TOP1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TOP1_MOUSE
• UniProt AC: Q04750
• Protein Name: DNA topoisomerase 1
• Gene Name: Top1
• Organism: Mus musculus (Mouse).
• Sequence Length: 767
• Subcellular Localization: Nucleus, nucleolus . Nucleus, nucleoplasm . Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms found in both nucleoplasm and nucleoli.
• Protein Description: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter..
• Protein Sequence: MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKDKDKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKERRKEEKIRAAGDAKIKKEKENGFSSPPRIKDEPEDDGYFAPPKEDIKPLKRLRDEDDADYKPKKIKTEDIKKEKKRKSEEEEDGKLKKPKNKDKDKKVAEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPESVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNDEKNTITNLSKCDFTQMSQYFKAQSEARKQMSKEEKLKIKEENEKLLKEYGFCVMDNHRERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFPGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENVPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQSKIDAKKDQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMTDEDYEF

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	------MSGDHLHND ------CCCCCCCCC	53.58	-
2	Phosphorylation	------MSGDHLHND ------CCCCCCCCC	53.58	26824392
10	Phosphorylation	GDHLHNDSQIEADFR CCCCCCCHHHHHHEE	38.07	26824392
59	Phosphorylation	SNSEHKDSEKKHKEK CCCCCCHHHHHHHHH	57.00	-
113	Phosphorylation	KEKENGFSSPPRIKD HHHHCCCCCCCCCCC	43.25	25521595
114	Phosphorylation	EKENGFSSPPRIKDE HHHCCCCCCCCCCCC	36.34	25521595
127	Phosphorylation	DEPEDDGYFAPPKED CCCCCCCCCCCCHHH	11.99	29899451
149	Phosphorylation	RDEDDADYKPKKIKT CCCCCCCCCCCCCCH	30.80	25159016
167	Phosphorylation	KKEKKRKSEEEEDGK HHHHHHCCHHHCCCC	55.03	22817900
174	Acetylation	SEEEEDGKLKKPKNK CHHHCCCCCCCCCCC	70.25	23806337
206	Acetylation	KEEEQKWKWWEEERY HHHHHHHHHHHHHHC	49.84	23806337
254	Ubiquitination	KVMKLSPKAEEVATF EEEECCCCHHHHHHH	66.12	22790023
270	Phosphorylation	AKMLDHEYTTKEIFR HHHHCCCCCHHHHHH	19.11	22817900
271	Phosphorylation	KMLDHEYTTKEIFRK HHHCCCCCHHHHHHH	28.54	-
282	Acetylation	IFRKNFFKDWRKEMT HHHHHHHHHHHHHCC	52.85	-
322	O-linked_Glycosylation	SEARKQMSKEEKLKI HHHHHHCCHHHHHHH	34.13	30059200
356	Acetylation	RERIANFKIEPPGLF HHHHHCCEECCCCCC	46.06	22826441
396	Phosphorylation	SKDAKVPSPPPGHKW CCCCCCCCCCCCCCC	53.69	25159016
506	S-nitrosylation	ETADTVGCCSLRVEH CCCCCCCEEEEEEEE	0.93	20925432
506	S-nitrosocysteine	ETADTVGCCSLRVEH CCCCCCCEEEEEEEE	0.93	-
508	Phosphorylation	ADTVGCCSLRVEHIN CCCCCEEEEEEEEEE	24.24	-
551	Acetylation	PVEKRVFKNLQLFME CHHHHHHHHHHHHHH	54.62	22826441
617	Acetylation	PDENVPAKILSYNRA CCCCCCHHHHCCHHC	37.80	23236377
632	S-nitrosocysteine	NRAVAILCNHQRAPP HHHHHHHHCCCCCCC	3.32	-
632	S-nitrosylation	NRAVAILCNHQRAPP HHHHHHHHCCCCCCC	3.32	20925432
714	Acetylation	ATDREENKQIALGTS CCCHHHHCEEEEECC	46.49	88479
725	Phosphorylation	LGTSKLNYLDPRITV EECCCCCCCCCCCCH	23.95	28418008

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
270	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
508	S	Phosphorylation	Kinase	CK2	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
119	K	Sumoylation	Lys-119 is the main site of sumoylation.	-
508	S	Phosphorylation	Phosphorylation at Ser-508 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of TOP1_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of TOP1_MOUSE !!

Drug and Disease Associations

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