ATM_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ATM_MOUSE
• UniProt AC: Q62388
• Protein Name: Serine-protein kinase ATM
• Gene Name: Atm
• Organism: Mus musculus (Mouse).
• Sequence Length: 3066
• Subcellular Localization: Nucleus . Cytoplasmic vesicle . Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin.
• Protein Description: 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. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. 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, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response..
• Protein Sequence: MSLALNDLLICCRQLEHDRATERRKEVDKFKRLIQDPETVQHLDRHSDSKQGKYLNWDAVFRFLQKYIQKEMESLRTAKSNVSATTQSSRQKKMQEISSLVRYFIKCANKRAPRLKCQDLLNYVMDTVKDSSNGLTYGADCSNILLKDILSVRKYWCEVSQQQWLELFSLYFRLYLKPSQDINRVLVARIIHAVTRGCCSQTDGLPSKFLDLFSKAIQYARQEKSSPGLSHILAALNIFLKSLAVNFRKRVCEAGDEILPTLLYIWTQHRLNDSLKEVIIELIQLQIYIHHPQGARAPEEGAYESMKWKSILYNLYDLLVNEISHIGSRGKYSSGSRNIAVKENLIDLMADICYQLFDADTRSVEISQSYVTQRESTDYSVPCKRRKIDVGWEVIKDYLQKSQSDFDLVPWLQITTRLISKYPSSLPNCELSPLILILYQLLPQQRRGERIPYVLRCLKEVALCQGKKSNLESSQKSDLLKLWIKIWSITFRGISSGQTQTENFGLLEAIIQGSLVELDREFWKLFTGSACKPSSPSVCCLTLALSICVVPDAIKMGTEQSVCEANRSFSVKESIMRWLLFYQLEDDLEDSTELPPILQSNFPHLVVEKILVSLTMKNSKAAMKFFQSVPECEQHCEDKEEPSFSEVEELFLQTTFDKMDFLTTVKEYAVEKFQSSVGFSVQQNLKESLDHYLLGLSEQLLSNYSSEITSSETLVRCSSLLVGVLGCYCYMGIITEDEAHKSELFQKAKSLMQCAGESISLFKNKTNEESRIGSLRNVMHLCTSCLCIHTKHTPNKIASGFFLRLLTSKLMNDIADICKSLASCTKKPLDHGVHPGEDDEDGGGCDSLMEAEGPSSTGLSTAYPASSVSDANDYGENQNAVGAMSPLAADYLSKQDHLLLDMLRFLGRSVTASQSHTVSFRGADIRRKLLLLLDSSILDLMKPLHLHMYLVLLKDLPGNEHSLPMEDVVELLQPLSLVCSLHRRDQDVCKTILSNVLHIVTNLGQGSVDMESTRIAQGHFLTVMGAFWHLTKEKKCVFSVRMALVKCLQTLLEADPYSEWAILNVKGQDFPVNEAFSQFLADDHHQVRMLAAGSVNRLFQDMRQGDFSRSLKALPLKFQQTSFNNAYTTAEAGIRGLLCDSQNPDLLDEIYNRKSVLLMMIAVVLHCSPVCEKQALFALCKSVKENRLEPHLVKKVLEKVSESFGCRSLEDFMISHLDYLVLEWLNLQDTEYSLSSFPFMLLNYTSIEDFYRSCYKILIPHLVIRSHFDEVKSIANQIQKCWKSLLVDCFPKILVHILPYFAYEGTRDSYVSQKRETATKVYDTLKGEDFLGKQIDQVFISNLPEIVVELLMTLHETADSADSDASQSATALCDFSGDLDPAPNPPYFPSHVIQATFAYISNCHKTKFKSILEILSKIPDSYQKILLAICEQAAETNNVFKKHRILKIYHLFVSLLLKDIQSGLGGAWAFVLRDVIYTLIHYINKRSSHFTDVSLRSFSLCCDLLSRVCHTAVTQCKDALESHLHVIVGTLIPLVDYQEVQEQVLDLLKYLVIDNKDNKNLSVTIKLLDPFPDHVIFKDLRLTQQKIKYSGGPFSLLEEINHFLSVSAYNPLPLTRLEGLKDLRRQLEQHKDQMLDLLRASQDNPQDGIVVKLVVSLLQLSKMAVNQTGEREVLEAVGRCLGEIGPLDFSTIAVQHNKDVSYTKAYGLPEDRELQWTLIMLTALNNTLVEDSVKIRSAAATCLKNILATKIGHIFWENYKTSADPMLTYLQPFRTSRKKFLEVPRSVKEDVLEGLDAVNLWVPQSESHDIWIKTLTCAFLDSGGINSEILQLLKPMCEVKTDFCQMLLPYLIHDVLLQDTHESWRTLLSAHVRGFFTSCFKHSSQASRSATPANSDSESENFLRCCLDKKSQRTMLAVVDYLRRQKRPSSGTAFDDAFWLDLNYLEVAKVAQSCSAHFTALLYAEIYSDKKSTDEQEKRSPTFEEGSQGTTISSLSEKSKEETGISLQDLLLEIYRSIGEPDSLYGCGGGKMLQPLTRIRTYEHEATWEKALVTYDLETSISSSTRQSGIIQALQNLGLSHILSVYLKGLDYERREWCAELQELRYQAAWRNMQWGLCASAGQEVEGTSYHESLYNALQCLRNREFSTFYESLRYASLFRVKEVEELSKGSLESVYSLYPTLSRLQAIGELENSGELFSRSVTDRERSEAYWKWQKHSQLLKDSDFSFQEPLMALRTVILETLVQKEMERSQGACSKDILTKHLVEFSVLARTFKNTQLPERAIFKIKQYNSAICGISEWHLEEAQVFWAKKEQSLALSILKQMIKKLDSSFKDKENDAGLKVIYAECLRVCGSWLAETCLENPAVIMQTYLEKAVKVAGSYDGNSRELRNGQMKAFLSLARFSDTQYQRIENYMKSSEFENKQTLLKRAKEEVGLLREHKIQTNRYTVKVQRELELDECALRALREDRKRFLCKAVENYINCLLSGEEHDLWVFRLCSLWLENSGVSEVNGMMKKDGMKISSYKFLPLMYQLAARMGTKMTGGLGFHEVLNNLISRISLDHPHHTLFIILALANANKDEFLSKPETTRRSRITKSTSKENSHLDEDRTEAATRIIHSIRSKRCKMVKDMEALCDAYIILANMDASQWRAQRKGINIPANQPITKLKNLEDVVVPTMEIKVDPTGEYENLVTIKSFKTEFRLAGGLNLPKIIDCVGSDGKERRQLVKGRDDLRQDAVMQQVFQMCNTLLQRNTETRKRKLTICTYKVVPLSQRSGVLEWCTGTVPIGEYLVNSEDGAHRRYRPNDFSANQCQKKMMEVQKKSFEEKYDTFMTICQNFEPVFRYFCMEKFLDPAVWFEKRLAYTRSVATSSIVGYILGLGDRHVQNILINEQSAELVHIDLGVAFEQGKILPTPETVPFRLSRDIVDGMGITGVEGVFRRCCEKTMEVMRSSQETLLTIVEVLLYDPLFDWTMNPLKALYLQQRPEDESDLHSTPNADDQECKQSLSDTDQSFNKVAERVLMRLQEKLKGVEEGTVLSVGGQVNLLIQQAMDPKNLSRLFPGWKAWV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSLALNDLL ------CCHHHHHHH	33.38	-
367	Phosphorylation	DTRSVEISQSYVTQR CCCEEEEEHHHCCCC	10.28	22817900
770	Phosphorylation	KNKTNEESRIGSLRN CCCCCCHHHHHHHHH	24.02	30482847
774	Phosphorylation	NEESRIGSLRNVMHL CCHHHHHHHHHHHHH	23.06	30482847
913	Phosphorylation	LGRSVTASQSHTVSF HCCCCCCCCCCCEEE	23.89	28285833
919	Phosphorylation	ASQSHTVSFRGADIR CCCCCCEEECCHHHH	15.47	28285833
1326	Ubiquitination	TKVYDTLKGEDFLGK HHHHHHHCCCCCCCC	63.45	22790023
1370	Phosphorylation	SDASQSATALCDFSG CCHHHHHHHHCCCCC	25.96	-
1421	Phosphorylation	ILSKIPDSYQKILLA HHHCCCHHHHHHHHH	24.90	20139300
1422	Phosphorylation	LSKIPDSYQKILLAI HHCCCHHHHHHHHHH	22.62	20139300
1449	Phosphorylation	KHRILKIYHLFVSLL HHHHHHHHHHHHHHH	7.29	23926118
1487	Phosphorylation	IHYINKRSSHFTDVS HHHHHHCCCCCCCCC	29.76	26026062
1494	Phosphorylation	SSHFTDVSLRSFSLC CCCCCCCCHHHHHHH	22.37	26026062
1727	Phosphorylation	MLTALNNTLVEDSVK HHHHHCCCCCCCCHH	30.98	26239621
1887	Phosphorylation	FKHSSQASRSATPAN HHCCHHHHHCCCCCC	21.09	25338131
1889	Phosphorylation	HSSQASRSATPANSD CCHHHHHCCCCCCCC	33.72	24704852
1891	Phosphorylation	SQASRSATPANSDSE HHHHHCCCCCCCCCC	24.95	23429704
1895	Phosphorylation	RSATPANSDSESENF HCCCCCCCCCCCHHH	44.62	29472430
1897	Phosphorylation	ATPANSDSESENFLR CCCCCCCCCCHHHHH	42.73	23429704
1899	Phosphorylation	PANSDSESENFLRCC CCCCCCCCHHHHHHH	41.62	23429704
1980	Phosphorylation	TDEQEKRSPTFEEGS CCCHHHCCCCCCCCC	39.08	28833060
1982	Phosphorylation	EQEKRSPTFEEGSQG CHHHCCCCCCCCCCC	44.95	28833060
1987	Phosphorylation	SPTFEEGSQGTTISS CCCCCCCCCCCCHHH	28.81	22322096
