168	C>G		No	ClinGen ExAC gnomAD
CA383191566 rs1234061120	171	L>S		No	ClinGen gnomAD
CA383191579 rs1340501726	172	P>S		No	ClinGen gnomAD
CA383191625 rs1158434447	174	V>A		No	ClinGen TOPMed
CA383191616 rs1378781957	174	V>L		No	ClinGen TOPMed
CA383191636 rs1340329656	175	A>S		No	ClinGen gnomAD
rs75583143 CA230486314	175	A>V		No	ClinGen Ensembl
CA230486317 rs1037595364	176	P>L		No	ClinGen Ensembl
rs755263451 CA6349436	180	K>L		No	ClinGen ExAC
CA6349439 rs771504275	180	K>N		No	ClinGen ExAC gnomAD
rs1591395964 CA383191725	181	R>G		No	ClinGen Ensembl
CA230486327 rs995839011	183	E>G		No	ClinGen gnomAD
CA6349440 rs760379838	185	H>R		No	ClinGen ExAC TOPMed gnomAD
rs1396311668 CA383191868	189	V>A		No	ClinGen TOPMed gnomAD
rs776333699 CA6349442	191	V>I		No	ClinGen ExAC gnomAD
CA383191947 rs1167618904	194	C>R		No	ClinGen TOPMed gnomAD
CA383192001 rs1463911220	196	I>T		No	ClinGen gnomAD
CA6349445 rs765113622	197	V>A		No	ClinGen ExAC gnomAD
rs1363161744 CA383192088	200	A>G		No	ClinGen gnomAD
CA6349448 rs771316687	201	M>V		No	ClinGen ExAC TOPMed gnomAD
rs376741119 CA6349450	203	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA6349451 rs778014033	205	E>*		No	ClinGen ExAC gnomAD
CA6349476 rs779394398	210	Q>R		No	ClinGen ExAC gnomAD
rs547707890 CA6349477	211	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA230487164 rs901928346	213	D>E		No	ClinGen TOPMed gnomAD
rs377704459 CA6349478	216	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1445875437 CA383193276	220	D>E		No	ClinGen gnomAD
CA6349479 rs780501566	220	D>Y		No	ClinGen ExAC gnomAD
CA383193284 rs1402782439	221	W>*		No	ClinGen gnomAD
rs35817404 CA383193299	223	E>G		No	ClinGen ExAC TOPMed gnomAD
rs35817404 CA6349482 VAR_040407	223	E>V		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
rs1266487380 CA383193307	224	K>I		No	ClinGen TOPMed
rs1042455164 CA230487180	225	K>E		No	ClinGen TOPMed gnomAD
rs1327022943 CA383193329	227	Y>*		No	ClinGen gnomAD
CA6349486 rs769305503	228	L>F		No	ClinGen ExAC gnomAD
CA6349487 rs773178839	229	N>S		No	ClinGen ExAC gnomAD
CA6349488 rs762794644	230	P>A		No	ClinGen ExAC gnomAD
rs1011779266 CA383193379	234	I>M		No	ClinGen TOPMed gnomAD
rs1255118863 CA383193380 COSM924554	235	D>N	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1190534193 CA383193400	238	P>S		No	ClinGen gnomAD
CA230487844 rs975304527	243	H>N		No	ClinGen TOPMed
CA383193441 rs975304527	243	H>Y		No	ClinGen TOPMed
rs777516943 CA6349505	245	I>V		No	ClinGen ExAC gnomAD
CA383193467 rs770782396	246	L>F		No	ClinGen ExAC TOPMed gnomAD
rs201395400 CA6349508	251	S>P		No	ClinGen 1000Genomes ExAC gnomAD
CA383193503 rs1158338803	252	A>S		No	ClinGen TOPMed
CA383193506 rs1434154060	252	A>V		No	ClinGen gnomAD
CA383193517 rs1302103336	254	I>T		No	ClinGen gnomAD
rs11553952 CA230487861	254	I>V		No	ClinGen Ensembl
rs745876688 CA6349509	255	T>I		No	ClinGen ExAC gnomAD
rs771882988 CA6349510	257	P>S		No	ClinGen ExAC gnomAD
CA383193539 rs201385540	258	D>H		No	ClinGen gnomAD
rs201385540 CA230487870	258	D>N		No	ClinGen gnomAD
rs1275492676 CA383193567	261	K>N		No	ClinGen gnomAD
