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Description:
Serine/threonine-protein kinase ATR (EC 2.7.1.37) (Ataxiatelangiectasia and Rad3-related protein).
Molecular weight: 3002
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
29-MAR-2005, sequence version 2.
07-MAR-2006, entry version 23.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Glires Rodentia Sciurognathi Muroidea Muridae Murinae Mus.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein ATR_MOUSE:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AC091531 | NOT_ANNOTATED_CDS | |
| EMBL | CAAA01189692 | NOT_ANNOTATED_CDS | |
| EMBL | CAAA01210650 | NOT_ANNOTATED_CDS | |
| EMBL | AF236887 | AAF61728.1 | - |
| Ensembl | ENSMUSG00000032409 | Mus musculus.1 | |
| MGI | MGI:108028 | Atr.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0004672 | F:protein kinase activity | IDA. |
| GO | GO:0000077 | P:DNA damage checkpoint | IMP. |
| GO | GO:0006281 | P:DNA repair | IDA. |
| GO | GO:0006468 | P:protein amino acid phosphorylation | IDA. |
| InterPro | IPR011989 | ARM-like. | |
| InterPro | IPR003152 | FATC. | |
| InterPro | IPR000357 | HEAT. | |
| InterPro | IPR000403 | PI3/4_kinase_cat. | |
| InterPro | IPR011990 | TPR-like_helical. | |
| InterPro | IPR012993 | UME. | |
| Pfam | PF02260 | FATC | 1. |
| Pfam | PF02985 | HEAT | 2. |
| Pfam | PF00454 | PI3_PI4_kinase | 1. |
| Pfam | PF08064 | UME | 1. |
| SMART | SM00146 | PI3Kc | 1. |
| PROSITE | PS50077 | HEAT_REPEAT | 1. |
| PROSITE | PS00915 | PI3_4_KINASE_1 | FALSE_NEG. |
| PROSITE | PS00916 | PI3_4_KINASE_2 | 1. |
| PROSITE | PS50290 | PI3_4_KINASE_3 | 1. |
Keywords:
Chromosomal protein; DNA damage; DNA repair; DNA-binding; Kinase; Manganese; Nuclear protein; Phosphorylation; Repeat; Serine/threonine-protein kinase; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2362-2635, AND FUNCTION.
RX PubMed=10801416; DOI=10.1016/S0960-9822(00)00447-4;
RA de Klein A., Muijtjens M., van Os R., Verhoeven Y., Smit B.,
RA Carr A.M., Lehmann A.R., Hoeijmakers J.H.J.;
RT "Targeted disruption of the cell-cycle checkpoint gene ATR leads to
RT early embryonic lethality in mice.";
RL Curr. Biol. 10:479-482(2000).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RA Keegan K.S., Holtzman D.A., Plug A.W., Christenson E.R.,
RA Brainerd E.E., Flaggs G., Bentley N.J., Taylor E.M., Meyn M.S.,
RA Moss S.B., Carr A.M., Ashley T., Hoekstra M.F.;
RT "The Atr and Atm protein kinases associate with different sites along
RT meiotically pairing chromosomes.";
RL Genes Dev. 10:2423-2437(1996).
RN [4]
RP FUNCTION.
RA Brown E.J., Baltimore D.;
RT "ATR disruption leads to chromosomal fragmentation and early embryonic
RT lethality.";
RL Genes Dev. 14:397-402(2000).
RN [5]
RP FUNCTION.
RX PubMed=12629044; DOI=10.1101/gad.1067403;
RA Brown E.J., Baltimore D.;
RT "Essential and dispensable roles of ATR in cell cycle arrest and
RT genome maintenance.";
RL Genes Dev. 17:615-628(2003).
Feature:
CHAIN 1 2635 Serine/threonine-protein kinase ATR.
/FTId=PRO_0000088845.
REPEAT 799 835 HEAT 1.
REPEAT 1329 1365 HEAT 2.
DOMAIN 2313 2558 PI3K/PI4K.
DOMAIN 2603 2635 FATC.
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 [S/T-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: 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 (By similarity).
-!- SUBCELLULAR LOCATION: Nuclear. 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).
-!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
-!- SIMILARITY: Contains 1 FATC domain.
-!- SIMILARITY: Contains 2 HEAT repeats.
-!- SIMILARITY: Contains 1 PI3K/PI4K domain.
-!- CAUTION: This is a conceptual translation.
