Search Results

Overview

Uniprot IDQ13315
Protein NameSerine-protein kinase ATM
Gene NameATM
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
2431 VGLLREHKIQTNRYT
385 SDYSVPCKRKKIELG

Function

Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:27941124, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:27941124, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4, UCHL3 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:27941124, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566)

Protein Sequence

10 MSLVLNDLLI 20 CCRQLEHDRA 30 TERKKEVEKF 40 KRLIRDPETI 50 KHLDRHSDSK 60 QGKYLNWDAV 70 FRFLQKYIQK 80 ETECLRIAKP 90 NVSASTQASR 100 QKKMQEISSL 110 VKYFIKCANR 120 RAPRLKCQEL 130 LNYIMDTVKD 140 SSNGAIYGAD 150 CSNILLKDIL 160 SVRKYWCEIS 170 QQQWLELFSV 180 YFRLYLKPSQ 190 DVHRVLVARI 200 IHAVTKGCCS 210 QTDGLNSKFL 220 DFFSKAIQCA 230 RQEKSSSGLN 240 HILAALTIFL 250 KTLAVNFRIR 260 VCELGDEILP 270 TLLYIWTQHR 280 LNDSLKEVII 290 ELFQLQIYIH 300 HPKGAKTQEK 310 GAYESTKWRS 320 ILYNLYDLLV 330 NEISHIGSRG 340 KYSSGFRNIA 350 VKENLIELMA 360 DICHQVFNED 370 TRSLEISQSY 380 TTTQRESSDY 390 SVPCKRKKIE 400 LGWEVIKDHL 410 QKSQNDFDLV 420 PWLQIATQLI 430 SKYPASLPNC 440 ELSPLLMILS 450 QLLPQQRHGE 460 RTPYVLRCLT 470 EVALCQDKRS 480 NLESSQKSDL 490 LKLWNKIWCI 500 TFRGISSEQI 510 QAENFGLLGA 520 IIQGSLVEVD 530 REFWKLFTGS 540 ACRPSCPAVC 550 CLTLALTTSI 560 VPGTVKMGIE 570 QNMCEVNRSF 580 SLKESIMKWL 590 LFYQLEGDLE 600 NSTEVPPILH 610 SNFPHLVLEK 620 ILVSLTMKNC 630 KAAMNFFQSV 640 PECEHHQKDK 650 EELSFSEVEE 660 LFLQTTFDKM 670 DFLTIVRECG 680 IEKHQSSIGF 690 SVHQNLKESL 700 DRCLLGLSEQ 710 LLNNYSSEIT 720 NSETLVRCSR 730 LLVGVLGCYC 740 YMGVIAEEEA 750 YKSELFQKAK 760 SLMQCAGESI 770 TLFKNKTNEE 780 FRIGSLRNMM 790 QLCTRCLSNC 800 TKKSPNKIAS 810 GFFLRLLTSK 820 LMNDIADICK 830 SLASFIKKPF 840 DRGEVESMED 850 DTNGNLMEVE 860 DQSSMNLFND 870 YPDSSVSDAN 880 EPGESQSTIG 890 AINPLAEEYL 900 SKQDLLFLDM 910 LKFLCLCVTT 920 AQTNTVSFRA 930 ADIRRKLLML 940 IDSSTLEPTK 950 SLHLHMYLML 960 LKELPGEEYP 970 LPMEDVLELL 980 KPLSNVCSLY 990 RRDQDVCKTI 1000 LNHVLHVVKN 1010 LGQSNMDSEN 1020 TRDAQGQFLT 1030 VIGAFWHLTK 1040 ERKYIFSVRM 1050 ALVNCLKTLL 1060 EADPYSKWAI 1070 LNVMGKDFPV 1080 NEVFTQFLAD 1090 NHHQVRMLAA 1100 ESINRLFQDT 1110 KGDSSRLLKA 1120 LPLKLQQTAF 1130 ENAYLKAQEG 1140 MREMSHSAEN 1150 PETLDEIYNR 1160 KSVLLTLIAV 1170 VLSCSPICEK 1180 QALFALCKSV 1190 KENGLEPHLV 1200 KKVLEKVSET 1210 FGYRRLEDFM 1220 ASHLDYLVLE 1230 WLNLQDTEYN 1240 LSSFPFILLN 1250 YTNIEDFYRS 1260 CYKVLIPHLV 1270 IRSHFDEVKS 1280 IANQIQEDWK 1290 SLLTDCFPKI 1300 LVNILPYFAY 1310 EGTRDSGMAQ 1320 QRETATKVYD 1330 MLKSENLLGK 1340 QIDHLFISNL 1350 PEIVVELLMT 1360 LHEPANSSAS 1370 QSTDLCDFSG 1380 DLDPAPNPPH 1390 FPSHVIKATF 1400 AYISNCHKTK 1410 LKSILEILSK 1420 SPDSYQKILL 1430 AICEQAAETN 1440 NVYKKHRILK 1450 IYHLFVSLLL 1460 KDIKSGLGGA 1470 WAFVLRDVIY 1480 TLIHYINQRP 1490 SCIMDVSLRS 1500 FSLCCDLLSQ 1510 VCQTAVTYCK 1520 DALENHLHVI 1530 VGTLIPLVYE 1540 QVEVQKQVLD 1550 LLKYLVIDNK 1560 DNENLYITIK 1570 LLDPFPDHVV 1580 FKDLRITQQK 1590 IKYSRGPFSL 1600 LEEINHFLSV 1610 SVYDALPLTR 1620 LEGLKDLRRQ 1630 LELHKDQMVD 1640 IMRASQDNPQ 1650 DGIMVKLVVN 1660 LLQLSKMAIN 1670 HTGEKEVLEA 1680 VGSCLGEVGP 1690 IDFSTIAIQH 1700 