FZR1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FZR1_MOUSE
• UniProt AC: Q9R1K5
• Protein Name: Fizzy-related protein homolog
• Gene Name: Fzr1
• Organism: Mus musculus (Mouse).
• Sequence Length: 493
• Protein Description: Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR)..
• Protein Sequence: MDQDYERRLLRQIIIQNENTVPCVSEMRRTLTPANSPVSSPSKHGDRFIPSRAGANWSVNFHRINENEKSPSQNRKAKDATSDNGKDGLAYSALLKNELLGAGIEKVQDPQTEDRRLQPSTPEHKGLFTYSLSSKRSSPDDGNDVSPYSLSPVSNKSQKLLRSPRKPTRKISKIPFKVLDAPELQDDFYLNLVDWSSLNVLSVGLGTCVYLWSACTSQVTRLCDLSVEGDSVTSVGWSERGNLVAVGTHKGFVQIWDAAAGKKLSMLEGHTARVGALAWNADQLSSGSRDRMILQRDIRTPPLQSERRLQGHRQEVCGLKWSTDHQLLASGGNDNKLLVWNHSSLSPVQQYTEHLAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTLTGQPLQCIDTGSQVCNLAWSKHANELVSTHGYSQNQILVWKYPSLTQVAKLTGHSYRVLYLAMSPDGEAIVTGAGDETLRFWNVFSKTRSTKESVSVLNLFTRIR

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
30	Phosphorylation	CVSEMRRTLTPANSP CCHHHHCCCCCCCCC		25619855
32	Phosphorylation	SEMRRTLTPANSPVS HHHHCCCCCCCCCCC		25619855
36	Phosphorylation	RTLTPANSPVSSPSK CCCCCCCCCCCCCCC		27149854
39	Phosphorylation	TPANSPVSSPSKHGD CCCCCCCCCCCCCCC		25619855
40	Phosphorylation	PANSPVSSPSKHGDR CCCCCCCCCCCCCCC		27149854
42	Phosphorylation	NSPVSSPSKHGDRFI CCCCCCCCCCCCCCC		25619855
69	Acetylation	HRINENEKSPSQNRK EECCCCCCCHHHCCC		-
70	Phosphorylation	RINENEKSPSQNRKA ECCCCCCCHHHCCCC		25263469
72	Phosphorylation	NENEKSPSQNRKAKD CCCCCCHHHCCCCCC		23684622
92	Phosphorylation	GKDGLAYSALLKNEL CCCCHHHHHHHHHHH		29895711
120	Phosphorylation	EDRRLQPSTPEHKGL CCCCCCCCCCCCCCC		27149854
121	Phosphorylation	DRRLQPSTPEHKGLF CCCCCCCCCCCCCCE		25263469
131	Phosphorylation	HKGLFTYSLSSKRSS CCCCEEEECCCCCCC		26643407
133	Phosphorylation	GLFTYSLSSKRSSPD CCEEEECCCCCCCCC		26643407
134	Phosphorylation	LFTYSLSSKRSSPDD CEEEECCCCCCCCCC		26643407
137	Phosphorylation	YSLSSKRSSPDDGND EECCCCCCCCCCCCC		21082442
138	Phosphorylation	SLSSKRSSPDDGNDV ECCCCCCCCCCCCCC		21082442
146	Phosphorylation	PDDGNDVSPYSLSPV CCCCCCCCCCCCCCC		21082442
148	Phosphorylation	DGNDVSPYSLSPVSN CCCCCCCCCCCCCCC		26643407
149	Phosphorylation	GNDVSPYSLSPVSNK CCCCCCCCCCCCCCH		26643407
151	Phosphorylation	DVSPYSLSPVSNKSQ CCCCCCCCCCCCHHH		27149854
154	Phosphorylation	PYSLSPVSNKSQKLL CCCCCCCCCHHHHHH		26643407
157	Phosphorylation	LSPVSNKSQKLLRSP CCCCCCHHHHHHCCC		22418434
159	Acetylation	PVSNKSQKLLRSPRK CCCCHHHHHHCCCCC		-
163	Phosphorylation	KSQKLLRSPRKPTRK HHHHHHCCCCCCCCC		27149854
262	Ubiquitination	IWDAAAGKKLSMLEG HHHHHCCCCEECCCC		-

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

Oops, there are no upstream regulatory protein records of FZR1_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
69	K	Acetylation	Deacetylated by SIRT2 at Lys-69 and Lys-159; deacetylation enhances the interaction of FZR1 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).	-
159	K	Acetylation	Deacetylated by SIRT2 at Lys-69 and Lys-159; deacetylation enhances the interaction of FZR1 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of FZR1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SMUF1_MOUSE	Smurf1	physical	22949615
CDC27_RAT	Cdc27	physical	22949615
CCNB1_MOUSE	Ccnb1	physical	21241890
SIR2_MOUSE	Sirt2	physical	22014574
CDC27_MOUSE	Cdc27	physical	22014574
RIR2_MOUSE	Rrm2	physical	12655059
RHG35_MOUSE	Arhgap35	physical	20530197
MEF2C_MOUSE	Mef2c	physical	25789873

Drug and Disease Associations

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