UHRF1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: UHRF1_MOUSE
• UniProt AC: Q8VDF2
• Protein Name: E3 ubiquitin-protein ligase UHRF1
• Gene Name: Uhrf1
• Organism: Mus musculus (Mouse).
• Sequence Length: 782
• Subcellular Localization: Nucleus . Localizes to replication foci. Enriched in pericentric heterochromatin. Also localizes to euchromatic regions.
• Protein Description: Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair..
• Protein Sequence: MWIQVRTMDGKETHTVNSLSRLTKVQELRKKIEEVFHVEPQLQRLFYRGKQMEDGHTLFDYDVRLNDTIQLLVRQSLALPLSTKERDSELSDSDSGYGVGHSESDKSSTHGEGAAEADDKTVWEDTDLGLYKVNEYVDVRDNIFGAWFEAQVVQVQKRALSEDEPCSSSAVKTSEDDIMYHVKYDDYPEHGVDIVKAKNVRARARTVIPWENLEVGQVVMANYNVDYPRKRGFWYDVEICRKRQTRTARELYGNIRLLNDSQLNNCRIMFVDEVLMIELPKERRPLIASPSQPPPALRNTGKSGPSCRFCKDDENKPCRKCACHVCGGREAPEKQLLCDECDMAFHLYCLKPPLTSVPPEPEWYCPSCRTDSSEVVQAGEKLKESKKKAKMASATSSSRRDWGKGMACVGRTTECTIVPANHFGPIPGVPVGTMWRFRVQVSESGVHRPHVAGIHGRSNDGAYSLVLAGGYEDDVDNGNYFTYTGSGGRDLSGNKRTAGQSSDQKLTNNNRALALNCHSPINEKGAEAEDWRQGKPVRVVRNMKGGKHSKYAPAEGNRYDGIYKVVKYWPERGKSGFLVWRYLLRRDDTEPEPWTREGKDRTRQLGLTMQYPEGYLEALANKEKSRKRPAKALEQGPSSSKTGKSKQKSTGPTLSSPRASKKSKLEPYTLSEQQANLIKEDKGNAKLWDDVLTSLQDGPYQIFLSKVKEAFQCICCQELVFRPVTTVCQHNVCKDCLDRSFRAQVFSCPACRFELDHSSPTRVNQPLQTILNQLFPGYGSGR

