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Protein

Serine/threonine-protein kinase ATR

Gene

Atr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mn2+By similarity

Activity regulationi

Serine/threonine-protein kinase activity is directly stimulated by TOPBP1. ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1. Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological processDNA damage, DNA repair
LigandATP-binding, Manganese, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ATR (EC:2.7.11.1)
Alternative name(s):
Ataxia telangiectasia and Rad3-related protein
Gene namesi
Name:Atr
Synonyms:Kiaa4069
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:108028 Atr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000888451 – 2635Serine/threonine-protein kinase ATRAdd BLAST2635

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei431PhosphoserineCombined sources1
Modified residuei438PhosphoserineBy similarity1
Modified residuei439PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated; autophosphorylates in vitro.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9JKK8
MaxQBiQ9JKK8
PaxDbiQ9JKK8
PRIDEiQ9JKK8

PTM databases

iPTMnetiQ9JKK8
PhosphoSitePlusiQ9JKK8

Expressioni

Tissue specificityi

Ubiquitous. Expression is highest in testis, where it is restricted to primary spermatocytes. Expression decreases as spermiogenesis proceeds (at protein level).1 Publication

Gene expression databases

CleanExiMM_ATR

Interactioni

Subunit structurei

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 (PubMed:20801936).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AtripQ8BMG12EBI-1202426,EBI-5235246

Protein-protein interaction databases

ComplexPortaliCPX-3623 ATR-ATRIP DNA damage-sensing kinase complex
IntActiQ9JKK8, 2 interactors
STRINGi10090.ENSMUSP00000034980

Structurei

3D structure databases

ProteinModelPortaliQ9JKK8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati799 – 835HEAT 1Add BLAST37
Repeati1329 – 1365HEAT 2Add BLAST37
Domaini1634 – 2179FATPROSITE-ProRule annotationAdd BLAST546
Domaini2313 – 2558PI3K/PI4KPROSITE-ProRule annotationAdd BLAST246
Domaini2603 – 2635FATCPROSITE-ProRule annotationAdd BLAST33

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family. ATM subfamily.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0890 Eukaryota
COG5032 LUCA
HOVERGENiHBG050619
InParanoidiQ9JKK8
PhylomeDBiQ9JKK8