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Sequence length: 2635
MGDHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VALELVKKTD
AQPTSVMLLD FIQHIMKSSP LMFVNVNGSQ GQNEAKDSCI EFSHWIITRL LRIAATPSCH
MLHKKICEVI CSLLFLFKSK NPAIFGVLTR ELLYLFEDLI YLHKRNAVGE VMEWPVVVSR
FLSRLDEHMG CLQPAPLQFM NVQNVEFIEV TLLMVLIHIV PTVFFRRQEL LLWQIGCALL
EHGSPKIRSL AISLLTELFE LGGLPAQPAS TFFSLFLELL QHLVGMDADQ LKLYEEPLSK
LLKTLFPFEA EAYRNIEPVY LNVLLEKLSV MFEDRVLMRL KSDLLKAALC HLLQYFLTFV
PAGYESALQV RKVYVTNICR ALVDALGVQK HVGYLLGPFY AALKMESKEI IERIQCQAQQ
ENLSGNNDEV SPKRRKLSSS LSSYKKPSRQ PEEIIHVDMD KKSILWNVLK QKAESLQISL
ECGTLKNSVA EALEGITVVL QLTALCTVHC SHQDMDGHNV KDHQHKYKKK PPVVVTWMSL
DFYTKVLKSC RSLLESVQKL ELELVIDSMV RICDALMYMQ VKSSFKDHVL EELCGMLSLP
WIYSYSDDNS LKMTTFATNL LPLSQRVWDS YSPQAQSKCV FLLTLFPRRI FLEWRTAVYN
WALKSSHEVI RASCVKGFFI LLHQQNSCNQ IPKMLVDRVK DDSDMVKKEF ASVLGQLVCT
LHGMFYLSSS VEPCFEHMDL FSKNLKATSQ HECSSSQVKA STCKPFLFLL TKNTPSPVKL
AFIDNLHHLC KHLDFQEDER EVKAVLGTLL NLMEDPDKDV RIAFSGNIKY ILESLNSEDG
FVKELFVLRM KEAYTHAQIA RNNELKDTLI LTTGDIGRAA KGDLIPFALL HLLHCLLSKS
ASVSGAAYTE IRALVAAKSV KLQNFFSQYK KPICQFLVES LHSSQMTALP SAPCQSSEIR
KQDVAHHREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ
LNVSRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL
LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDITSPELMA DYLQPKLLGI LAFFNMQLLS
SSVGIEDKKM ALTSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV
RCLDHAYLGP LLSHVIVALL PLIHMQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE
LEKIKAVLQE YRKETSETTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK
YATDSETVEP VISQLVTVIL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD
FTFVTGVEDL SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMQSNGPGY
QLWKRFPEHV REILEPHLNT RYKSSQKSTD WSGVTKPIYL SKLGNNFAEW SSSWAGYLIT
KVRDNLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDE
QHAISTQDSA SDLCQLSTQT VFSVLDHLTQ WARHKFQALN AEKLAQNKPK GVSNVNFEDY
QSVTRFLDLI PQDTLAVASF RSKAYTRAVM HFESFITEKK QNIQKHLGFL QKLYAAMHEP
DGVAGVSAIR KAEPSLKEQI LEHESIGLLR DATACYDRAI QLEPDQIIHY HGVVKSMLGL
GQLSTVITQV NGVHANRSEW TDELNTYRVE AAWKLSQWDL VENYLAADGK STTWSVRLGQ
LLLSAKKRDT TTFYDTLKLV RAEQIVPLSA ASFERGSYQR GYEFIVRLHM LCELEHSLKP
LFRKSPGDSC NEDSLNWGAR LEMTQNSYRA KEPILALRRA LLSLNKRPDY NEMVGECWLQ
SARVARKAGH HQTAYNALLN AGESRLAELY VERAKWLWSK GDVHQALIVL QKGVELCFPE
NKSPSESKHM LIHGRATLLV GRFMEETANF ESNAVMKKYK DVTLFLPEWE DGHFYLAKYY
DKLMPMVTDN KMEKQGDLIR YIVLHFGRSL QYGNQFIYQS MPRMLSLWLD FGAKAYEWEK
GGRSDRLQMR NDLAKINSVL TEHTNRLAPY QFLTAFSQLI SRICHSHDEV FVVLMEIIAK
VFLAYPQQAM WMMTAVSKSS YPMRVNRCKE ILTKAIHMKK SLEKFVGDAT RLTDKLLELC
NKSVDGSNST LSMSTHFKML KRLVEDPTFS EILIPLQSVM IPTLPSVLGA HANHDPFPGH
WAYLAGFDDV VEILSSLQKP KKISLKGSDG KFYIMMCKPK DDLRKDCRLM EFNSLINKSL
RKDAESRRRE LHIRTYAVIP LNDECGIIEW VNNTAGLRPI LTKIYKEKGV YMTGKELRQC
MLPKSAALSE KLKVFQELLL PRHPPVFHEW FLRTFPDPTS WYSSRSAYCR STAVMSMVGY
ILGLGDRHGE NILFDSFTGE CVHVDFNCLF NKGETFEVPE IVPFRLTHNM VNGMGPMGTE
GLFRRACEVT LRLMRDQREP LMSVLKTFLH DPLVEGSKPV KGHSKAPLNE TGEVVNEKAK
THVLDIEQRL QGVIKTRNRV TGLPLSIEGH VHYLIQEATD ENLLCQMYLG WTPYM