ATM_PIG
ID ATM_PIG Reviewed; 3057 AA.
AC Q6PQD5;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Serine-protein kinase ATM;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q13315};
DE AltName: Full=Ataxia telangiectasia mutated homolog;
DE Short=A-T mutated homolog;
GN Name=ATM;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Fritz K.L., Rogatcheva M.B., Counter C.M., Schook L.B., Beever J.E.;
RT "Genomic organization and comparative analysis of the porcine ataxia-
RT telangiectasia mutated (ATM) gene.";
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine protein kinase which activates checkpoint
CC signaling upon double strand breaks (DSBs), apoptosis and genotoxic
CC stresses such as ionizing ultraviolet A light (UVA), thereby acting as
CC a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-
CC Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand
CC breaks (DSBs), thereby regulating DNA damage response mechanism. Also
CC plays a role in pre-B cell allelic exclusion, a process leading to
CC expression of a single immunoglobulin heavy chain allele to enforce
CC clonality and monospecific recognition by the B-cell antigen receptor
CC (BCR) expressed on individual B-lymphocytes. After the introduction of
CC DNA breaks by the RAG complex on one immunoglobulin allele, acts by
CC mediating a repositioning of the second allele to pericentromeric
CC heterochromatin, preventing accessibility to the RAG complex and
CC recombination of the second allele. Also involved in signal
CC transduction and cell cycle control. May function as a tumor
CC suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates
CC DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CTIP, nibrin
CC (NBN), TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C. May play a role in
CC vesicle and/or protein transport. Could play a role in T-cell
CC development, gonad and neurological function. Binds DNA ends. Plays a
CC role in replication-dependent histone mRNA degradation. Phosphorylation
CC of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-
CC mediated ubiquitination and subsequent proteasome degradation.
CC Phosphorylates ATF2 which stimulates its function in DNA damage
CC response (By similarity). Phosphorylates ERCC6 which is essential for
CC its chromatin remodeling activity at DNA double-strand breaks (By
CC similarity). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in
CC response to DNA damage, which promotes TTC5/STRAP nuclear localization
CC (By similarity). {ECO:0000250|UniProtKB:Q13315}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q13315};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:Q13315};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q13315};
CC -!- ACTIVITY REGULATION: Inhibited by wortmannin.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- SUBUNIT: Homodimer (By similarity). Dimers or tetramers in inactive
CC state. On DNA damage, autophosphorylation dissociates ATM into monomers
CC rendering them catalytically active. Binds p53/TP53, ABL1, BRCA1,
CC NBN/nibrin and TERF1. Part of the BRCA1-associated genome surveillance
CC complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2
CC and the RAD50-MRE11-NBN protein complex. This association could be a
CC dynamic process changing throughout the cell cycle and within
CC subnuclear domains. Interacts with RAD17; DNA damage promotes the
CC association. Interacts with EEF1E1; the interaction, induced on DNA
CC damage, up-regulates TP53. Interacts with DCLRE1C, KAT8, KAT5, NABP2,
CC ATMIN and CEP164. Interacts with AP2B1 and AP3B2; the interaction
CC occurs in cytoplasmic vesicles (By similarity). Interacts with TELO2
CC and TTI1. Interacts with DDX1. Interacts with BRAT1 (By similarity).
CC Interacts with CYREN (via XLF motif) (By similarity).
CC {ECO:0000250|UniProtKB:Q13315, ECO:0000250|UniProtKB:Q62388}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13315}.
CC Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q13315}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q62388}. Note=Primarily nuclear. Found also in
CC endocytic vesicles in association with beta-adaptin.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- DOMAIN: The FATC domain is required for interaction with KAT5.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- PTM: Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-
CC 1894, Ser-1982 correlates with DNA damage-mediated activation of the
CC kinase. During the late stages of DNA damage response, dephosphorylated
CC following deacetylation by SIRT7, leading to ATM deactivation.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- PTM: Acetylation, on DNA damage, is required for activation of the
CC kinase activity, dimer-monomer transition, and subsequent
CC autophosphorylation on Ser-1982. Acetylated in vitro by KAT5/TIP60.
CC Deacetylated by SIRT7 during the late stages of DNA damage response,
CC promoting ATM dephosphorylation and subsequent deactivation.
CC {ECO:0000250|UniProtKB:Q13315}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000305}.
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DR EMBL; AY587061; AAT01608.2; -; Genomic_DNA.
DR RefSeq; NP_001116552.1; NM_001123080.1.
DR SMR; Q6PQD5; -.
DR STRING; 9823.ENSSSCP00000019250; -.
DR PaxDb; Q6PQD5; -.
DR PeptideAtlas; Q6PQD5; -.
