Aliases for FZR1 Gene

Aliases for FZR1 Gene

  • Fizzy And Cell Division Cycle 20 Related 1 2 3 5
  • HCDH1 2 3 4
  • CDH1 2 3 4
  • FZR 2 3 4
  • Fizzy/Cell Division Cycle 20 Related 1 2 3
  • Fizzy-Related Protein Homolog 3 4
  • CDC20-Like Protein 1 3 4
  • Cdh1/Hct1 Homolog 3 4
  • CDC20 Homolog 1 2 3
  • KIAA1242 2 4
  • CDC20C 2 3
  • FZR2 2 3
  • HCDH 2 3
  • Fizzy/Cell Division Cycle 20 Related 1 (Drosophila) 2
  • CDC20-Like 1b 3
  • FZR1 5
  • FYR 4
  • Fzr 4

External Ids for FZR1 Gene

Previous GeneCards Identifiers for FZR1 Gene

  • GC19P003598
  • GC19P003446
  • GC19P003457
  • GC19P003473
  • GC19P003272

Summaries for FZR1 Gene

GeneCards Summary for FZR1 Gene

FZR1 (Fizzy And Cell Division Cycle 20 Related 1) is a Protein Coding gene. Diseases associated with FZR1 include Breast Cancer. Among its related pathways are Regulation of activated PAK-2p34 by proteasome mediated degradation and Cell cycle_Role of APC in cell cycle regulation. An important paralog of this gene is CDC20.

UniProtKB/Swiss-Prot Summary for FZR1 Gene

  • 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).

Gene Wiki entry for FZR1 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FZR1 Gene

Genomics for FZR1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for FZR1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FZR1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FZR1

Top Transcription factor binding sites by QIAGEN in the FZR1 gene promoter:
  • AP-2gamma
  • AP-4
  • ATF6
  • Elk-1
  • FOXF2
  • NRF-2
  • PPAR-alpha

Genomic Locations for FZR1 Gene

Genomic Locations for FZR1 Gene
chr19:3,506,263-3,538,334
(GRCh38/hg38)
Size:
32,072 bases
Orientation:
Plus strand
chr19:3,506,271-3,538,328
(GRCh37/hg19)
Size:
32,058 bases
Orientation:
Plus strand

Genomic View for FZR1 Gene

Genes around FZR1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FZR1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FZR1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FZR1 Gene

Proteins for FZR1 Gene

  • Protein details for FZR1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UM11-FZR1_HUMAN
    Recommended name:
    Fizzy-related protein homolog
    Protein Accession:
    Q9UM11
    Secondary Accessions:
    • O75869
    • Q86U66
    • Q96NW8
    • Q9UI96
    • Q9ULH8
    • Q9UM10
    • Q9UNQ1
    • Q9Y2T8

    Protein attributes for FZR1 Gene

    Size:
    496 amino acids
    Molecular mass:
    55179 Da
    Quaternary structure:
    • 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).
    SequenceCaution:
    • Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAA86556.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: Major.
    • [Isoform 3]: Minor.

    Three dimensional structures from OCA and Proteopedia for FZR1 Gene

    Alternative splice isoforms for FZR1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FZR1 Gene

Post-translational modifications for FZR1 Gene

  • 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.
  • Ubiquitination at Lys135 and Lys263
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for FZR1 Gene

Domains & Families for FZR1 Gene

Gene Families for FZR1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for FZR1 Gene

InterPro:
Blocks:
  • G-protein beta WD-40 repeat signature
  • Cdc20/Fizzy
ProtoNet:

Suggested Antigen Peptide Sequences for FZR1 Gene

GenScript: Design optimal peptide antigens:
  • Cdh1/Hct1 homolog (FZR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UM11

UniProtKB/Swiss-Prot:

FZR1_HUMAN :
  • Belongs to the WD repeat CDC20/Fizzy family.
Family:
  • Belongs to the WD repeat CDC20/Fizzy family.
genes like me logo Genes that share domains with FZR1: view

Function for FZR1 Gene

Molecular function for FZR1 Gene

UniProtKB/Swiss-Prot 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).

Phenotypes From GWAS Catalog for FZR1 Gene

Gene Ontology (GO) - Molecular Function for FZR1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 10548110
GO:0010997 anaphase-promoting complex binding IEA,IBA 21873635
GO:0097027 ubiquitin-protein transferase activator activity IEA --
GO:1990757 ubiquitin ligase activator activity IBA 21873635
genes like me logo Genes that share ontologies with FZR1: view
genes like me logo Genes that share phenotypes with FZR1: view

Animal Models for FZR1 Gene

MGI Knock Outs for FZR1:
  • Fzr1 Fzr1<tm1.1Mama>
  • Fzr1 Fzr1<tm1.1(KOMP)Vlcg>
  • Fzr1 Fzr1<tm1.2Stge>

Animal Model Products

CRISPR Products

miRNA for FZR1 Gene

miRTarBase miRNAs that target FZR1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FZR1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FZR1 Gene

Localization for FZR1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FZR1 Gene

[Isoform 2]: Nucleus.
[Isoform 3]: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FZR1 gene
Compartment Confidence
nucleus 5
cytosol 4
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear membrane (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FZR1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005680 colocalizes_with anaphase-promoting complex IDA 11459825
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with FZR1: view

Pathways & Interactions for FZR1 Gene

genes like me logo Genes that share pathways with FZR1: view

Pathways by source for FZR1 Gene

4 GeneGo (Thomson Reuters) pathways for FZR1 Gene
  • Cell cycle Regulation of G1/S transition (part 1)
  • Cell cycle Role of SCF complex in cell cycle regulation
  • Cell cycle_Role of APC in cell cycle regulation
  • Development_TGF-beta receptor signaling
1 Qiagen pathway for FZR1 Gene
  • Mitotic Roles of Polo Like Kinases