rs1215535083 CA383193564	261	K>R		No	ClinGen gnomAD
CA383193570 rs1591400664	262	D>H		No	ClinGen Ensembl
rs1450424448 CA383193578	263	R>K		No	ClinGen TOPMed gnomAD
rs1470286568 CA383193588	264	W>*		No	ClinGen gnomAD
CA230487877 rs922245598	264	W>R		No	ClinGen gnomAD
CA383193606 rs1254148750	266	N>K		No	ClinGen gnomAD
CA383193611 rs1469921398	267	K>R		No	ClinGen gnomAD
CA230487882 rs933668612	269	L>H		No	ClinGen TOPMed gnomAD
CA383193638 rs1389785450	271	K>R		No	ClinGen gnomAD
rs1475833328 CA383193644	272	G>W		No	ClinGen gnomAD
CA383187637 rs1383668839	273	A>E		No	ClinGen gnomAD
CA6349530 rs778901513	273	A>S		No	ClinGen ExAC gnomAD
rs1382274821 CA383187642	274	K>*		No	ClinGen gnomAD
rs1382274821 CA383187641	274	K>E		No	ClinGen gnomAD
rs1308818250 CA383187644	274	K>R		No	ClinGen gnomAD
rs745620670 CA6349531	275	R>M		No	ClinGen ExAC TOPMed gnomAD
CA383187652 rs1351213254	275	R>S		No	ClinGen TOPMed gnomAD
CA6349532 rs772079899	277	R>*		No	ClinGen ExAC TOPMed gnomAD
CA383187660 rs772079899	277	R>G		No	ClinGen ExAC TOPMed gnomAD
rs775245290 CA6349533	277	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs748276359 CA6349534	282	G>R		No	ClinGen ExAC gnomAD
CA6349535 rs748276359	282	G>S		No	ClinGen ExAC gnomAD
CA383187691 rs1227056031	283	V>M		No	ClinGen gnomAD
CA383187707 rs1260622411	285	E>G		No	ClinGen gnomAD
CA383187722 rs1314732435	287	P>L		No	ClinGen TOPMed
rs1355494579 CA383187719	287	P>S		No	ClinGen gnomAD
rs763207260 CA383187727	288	S>I		No	ClinGen ExAC gnomAD
rs763207260 CA6349537	288	S>N		No	ClinGen ExAC gnomAD
rs1485430319 CA383187730	289	G>R		No	ClinGen gnomAD
rs147323405 CA230472755	293	H>Y		No	ClinGen ESP
CA383187774 rs1186977956	295	Q>*		No	ClinGen TOPMed gnomAD
CA383187772 rs1186977956	295	Q>E		No	ClinGen TOPMed gnomAD
CA230472760 rs1003827905	297	N>S		No	ClinGen TOPMed gnomAD
rs1179637125 CA383187820	301	S>F		No	ClinGen gnomAD
CA230472763 rs1025553804	301	S>P		No	ClinGen Ensembl
rs1363144435 CA383187826	302	P>L		No	ClinGen gnomAD
CA6349539 rs182542971	304	N>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1159724450 CA383187846	305	S>R		No	ClinGen gnomAD
CA383187850 rs1399624091	306	A>S		No	ClinGen gnomAD
rs1433658665 CA383187853	306	A>V		No	ClinGen gnomAD
rs1437919116 CA383187859	307	S>F		No	ClinGen gnomAD
CA230472859 VAR_040408 rs34097480	312	V>M		No	ClinGen UniProt Ensembl dbSNP
CA383187916 rs1322109311	313	K>N		No	ClinGen gnomAD
rs1370402981 CA383187919	314	Y>D		No	ClinGen gnomAD
rs1398654305 CA383187932	316	S>G		No	ClinGen gnomAD
rs1235097713 CA383187934	316	S>N		No	ClinGen gnomAD
CA383187972 rs1298017021	321	P>L		No	ClinGen TOPMed
rs1340219994 CA383187967	321	P>T		No	ClinGen gnomAD
rs775909758 CA6349562	322	R>C		No	ClinGen ExAC TOPMed gnomAD
CA6349563 COSM1352378 rs761313560	322	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA383187976 rs761313560	322	R>L		No	ClinGen ExAC TOPMed gnomAD
CA383187980 rs764666835	323	T>K		No	ClinGen ExAC TOPMed gnomAD
rs764666835 CA6349564	323	T>R		No	ClinGen ExAC TOPMed gnomAD
