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Protein

Fizzy-related protein homolog

Gene

Fzr1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key regulator of ligase activity of the anaphase promoting complex/cyclosome (APC/C), which confers substrate specificity upon the 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 (By similarity).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 division Source: UniProtKB-KW
  • DNA repair Source: UniProtKB-KW
  • G2 DNA damage checkpoint Source: UniProtKB
  • lens fiber cell differentiation Source: MGI
  • mitotic nuclear division Source: UniProtKB-KW
  • 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
Complete GO annotation...

Keywords - Biological processi

Cell 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-68949. Orc1 removal from chromatin.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1926790. Fzr1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 493493Fizzy-related protein homologPRO_0000051002Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei32 – 321PhosphothreonineBy similarity
Modified residuei36 – 361PhosphoserineCombined sources
Modified residuei69 – 691N6-acetyllysineBy similarity
Modified residuei133 – 1331PhosphoserineBy similarity
Modified residuei138 – 1381PhosphoserineCombined sources
Modified residuei146 – 1461PhosphoserineCombined sources
Modified residuei151 – 1511PhosphoserineCombined sources
Modified residuei159 – 1591N6-acetyllysineBy similarity

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.
PhosphoSiteiQ9R1K5.

Expressioni

Gene expression databases

BgeeiQ9R1K5.
ExpressionAtlasiQ9R1K5. baseline and differential.
GenevisibleiQ9R1K5. MM.

Interactioni

Subunit structurei

The unphosphorylated form interacts with APC/C during mitosis. Interacts with NINL. Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation. Interacts with USP37 (By similarity). Interacts (via WD repeats) with MAK (By similarity). Interacts with SIRT2.By similarity1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi207933. 11 interactions.
IntActiQ9R1K5. 1 interaction.
STRINGi10090.ENSMUSP00000114203.

Structurei

3D structure databases

ProteinModelPortaliQ9R1K5.
SMRiQ9R1K5. Positions 42-493.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati182 – 22241WD 1Add
BLAST
Repeati227 – 26640WD 2Add
BLAST
Repeati269 – 30638WD 3Add
BLAST
Repeati311 – 35040WD 4Add
BLAST
Repeati353 – 39543WD 5Add
BLAST
Repeati397 – 43842WD 6Add
BLAST
Repeati441 – 48040WD 7Add
BLAST

Sequence similaritiesi

Belongs to the WD repeat CDC20/Fizzy family.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0305. Eukaryota.
ENOG410XQ8I. LUCA.
GeneTreeiENSGT00840000129804.
HOGENOMiHOG000195514.
HOVERGENiHBG001024.
InParanoidiQ9R1K5.
KOiK03364.
OMAiIEKSHNQ.
OrthoDBiEOG76X602.
PhylomeDBiQ9R1K5.
TreeFamiTF101066.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR024977. Apc4_WD40_dom.
IPR033010. Cdc20/Fizzy.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR19918. PTHR19918. 1 hit.
PfamiPF12894. ANAPC4_WD40. 1 hit.
PF00400. WD40. 3 hits.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9R1K5.
SMRiQ9R1K5. Positions 42-493.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207933. 11 interactions.
IntActiQ9R1K5. 1 interaction.
STRINGi10090.ENSMUSP00000114203.

PTM databases

iPTMnetiQ9R1K5.
PhosphoSiteiQ9R1K5.

Proteomic databases

EPDiQ9R1K5.
MaxQBiQ9R1K5.
PaxDbiQ9R1K5.
PRIDEiQ9R1K5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi51343.
MGIiMGI:1926790. Fzr1.

Phylogenomic databases

eggNOGiKOG0305. Eukaryota.
ENOG410XQ8I. LUCA.
GeneTreeiENSGT00840000129804.
HOGENOMiHOG000195514.
HOVERGENiHBG001024.
InParanoidiQ9R1K5.
KOiK03364.
OMAiIEKSHNQ.
OrthoDBiEOG76X602.
PhylomeDBiQ9R1K5.
TreeFamiTF101066.

Enzyme and pathway databases

UniPathwayiUPA00143.
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-68949. Orc1 removal from chromatin.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.

Miscellaneous databases

ChiTaRSiFzr1. mouse.
PROiQ9R1K5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9R1K5.
ExpressionAtlasiQ9R1K5. baseline and differential.
GenevisibleiQ9R1K5. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR024977. Apc4_WD40_dom.
IPR033010. Cdc20/Fizzy.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR19918. PTHR19918. 1 hit.
PfamiPF12894. ANAPC4_WD40. 1 hit.
PF00400. WD40. 3 hits.
[Graphical view]
SMARTiSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Differential expression, localization and activity of two alternatively spliced isoforms of human APC regulator CDH1."
    Zhou Y., Ching Y.-P., Ng R.W.M., Jin D.-Y.
    Biochem. J. 374:349-358(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-138; SER-146 AND SER-151, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Lung, Spleen and Testis.
  5. "SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity."
    Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X., Li C., Veenstra T.D., Li B., Yu H., Ji J., Wang X.W., Park S.H., Cha Y.I., Gius D., Deng C.X.
    Cancer Cell 20:487-499(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEACETYLATION BY SIRT2, INTERACTION WITH SIRT2.

Entry informationi

Entry nameiFZR_MOUSE
AccessioniPrimary (citable) accession number: Q9R1K5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: May 1, 2000
Last modified: July 6, 2016
This is version 125 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.