ID A0A091CT98_FUKDA Unreviewed; 3056 AA.
AC A0A091CT98;
DT 26-NOV-2014, integrated into UniProtKB/TrEMBL.
DT 26-NOV-2014, sequence version 1.
DT 27-MAR-2024, entry version 57.
DE RecName: Full=Serine-protein kinase ATM {ECO:0000256|RuleBase:RU365027};
DE EC=2.7.11.1 {ECO:0000256|RuleBase:RU365027};
GN ORFNames=H920_17873 {ECO:0000313|EMBL:KFO20710.1};
OS Fukomys damarensis (Damaraland mole rat) (Cryptomys damarensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Bathyergidae;
OC Fukomys.
OX NCBI_TaxID=885580 {ECO:0000313|EMBL:KFO20710.1, ECO:0000313|Proteomes:UP000028990};
RN [1] {ECO:0000313|EMBL:KFO20710.1, ECO:0000313|Proteomes:UP000028990}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Liver {ECO:0000313|EMBL:KFO20710.1};
RA Gladyshev V.N., Fang X.;
RT "The Damaraland mole rat (Fukomys damarensis) genome and evolution of
RT African mole rats.";
RL Submitted (NOV-2013) 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, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN),
CC TERF1, RAD9, UBQLN4 and DCLRE1C. May play a role in vesicle and/or
CC protein transport. Could play a role in T-cell development, gonad and
CC neurological function. Binds DNA ends. Plays a role in replication-
CC dependent histone mRNA degradation. Phosphorylation of DYRK2 in nucleus
CC in response to genotoxic stress prevents its MDM2-mediated
CC ubiquitination and subsequent proteasome degradation. Phosphorylates
CC ATF2 which stimulates its function in DNA damage response.
CC Phosphorylates ERCC6 which is essential for its chromatin remodeling
CC activity at DNA double-strand breaks. {ECO:0000256|RuleBase:RU365027}.
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:0000256|ARBA:ARBA00000775,
CC ECO:0000256|RuleBase:RU365027};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000256|RuleBase:RU365027}. Nucleus
CC {ECO:0000256|ARBA:ARBA00004123, ECO:0000256|RuleBase:RU365027}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.
CC {ECO:0000256|ARBA:ARBA00010769, ECO:0000256|RuleBase:RU365027}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KN124601; KFO20710.1; -; Genomic_DNA.
DR STRING; 885580.ENSFDAP00000012956; -.
DR eggNOG; KOG0892; Eukaryota.
DR Proteomes; UP000028990; Unassembled WGS sequence.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:InterPro.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0051173; P:positive regulation of nitrogen compound metabolic process; IEA:UniProt.
DR GO; GO:0060255; P:regulation of macromolecule metabolic process; IEA:UniProt.
DR GO; GO:0080090; P:regulation of primary metabolic process; IEA:UniProt.
DR GO; GO:0022414; P:reproductive process; IEA:UniProt.
DR CDD; cd05171; PIKKc_ATM; 1.
DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR038980; ATM_plant.
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; IPR021668; TAN.
DR PANTHER; PTHR37079; SERINE/THREONINE-PROTEIN KINASE ATM; 1.
DR PANTHER; PTHR37079:SF4; SERINE_THREONINE-PROTEIN KINASE ATM; 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; ARM repeat; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|RuleBase:RU365027};
KW Cytoplasmic vesicle {ECO:0000256|RuleBase:RU365027};
KW DNA damage {ECO:0000256|ARBA:ARBA00022763, ECO:0000256|RuleBase:RU365027};
KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|RuleBase:RU365027};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|RuleBase:RU365027};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU365027};
KW Reference proteome {ECO:0000313|Proteomes:UP000028990};
KW Serine/threonine-protein kinase {ECO:0000256|RuleBase:RU365027};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU365027}.
FT DOMAIN 1940..2566
FT /note="FAT"
FT /evidence="ECO:0000259|PROSITE:PS51189"
FT DOMAIN 2686..2998