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
1.25.10.10, 2 hits
1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR003152 FATC_dom
IPR021133 HEAT_type_2
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
IPR011990 TPR-like_helical_dom_sf
IPR012993 UME
PfamiView protein in Pfam
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
PF08064 UME, 1 hit
SMARTiView protein in SMART
SM01343 FATC, 1 hit
SM00146 PI3Kc, 1 hit
SM00802 UME, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF48452 SSF48452, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51189 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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9JKK8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGDHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV
60 70 80 90 100
VALELVKKTD AQPTSVMLLD FIQHIMKSSP LMFVNVNGSQ GQNEAKDSCI
110 120 130 140 150
EFSHWIITRL LRIAATPSCH MLHKKICEVI CSLLFLFKSK NPAIFGVLTR
160 170 180 190 200
ELLYLFEDLI YLHKRNAVGE VMEWPVVVSR FLSRLDEHMG CLQPAPLQFM
210 220 230 240 250
NVQNVEFIEV TLLMVLIHIV PTVFFRRQEL LLWQIGCALL EHGSPKIRSL
260 270 280 290 300
AISLLTELFE LGGLPAQPAS TFFSLFLELL QHLVGMDADQ LKLYEEPLSK
310 320 330 340 350
LLKTLFPFEA EAYRNIEPVY LNVLLEKLSV MFEDRVLMRL KSDLLKAALC
360 370 380 390 400
HLLQYFLTFV PAGYESALQV RKVYVTNICR ALVDALGVQK HVGYLLGPFY
410 420 430 440 450
AALKMESKEI IERIQCQAQQ ENLSGNNDEV SPKRRKLSSS LSSYKKPSRQ
460 470 480 490 500
PEEIIHVDMD KKSILWNVLK QKAESLQISL ECGTLKNSVA EALEGITVVL
510 520 530 540 550
QLTALCTVHC SHQDMDGHNV KDHQHKYKKK PPVVVTWMSL DFYTKVLKSC
560 570 580 590 600
RSLLESVQKL ELELVIDSMV RICDALMYMQ VKSSFKDHVL EELCGMLSLP
610 620 630 640 650
WIYSYSDDNS LKMTTFATNL LPLSQRVWDS YSPQAQSKCV FLLTLFPRRI
660 670 680 690 700
FLEWRTAVYN WALKSSHEVI RASCVKGFFI LLHQQNSCNQ IPKMLVDRVK
710 720 730 740 750
DDSDMVKKEF ASVLGQLVCT LHGMFYLSSS VEPCFEHMDL FSKNLKATSQ
760 770 780 790 800
HECSSSQVKA STCKPFLFLL TKNTPSPVKL AFIDNLHHLC KHLDFQEDER
810 820 830 840 850
EVKAVLGTLL NLMEDPDKDV RIAFSGNIKY ILESLNSEDG FVKELFVLRM
860 870 880 890 900
KEAYTHAQIA RNNELKDTLI LTTGDIGRAA KGDLIPFALL HLLHCLLSKS
910 920 930 940 950
ASVSGAAYTE IRALVAAKSV KLQNFFSQYK KPICQFLVES LHSSQMTALP
960 970 980 990 1000
SAPCQSSEIR KQDVAHHREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP
1010 1020 1030 1040 1050
DLAAKASPAA SALIRTLGKQ LNVSRREILI NNFKYIFSHL VCSCSKDELE
1060 1070 1080 1090 1100
RALHYLKNET EIELGSLLRQ DFQGLHNELL LRIGEHYQQV FNGLSILASF
1110 1120 1130 1140 1150
ASSDDPYQGP RDITSPELMA DYLQPKLLGI LAFFNMQLLS SSVGIEDKKM
1160 1170 1180 1190 1200
ALTSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV
1210 1220 1230 1240 1250
RCLDHAYLGP LLSHVIVALL PLIHMQPKET AAIFHYLIIE NRDAVQDFLH
1260 1270 1280 1290 1300
EIYFLPDHPE LEKIKAVLQE YRKETSETTD LQTTLQLSMK AIQHENVDVR
1310 1320 1330 1340 1350
IHALTSLKET LYKNQEKLIK YATDSETVEP VISQLVTVIL KGCQDANSQA
1360 1370 1380 1390 1400
RLLCGECLGE LGAIDPGRLD FSTTETQGKD FTFVTGVEDL SFAYGLLMEL
1410 1420 1430 1440 1450
TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMQSNGPGY QLWKRFPEHV
1460 1470 1480 1490 1500
REILEPHLNT RYKSSQKSTD WSGVTKPIYL SKLGNNFAEW SSSWAGYLIT
1510 1520 1530 1540 1550
KVRDNLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA
1560 1570 1580 1590 1600
EIMAVLKHDE QHAISTQDSA SDLCQLSTQT VFSVLDHLTQ WARHKFQALN
1610 1620 1630 1640 1650
AEKLAQNKPK GVSNVNFEDY QSVTRFLDLI PQDTLAVASF RSKAYTRAVM
1660 1670 1680 1690 1700
HFESFITEKK QNIQKHLGFL QKLYAAMHEP DGVAGVSAIR KAEPSLKEQI
1710 1720 1730 1740 1750
LEHESIGLLR DATACYDRAI QLEPDQIIHY HGVVKSMLGL GQLSTVITQV
1760 1770 1780 1790 1800
NGVHANRSEW TDELNTYRVE AAWKLSQWDL VENYLAADGK STTWSVRLGQ
1810 1820 1830 1840 1850
LLLSAKKRDT TTFYDTLKLV RAEQIVPLSA ASFERGSYQR GYEFIVRLHM
1860 1870 1880 1890 1900
LCELEHSLKP LFRKSPGDSC NEDSLNWGAR LEMTQNSYRA KEPILALRRA
1910 1920 1930 1940 1950
LLSLNKRPDY NEMVGECWLQ SARVARKAGH HQTAYNALLN AGESRLAELY
1960 1970 1980 1990 2000
VERAKWLWSK GDVHQALIVL QKGVELCFPE NKSPSESKHM LIHGRATLLV
2010 2020 2030 2040 2050
GRFMEETANF ESNAVMKKYK DVTLFLPEWE DGHFYLAKYY DKLMPMVTDN
2060 2070 2080 2090 2100
KMEKQGDLIR YIVLHFGRSL QYGNQFIYQS MPRMLSLWLD FGAKAYEWEK
2110 2120 2130 2140 2150
GGRSDRLQMR NDLAKINSVL TEHTNRLAPY QFLTAFSQLI SRICHSHDEV
2160 2170 2180 2190 2200
FVVLMEIIAK VFLAYPQQAM WMMTAVSKSS YPMRVNRCKE ILTKAIHMKK
2210 2220 2230 2240 2250
SLEKFVGDAT RLTDKLLELC NKSVDGSNST LSMSTHFKML KRLVEDPTFS
2260 2270 2280 2290 2300
EILIPLQSVM IPTLPSVLGA HANHDPFPGH WAYLAGFDDV VEILSSLQKP
2310 2320 2330 2340 2350
KKISLKGSDG KFYIMMCKPK DDLRKDCRLM EFNSLINKSL RKDAESRRRE
2360 2370 2380 2390 2400
LHIRTYAVIP LNDECGIIEW VNNTAGLRPI LTKIYKEKGV YMTGKELRQC
2410 2420 2430 2440 2450
MLPKSAALSE KLKVFQELLL PRHPPVFHEW FLRTFPDPTS WYSSRSAYCR
2460 2470 2480 2490 2500
STAVMSMVGY ILGLGDRHGE NILFDSFTGE CVHVDFNCLF NKGETFEVPE
2510 2520 2530 2540 2550
IVPFRLTHNM VNGMGPMGTE GLFRRACEVT LRLMRDQREP LMSVLKTFLH
2560 2570 2580 2590 2600
DPLVEGSKPV KGHSKAPLNE TGEVVNEKAK THVLDIEQRL QGVIKTRNRV
2610 2620 2630
TGLPLSIEGH VHYLIQEATD ENLLCQMYLG WTPYM
Length:2,635
Mass (Da):300,224
Last modified:March 29, 2005 - v2
Checksum:iC126413D15ACB8DC
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1L1SSL9A0A1L1SSL9_MOUSE
Serine/threonine-protein kinase ATR
Atr
2,641Annotation score:
E9QPK4E9QPK4_MOUSE
Serine/threonine-protein kinase ATR
Atr
2,635Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19G → A in BAE24154 (PubMed:16141072).Curated1
Sequence conflicti19G → A in BAE34182 (PubMed:16141072).Curated1
Sequence conflicti19G → A in BAE42229 (PubMed:16141072).Curated1
Sequence conflicti2208D → E in BAE37964 (PubMed:16141072).Curated1
Sequence conflicti2347R → C in BAE37964 (PubMed:16141072).Curated1
Sequence conflicti2556G → W in BAE21043 (PubMed:16141072).Curated1
Sequence conflicti2556G → W in BAD90361 (PubMed:15449545).Curated1
Sequence conflicti2563H → R in BAE21043 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
UniGeneiMm.212462

