ATR

Protein identityUniProt · HPA

UniProt accession

Q13535

Gene

ATR

Ensembl

ENSG00000175054

Chromosome

3

Canonical length

2644 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted membrane proteins

Subcellular location

Nucleoplasm,Golgi apparatus

OverviewNCBI Gene

The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

2644 residues, UniProt reviewed canonical sequence.

>Q13535|ATR
     1  MGEHGLELAS MIPALRELGS ATPEEYNTVV QKPRQILCQF IDRILTDVNV VAVELVKKTD
    61  SQPTSVMLLD FIQHIMKSSP LMFVNVSGSH EAKGSCIEFS NWIITRLLRI AATPSCHLLH
   121  KKICEVICSL LFLFKSKSPA IFGVLTKELL QLFEDLVYLH RRNVMGHAVE WPVVMSRFLS
   181  QLDEHMGYLQ SAPLQLMSMQ NLEFIEVTLL MVLTRIIAIV FFRRQELLLW QIGCVLLEYG
   241  SPKIKSLAIS FLTELFQLGG LPAQPASTFF SSFLELLKHL VEMDTDQLKL YEEPLSKLIK
   301  TLFPFEAEAY RNIEPVYLNM LLEKLCVMFE DGVLMRLKSD LLKAALCHLL QYFLKFVPAG
   361  YESALQVRKV YVRNICKALL DVLGIEVDAE YLLGPLYAAL KMESMEIIEE IQCQTQQENL
   421  SSNSDGISPK RRRLSSSLNP SKRAPKQTEE IKHVDMNQKS ILWSALKQKA ESLQISLEYS
   481  GLKNPVIEML EGIAVVLQLT ALCTVHCSHQ NMNCRTFKDC QHKSKKKPSV VITWMSLDFY
   541  TKVLKSCRSL LESVQKLDLE ATIDKVVKIY DALIYMQVNS SFEDHILEDL CGMLSLPWIY
   601  SHSDDGCLKL TTFAANLLTL SCRISDSYSP QAQSRCVFLL TLFPRRIFLE WRTAVYNWAL
   661  QSSHEVIRAS CVSGFFILLQ QQNSCNRVPK ILIDKVKDDS DIVKKEFASI LGQLVCTLHG
   721  MFYLTSSLTE PFSEHGHVDL FCRNLKATSQ HECSSSQLKA SVCKPFLFLL KKKIPSPVKL
   781  AFIDNLHHLC KHLDFREDET DVKAVLGTLL NLMEDPDKDV RVAFSGNIKH ILESLDSEDG
   841  FIKELFVLRM KEAYTHAQIS RNNELKDTLI LTTGDIGRAA KGDLVPFALL HLLHCLLSKS
   901  ASVSGAAYTE IRALVAAKSV KLQSFFSQYK KPICQFLVES LHSSQMTALP NTPCQNADVR
   961  KQDVAHQREM ALNTLSEIAN VFDFPDLNRF LTRTLQVLLP DLAAKASPAA SALIRTLGKQ
  1021  LNVNRREILI NNFKYIFSHL VCSCSKDELE RALHYLKNET EIELGSLLRQ DFQGLHNELL
  1081  LRIGEHYQQV FNGLSILASF ASSDDPYQGP RDIISPELMA DYLQPKLLGI LAFFNMQLLS
  1141  SSVGIEDKKM ALNSLMSLMK LMGPKHVSSV RVKMMTTLRT GLRFKDDFPE LCCRAWDCFV
  1201  RCLDHACLGS LLSHVIVALL PLIHIQPKET AAIFHYLIIE NRDAVQDFLH EIYFLPDHPE
  1261  LKKIKAVLQE YRKETSESTD LQTTLQLSMK AIQHENVDVR IHALTSLKET LYKNQEKLIK
  1321  YATDSETVEP IISQLVTVLL KGCQDANSQA RLLCGECLGE LGAIDPGRLD FSTTETQGKD
  1381  FTFVTGVEDS SFAYGLLMEL TRAYLAYADN SRAQDSAAYA IQELLSIYDC REMETNGPGH
  1441  QLWRRFPEHV REILEPHLNT RYKSSQKSTD WSGVKKPIYL SKLGSNFAEW SASWAGYLIT
  1501  KVRHDLASKI FTCCSIMMKH DFKVTIYLLP HILVYVLLGC NQEDQQEVYA EIMAVLKHDD
  1561  QHTINTQDIA SDLCQLSTQT VFSMLDHLTQ WARHKFQALK AEKCPHSKSN RNKVDSMVST
  1621  VDYEDYQSVT RFLDLIPQDT LAVASFRSKA YTRAVMHFES FITEKKQNIQ EHLGFLQKLY
  1681  AAMHEPDGVA GVSAIRKAEP SLKEQILEHE SLGLLRDATA CYDRAIQLEP DQIIHYHGVV
  1741  KSMLGLGQLS TVITQVNGVH ANRSEWTDEL NTYRVEAAWK LSQWDLVENY LAADGKSTTW
  1801  SVRLGQLLLS AKKRDITAFY DSLKLVRAEQ IVPLSAASFE RGSYQRGYEY IVRLHMLCEL
  1861  EHSIKPLFQH SPGDSSQEDS LNWVARLEMT QNSYRAKEPI LALRRALLSL NKRPDYNEMV
  1921  GECWLQSARV ARKAGHHQTA YNALLNAGES RLAELYVERA KWLWSKGDVH QALIVLQKGV
  1981  ELCFPENETP PEGKNMLIHG RAMLLVGRFM EETANFESNA IMKKYKDVTA CLPEWEDGHF
  2041  YLAKYYDKLM PMVTDNKMEK QGDLIRYIVL HFGRSLQYGN QFIYQSMPRM LTLWLDYGTK
  2101  AYEWEKAGRS DRVQMRNDLG KINKVITEHT NYLAPYQFLT AFSQLISRIC HSHDEVFVVL
  2161  MEIIAKVFLA YPQQAMWMMT AVSKSSYPMR VNRCKEILNK AIHMKKSLEK FVGDATRLTD
  2221  KLLELCNKPV DGSSSTLSMS THFKMLKKLV EEATFSEILI PLQSVMIPTL PSILGTHANH
  2281  ASHEPFPGHW AYIAGFDDMV EILASLQKPK KISLKGSDGK FYIMMCKPKD DLRKDCRLME
  2341  FNSLINKCLR KDAESRRREL HIRTYAVIPL NDECGIIEWV NNTAGLRPIL TKLYKEKGVY
  2401  MTGKELRQCM LPKSAALSEK LKVFREFLLP RHPPIFHEWF LRTFPDPTSW YSSRSAYCRS
  2461  TAVMSMVGYI LGLGDRHGEN ILFDSLTGEC VHVDFNCLFN KGETFEVPEI VPFRLTHNMV
  2521  NGMGPMGTEG LFRRACEVTM RLMRDQREPL MSVLKTFLHD PLVEWSKPVK GHSKAPLNET
  2581  GEVVNEKAKT HVLDIEQRLQ GVIKTRNRVT GLPLSIEGHV HYLIQEATDE NLLCQMYLGW
  2641  TPYM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