SKDASYTKAL 1710 KLFEDKELQW 1720 TFIMLTYLNN 1730 TLVEDCVKVR 1740 SAAVTCLKNI 1750 LATKTGHSFW 1760 EIYKMTTDPM 1770 LAYLQPFRTS 1780 RKKFLEVPRF 1790 DKENPFEGLD 1800 DINLWIPLSE 1810 NHDIWIKTLT 1820 CAFLDSGGTK 1830 CEILQLLKPM 1840 CEVKTDFCQT 1850 VLPYLIHDIL 1860 LQDTNESWRN 1870 LLSTHVQGFF 1880 TSCLRHFSQT 1890 SRSTTPANLD 1900 SESEHFFRCC 1910 LDKKSQRTML 1920 AVVDYMRRQK 1930 RPSSGTIFND 1940 AFWLDLNYLE 1950 VAKVAQSCAA 1960 HFTALLYAEI 1970 YADKKSMDDQ 1980 EKRSLAFEEG 1990 SQSTTISSLS 2000 EKSKEETGIS 2010 LQDLLLEIYR 2020 SIGEPDSLYG 2030 CGGGKMLQPI 2040 TRLRTYEHEA 2050 MWGKALVTYD 2060 LETAIPSSTR 2070 QAGIIQALQN 2080 LGLCHILSVY 2090 LKGLDYENKD 2100 WCPELEELHY 2110 QAAWRNMQWD 2120 HCTSVSKEVE 2130 GTSYHESLYN 2140 ALQSLRDREF 2150 STFYESLKYA 2160 RVKEVEEMCK 2170 RSLESVYSLY 2180 PTLSRLQAIG 2190 ELESIGELFS 2200 RSVTHRQLSE 2210 VYIKWQKHSQ 2220 LLKDSDFSFQ 2230 EPIMALRTVI 2240 LEILMEKEMD 2250 NSQRECIKDI 2260 LTKHLVELSI 2270 LARTFKNTQL 2280 PERAIFQIKQ 2290 YNSVSCGVSE 2300 WQLEEAQVFW 2310 AKKEQSLALS 2320 ILKQMIKKLD 2330 ASCAANNPSL 2340 KLTYTECLRV 2350 CGNWLAETCL 2360 ENPAVIMQTY 2370 LEKAVEVAGN 2380 YDGESSDELR 2390 NGKMKAFLSL 2400 ARFSDTQYQR 2410 IENYMKSSEF 2420 ENKQALLKRA 2430 KEEVGLLREH 2440 KIQTNRYTVK 2450 VQRELELDEL 2460 ALRALKEDRK 2470 RFLCKAVENY 2480 INCLLSGEEH 2490 DMWVFRLCSL 2500 WLENSGVSEV 2510 NGMMKRDGMK 2520 IPTYKFLPLM 2530 YQLAARMGTK 2540 MMGGLGFHEV 2550 LNNLISRISM 2560 DHPHHTLFII 2570 LALANANRDE 2580 FLTKPEVARR 2590 SRITKNVPKQ 2600 SSQLDEDRTE 2610 AANRIICTIR 2620 SRRPQMVRSV 2630 EALCDAYIIL 2640 ANLDATQWKT 2650 QRKGINIPAD 2660 QPITKLKNLE 2670 DVVVPTMEIK 2680 VDHTGEYGNL 2690 VTIQSFKAEF 2700 RLAGGVNLPK 2710 IIDCVGSDGK 2720 ERRQLVKGRD 2730 DLRQDAVMQQ 2740 VFQMCNTLLQ 2750 RNTETRKRKL 2760 TICTYKVVPL 2770 SQRSGVLEWC 2780 TGTVPIGEFL 2790 VNNEDGAHKR 2800 YRPNDFSAFQ 2810 CQKKMMEVQK 2820 KSFEEKYEVF 2830 MDVCQNFQPV 2840 FRYFCMEKFL 2850 DPAIWFEKRL 2860 AYTRSVATSS 2870 IVGYILGLGD 2880 RHVQNILINE 2890 QSAELVHIDL 2900 GVAFEQGKIL 2910 PTPETVPFRL 2920 TRDIVDGMGI 2930 TGVEGVFRRC 2940 CEKTMEVMRN 2950 SQETLLTIVE 2960 VLLYDPLFDW 2970 TMNPLKALYL 2980 QQRPEDETEL 2990 HPTLNADDQE 3000 CKRNLSDIDQ 3010 SFNKVAERVL 3020 MRLQEKLKGV 3030 EEGTVLSVGG 3040 QVNLLIQQAI 3050 DPKNLSRLFP GWKAWV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005813 centrosome
Cellular Component GO:0005694 chromosome
Biological Process GO:0000723 telomere maintenance
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:1990391 DNA repair complex
Cellular Component GO:0098850 extrinsic component of synaptic vesicle membrane
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005782 peroxisomal matrix
Cellular Component GO:0035861 site of double-strand break
Cellular Component GO:0005819 spindle
Molecular Function GO:0016303 1-phosphatidylinositol-3-kinase activity
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0004677 DNA-dependent protein kinase activity
Molecular Function GO:0035979 histone H2AXS139 kinase activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0044877 protein-containing complex binding
Biological Process GO:0071480 cellular response to gamma radiation
Biological Process GO:0071500 cellular response to nitrosative stress
