Reviewed, UniProtKB/Swiss-Prot Q9JKK8 (ATR_MOUSE)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase ATR
    EC=2.7.11.1
Alternative name(s):
    Ataxia telangiectasia and Rad3-related protein

Gene names

Name:	Atr
Synonyms:	Kiaa4069

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	2635 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and TP53/p53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates Ser-139 of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication By similarity. Essential for preventing the occurrence of DNA damage during early embryogenesis.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Manganese By similarity.
Enzyme regulation	Activated by DNA, and slightly by ATRIP. Inhibited by caffeine, wortmannin and LY294002 By similarity.
Subunit structure	Forms an heterodimer with ATRIP. Binds to DNA, and to UV-damaged DNA with higher affinity. Interacts with RAD17, MSH2 and HDAC2. Present in a complex containing ATRIP and RPA-coated single-stranded DNA. Present in a complex containing CHD4 and HDAC2. Interacts with EEF1E1. This interaction is enhanced by UV irradiation. Interacts with CLSPN and CEP164 By similarity.
Subcellular location	Nucleus By similarity. Note: Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling By similarity.
Tissue specificity	Ubiquitous. Expression is highest in testis, where it is restricted to primary spermatocytes. Expression decreases as spermiogenesis proceeds (at protein level). Ref.5
Sequence similarities	Belongs to the PI3/PI4-kinase family. ATM subfamily. Contains 1 FAT domain. Contains 1 FATC domain. Contains 2 HEAT repeats. Contains 1 PI3K/PI4K domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Chromosomal protein Nucleus
Domain	Repeat
Ligand	ATP-binding DNA-binding Manganese Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA damage checkpoint Inferred from mutant phenotype. Source: MGI DNA repair Inferred from direct assay. Source: MGI protein amino acid phosphorylation Inferred from direct assay. Source: MGI regulation of protein binding Inferred from direct assay. Source: MGI
Cellular component	XY body Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ppp1ca	P62137	1	EBI-1202426,EBI-357187