4.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATR.

Disease | AllUniProt

Conditions ATR is implicated in, by any mechanism.

• Seckel syndrome 1 (SCKL1) MIM:210600
• Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) MIM:614564

Disease | GeneticClinVar

137 pathogenic / likely-pathogenic of 4,172 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Seckel syndrome 1
• Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
• Inborn genetic diseases
• ATR-related disorder
• Hereditary cancer-predisposing syndrome

Disease | ImmuneIEDB

Conditions an epitope on ATR was assayed in.

• melanoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.4

gnomAD pLI

0

gnomAD missense Z

4.36

DepMap mean gene effect

-1.35

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 11% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to gamma radiation
• cellular response to UV
• DNA damage checkpoint signaling
• DNA damage response
• DNA repair
• DNA replication
• double-strand break repair
• establishment of protein-containing complex localization to telomere
• establishment of RNA localization to telomere
• interstrand cross-link repair
• mitotic G2/M transition checkpoint
• negative regulation of DNA replication
• nuclear membrane disassembly
• nucleobase-containing compound metabolic process
• positive regulation of DNA damage response, signal transduction by p53 class mediator
• positive regulation of telomerase catalytic core complex assembly
• positive regulation of telomere maintenance via telomerase
• protein localization to chromosome, telomeric region
• regulation of cellular response to heat
• regulation of double-strand break repair
• replication fork processing
• replicative senescence
• response to arsenic-containing substance
• response to mechanical stimulus
• response to xenobiotic stimulus
• telomere maintenance

Molecular functions

• ATP binding
• DNA binding
• histone H2AXS139 kinase activity
• MutLalpha complex binding
• MutSalpha complex binding
• protein kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• ATR-ATRIP complex
• chromosome
• Golgi apparatus
• nuclear envelope
• nucleoplasm
• nucleus
• PML body
• site of DNA damage

Protein domainsUniProt · Pfam · InterPro

• Phosphatidylinositol 3-/4-kinase, catalytic domain
• PIK-related kinase, FAT
• FATC domain
• Protein kinase-like domain superfamily
• Armadillo-like helical
• Tetratricopeptide-like helical domain superfamily
• PIK-related kinase, FAT domain
• Armadillo-type fold
• Phosphatidylinositol 3-/4-kinase, conserved site
• HEAT, type 2
• Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily
• DNA Damage Response and Repair Kinase
• Serine/threonine-protein kinase ATR-like, HEAT repeats
• Phosphatidylinositol 3- and 4-kinase
• FAT domain
• FATC domain
• Serine/threonine-protein kinase ATR-like, HEAT repeats
• UME domain
• Serine/threonine-protein kinase ATR-like, M-HEAT region
• Serine/threonine-protein kinase ATR-like, N-HEAT region
• UME (NUC010) domain
• Serine/threonine-protein kinase ATR, M-HEAT region
• Serine/threonine-protein kinase ATR, N-HEAT region

KeywordsUniProt

• ATP-binding
• Chromosome
• DNA damage
• DNA repair
• DNA-binding
• Dwarfism
• Intellectual disability
• Kinase
• Manganese
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Repeat
• Serine/threonine-protein kinase
• Transferase

InteractionsUniProt · HPA

Protein binding partners of ATR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CEP164
• CLSPN
• EEF1E1
• HDAC2
• MSH2
• TELO2
• TTI1
• UHRF2
• ATRIP
• PPP5C
• TIMELESS