rs753432559 CA6349565	324	G>S		No	ClinGen ExAC gnomAD
CA230472882 rs1026455651	328	W>C		No	ClinGen TOPMed
rs764958538 CA6349569	333	S>*		No	ClinGen ExAC gnomAD
rs764958538 CA383188046	333	S>L		No	ClinGen ExAC gnomAD
rs1426308049 CA383188042	333	S>T		No	ClinGen gnomAD
CA6349570 rs749980029	334	Y>*		No	ClinGen ExAC TOPMed gnomAD
CA230472890 rs781018582	334	Y>C		No	ClinGen gnomAD
CA383188049 rs781018582	334	Y>F		No	ClinGen gnomAD
CA230472888 rs139936669	334	Y>N		No	ClinGen ESP TOPMed gnomAD
rs1441734268 CA383188055	335	I>T		No	ClinGen gnomAD
rs758069861 CA6349571	335	I>V		No	ClinGen ExAC TOPMed gnomAD
rs539323916 CA6349575	341	G>R		No	ClinGen 1000Genomes ExAC gnomAD
CA6349576 rs749381202	342	I>L		No	ClinGen ExAC gnomAD
rs1591409094 CA383188110	343	S>T		No	ClinGen Ensembl
rs199535573 CA501216	346	Q>*		No	ClinGen ESP ExAC TOPMed gnomAD
rs374866866 CA6349579	348	T>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs761070355 CA6349581	350	P>H		No	ClinGen ExAC gnomAD
CA6349580 rs775766777	350	P>S		No	ClinGen ExAC gnomAD
COSM107213 rs149667923 CA230472919	352	H>Y	skin [Cosmic]	No	ClinGen cosmic curated Ensembl
rs777209903 CA6349583	353	M>I		No	ClinGen ExAC
rs761418252 CA6349584	356	N>H		No	ClinGen ExAC TOPMed gnomAD
rs1163144259 CA383188206	357	S>T		No	ClinGen gnomAD
rs1207019231 CA383188210	358	Q>E		No	ClinGen TOPMed
rs1462376220 CA383188241	362	T>S		No	ClinGen gnomAD
rs764708405 CA6349585	363	P>S		No	ClinGen ExAC gnomAD
CA6349586 rs764708405	363	P>T		No	ClinGen ExAC gnomAD
rs542436508 CA230472939	366	S>L		No	ClinGen Ensembl
CA6349607 rs773937190	368	N>K		No	ClinGen ExAC gnomAD
rs867390301 CA230473027	368	N>S		No	ClinGen Ensembl
rs1318383609 CA383188291	369	P>S		No	ClinGen gnomAD
rs1279132447 CA383188298	370	W>*		No	ClinGen gnomAD
CA230473035 rs77764256	370	W>C		No	ClinGen Ensembl
CA383188297 rs1443980454	370	W>G		No	ClinGen TOPMed
rs1486238508 CA383188305	371	Q>*		No	ClinGen gnomAD
rs767367809 CA6349609	372	R>W		No	ClinGen ExAC TOPMed gnomAD
CA383188332 rs1183852401	375	K>R		No	ClinGen TOPMed gnomAD
CA6349610 rs752458006	377	M>V		No	ClinGen ExAC gnomAD
CA6349612 rs750498287	385	D>G		No	ClinGen ExAC gnomAD
rs1395913974 CA383188513	386	A>T		No	ClinGen gnomAD
CA6349613 rs758434651	389	S>F		No	ClinGen ExAC
rs372751798 CA230473054	390	Y>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1257217942 CA383188605	390	Y>F		No	ClinGen gnomAD
rs1435108441 CA383188602	390	Y>H		No	ClinGen gnomAD
CA6349615 rs747288732	395	E>G		No	ClinGen ExAC gnomAD
CA6349618 rs748478311	397	C>F		No	ClinGen ExAC gnomAD
rs1318978818 CA383188881	401	G>A		No	ClinGen TOPMed
CA230473068 rs115991933	403	Q>R		No	ClinGen 1000Genomes gnomAD
rs748763845 CA6349621	404	W>C		No	ClinGen ExAC gnomAD
rs145794689 CA6349623	406	K>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1403145263 CA383189030	408	C>S		No	ClinGen TOPMed
CA6349624 rs759227173	409	M>V		No	ClinGen ExAC TOPMed gnomAD
CA383189104 rs1455708220	411	Q>P		No	ClinGen gnomAD
CA230474784 rs753915531	412	V>I		No	ClinGen Ensembl
CA6349639 rs749874631	413	T>S		No	ClinGen ExAC gnomAD