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2635	2635	Serine/threonine-protein kinase ATR		PRO_0000088845
Regions
	Repeat	799 – 835	37	HEAT 1
	Repeat	1329 – 1365	37	HEAT 2
	Domain	1634 – 2179	546	FAT
	Domain	2313 – 2558	246	PI3K/PI4K
	Domain	2603 – 2635	33	FATC
Amino acid modifications
	Modified residue	431	1	Phosphoserine By similarity
	Modified residue	438	1	Phosphoserine By similarity
	Modified residue	919	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	19	1	G → A in BAE24154. Ref.2
	Sequence conflict	19	1	G → A in BAE34182. Ref.2
	Sequence conflict	19	1	G → A in BAE42229. Ref.2
	Sequence conflict	2208	1	D → E in BAE37964. Ref.2
	Sequence conflict	2347	1	R → C in BAE37964. Ref.2
	Sequence conflict	2556	1	G → W in BAE21043. Ref.2
	Sequence conflict	2556	1	G → W in BAD90361. Ref.3
	Sequence conflict	2563	1	H → R in BAE21043. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9JKK8-1 [UniParc]. Last modified March 29, 2005. Version 2. Checksum: C126413D15ACB8DC	FASTA	2,635	300,224
	10 20 30 40 50 60 MGDHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VALELVKKTD 70 80 90 100 110 120 AQPTSVMLLD FIQHIMKSSP LMFVNVNGSQ GQNEAKDSCI EFSHWIITRL LRIAATPSCH 130 140 150 160 170 180 MLHKKICEVI CSLLFLFKSK NPAIFGVLTR ELLYLFEDLI YLHKRNAVGE VMEWPVVVSR 190 200 210 220 230 240 FLSRLDEHMG CLQPAPLQFM NVQNVEFIEV TLLMVLIHIV PTVFFRRQEL LLWQIGCALL 250 260 270 280 290 300 EHGSPKIRSL AISLLTELFE LGGLPAQPAS TFFSLFLELL QHLVGMDADQ LKLYEEPLSK 310 320 330 340 350 360 LLKTLFPFEA EAYRNIEPVY LNVLLEKLSV MFEDRVLMRL KSDLLKAALC HLLQYFLTFV 370 380 390 400 410 420 PAGYESALQV RKVYVTNICR ALVDALGVQK HVGYLLGPFY AALKMESKEI IERIQCQAQQ 430 440 450 460 470 480 ENLSGNNDEV SPKRRKLSSS LSSYKKPSRQ PEEIIHVDMD KKSILWNVLK QKAESLQISL 490 500 510 520 530 540 ECGTLKNSVA EALEGITVVL QLTALCTVHC SHQDMDGHNV KDHQHKYKKK PPVVVTWMSL 550 560 570 580 590 600 DFYTKVLKSC RSLLESVQKL ELELVIDSMV RICDALMYMQ VKSSFKDHVL EELCGMLSLP 610 620 630 640 650 660 WIYSYSDDNS LKMTTFATNL LPLSQRVWDS YSPQAQSKCV FLLTLFPRRI FLEWRTAVYN 670 680 690 700 710 720 WALKSSHEVI RASCVKGFFI LLHQQNSCNQ IPKMLVDRVK DDSDMVKKEF ASVLGQLVCT 730 740 750 760 770 780 LHGMFYLSSS VEPCFEHMDL FSKNLKATSQ HECSSSQVKA STCKPFLFLL TKNTPSPVKL 790 800 810 820 830 840 AFIDNLHHLC KHLDFQEDER EVKAVLGTLL NLMEDPDKDV RIAFSGNIKY ILESLNSEDG 850 860 870 880 890 900 FVKELFVLRM KEAYTHAQIA RNNELKDTLI LTTGDIGRAA KGDLIPFALL HLLHCLLSKS 910 920 930 940 950 960 ASVSGAAYTE IRALVAAKSV KLQNFFSQYK KPICQFLVES LHSSQMTALP SAPCQSSEIR 970 980 990 1000 1010 1020 KQDVAHHREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ 1030 1040 1050 1060 1070 1080 LNVSRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL 1090 1100 1110 1120 1130 1140 LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDITSPELMA DYLQPKLLGI LAFFNMQLLS 1150 1160 1170 1180 1190 1200 SSVGIEDKKM ALTSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV 1210 1220 1230 1240 1250 1260 RCLDHAYLGP LLSHVIVALL PLIHMQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE 1270 1280 1290 1300 1310 1320 LEKIKAVLQE YRKETSETTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK 1330 1340 1350 1360 1370 1380 YATDSETVEP VISQLVTVIL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD 1390 1400 1410 1420 1430 1440 FTFVTGVEDL SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMQSNGPGY 1450 1460 1470 1480 1490 1500 QLWKRFPEHV REILEPHLNT RYKSSQKSTD WSGVTKPIYL SKLGNNFAEW SSSWAGYLIT 1510 1520 1530 1540 1550 1560 KVRDNLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDE 1570 1580 1590 1600 1610 1620 QHAISTQDSA SDLCQLSTQT VFSVLDHLTQ WARHKFQALN AEKLAQNKPK GVSNVNFEDY 1630 1640 1650 1660 1670 1680 QSVTRFLDLI PQDTLAVASF RSKAYTRAVM HFESFITEKK QNIQKHLGFL QKLYAAMHEP 1690 1700 1710 1720 1730 1740 DGVAGVSAIR KAEPSLKEQI LEHESIGLLR DATACYDRAI QLEPDQIIHY HGVVKSMLGL 1750 1760 1770 1780 1790 1800 GQLSTVITQV NGVHANRSEW TDELNTYRVE AAWKLSQWDL VENYLAADGK STTWSVRLGQ 1810 1820 1830 1840 1850 1860 LLLSAKKRDT TTFYDTLKLV RAEQIVPLSA ASFERGSYQR GYEFIVRLHM LCELEHSLKP 1870 1880 1890 1900 1910 1920 LFRKSPGDSC NEDSLNWGAR LEMTQNSYRA KEPILALRRA LLSLNKRPDY NEMVGECWLQ 1930 1940 1950 1960 1970 1980 SARVARKAGH HQTAYNALLN AGESRLAELY VERAKWLWSK GDVHQALIVL QKGVELCFPE 1990 2000 2010 2020 2030 2040 NKSPSESKHM LIHGRATLLV GRFMEETANF ESNAVMKKYK DVTLFLPEWE DGHFYLAKYY 2050 2060 2070 2080 2090 2100 DKLMPMVTDN KMEKQGDLIR YIVLHFGRSL