FZR1
entrez
51343
canonical
uniprot
Q9UM11
canonical
ensembl
ENSG00000105325
resolver
ensp
ENSP00000321800
resolver
ensp
ENSP00000378529
resolver
ensp
ENSP00000410369
resolver
genesymbol
FZR1
resolver
genesymbol_syn
CDH1
resolver
genesymbol_syn
FYR
resolver
genesymbol_syn
FZR
resolver
genesymbol_syn
KIAA1242
resolver
hgnc
HGNC:24824
resolver
uniprot
O75869
resolver
uniprot
Q86U66
resolver
uniprot
Q96NW8
resolver
uniprot
Q9UI96
resolver
uniprot
Q9ULH8
resolver
uniprot
Q9UM10
resolver
uniprot
Q9UNQ1
resolver
uniprot
Q9Y2T8
resolver
uniprot_entry
FZR1_HUMAN
resolver
uniprot_sec
O75869
resolver
uniprot_sec
Q86U66
resolver
uniprot_sec
Q96NW8
resolver
uniprot_sec
Q9UI96
resolver
uniprot_sec
Q9ULH8
resolver
uniprot_sec
Q9UM10
resolver
uniprot_sec
Q9UNQ1
resolver
uniprot_sec
Q9Y2T8
resolver
amino_acid_sequence
MDQDYERRLLRQIVIQNENTMPRVTEMRRTLTPASSPVSSPSKHGDRFIPSRAGANWSVNFHRINENEKSPSQNRKAKDATSDNGKDGLAYSALLKNELLGAGIEKVQDPQTEDRRLQPSTPEKKGLFTYSLSTKRSSPDDGNDVSPYSLSPVSNKSQKLLRSPRKPTRKISKIPFKVLDAPELQDDFYLNLVDWSSLNVLSVGLGTCVYLWSACTSQVTRLCDLSVEGDSVTSVGWSERGNLVAVGTHKGFVQIWDAAAGKKLSMLEGHTARVGALAWNAEQLSSGSRDRMILQRDIRTPPLQSERRLQGHRQEVCGLKWSTDHQLLASGGNDNKLLVWNHSSLSPVQQYTEHLAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTLTGQPLQCIDTGSQVCNLAWSKHANELVSTHGYSQNQILVWKYPSLTQVAKLTGHSYRVLYLAMSPDGEAIVTGAGDETLRFWNVFSKTRSTKVKWESVSVLNLFTRIR
uniprot
proteins
disease_involvement
DISEASE: Developmental and epileptic encephalopathy 109 (DEE109) [MIM:620145]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE109 is an autosomal dominant form characterized by the onset of various types of seizures in the first months or years of life. {ECO:0000269|PubMed:31318984, ECO:0000269|PubMed:34788397}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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) (PubMed:25349192). {ECO:0000269|PubMed:14701726, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.
uniprot
proteins
mass_dalton
55179
uniprot
proteins
mutagenesis
MUTAGEN 7..14; /note="RRLLRQIV->AAAAAQAA: Reduced interaction with CCNF. Impaired degradation."; /evidence="ECO:0000269|PubMed:27653696"; MUTAGEN 40; /note="S->A: Constitutively active; when associated with A-121; A-151 and A-163. Does not affect APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-121; A-151 and A-163. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-121 and A-151. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-121 and A-163."; /evidence="ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:26083744"; MUTAGEN 47; /note="R->A: Inhibits APC/FZR1 E3 ubiquitin-protein ligase complex activity."; /evidence="ECO:0000269|PubMed:26083744"; MUTAGEN 52; /note="R->A: Inhibits APC/FZR1 E3 ubiquitin-protein ligase complex activity."; /evidence="ECO:0000269|PubMed:26083744"; MUTAGEN 121; /note="T->A: Constitutively active; when associated with A-40; A-151 and A-163. Does not affect APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-40; A-151 and A-163. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-40 and A-151. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-40 and A-163. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-151 and A-163."; /evidence="ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:26083744"; MUTAGEN 151; /note="S->A: Constitutively active; when associated with A-40; A-121 and A-163. Does not affect ubiquitination; when associated with A-40; A-121 and A-163. Decreases ubiquitination; when associated with A-40 and A-163. Decreases ubiquitination; when associated with A-121 and A-163."; /evidence="ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:26083744"; MUTAGEN 163; /note="S->A: Constitutively active; when associated with A-40; A-121 and A-151. Does not affect APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-40; A-121 and A-151. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-40 and A-121. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-121 and A-151. Decreases ubiquitination; when associated with A-40 and A-151."; /evidence="ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:26083744"; MUTAGEN 445..447; /note="RVL->AVA: Reduced interaction with CCNF."; /evidence="ECO:0000269|PubMed:27653696
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Acetylated. 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). {ECO:0000269|PubMed:22014574}.; PTM: Following DNA damage, it is dephosphorylated by CDC14B in G2 phase, leading to its reassociation with the APC/C, and allowing an efficient G2 DNA damage checkpoint (PubMed:18662541). Phosphorylated by MAK (PubMed:21986944). {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21986944}.; PTM: Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase complex; leading to its degradation by the proteasome. {ECO:0000269|PubMed:27653696}.
uniprot
proteins
protein_family
WD repeat CDC20/Fizzy family
uniprot
proteins
pubmed
10459014
uniprot
proteins
pubmed
10574462
uniprot
proteins
pubmed
11459825
uniprot
proteins
pubmed
11459826
uniprot
proteins
pubmed
12797865
uniprot
proteins
pubmed
14701726
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15824138
uniprot
proteins
pubmed
17403670
uniprot
proteins
pubmed
18662541
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21596315
uniprot
proteins
pubmed
21986944
uniprot
proteins
pubmed
22014574
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24163370
uniprot
proteins
pubmed
25349192
uniprot
proteins
pubmed
26083744
uniprot
proteins
pubmed
26818844
uniprot
proteins
pubmed
27653696
uniprot
proteins
pubmed
31318984
uniprot
proteins
pubmed
31722219
uniprot
proteins
pubmed
34788397
uniprot
proteins
pubmed
9734353
uniprot
proteins
pubmed
9811605
uniprot
proteins
sequence_length
496
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:34788397}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.
uniprot
proteins