rs148568641 CA6349640	414	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs761805263 CA230474787	415	S>T		No	ClinGen Ensembl
CA6349641 rs778444034	417	T>N		No	ClinGen ExAC gnomAD
rs370268372 CA6349643	421	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA383191095 rs775056015	422	N>K		No	ClinGen ExAC gnomAD
CA230474793 rs914262719	434	D>V		No	ClinGen Ensembl
CA6349646 rs768550804	439	V>A		No	ClinGen ExAC gnomAD
CA230474797 rs968420616	442	R>W		No	ClinGen TOPMed gnomAD
rs751724890 CA6349650	445	K>E		No	ClinGen ExAC gnomAD
rs1055671859 CA230475067	457	K>R		No	ClinGen TOPMed gnomAD
rs1439749537 CA383191818	462	L>V		No	ClinGen gnomAD
CA6349673 rs775403114	463	I>M		No	ClinGen ExAC gnomAD
rs761007676 CA6349674	464	D>A		No	ClinGen ExAC gnomAD
CA6349676 rs529219511	465	I>T		No	ClinGen ExAC TOPMed gnomAD
CA6349675 rs764175263	465	I>V		No	ClinGen ExAC gnomAD
CA6349677 rs146590504	466	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs750985875 CA6349679	469	Q>L		No	ClinGen ExAC gnomAD
rs506504 CA230475078	471	I>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs506504 CA230475076	471	I>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs506504 CA6349680 RCV000589283 VAR_024571	471	I>V		No	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1242394353 CA383192090	473	L>P		No	ClinGen gnomAD
rs779651907 CA6349681	476	T>A		No	ClinGen ExAC TOPMed gnomAD
rs1202783491 CA383192159	476	T>I		No	ClinGen TOPMed

No associated diseases with O14757

4 regional properties for O14757

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	9 - 265	IPR000719
active_site	Serine/threonine-protein kinase, active site	126 - 138	IPR008271
binding_site	Protein kinase, ATP binding site	15 - 38	IPR017441
domain	Checkpoint kinase 1, catalytic domain	7 - 265	IPR034670

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Nucleus Chromosome Cytoplasm Cytoplasm, cytoskeleton, microtubule organizing center, centrosome	Nuclear export is mediated at least in part by XPO1/CRM1 (PubMed:12676962) Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B (PubMed:15311285) Proteolytic cleavage at the C-terminus by SPRTN promotes removal from chromatin (PubMed:31316063)
PANTHER Family	PTHR24346	MAP/MICROTUBULE AFFINITY-REGULATING KINASE
PANTHER Subfamily	PTHR24346:SF73	SERINE_THREONINE-PROTEIN KINASE CHK1
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	No pathway information available

11 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.
chromatin	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
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.
extracellular space	That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
intracellular membrane-bounded organelle	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
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.
replication fork	The Y-shaped region of a replicating DNA molecule, resulting from the separation of the DNA strands and in which the synthesis of new strands takes place. Also includes associated protein complexes.