Biological Process GO:0034614 cellular response to reactive oxygen species
Biological Process GO:0071300 cellular response to retinoic acid
Biological Process GO:0033554 cellular response to stress
Biological Process GO:0071481 cellular response to X-ray
Biological Process GO:0090398 cellular senescence
Biological Process GO:0000077 DNA damage checkpoint signaling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0030330 DNA damage response, signal transduction by p53 class mediator
Biological Process GO:0000729 DNA double-strand break processing
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0006303 double-strand break repair via nonhomologous end joining
Biological Process GO:0097695 establishment of protein-containing complex localization to telomere
Biological Process GO:0097694 establishment of RNA localization to telomere
Biological Process GO:0071044 histone mRNA catabolic process
Biological Process GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
Biological Process GO:0007095 mitotic G2 DNA damage checkpoint signaling
Biological Process GO:0007094 mitotic spindle assembly checkpoint signaling
Biological Process GO:0030889 negative regulation of B cell proliferation
Biological Process GO:1904354 negative regulation of telomere capping
Biological Process GO:1904262 negative regulation of TORC1 signaling
Biological Process GO:0036289 peptidyl-serine autophosphorylation
Biological Process GO:0000425 pexophagy
Biological Process GO:0043065 positive regulation of apoptotic process
Biological Process GO:0045785 positive regulation of cell adhesion
Biological Process GO:0030335 positive regulation of cell migration
Biological Process GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
Biological Process GO:2000781 positive regulation of double-strand break repair
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:1904884 positive regulation of telomerase catalytic core complex assembly
Biological Process GO:0032212 positive regulation of telomere maintenance via telomerase
Biological Process GO:1904358 positive regulation of telomere maintenance via telomere lengthening
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0002331 pre-B cell allelic exclusion
Biological Process GO:0046777 protein autophosphorylation
Biological Process GO:0050821 protein stabilization
Biological Process GO:0007131 reciprocal meiotic recombination
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:2000785 regulation of autophagosome assembly
Biological Process GO:0010506 regulation of autophagy
Biological Process GO:0051726 regulation of cell cycle
Biological Process GO:1900034 regulation of cellular response to heat
Biological Process GO:1901796 regulation of signal transduction by p53 class mediator
Biological Process GO:0032210 regulation of telomere maintenance via telomerase
Biological Process GO:0090399 replicative senescence
Biological Process GO:0010212 response to ionizing radiation
Biological Process GO:0007165 signal transduction
Biological Process GO:0042770 signal transduction in response to DNA damage

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.