DR PRIDE; Q6PQD5; -.
DR GeneID; 100101922; -.
DR KEGG; ssc:100101922; -.
DR CTD; 472; -.
DR eggNOG; KOG0892; Eukaryota.
DR InParanoid; Q6PQD5; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005840; C:ribosome; IEA:InterPro.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0047485; F:protein N-terminus binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0003735; F:structural constituent of ribosome; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR GO; GO:0071044; P:histone mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IEA:InterPro.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0007094; P:mitotic spindle assembly checkpoint signaling; ISS:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051171; P:regulation of nitrogen compound metabolic process; IEA:UniProt.
DR GO; GO:0080090; P:regulation of primary metabolic process; IEA:UniProt.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR GO; GO:0006412; P:translation; IEA:InterPro.
DR CDD; cd05171; PIKKc_ATM; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR015519; ATM/Tel1.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR044107; PIKKc_ATM.
DR InterPro; IPR018278; Ribosomal_S21_CS.
DR InterPro; IPR021668; TAN.
DR PANTHER; PTHR11139:SF72; PTHR11139:SF72; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF11640; TAN; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SMART; SM01342; TAN; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS01181; RIBOSOMAL_S21; 1.
PE 3: Inferred from homology;
KW Acetylation; ATP-binding; Cell cycle; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; DNA damage; DNA-binding; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tumor suppressor.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT CHAIN 2..3057
FT /note="Serine-protein kinase ATM"
FT /id="PRO_0000088842"
FT DOMAIN 1941..2567
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT DOMAIN 2687..2999
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 3025..3057
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1374..1383
FT /note="Interaction with ABL1"
FT /evidence="ECO:0000250"
FT REGION 1970..1995
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2578..2598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2693..2699
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2868..2876
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2888..2912
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2977..2998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1978..1995
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 1894
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 1982
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 1984
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 2997
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
FT MOD_RES 3017
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13315"
SQ SEQUENCE 3057 AA; 350564 MW; BE5546AA0BF9E32C CRC64;
MSLALNDLLI CCRQLEHDRA TERRKAVENF RHLIQDPETV QHLDQHSDSK QGKYLNWDAA
FRFLQKYIQK ETECLRTAKQ NVSASTQATR QKKMQEISSL VKYFIKCANK RAPRLKCQEL
LNYIMDTVRD SSNNPIYGAD YSNILLKDIL SVRKYWCEIS QQQWRELFLI YFTLYLKPSQ