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
UniGeneiMm.212462

3D structure databases

ProteinModelPortaliQ9JKK8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-3623 ATR-ATRIP DNA damage-sensing kinase complex
IntActiQ9JKK8, 2 interactors
STRINGi10090.ENSMUSP00000034980

PTM databases

iPTMnetiQ9JKK8
PhosphoSitePlusiQ9JKK8

Proteomic databases

EPDiQ9JKK8
MaxQBiQ9JKK8
PaxDbiQ9JKK8
PRIDEiQ9JKK8

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:108028 Atr
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0890 Eukaryota
COG5032 LUCA
HOVERGENiHBG050619
InParanoidiQ9JKK8
PhylomeDBiQ9JKK8

Miscellaneous databases

ChiTaRSiAtr mouse
PROiPR:Q9JKK8
SOURCEiSearch...

Gene expression databases

CleanExiMM_ATR

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
1.25.10.10, 2 hits
1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR003152 FATC_dom
IPR021133 HEAT_type_2
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
IPR011990 TPR-like_helical_dom_sf
IPR012993 UME
PfamiView protein in Pfam
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
PF08064 UME, 1 hit
SMARTiView protein in SMART
SM01343 FATC, 1 hit
SM00146 PI3Kc, 1 hit
SM00802 UME, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
SSF48452 SSF48452, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51189 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
ProtoNetiSearch...

Entry informationi

Entry nameiATR_MOUSE
AccessioniPrimary (citable) accession number: Q9JKK8
Secondary accession number(s): Q3TBS8
, Q3TNX3, Q3TZM6, Q3UT26, Q3V1V6, Q571L3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: November 7, 2018
This is version 141 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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