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Protein

Fizzy-related protein homolog

Gene

Fzr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

  • anaphase-promoting complex-dependent catabolic process Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • DNA repair Source: UniProtKB-KW
  • lens fiber cell differentiation Source: MGI
  • negative regulation of cell aging Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of protein catabolic process Source: UniProtKB
  • positive regulation of ubiquitin protein ligase activity Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of meiotic nuclear division Source: MGI
  • signal transduction involved in G2 DNA damage checkpoint Source: UniProtKB

Keywordsi

Biological processCell cycle, Cell division, DNA damage, DNA repair, Mitosis, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-174084 Autodegradation of Cdh1 by Cdh1:APC/C
R-MMU-174113 SCF-beta-TrCP mediated degradation of Emi1
R-MMU-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-MMU-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-MMU-176408 Regulation of APC/C activators between G1/S and early anaphase
R-MMU-176417 Phosphorylation of Emi1
R-MMU-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-MMU-69017 CDK-mediated phosphorylation and removal of Cdc6
R-MMU-69656 Cyclin A:Cdk2-associated events at S phase entry
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Fizzy-related protein homolog
Short name:
Fzr
Alternative name(s):
Cdh1/Hct1 homolog
Gene namesi
Name:Fzr1
Synonyms:Fyr, Fzr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1926790 Fzr1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000510021 – 493Fizzy-related protein homologAdd BLAST493

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32PhosphothreonineBy similarity1
Modified residuei36PhosphoserineCombined sources1
Modified residuei69N6-acetyllysineBy similarity1
Modified residuei133PhosphoserineBy similarity1
Modified residuei138PhosphoserineCombined sources1
Modified residuei146PhosphoserineCombined sources1
Modified residuei151PhosphoserineCombined sources1
Modified residuei159N6-acetyllysineBy similarity1

Post-translational modificationi

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).
Phosphorylated during mitosis, probably by maturation promoting factor (MPF), leading to its dissociation of the APC/C. 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. Phosphorylated by MAK (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9R1K5
MaxQBiQ9R1K5
PaxDbiQ9R1K5
PRIDEiQ9R1K5

PTM databases

iPTMnetiQ9R1K5
PhosphoSitePlusiQ9R1K5

Expressioni

Gene expression databases

BgeeiENSMUSG00000020235
ExpressionAtlasiQ9R1K5 baseline and differential
GenevisibleiQ9R1K5 MM

Interactioni

Subunit structurei

The unphosphorylated form interacts with APC/C during mitosis (By similarity). Interacts with NINL. Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (By similarity). Interacts with SIRT2 (PubMed:22014574). Interacts with USP37 (By similarity). Interacts (via WD repeats) with MAK (By similarity). Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation (By similarity). Interacts with HECW2 (By similarity).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Sirt2Q8VDQ82EBI-5238560,EBI-911012

Protein-protein interaction databases

BioGridi207933, 11 interactors
IntActiQ9R1K5, 1 interactor
STRINGi10090.ENSMUSP00000114203

Structurei

3D structure databases

ProteinModelPortaliQ9R1K5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati182 – 222WD 1Add BLAST41
Repeati227 – 266WD 2Add BLAST40
Repeati269 – 306WD 3Add BLAST38
Repeati311 – 350WD 4Add BLAST40
Repeati353 – 395WD 5Add BLAST43
Repeati397 – 438WD 6Add BLAST42
Repeati441 – 480WD 7Add BLAST40

Sequence similaritiesi

Belongs to the WD repeat CDC20/Fizzy family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0305 Eukaryota
ENOG410XQ8I LUCA
GeneTreeiENSGT00870000136444
HOGENOMiHOG000195514
HOVERGENiHBG001024
InParanoidiQ9R1K5
KOiK03364
OMAiSVCSVQW
OrthoDBiEOG091G06FJ
PhylomeDBiQ9R1K5
TreeFamiTF101066

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR024977 Apc4_WD40_dom
IPR033010 Cdc20/Fizzy
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR19918 PTHR19918, 1 hit
PfamiView protein in Pfam
PF12894 ANAPC4_WD40, 1 hit
PF00400 WD40, 3 hits
SMARTiView protein in SMART
SM00320 WD40, 6 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 2 hits
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequencei

Sequence statusi: Complete.

Q9R1K5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDQDYERRLL RQIIIQNENT VPCVSEMRRT LTPANSPVSS PSKHGDRFIP
60 70 80 90 100
SRAGANWSVN FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL
110 120 130 140 150
GAGIEKVQDP QTEDRRLQPS TPEHKGLFTY SLSSKRSSPD DGNDVSPYSL
160 170 180 190 200
SPVSNKSQKL LRSPRKPTRK ISKIPFKVLD APELQDDFYL NLVDWSSLNV
210 220 230 240 250
LSVGLGTCVY LWSACTSQVT RLCDLSVEGD SVTSVGWSER GNLVAVGTHK
260 270 280 290 300
GFVQIWDAAA GKKLSMLEGH TARVGALAWN ADQLSSGSRD RMILQRDIRT
310 320 330 340 350
PPLQSERRLQ GHRQEVCGLK WSTDHQLLAS GGNDNKLLVW NHSSLSPVQQ
360 370 380 390 400
YTEHLAAVKA IAWSPHQHGL LASGGGTADR CIRFWNTLTG QPLQCIDTGS
410 420 430 440 450
QVCNLAWSKH ANELVSTHGY SQNQILVWKY PSLTQVAKLT GHSYRVLYLA
460 470 480 490
MSPDGEAIVT GAGDETLRFW NVFSKTRSTK ESVSVLNLFT RIR
Length:493
Mass (Da):54,689
Last modified:May 1, 2000 - v1
Checksum:iB5DC86653D74D9A5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083809 mRNA Translation: AAD52029.1
BC006616 mRNA Translation: AAH06616.1
CCDSiCCDS24057.1
RefSeqiNP_062731.1, NM_019757.1
UniGeneiMm.24202

Genome annotation databases

EnsembliENSMUST00000140901; ENSMUSP00000114203; ENSMUSG00000020235
GeneIDi56371
KEGGimmu:56371
UCSCiuc007ght.1 mouse

Similar proteinsi

Entry informationi

Entry nameiFZR1_MOUSE
AccessioniPrimary (citable) accession number: Q9R1K5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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