7 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
histone kinase activity (H3-T11 specific)	Catalysis of the transfer of a phosphate group to the threonine-11 residue of the N-terminal tail of histone H3.
protein domain specific binding	Binding to a specific domain of a protein.
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 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.

29 GO annotations of biological process

Name	Definition
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
apoptotic process involved in development	Any apoptotic process that is involved in anatomical structure development.
cellular response to caffeine	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 caffeine stimulus. Caffeine is an alkaloid found in numerous plant species, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.
cellular response to DNA damage stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to mechanical stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a mechanical stimulus.
DNA damage checkpoint signaling	A signal transduction process that contributes to a DNA damage checkpoint.
DNA damage induced protein phosphorylation	The widespread phosphorylation of various molecules, triggering many downstream processes, that occurs in response to the detection of DNA damage.
DNA repair	The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
DNA replication	The cellular metabolic process in which a cell duplicates one or more molecules of DNA. DNA replication begins when specific sequences, known as origins of replication, are recognized and bound by initiation proteins, and ends when the original DNA molecule has been completely duplicated and the copies topologically separated. The unit of replication usually corresponds to the genome of the cell, an organelle, or a virus. The template for replication can either be an existing DNA molecule or RNA.
epigenetic maintenance of chromatin in transcription-competent conformation	An epigenetic process that capacitates gene expression by remodelling of chromatin by either modifying the chromatin fiber, the nucleosomal histones, or the DNA.
G2/M transition of mitotic cell cycle	The mitotic cell cycle transition by which a cell in G2 commits to M phase. The process begins when the kinase activity of M cyclin/CDK complex reaches a threshold high enough for the cell cycle to proceed. This is accomplished by activating a positive feedback loop that results in the accumulation of unphosphorylated and active M cyclin/CDK complex.
inner cell mass cell proliferation	The proliferation of cells in the inner cell mass.
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.
mitotic G2 DNA damage checkpoint signaling	A mitotic cell cycle checkpoint that detects and negatively regulates progression through the G2/M transition of the cell cycle in response to DNA damage.
mitotic G2/M transition checkpoint	A cell cycle checkpoint that detects and negatively regulates progression from G2 to M phase as part of a mitotic cell cycle.
negative regulation of DNA biosynthetic process	Any process that stops, prevents or reduces the frequency, rate or extent of DNA biosynthetic process.
negative regulation of G0 to G1 transition	A cell cycle process that stops, prevents, or reduces the rate or extent of the transition from the G0 quiescent state to the G1 phase.
negative regulation of mitotic nuclear division	Any process that stops, prevents or reduces the rate or extent of mitosis. Mitosis is the division of the eukaryotic cell nucleus to produce two daughter nuclei that, usually, contain the identical chromosome complement to their mother.
nucleus organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the nucleus.
peptidyl-threonine phosphorylation	The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
positive regulation of cell cycle	Any process that activates or increases the rate or extent of progression through the cell cycle.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of cell population proliferation	Any process that modulates the frequency, rate or extent of cell proliferation.
regulation of double-strand break repair via homologous recombination	Any process that modulates the frequency, rate or extent of the error-free repair of a double-strand break in DNA in which the broken DNA molecule is repaired using homologous sequences.
regulation of histone H3-K9 acetylation	Any process that modulates the frequency, rate or extent of histone H3-K9 acetylation.
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 signal transduction by p53 class mediator	Any process that modulates the frequency, rate or extent of signal transduction by p53 class mediator.
regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage	Any process that modulates the frequency, rate or extent of transcription from an RNA polymerase II promoter as a result of a UV damage stimulus.
replicative senescence	A cell aging process associated with the dismantling of a cell as a response to telomere shortening and/or cellular aging.

