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Q9JKK8 (ATR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length2635 AA.
Sequence statusComplete.
Protein existenceEvidence 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 p53/TP53, 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. Ref.4 Ref.5 Ref.6 Ref.7

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 a 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. Interacts with TELO2 AND TTI1 By similarity. Interacts with ATRIP. Ref.8

Subcellular location

Nucleus By similarity. Chromosome. Note: Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling By similarity. Ref.5 Ref.9 Ref.10

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AtripQ8BMG12EBI-1202426,EBI-5235246

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 26352635Serine/threonine-protein kinase ATR
PRO_0000088845

Regions

Repeat799 – 83537HEAT 1
Repeat1329 – 136537HEAT 2
Domain1634 – 2179546FAT
Domain2313 – 2558246PI3K/PI4K
Domain2603 – 263533FATC

Amino acid modifications

Modified residue4311Phosphoserine By similarity

Experimental info

Sequence conflict191G → A in BAE24154. Ref.2
Sequence conflict191G → A in BAE34182. Ref.2
Sequence conflict191G → A in BAE42229. Ref.2
Sequence conflict22081D → E in BAE37964. Ref.2
Sequence conflict23471R → C in BAE37964. Ref.2
Sequence conflict25561G → W in BAE21043. Ref.2
Sequence conflict25561G → W in BAD90361. Ref.3
Sequence conflict25631H → R in BAE21043. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9JKK8 [UniParc].

Last modified March 29, 2005. Version 2.
Checksum: C126413D15ACB8DC

FASTA2,635300,224
        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 

« Hide

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
Takai H., Xie Y., de Lange T., Pavletich N.P.
Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATRIP.
[9]"HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity."
Kogo H., Tsutsumi M., Inagaki H., Ohye T., Kiyonari H., Kurahashi H.
Genes Cells 17:897-912(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms."
Wojtasz L., Cloutier J.M., Baumann M., Daniel K., Varga J., Fu J., Anastassiadis K., Stewart A.F., Remenyi A., Turner J.M., Toth A.
Genes Dev. 26:958-973(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
UniGeneMm.212462.

3D structure databases

ProteinModelPortalQ9JKK8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9JKK8. 2 interactions.

PTM databases

PhosphoSiteQ9JKK8.

Proteomic databases

PaxDbQ9JKK8.
PRIDEQ9JKK8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:108028. Atr.
RougeSearch...

Phylogenomic databases

eggNOGCOG5032.
HOVERGENHBG050619.
InParanoidQ3TBS8.
PhylomeDBQ9JKK8.

Enzyme and pathway databases

ReactomeREACT_188804. Cell Cycle.
REACT_198624. Meiosis.
REACT_75800. Meiotic Synapsis.

Gene expression databases

CleanExMM_ATR.
GenevestigatorQ9JKK8.

Family and domain databases

Gene3D1.10.1070.11. 2 hits.
1.25.10.10. 4 hits.
1.25.40.10. 2 hits.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR003152. FATC.
IPR021133. HEAT_type_2.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003151. PIK-rel_kinase_FAT.
IPR014009. PIK_FAT.
IPR011990. TPR-like_helical.
IPR012993. UME.
[Graphical view]
PfamPF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08064. UME. 1 hit.
[Graphical view]
SMARTSM00146. PI3Kc. 1 hit.
SM00802. UME. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS51189. FAT. 1 hit.
PS51190. FATC. 1 hit.
PS50077. HEAT_REPEAT. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATR. mouse.
PROQ9JKK8.
SOURCESearch...

Entry information

Entry nameATR_MOUSE
AccessionPrimary (citable) accession number: Q9JKK8
Secondary accession number(s): Q3TBS8 expand/collapse secondary AC list , Q3TNX3, Q3TZM6, Q3UT26, Q3V1V6, Q571L3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot