Reactome | UniProt:Q9UM11 FZR1

Schema > ReferenceGeneProduct > Entries

UniProt:Q9UM11 FZR1 Show undefined attributes

chain	chain:1-496
checksum	F6C8FDAF81D8103A
comment	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).PATHWAY Protein modification; protein ubiquitination.SUBUNIT The unphosphorylated form interacts with APC/C during mitosis (PubMed:26083744, PubMed:9734353). Interacts with NINL (PubMed:17403670). Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (PubMed:11459825, PubMed:11459826). Interacts with SIRT2 and USP37 (PubMed:21596315, PubMed:22014574). Interacts (via WD repeats) with MAK (PubMed:21986944). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (PubMed:25349192). Interacts with HECW2 (PubMed:24163370). Interacts with SASS6; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation (PubMed:31722219). Interacts (via N-terminus) with CCNF (PubMed:27653696). Interacts with CDC6 (PubMed:26818844). Interacts with TK1 (via the KEN box) (PubMed:14701726).INTERACTION Isoform 2 is expressed at high levels in heart, liver, spleen and some cancer cell lines whereas isoform 3 is expressed only at low levels in these tissues.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).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).PTM Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase complex; leading to its degradation by the proteasome.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Major.MISCELLANEOUS Minor.SIMILARITY Belongs to the WD repeat CDC20/Fizzy family.CAUTION Originally thought to be phosphorylated by MPF during mitosis. However this paper was retracted due to falsification of data.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the C-terminal part.SEQUENCE CAUTION Contaminating sequence. Sequence of unknown origin in the N-terminal part.SEQUENCE CAUTION Extended N-terminus.
crossReference	[DatabaseIdentifier:11595234] ENSEMBL:ENSP00000378529 [DatabaseIdentifier:12406645] RefSeq:NP_057347.2 [DatabaseIdentifier:12406642] RefSeq:XP_054177155.1 [DatabaseIdentifier:12406641] RefSeq:NP_001129669.1 [DatabaseIdentifier:12406643] RefSeq:NP_001129670.1 [DatabaseIdentifier:12406644] RefSeq:XP_005259630.1 [DatabaseIdentifier:12283516] Pharos - Targets:Q9UM11 [DatabaseIdentifier:12242223] PRO:Q9UM11 [DatabaseIdentifier:12147543] PDB:8TAU [DatabaseIdentifier:12139530] PDB:9GAW [DatabaseIdentifier:12147553] PDB:8TAR [DatabaseIdentifier:12147542] PDB:5L9U [DatabaseIdentifier:12139529] PDB:4UI9 [DatabaseIdentifier:12147544] PDB:5L9T [DatabaseIdentifier:12123198] OpenTargets:ENSG00000105325 [DatabaseIdentifier:11838684] HPA:ENSG00000105325-FZR1 [DatabaseIdentifier:11801154] GlyGen:Q9UM11 [DatabaseIdentifier:11785600] GeneCards:FZR1 [DatabaseIdentifier:11717932] ENSEMBL:ENST00000441788 [DatabaseIdentifier:11717931] ENSEMBL:ENST00000652521 [DatabaseIdentifier:11717933] ENSEMBL:ENST00000395095 [DatabaseIdentifier:11717930] ENSEMBL:ENST00000313639 [DatabaseIdentifier:11595231] ENSEMBL:ENSP00000321800 [DatabaseIdentifier:11595233] ENSEMBL:ENSP00000498659 [DatabaseIdentifier:11595232] ENSEMBL:ENSP00000410369 [DatabaseIdentifier:11489358] ENSEMBL:ENSG00000105325
databaseName	UniProt