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
24	Ubiquitination	NSLSRLTKVQELRKK HHHHHHHHHHHHHHH	46.65	-
76	Phosphorylation	IQLLVRQSLALPLST HHHHHHHHHCCCCCC	12.68	26824392
82	Phosphorylation	QSLALPLSTKERDSE HHHCCCCCCHHCCCC	35.18	25777480
83	Phosphorylation	SLALPLSTKERDSEL HHCCCCCCHHCCCCC	44.61	25777480
88	Phosphorylation	LSTKERDSELSDSDS CCCHHCCCCCCCCCC	46.81	22802335
91	Phosphorylation	KERDSELSDSDSGYG HHCCCCCCCCCCCCC	30.89	27087446
93	Phosphorylation	RDSELSDSDSGYGVG CCCCCCCCCCCCCCC	30.24	28973931
95	Phosphorylation	SELSDSDSGYGVGHS CCCCCCCCCCCCCCC	37.55	27087446
97	Phosphorylation	LSDSDSGYGVGHSES CCCCCCCCCCCCCCC	16.76	25619855
102	Phosphorylation	SGYGVGHSESDKSST CCCCCCCCCCCCCCC	32.63	25619855
104	Phosphorylation	YGVGHSESDKSSTHG CCCCCCCCCCCCCCC	54.04	25619855
107	Phosphorylation	GHSESDKSSTHGEGA CCCCCCCCCCCCCCC	45.52	18846507
108	Phosphorylation	HSESDKSSTHGEGAA CCCCCCCCCCCCCCC	30.11	18846507
109	Phosphorylation	SESDKSSTHGEGAAE CCCCCCCCCCCCCCC	40.78	27087446
120	Ubiquitination	GAAEADDKTVWEDTD CCCCCCCCCEEEECC	45.59	-
136	Phosphorylation	GLYKVNEYVDVRDNI CEEECCCCEECCCCC	9.21	28066266
157	Ubiquitination	AQVVQVQKRALSEDE HHHHHHHHHHCCCCC	40.56	-
161	Phosphorylation	QVQKRALSEDEPCSS HHHHHHCCCCCCCCC	41.85	26824392
167	Phosphorylation	LSEDEPCSSSAVKTS CCCCCCCCCCCCCCC	37.73	28066266
168	Phosphorylation	SEDEPCSSSAVKTSE CCCCCCCCCCCCCCC	29.09	28066266
169	Phosphorylation	EDEPCSSSAVKTSED CCCCCCCCCCCCCCC	22.31	25619855
183	Ubiquitination	DDIMYHVKYDDYPEH CCCEEEEECCCCCCC	29.65	-
196	Ubiquitination	EHGVDIVKAKNVRAR CCCCCEEEECCHHHH	54.71	-
198	Ubiquitination	GVDIVKAKNVRARAR CCCEEEECCHHHHCC	50.70	-
261	Phosphorylation	NIRLLNDSQLNNCRI HEEECCHHHCCCCEE	35.18	-
289	Phosphorylation	ERRPLIASPSQPPPA HHCCCCCCCCCCCCH	20.35	26824392
289 (in isoform 2)	Phosphorylation	-	20.35	25159016
291 (in isoform 2)	Phosphorylation	-	53.47	25159016
291	Phosphorylation	RPLIASPSQPPPALR CCCCCCCCCCCCHHH	53.47	26824392
303	Phosphorylation	ALRNTGKSGPSCRFC HHHCCCCCCCCCCCC	58.23	25266776
351	Ubiquitination	AFHLYCLKPPLTSVP EEEEHHCCCCCCCCC	40.82	-
372	Phosphorylation	CPSCRTDSSEVVQAG CCCCCCCHHHHHHHH	27.99	27841257
373	Phosphorylation	PSCRTDSSEVVQAGE CCCCCCHHHHHHHHH	36.90	25266776
381	Ubiquitination	EVVQAGEKLKESKKK HHHHHHHHHHHHHHH	65.03	-
381	Acetylation	EVVQAGEKLKESKKK HHHHHHHHHHHHHHH	65.03	23806337
393	Phosphorylation	KKKAKMASATSSSRR HHHHHHHHCCCCCCC	28.69	28059163
397	Phosphorylation	KMASATSSSRRDWGK HHHHCCCCCCCCCCC	24.41	22871156
404	Acetylation	SSRRDWGKGMACVGR CCCCCCCCCCCCCCC	41.06	-
404	Ubiquitination	SSRRDWGKGMACVGR CCCCCCCCCCCCCCC	41.06	-
411	Dimethylation	KGMACVGRTTECTIV CCCCCCCCCEEEEEE	20.34	-
411	Methylation	KGMACVGRTTECTIV CCCCCCCCCEEEEEE	20.34	18964545
505	Ubiquitination	AGQSSDQKLTNNNRA CCCCCCCCCCCCCCE	63.37	-
519	Phosphorylation	ALALNCHSPINEKGA EEEEECCCCCCCCCC	29.67	21082442
524	Ubiquitination	CHSPINEKGAEAEDW CCCCCCCCCCCHHHH	59.96	-
550	Acetylation	MKGGKHSKYAPAEGN CCCCCCCCCCCCCCC	45.19	-
564	Ubiquitination	NRYDGIYKVVKYWPE CCCCCEEEEEECCCC	38.33	-
574	Ubiquitination	KYWPERGKSGFLVWR ECCCCCCCCCEEEEH	54.34	-
622	Ubiquitination	YLEALANKEKSRKRP HHHHHHCHHHHCCCC	61.99	-
631	Ubiquitination	KSRKRPAKALEQGPS HHCCCCHHHHHCCCC	57.07	-
639	Phosphorylation	ALEQGPSSSKTGKSK HHHCCCCCCCCCCCC	38.70	-
649	Phosphorylation	TGKSKQKSTGPTLSS CCCCCCCCCCCCCCC	35.78	25266776
650	Phosphorylation	GKSKQKSTGPTLSSP CCCCCCCCCCCCCCC	54.97	25777480
653	Phosphorylation	KQKSTGPTLSSPRAS CCCCCCCCCCCCCCC	40.39	25159016
655	Phosphorylation	KSTGPTLSSPRASKK CCCCCCCCCCCCCCC	40.55	26824392
656	Phosphorylation	STGPTLSSPRASKKS CCCCCCCCCCCCCCC	22.86	26824392
660	Phosphorylation	TLSSPRASKKSKLEP CCCCCCCCCCCCCCC	41.73	29514104
664	Acetylation	PRASKKSKLEPYTLS CCCCCCCCCCCCCCC	66.79	23806337
758	Phosphorylation	CRFELDHSSPTRVNQ CCEECCCCCCCCCCH	37.37	28066266
759	Phosphorylation	RFELDHSSPTRVNQP CEECCCCCCCCCCHH	27.20	19060867
761	Phosphorylation	ELDHSSPTRVNQPLQ ECCCCCCCCCCHHHH	49.55	28066266

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
303	S	Phosphorylation	Kinase	PKA	-	Uniprot
639	S	Phosphorylation	Kinase	CDK1	P11440	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
303	S	Phosphorylation	Phosphorylation at Ser-303 of the linker region decreases the binding to H3K9me3.	-
639	S	Phosphorylation	Phosphorylation at Ser-639 by CDK1 during M phase impairs interaction with USP7, preventing deubiquitination and leading to degradation by the proteasome (By similarity).	-
639	S	Phosphorylation	Ubiquitination and degradation takes place during M phase, when phosphorylation at Ser-639 prevents interaction with USP7 and subsequent deubiquitination.	21268065
639	S	ubiquitylation	Phosphorylation at Ser-639 by CDK1 during M phase impairs interaction with USP7, preventing deubiquitination and leading to degradation by the proteasome (By similarity).	-
639	S	ubiquitylation	Ubiquitination and degradation takes place during M phase, when phosphorylation at Ser-639 prevents interaction with USP7 and subsequent deubiquitination.	21268065

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of UHRF1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MUS81_MOUSE	Mus81	physical	18692478
EME1_MOUSE	Eme1	physical	18692478
H33_MOUSE	H3f3a	physical	14993289
UHRF1_MOUSE	Uhrf1	physical	14993289
H2B11_XENLA	hist1h2bj	physical	14993289
H2AX_XENLA	hist2h2ab	physical	14993289
H4_XENLA	hist1h4a	physical	14993289
H31_HUMAN	HIST1H3A	physical	14993289
H2A2C_HUMAN	HIST2H2AC	physical	14993289
H2B2E_HUMAN	HIST2H2BE	physical	14993289
DNMT1_MOUSE	Dnmt1	physical	24782312
DNMT1_MOUSE	Dnmt1	physical	23463006
TOP2A_MOUSE	Top2a	physical	25451918
RCC1_MOUSE	Rcc1	physical	25451918
TOP2B_MOUSE	Top2b	physical	25451918
SP16H_MOUSE	Supt16	physical	25451918

Drug and Disease Associations

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