1990	Phosphorylation	FEEGSQGTTISSLSE CCCCCCCCCHHHHCH	17.20	28833060
1991	Phosphorylation	EEGSQGTTISSLSEK CCCCCCCCHHHHCHH	26.20	28833060
1993	Phosphorylation	GSQGTTISSLSEKSK CCCCCCHHHHCHHCH	24.12	28833060
1994	Phosphorylation	SQGTTISSLSEKSKE CCCCCHHHHCHHCHH	31.87	28833060
1996	Phosphorylation	GTTISSLSEKSKEET CCCHHHHCHHCHHHH	44.95	28833060
2820	Acetylation	KKMMEVQKKSFEEKY HHHHHHHHHHHHHHH	56.41	23576753
2821	Acetylation	KMMEVQKKSFEEKYD HHHHHHHHHHHHHHH	43.20	23576753
3004	Phosphorylation	DDQECKQSLSDTDQS CHHHHHHHHCHHHHH	18.48	29550500
3006	Phosphorylation	QECKQSLSDTDQSFN HHHHHHHCHHHHHHH	43.65	21149446
3008	Phosphorylation	CKQSLSDTDQSFNKV HHHHHCHHHHHHHHH	32.34	29550500
3026	Acetylation	VLMRLQEKLKGVEEG HHHHHHHHHCCCCCC	42.40	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
367	S	Phosphorylation	Kinase	ATM	Q62388	GPS
1899	S	Phosphorylation	Kinase	ATM	Q62388	GPS
1987	S	Phosphorylation	Kinase	ATM	Q62388	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
367	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	-
367	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	19047460
1899	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	-
1899	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	19047460
1987	S	Acetylation	Acetylation, on DNA damage, is required for activation of the kinase activity, dimer-monomer transition, and subsequent autophosphorylation on Ser-1987.	-
1987	S	Phosphorylation	Acetylation, on DNA damage, is required for activation of the kinase activity, dimer-monomer transition, and subsequent autophosphorylation on Ser-1987.	-
1987	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	-
1987	S	Phosphorylation	Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.	19047460

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of ATM_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
H2AX_MOUSE	H2afx	physical	11571274
DCAF6_HUMAN	DCAF6	physical	20360068
LMNB1_HUMAN	LMNB1	physical	20360068
CUL4A_HUMAN	CUL4A	physical	20360068
ATM_HUMAN	ATM	physical	20360068
DDB1_HUMAN	DDB1	physical	20360068
DCAF8_HUMAN	DCAF8	physical	20360068
2AAA_MOUSE	Ppp2r1a	physical	22466704
DNMT1_MOUSE	Dnmt1	physical	23754744
KAT5_MOUSE	Kat5	physical	23754744
UHRF1_MOUSE	Uhrf1	physical	23754744
P53_MOUSE	Trp53	physical	21706008

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Multiple autophosphorylation sites are dispensable for murine ATMactivation in vivo.";
Daniel J.A., Pellegrini M., Lee J.H., Paull T.T., Feigenbaum L.,Nussenzweig A.;
J. Cell Biol. 183:777-783(2008).
Cited for: AUTOPHOSPHORYLATION AT SER-367; SER-1899 AND SER-1987, FUNCTION, ANDMUTAGENESIS OF SER-367; SER-1899 AND SER-1987.
PubMed: 19047460