dbId	90773
description	recommendedName: fullName evidence="29"Fizzy-related protein homolog shortName: Fzr alternativeName: CDC20-like protein 1 alternativeName: Cdh1/Hct1 homolog shortName evidence="24"hCDH1
displayName	UniProt:Q9UM11 FZR1
geneName	FZR1 CDH1 FYR FZR KIAA1242
identifier	Q9UM11
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Cell cycle Cell division Cytoplasm Disease variant DNA damage DNA repair Epilepsy Intellectual disability Mitosis Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Ubl conjugation Ubl conjugation pathway WD repeat
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	FZR1
otherIdentifier	11724896_a_at 11724897_a_at 11742066_a_at 16856959 209414_PM_at 209414_at 209415_PM_at 209415_at 209416_3p_s_at 209416_PM_s_at 209416_s_at 211865_PM_s_at 211865_s_at 3816989 3816995 3816996 3816997 3816998 3816999 3817000 3817001 3817002 3817005 3817007 3817008 3817009 3817010 3817011 3817012 3817013 3817014 3817015 3817016 3817017 3817018 3817019 3817020 3817021 3817023 3817024 39855_at 41623_s_at 41624_r_at 51343 77105_at 78663_r_at 8024637 A_14_P100190 A_23_P142325 A_23_P142333 A_24_P318836 A_24_P944291 A_33_P3268368 GE62170 GE82097 GO:0005515 GO:0005634 GO:0005654 GO:0005680 GO:0005737 GO:0005829 GO:0006281 GO:0006974 GO:0007095 GO:0007346 GO:0008284 GO:0010997 GO:0016567 GO:0030163 GO:0031145 GO:0031965 GO:0040020 GO:0046105 GO:0051301 GO:0051445 GO:0051603 GO:0055086 GO:0060090 GO:0070306 GO:0070979 GO:0097027 GO:0098772 GO:1901135 GO:1904668 GO:1904860 GO:1905786 GO:1990756 GO:1990757 GO:2000773 HMNXSV003003015 HMNXSV003030853 Hs.268384.0.S3_3p_at Hs.268384.0.S3_3p_x_at Hs.268384.0.S4_3p_at ILMN_1753207 PH_hs_0028369 TC19000070.hg g5813826_3p_a_at g5813826_3p_x_at g6463684_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-174249] FZR1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-174099] FZR1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-174257] p-FZR1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-174193] p-FZR1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9929805] p-S151-FZR1 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000105325] ENSEMBL:ENSG00000105325 FZR1 [ReferenceDNASequence:12748054] UCSC:Q9UM11 FZR1 [ReferenceDNASequence:12108740] OMIM:603619 FZR1 [ReferenceDNASequence:12068481] NCBI Gene:51343 FZR1 [ReferenceDNASequence:11984388] Monarch:51343 FZR1 [ReferenceDNASequence:11894136] KEGG:hsa:51343 FZR1 [ReferenceDNASequence:11817230] HGNC:24824 FZR1 [ReferenceDNASequence:11354599] BioGPS Gene:51343 FZR1 [ReferenceDNASequence:11401328] COSMIC - genes:FZR1 FZR1 [ReferenceDNASequence:11394294] COSMIC - genes:CDH1 CDH1 [ReferenceDNASequence:11410181] CTD Gene:51343 FZR1 [ReferenceDNASequence:11438623] dbSNP Gene:51343 FZR1
referenceTranscript	[ReferenceRNASequence:12588335] RefSeq:NM_001136198.1 FZR1 [ReferenceRNASequence:12588337] RefSeq:NM_016263.3 FZR1 [ReferenceRNASequence:12588338] RefSeq:NM_001136197.1 FZR1 [ReferenceRNASequence:12588336] RefSeq:XM_054321180.1 FZR1 [ReferenceRNASequence:12588339] RefSeq:XM_005259573.6 FZR1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	FZR1_HUMAN O75869 Q86U66 Q96NW8 Q9UI96 Q9ULH8 Q9UM10 Q9UNQ1 Q9Y2T8
sequenceLength	496
species	[Species:48887] Homo sapiens
stId	uniprot:Q9UM11
url	http://purl.uniprot.org/uniprot/Q9UM11

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-174249] FZR1 [cytosol] [EntityWithAccessionedSequence:R-HSA-174099] FZR1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-174257] p-FZR1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-174193] p-FZR1 [cytosol] [EntityWithAccessionedSequence:R-HSA-9929805] p-S151-FZR1 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:174179] phosphorylated residue at unknown position [ModifiedResidue:9929826] O-phospho-L-serine at 151
(interactor)	[UndirectedInteraction:11135103] UniProt:P04183 <-> UniProt:Q9UM11 (IntAct) [UndirectedInteraction:11144867] UniProt:Q9UM11 <-> UniProt:P30260 (IntAct) [UndirectedInteraction:11144869] UniProt:Q9UM11 <-> UniProt:Q9UJX6 (IntAct) [UndirectedInteraction:11144871] UniProt:Q9UM11 <-> UniProt:Q9UJX5 (IntAct) [UndirectedInteraction:11144873] UniProt:Q9UM11 <-> UniProt:Q9UJX2 (IntAct) [UndirectedInteraction:11144875] UniProt:Q9UM11 <-> UniProt:P31350 (IntAct) [UndirectedInteraction:11144877] UniProt:Q9UM11 <-> UniProt:Q13309 (IntAct) [UndirectedInteraction:11144879] UniProt:Q9UM11 <-> UniProt:Q8NHZ8 (IntAct) [UndirectedInteraction:11144881] UniProt:Q9UM11 <-> UniProt:Q96DE5 (IntAct) [UndirectedInteraction:11144883] UniProt:Q9UM11 <-> UniProt:Q13042 (IntAct) [UndirectedInteraction:11144885] UniProt:Q9UM11 <-> UniProt:Q9HAW4 (IntAct) [UndirectedInteraction:11144889] UniProt:Q9UM11 <-> UniProt:P20794 (IntAct) [UndirectedInteraction:11144893] UniProt:Q9UM11 <-> UniProt:P40337-1 (IntAct) [UndirectedInteraction:11144897] UniProt:Q9UM11 <-> UniProt:Q8IXJ6-2 (IntAct) [UndirectedInteraction:11144899] UniProt:Q9UM11 <-> UniProt:Q96FV0 (IntAct) [UndirectedInteraction:11144901] UniProt:Q9UM11 <-> UniProt:P10619 (IntAct) [UndirectedInteraction:11144905] UniProt:Q9UM11 <-> UniProt:Q9H467 (IntAct) [UndirectedInteraction:11144907] UniProt:Q9UM11 <-> UniProt:Q6PGQ7 (IntAct) [UndirectedInteraction:11144909] UniProt:Q9UM11 <-> UniProt:Q9UJX4 (IntAct) [UndirectedInteraction:11144913] UniProt:Q9UM11 <-> UniProt:P33552 (IntAct) [UndirectedInteraction:11144915] UniProt:Q9UM11 <-> UniProt:P16278 (IntAct) [UndirectedInteraction:11144917] UniProt:Q9UM11 <-> UniProt:Q7LG56 (IntAct) [UndirectedInteraction:11144919] UniProt:Q9UM11 <-> UniProt:Q86T82 (IntAct) [UndirectedInteraction:11144921] UniProt:Q9UM11 <-> UniProt:P20248 (IntAct) [UndirectedInteraction:11144925] UniProt:Q9UM11 <-> UniProt:Q6PH81 (IntAct) [UndirectedInteraction:11144927] UniProt:Q9UM11 <-> UniProt:P24941 (IntAct) [UndirectedInteraction:11144929] UniProt:Q9UM11 <-> UniProt:Q9H1A4 (IntAct) [UndirectedInteraction:11144931] UniProt:Q9UM11 <-> UniProt:Q9UI95 (IntAct) [UndirectedInteraction:11144933] UniProt:Q9UM11 <-> UniProt:Q8VDQ8 (IntAct) [UndirectedInteraction:11144935] UniProt:Q9UM11 <-> UniProt:A2A6Q5 (IntAct) [UndirectedInteraction:11144937] UniProt:Q9UM11 <-> UniProt:P14635 (IntAct) [UndirectedInteraction:11144939] UniProt:Q9UM11 <-> UniProt:P0DTD8 (IntAct) [UndirectedInteraction:11144941] UniProt:Q9UM11 <-> UniProt:Q8IXJ6 (IntAct)