QYGNQFIYQS MPRMLSLWLD FGAKAYEWEK 2110 2120 2130 2140 2150 2160 GGRSDRLQMR NDLAKINSVL TEHTNRLAPY QFLTAFSQLI SRICHSHDEV FVVLMEIIAK 2170 2180 2190 2200 2210 2220 VFLAYPQQAM WMMTAVSKSS YPMRVNRCKE ILTKAIHMKK SLEKFVGDAT RLTDKLLELC 2230 2240 2250 2260 2270 2280 NKSVDGSNST LSMSTHFKML KRLVEDPTFS EILIPLQSVM IPTLPSVLGA HANHDPFPGH 2290 2300 2310 2320 2330 2340 WAYLAGFDDV VEILSSLQKP KKISLKGSDG KFYIMMCKPK DDLRKDCRLM EFNSLINKSL 2350 2360 2370 2380 2390 2400 RKDAESRRRE LHIRTYAVIP LNDECGIIEW VNNTAGLRPI LTKIYKEKGV YMTGKELRQC 2410 2420 2430 2440 2450 2460 MLPKSAALSE KLKVFQELLL PRHPPVFHEW FLRTFPDPTS WYSSRSAYCR STAVMSMVGY 2470 2480 2490 2500 2510 2520 ILGLGDRHGE NILFDSFTGE CVHVDFNCLF NKGETFEVPE IVPFRLTHNM VNGMGPMGTE 2530 2540 2550 2560 2570 2580 GLFRRACEVT LRLMRDQREP LMSVLKTFLH DPLVEGSKPV KGHSKAPLNE TGEVVNEKAK 2590 2600 2610 2620 2630 THVLDIEQRL QGVIKTRNRV TGLPLSIEGH VHYLIQEATD ENLLCQMYLG WTPYM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	The mouse genome sequencing consortium Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1134 AND 1578-2635. Strain: C57BL/6J and NOD. Tissue: Brain, Dendritic cell, Egg, Embryo and Lung.
[3]	"Prediction of the coding sequences of mouse homologues of FLJ genes: the complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H. DNA Res. 11:127-135(2004) [PubMed: 15449545] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1684-2635. Tissue: Embryonic intestine.
[4]	"Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice." de Klein A., Muijtjens M., van Os R., Verhoeven Y., Smit B., Carr A.M., Lehmann A.R., Hoeijmakers J.H.J. Curr. Biol. 10:479-482(2000) [PubMed: 10801416] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2362-2635, FUNCTION.
[5]	"The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes." Keegan K.S., Holtzman D.A., Plug A.W., Christenson E.R., Brainerd E.E., Flaggs G., Bentley N.J., Taylor E.M., Meyn M.S., Moss S.B., Carr A.M., Ashley T., Hoekstra M.F. Genes Dev. 10:2423-2437(1996) [PubMed: 8843195] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"ATR disruption leads to chromosomal fragmentation and early embryonic lethality." Brown E.J., Baltimore D. Genes Dev. 14:397-402(2000) [PubMed: 10691732] [Abstract] Cited for: FUNCTION.
[7]	"Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance." Brown E.J., Baltimore D. Genes Dev. 17:615-628(2003) [PubMed: 12629044] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AC091531 Genomic DNA. No translation available. AC121499 Genomic DNA. No translation available. AK132223 mRNA. Translation: BAE21043.1. AK139834 mRNA. Translation: BAE24154.1. AK157754 mRNA. Translation: BAE34182.1. AK164916 mRNA. Translation: BAE37964.1. AK171072 mRNA. Translation: BAE42229.1. AK220176 mRNA. Translation: BAD90361.1. AF236887 mRNA. Translation: AAF61728.1.
IPI	IPI00123119.
UniGene	Mm.212462
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9JKK8. 1 interaction.
PTM databases
PhosphoSite	Q9JKK8.
Genome annotation databases
Ensembl	ENSMUSG00000032409. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:108028. Atr.
Rouge	Search...
Phylogenomic databases
HOGENOM	Q9JKK8.
HOVERGEN	Q9JKK8.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244.
Gene expression databases
ArrayExpress	Q9JKK8.
Bgee	Q9JKK8.
CleanEx	MM_ATR.
GermOnline	ENSMUSG00000032409. Mus musculus.
Family and domain databases
InterPro	IPR003152. FATC. IPR000357. HEAT. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR003151. PIK-rel_kinase_FAT. IPR014009. PIK_FAT. IPR012993. UME. [Graphical view]
Gene3D	G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit.
Pfam	PF02259. FAT. 1 hit. PF02260. FATC. 1 hit. PF02985. HEAT. 2 hits. PF00454. PI3_PI4_kinase. 1 hit. PF08064. UME. 1 hit. [Graphical view]
SMART	SM00146. PI3Kc. 1 hit. SM00802. UME. 1 hit. [Graphical view]
PROSITE	PS51189. FAT. 1 hit. PS51190. FATC. 1 hit. PS50077. HEAT_REPEAT. 1 hit. PS00915. PI3_4_KINASE_1. False negative. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

ATR_MOUSE

Accession

Primary (citable) accession number: Q9JKK8
Secondary accession number(s): Q3TBS8 , Q3TNX3, Q3TZM6, Q3UT26, Q3V1V6, Q571L3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2005
Last sequence update:	March 29, 2005
Last modified:	June 16, 2009
This is version 57 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)