UniProtKB/Swiss-Prot Q9UM11-FZR1_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for FZR1 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for FZR1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006511 ubiquitin-dependent protein catabolic process TAS --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007049 cell cycle IEA --
GO:0008284 positive regulation of cell proliferation IEA --
genes like me logo Genes that share ontologies with FZR1: view

Drugs & Compounds for FZR1 Gene

(1) Drugs for FZR1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with FZR1: view

Transcripts for FZR1 Gene

mRNA/cDNA for FZR1 Gene

3 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FZR1

Alternative Splicing Database (ASD) splice patterns (SP) for FZR1 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b · 13c ^ 14a · 14b · 14c
SP1: - - -
SP2: - -
SP3: - - - - -
SP4:
SP5:
SP6: -

Relevant External Links for FZR1 Gene

GeneLoc Exon Structure for
FZR1

Expression for FZR1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FZR1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Testis (Reproductive System)

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for FZR1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FZR1

SOURCE GeneReport for Unigene cluster for FZR1 Gene:

Hs.413133

mRNA Expression by UniProt/SwissProt for FZR1 Gene:

Q9UM11-FZR1_HUMAN
Tissue specificity: 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.

Evidence on tissue expression from TISSUES for FZR1 Gene

  • Nervous system(4.6)
  • Skin(2.4)
  • Intestine(2.1)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with FZR1: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for FZR1 Gene

Orthologs for FZR1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for FZR1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia FZR1 31
  • 99 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia FZR1 31
  • 98 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia FZR1 31
  • 98 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia FZR1 30 31
  • 91.28 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia FZR1 30 31
  • 90.53 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Fzr1 30 17 31
  • 88.03 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Fzr1 30
  • 87.63 (n)
Chicken
(Gallus gallus)
Aves CDH1-A 30 31
  • 83.37 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia fzr1 30
  • 77.89 (n)
Str.20252 30
African clawed frog
(Xenopus laevis)
Amphibia fzr1-prov 30
Zebrafish
(Danio rerio)
Actinopterygii fzr1 30 31
  • 75.81 (n)
OneToOne
zgc55450 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002114 30
  • 70.21 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta rap 30 31 32
  • 68.85 (n)
OneToMany
fzr2 31 32
  • 49 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea fzr-1 30 31
  • 57.43 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AFL007C 30
  • 52.3 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CDH1 30 31
  • 48.84 (n)
OneToMany
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A08822g 30
  • 48.29 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons FZR3 30
  • 55.45 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.3232 30
Soybean
(Glycine max)
eudicotyledons Gma.12561 30
Rice
(Oryza sativa)
Liliopsida Os01g0972900 30
  • 57.03 (n)
Barley
(Hordeum vulgare)
Liliopsida Hv.6041 30
Wheat
(Triticum aestivum)
Liliopsida Ta.27562 30
Corn
(Zea mays)
Liliopsida Zm.14057 30
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 66 (a)
OneToOne
Bread mold
(Neurospora crassa)
Ascomycetes NCU01269 30
  • 58.06 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes srw1 30
  • 50.16 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.4550 30
Species where no ortholog for FZR1 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for FZR1 Gene

ENSEMBL:
Gene Tree for FZR1 (if available)
TreeFam:
Gene Tree for FZR1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FZR1: view image

Paralogs for FZR1 Gene

Paralogs for FZR1 Gene

(3) SIMAP similar genes for FZR1 Gene using alignment to 2 proteins:

  • FZR_HUMAN
  • K7EQT1_HUMAN
genes like me logo Genes that share paralogs with FZR1: view

Variants for FZR1 Gene

Additional dbSNP identifiers (rs#s) for FZR1 Gene

Structural Variations from Database of Genomic Variants (DGV) for FZR1 Gene

Variant ID Type Subtype PubMed ID
dgv613e199 CNV deletion 23128226
esv2663038 CNV deletion 23128226
esv2669455 CNV deletion 23128226
esv2675938 CNV deletion 23128226
esv26869 CNV loss 19812545
esv2717946 CNV deletion 23290073
esv2717947 CNV deletion 23290073
esv2717948 CNV deletion 23290073
esv3364166 CNV insertion 20981092
nsv470114 CNV loss 18288195
nsv953948 CNV deletion 24416366

Variation tolerance for FZR1 Gene

Residual Variation Intolerance Score: 8.61% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.38; 8.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FZR1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FZR1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FZR1 Gene

Disorders for FZR1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for FZR1 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
breast cancer
  • breast lobular carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search FZR1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FZR1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with FZR1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FZR1 Gene

Publications for FZR1 Gene

  1. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. (PMID: 9734353) Fang G … Kirschner MW (Molecular cell 1998) 2 3 4 23
  2. Cell cycle-dependent expression of centrosomal ninein-like protein in human cells is regulated by the anaphase-promoting complex. (PMID: 17403670) Wang Y … Zhan Q (The Journal of biological chemistry 2007) 3 4 23
  3. MAD2B is an inhibitor of the anaphase-promoting complex. (PMID: 11459826) Chen J … Fang G (Genes & development 2001) 3 4 23
  4. Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. (PMID: 9811605) Kramer ER … Peters JM (Current biology : CB 1998) 3 4 23
  5. Atomic structure of the APC/C and its mechanism of protein ubiquitination. (PMID: 26083744) Chang L … Barford D (Nature 2015) 3 4

Products for FZR1 Gene

  • Signalway Proteins for FZR1

Sources for FZR1 Gene