21 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P28708	PRR1	Serine/threonine-protein kinase PRR1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
P47116	PTK2	Serine/threonine-protein kinase PTK2/STK2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q8AYC9	CHEK1	Serine/threonine-protein kinase Chk1	Gallus gallus (Chicken)	PR
O61661	grp	Serine/threonine-protein kinase grp	Drosophila melanogaster (Fruit fly)	SS
Q8IWQ3	BRSK2	Serine/threonine-protein kinase BRSK2	Homo sapiens (Human)	PR
Q8TDC3	BRSK1	Serine/threonine-protein kinase BRSK1	Homo sapiens (Human)	SS
Q14680	MELK	Maternal embryonic leucine zipper kinase	Homo sapiens (Human)	EV
P57059	SIK1	Serine/threonine-protein kinase SIK1	Homo sapiens (Human)	PR
Q9NRH2	SNRK	SNF-related serine/threonine-protein kinase	Homo sapiens (Human)	SS
Q9BXA7	TSSK1B	Testis-specific serine/threonine-protein kinase 1	Homo sapiens (Human)	PR
O60285	NUAK1	NUAK family SNF1-like kinase 1	Homo sapiens (Human)	PR
Q13131	PRKAA1	5'-AMP-activated protein kinase catalytic subunit alpha-1	Homo sapiens (Human)	EV
P54646	PRKAA2	5'-AMP-activated protein kinase catalytic subunit alpha-2	Homo sapiens (Human)	EV
O35280	Chek1	Serine/threonine-protein kinase Chk1	Mus musculus (Mouse)	PR
Q91ZN7	Chek1	Serine/threonine-protein kinase Chk1	Rattus norvegicus (Rat)	PR
Q8LIG4	CIPK3	CBL-interacting protein kinase 3	Oryza sativa subsp japonica (Rice)	PR
Q5JLQ9	CIPK30	CBL-interacting protein kinase 30	Oryza sativa subsp japonica (Rice)	PR
Q6ERS4	CIPK16	CBL-interacting protein kinase 16	Oryza sativa subsp japonica (Rice)	PR
Q6ZLP5	CIPK23	CBL-interacting protein kinase 23	Oryza sativa subsp japonica (Rice)	PR
Q2QY53	CIPK32	CBL-interacting protein kinase 32	Oryza sativa subsp japonica (Rice)	PR
Q2RAX3	CIPK33	CBL-interacting protein kinase 33	Oryza sativa subsp japonica (Rice)	PR

10	20	30	40	50	60
MAVPFVEDWD	LVQTLGEGAY	GEVQLAVNRV	TEEAVAVKIV	DMKRAVDCPE	NIKKEICINK
70	80	90	100	110	120
MLNHENVVKF	YGHRREGNIQ	YLFLEYCSGG	ELFDRIEPDI	GMPEPDAQRF	FHQLMAGVVY
130	140	150	160	170	180
LHGIGITHRD	IKPENLLLDE	RDNLKISDFG	LATVFRYNNR	ERLLNKMCGT	LPYVAPELLK
190	200	210	220	230	240
RREFHAEPVD	VWSCGIVLTA	MLAGELPWDQ	PSDSCQEYSD	WKEKKTYLNP	WKKIDSAPLA
250	260	270	280	290	300
LLHKILVENP	SARITIPDIK	KDRWYNKPLK	KGAKRPRVTS	GGVSESPSGF	SKHIQSNLDF
310	320	330	340	350	360
SPVNSASSEE	NVKYSSSQPE	PRTGLSLWDT	SPSYIDKLVQ	GISFSQPTCP	DHMLLNSQLL
370	380	390	400	410	420
GTPGSSQNPW	QRLVKRMTRF	FTKLDADKSY	QCLKETCEKL	GYQWKKSCMN	QVTISTTDRR
430	440	450	460	470
NNKLIFKVNL	LEMDDKILVD	FRLSKGDGLE	FKRHFLKIKG	KLIDIVSSQK	IWLPAT