DINRLLVARI IQAVTKGCCS QTDGLNSEFL DFFTKAIQNA RQEKSSPGLN HILAAYVIFL
KTLAANFRIR VCELGDKILP TLLYIWTQHR LNDSLKEVIV ELFQLQVYMH HPKGAKTQEK
GAYESAKWKS ILYNLYDLLV NEISRIGSRG KYSSGSRNIA VKENLIELMA DICHQVFNED
TRSLEISQSY TTTQREFSDY NAPCKKRKIE LGWGVIKDHL QKSQNDFDVV PWLQIATQLI
SKYPASLPNC ELSPLLMILY QLLPQQRRGE RTPYVLRCLM EVALCQGKKP NLESSHKSDL
LKIWIKIWSI TFRGISSEQI QAENFGLLGA IIQGSLVEVD REFWKLFTGS ACKPSCPTVC
CLTLALKTCV VPETVETGME NICDGNRKFS LKESIMKWLL FCQLEDDFED RIELPPILHS
NFPHLALEKI LVSLIMKNCK AAMNFFQSVP ECEQHQKDTE EPSLLEVEEL FLQTTFDKMD
FLTVVQECTI EKHQSSVGFS FHQNLKESLD RYLLGLSEQL LNNYLPETSD SETLVRCSSL
LVGVLGCYCY VGVIAEEEAY TSELFQKAKS LMQCAGESIT LFKSKTNEES RIISLRNMMH
LCTNCLYKCA KRSPNKIASG FFLRLLTSKL MHDIADVCRS LAFIIKKPFD CREVESMEDD
TDKNLMEMND QSSMSLFNDN PASSVIDANE SGESQITMGA MNPLAEEHLS KQDLLVLDML
RFLCMCITIA QSNTMSFRAA DIRRKLLMLI DSDRLDPTKS LHLHMYLVLL KELPGEEYPL
PMEDVVELLK PLSSVCSLYR RDQDVCKTIL NHVLHIVPNL CRENVDAEST RDAQGQFLTV
IGAFWHLTKE GKCTFSVRLA LVKCLKTLLE ADPYSRWAIL NVMEKDFPVN EVFPQFLADN
HHQVCMLAAG LINRLFQHMK QGDSSTIMRA LPLKLQQTAF ENAYLKAQER IRQVKSQGGE
NRELLDEICN RKAVLLTMIA VVLCCSPVCE KQALFALCKS VKENGLEPHL IKKVLEKVSE
TFGYRHLEDF MASHLDYLVL EWLHLQDAEY SLSSFPFILL NYTNIEDFYR SCYKVLIPHL
VMRCHFDEVK SIANQIQGDW KSLLTDCFPK ILVNILPYFA YEDTGDRGMA QQRETASKVY
DMLKDENLLG KQIDQLFINN LPEIVVELLM TLHEPATSDA SQSTDPCDFS GDLDPRPNPP
HFPSHVIKAT FAYISNCHKT KLKSILEVLS KSPDSYQKIL LAICEQAAET NNVYKKHRIL
KIYHLFVSLL LKDMKSGLGG AWAFVLRDVI YTLIHYINKR PSRFMDVSLR SFSLCCDLLS
RVCHTAVTYS KDALESHLHV IVGTLIPLVD GQMEVQKQVL DLLKYLVIDN KDNENLYVMI
KLLDPFPDNA VFKDLRITQQ EIKYSKGPFS LLEEINHFLS VSVYDALPLT RLEGLKDLRR
QLAQHKDQMM DLMRASQDNP QDGIVVKLVV SLLQLSKMAV NHTGEREVLE AVGRCLGEVG
PIDFSTIAIQ HSKDMPYTKA LELFEDKEHH WTLMMLTYLN STLVEDCVKV RSAAVTCLKS
ILATKTGHGF WEIFKTTADP MLTYLLPFRT SRKKFLEVPR LNKESPLEGL DDISLWIPQS
ENHDIWIKTL TCALLDSGGI NSEVLQLLKP MCEVKTDFCQ TVLPYLIHDI LLQDTNESWR
SLLSTHIQGF FTNCFRHSSQ TSRSTTPANM DSESEHVFRC HLDKKSQRTM LAVVDYMRRQ
KRSSSGTVFD DAFWLELNYL EVAKVAQSCA AHFTALLYAE IYADKKNMDD QEKRSPTFEE
GSQSTTISSL SEKSKEETGI SLQDLLLEIY RSIGEPDSLY GCGGGKMLQP LTRLRTYEHE
AMWGKALVTY DLETAISSST RQAGIIQALQ NLGLCHILSV YLKGLDHENK EQCAELQELH
YQVAWRNMQW DSCVSVNKGM EGTSYHESLY NALQSLRDRE FSTFYESLKY ARVKEVEELC
KGSLESVYSL YPTLSRLQAI GELENIGELF SRSVTDRQPS EVYNKWWKHS QLLKDSDFSF
QEPIMALRTV ILEILMEKEM ENSQRECLKD ILTKHLVELS LLARTFQNTQ LPERAIFQIK
QYNSANCGVS EWQLEEAQVF WAKKEQSLAL SILKQMIKKL DASCTENDPR LKLIHIECLR
VCGTWLAETC LENPAVIMQT YLEKAVELAG NYDGESNDEL RNGKMKAFLS LARFSDTQYQ
RIENYMKSSE FENKQALLKR AKEEVGLLRE HKIQTNRYTI KVQRELELDE GALRALKKDR
KRFLCKAVEN YINCLLSGEG HDMWIFRLCS LWLENSGVSE VNGMMKRDGM KIPSYKFLPL
MYQLAARMGT KMMGGLGFHD VLNSLISRIS VDHPHHTLFI ILALANANKD EFLTKPEAAR
SSRITKNTPK ESSQLDEDRT EAANKVICTL RNRRRQMVRS VEALCDAYII LANLDATQWR
TQRKGIRIPA DQPITKLKNL EDVVVPTMEI KVDPTGEYGN MVTIQSFKPE FRLAGGLNLP
KIIDCVGSDG KERRQLVKGR DDLRQDAVMQ QVFQMCNTLL QRNTETRKRK LTICTYKVVP
LSQRSGVLEW CTGTVPIGEY LVNNDTGAHK RYRPKDFSPV QCQKKMMEAQ NKSFEEKYEI
FMNICQNFQP VFRYFCMEKF LDPAVWFERR LAYTQSVATS SIVGYILGLG DRHVQNILIN
EQSAELVHID LGVAFEQGKI LPTPETVPFR LTRDIVDGMG ITGVEGVFRR CCEKTMEVMR
NSQETLLTIV EVLLYDPLFD WTMNPLKALY LQQRPEDESE LHSTPRADDQ ECKRNLSDTD
QSFNKVAERV LMRLQEKLKG VEEGTVLSVG GQVNFLIQQA MDPKNLSKLF SGWKAWV