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000259|PROSITE:PS50290"
FT DOMAIN 3024..3056
FT /note="FATC"
FT /evidence="ECO:0000259|PROSITE:PS51190"
FT REGION 848..877
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2572..2596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 3056 AA; 350177 MW; BF387468385832F3 CRC64;
MSLALNNLLI CCRQLENDRA TERRKEVETF KRLIRDPEIV QDLDRHSDSK QGKYLNWDAV
FRFLQKYIQK ETECLRTAKP NVSISTQTSR QKKMQEISSL IRFFIKCANK RGPRLKCQEL
LNYVMDTVKD SSNSVIYGSD CSNILLKDIL SVRKYWCEIS QQQWLELFAV YFRLYLKPSQ
DINRVLVARI IHIVTKGCCS QTDGINSKSL DFFSEAIQYA RQEKKSAGLN YILAALIIFL
KTLAVNFRMR VCELGDEILP TLLYIWTQHI LNDSLKGVII ELFQLQISIH HPKGAKTHEK
GAYKSTKWQS ILYSLYDLLV NEISHIGSRG KYSAGFRNIA VKENLIELMA DICHQIFDED
TRSLEISQFY TTTQRESNDY SVPCKRRKIE VGWEVIKDYL QKLQNDFDLV PWLQIITQLI
SKYPASLPNY ELCPLLMILY QLLPQQRCGE RTPYVLRCLT EIALCQGKKT NLESSQKSDL
SKLWIKVWSV TFRGINSVQI QTENFGLLGA IIQGSLVEVD REFWKLFTGS ACKPSSSVVC
CLTLALTICV IPEVLKTRTE QNVCEVNRSF SLKESIMRWL LFHQSEDDLE DSKELPPILQ
SNFPHLILEK ILVSLTMKNC KAAMNFFQSV SECEHHQKDK EELSFSEVEE LFLQTTFDKM
DFLSIVKQCA IEKCQSNIGF SVHQNLKESL NRYLLGLSEQ LLNNSSEVTN SETLVQCSIL
LVGVLGCYCY VGIITEEEAY KSELFQKAKS LMQCAGESIS LFKNKTDEES RIGSLRNMMC
LCTSCFCNCS KQNPNKITSG FFLRLLTSKL MNDIADICKS LASFIKNPFD YGEVESVEDD
TNENLNDVNE SSSMNLFHDN PSSSANDAND PAENQSTIGS MNPLAEEYLS KQDLLLLDML
KFLCMCVTTS QTKYVSFRAA DIRRKLLMLI DSSTLDLTKS LHLHMYLVLL KELPGEQYPL
PVEDVVELLK PLSSVCSLYR RDQDVCKTIL KHVLHIVTNL AQDNIDTENT KEAQGQFLTV
IGAFWHLTKE RKCTFSVRMA IVRCLKTLLE ADPYSKWAIL NVMGEGFPVN EVFPQFLADD
NHHVRMLTAG SINRLFQHMK QGDSSMLLKA LPLKLQQTAF ENAYLKAWEG MKEVSHDAEN
PELLDETYNR KSVFLMMIAV VLYSSPICEK QALFALCKSV KENGLDPHLV KKVLKKVSET
FGCKHLEDFM ASHLDYLVSE WLNLQDTAYG LSSFPFILLN CSNVEDFYRS YYKVLIPHLV
IRSYFDDVKS IANQIQEDWK RLLIGCFPKI LVNILPYFAY EGTADSRMAQ QRVTATEVYD
MLKGENLLGK QIDHLFISNL PEIVVELLMT LHEPADFGAS QSTDLCNFSG DLDPAPNPPY
FPSHVIKATF AYISNCHKTK RKSILEILSK SPDSYQKILL AICEQAAETN NAYKKHRILK
IYHLFVSLLL KDIKSGLGGA WAFVLRDVIY TLIHYINQRS SRLMDVSLRS FSLCCDLLSR
VCQTAVTHCK DALENHLHVI VGTLTPLVND QVEVQEQVLD LLKYLVIDNK DNENLYLTIK
LLDPFPDHVV FKDLRITQQK IKYSKGSFSL LEEINHFLSV SLYDALPLTR LEGLKDLRRQ
LEQHKDQMMS LMRASQDNPQ DGIMVKLVVS LLQLSKMAVN HMGEKEVLEA VASCLGEVGP
IDFSTIAIQH NKDTSYTKAL ELFGDKELQW TLIMLTYLNN TLVEDGVKVR SAAVTCLKNI
LATKTGHNFW EVYKMTTDPM LTYLQPFRTS RKKFLEVPRL DTESPLEDLD DTNLWIPQSQ
NHNIWIKTLT CAILDSGGLK SEILQLLKPL CEVKTGFCQT VLPYLIHDIL LQDINESWRN
LLSTHVQEFF TSCFKHLSQT SRSTTPANLD SESELFSQCC LDKKSQRTML AVVDYLRRQK
RPSSETVFED AFWLDLNYLE VAKVAQSCAA HFTALLYAEI YADKKKIDDQ EKRSLTFEEG
SQSTSISSLS EKSKEETGIS LQDLLLEIYR SIGEPDSLYG CGGGKMLQPL TRLRTYEHEA
MWGKALVTYD LEKAISSSTR QAGIIQALQN LGLCHILSVY LKGLDNENKE WCAELQELHY
QTAWRNMQWD HCDSVNKGIE GSGYHESLYS ALQSLRDREF STFFECLRYA RVKEVEELCK
GSLESVYSLY PALSRLQAIG ELENIGELFS RSVRDIQLSE VYMKWQKHSQ LLKDSDFSFQ
EPIMALRTVI LEILMETEME NSQRECFKDI LTKHLVKFSI LARTFKNTQL PERAMFQIKQ
YNSTVCGVSE WQLEEAQVFW AKKEQSLALS ILKQMIKKLD ASFTESNPNL KLIYTECLRV
CGTWLAETCL ENPAVIMQTY LEKAVQIAGS YDGESNDELR NGKTKAFLSL ARFSDTQYQR
IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEC ALRALKEDRK
RFLCKAVENY INCLLSGEEH DMWVFRLCSL WLENSGVFEV NAMMKANGMK ISSYKFLPLM
YQLAARMGTK TMGDLGFHEV LNNLISRITM DHPHHTLFII LALANANKDE SLTKPEAARR
SRITKNASKQ NSQLDEDRTE AANRIICSIR SKRPQMVKNI EALCDAYIIL ANLDATQWKT
QRKGINIPAD QPINKLKNLE DVVVPTMEIK VDPTGEYGNL VTIQSFKTEF RLAGGLNLPK
IIDCIGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RDSETRKRKL TICTYKVVPL
SQRSGVLEWC TGTVPIGEFL INNEGGAHKR YRPMDFSAFQ CQKKMMDVQK KSFEEKYETF
MDICQNFQPV FRYFCMEKFL DPAVWFEKRL AYTRSVATSS IVGYILGLGD RHVQNILINE
QSAELVHIDL GVAFEQGKIL PTPETVPFRL TRDIVDGMGI TGVEGVFRRC CEKTMEVMRN
SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDENEL HSTLNADDQQ CKRNLSDTDQ
SLNKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAM DPKNLSRLFP GWKAWV
//
