Human Gene FZR1 (uc010dtk.2)
  Description: Homo sapiens fizzy/cell division cycle 20 related 1 (Drosophila) (FZR1), transcript variant 1, mRNA.
Transcript (Including UTRs)
   Position: hg19 chr19:3,522,954-3,536,755 Size: 13,802 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr19:3,522,988-3,534,834 Size: 11,847 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:3,522,954-3,536,755)mRNA (may differ from genome)Protein (496 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer
GeneCardsH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeTreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: FZR_HUMAN
DESCRIPTION: RecName: Full=Fizzy-related protein homolog; Short=Fzr; AltName: Full=CDC20-like protein 1; AltName: Full=Cdh1/Hct1 homolog; Short=hCDH1;
FUNCTION: 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.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: 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. Interacts (via WD repeats) with MAK.
INTERACTION: P30260:CDC27; NbExp=8; IntAct=EBI-724997, EBI-994813; Q9HAW4:CLSPN; NbExp=4; IntAct=EBI-724997, EBI-1369377; Q9UI95:MAD2L2; NbExp=2; IntAct=EBI-724997, EBI-77889; P20794:MAK; NbExp=7; IntAct=EBI-724997, EBI-3911321; P31350:RRM2; NbExp=2; IntAct=EBI-724997, EBI-2339245; Q8IXJ6-2:SIRT2; NbExp=2; IntAct=EBI-724997, EBI-5240785; Q13309:SKP2; NbExp=2; IntAct=EBI-724997, EBI-456291; P40337:VHL; NbExp=2; IntAct=EBI-724997, EBI-301246; P40337-1:VHL; NbExp=2; IntAct=EBI-724997, EBI-3504450; P40337-3:VHL; NbExp=2; IntAct=EBI-724997, EBI-301270;
SUBCELLULAR LOCATION: Isoform 2: Nucleus.
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
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.
PTM: 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.
SIMILARITY: Belongs to the WD repeat CDC20/Fizzy family.
SIMILARITY: Contains 7 WD repeats.
SEQUENCE CAUTION: Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part; Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; Sequence=BAA86556.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): FZR1
CDC HuGE Published Literature: FZR1

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 57.31 RPKM in Testis
Total median expression: 727.88 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.6034-0.253 Picture PostScript Text
3' UTR -898.021921-0.467 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR019775 - WD40_repeat_CS
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00400 - WD domain, G-beta repeat
PF12894 - Anaphase-promoting complex subunit 4 WD40 domain

SCOP Domains:
50952 - Soluble quinoprotein glucose dehydrogenase
50960 - TolB, C-terminal domain
63825 - YWTD domain
63829 - Calcium-dependent phosphotriesterase
69304 - Tricorn protease N-terminal domain
101898 - NHL repeat
50965 - Galactose oxidase, central domain
75011 - 3-carboxy-cis,cis-mucoante lactonizing enzyme
101908 - Putative isomerase YbhE
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50974 - Nitrous oxide reductase, N-terminal domain
50978 - WD40 repeat-like
50993 - Prolyl oligopeptidase, N-terminal domain
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
82171 - Dipeptidyl peptidase IV/CD26, N-terminal domain

ModBase Predicted Comparative 3D Structure on Q9UM11
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
     SGD
     Protein Sequence
     Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0010997 anaphase-promoting complex binding
GO:0097027 ubiquitin-protein transferase activator activity

Biological Process:
GO:0006281 DNA repair
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0008284 positive regulation of cell proliferation
GO:0016567 protein ubiquitination
GO:0031145 anaphase-promoting complex-dependent catabolic process
GO:0040020 regulation of meiotic nuclear division
GO:0045732 positive regulation of protein catabolic process
GO:0051301 cell division
GO:0070306 lens fiber cell differentiation
GO:0070979 protein K11-linked ubiquitination
GO:0072425 signal transduction involved in G2 DNA damage checkpoint
GO:0090344 negative regulation of cell aging
GO:1904668 positive regulation of ubiquitin protein ligase activity

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0031965 nuclear membrane
GO:0005680 anaphase-promoting complex


-  Descriptions from all associated GenBank mRNAs
  BC013413 - Homo sapiens fizzy/cell division cycle 20 related 1 (Drosophila), mRNA (cDNA clone MGC:4589 IMAGE:3160334), complete cds.
AF102507 - Homo sapiens fizzy-related protein mRNA, partial cds.
AF083810 - Homo sapiens fizzy-related protein (FYR) mRNA, complete cds.
AB033068 - Homo sapiens KIAA1242 mRNA for KIAA1242 protein.
AB384150 - Synthetic construct DNA, clone: pF1KSDA1242, Homo sapiens FZR1 gene for fizzy-related protein homolog, complete cds, without stop codon, in Flexi system.
DQ890739 - Synthetic construct clone IMAGE:100003369; FLH165584.01X; RZPDo839E03160D fizzy/cell division cycle 20 related 1 (Drosophila) (FZR1) gene, encodes complete protein.
CU680596 - Synthetic construct Homo sapiens gateway clone IMAGE:100019657 5' read FZR1 mRNA.
HQ448330 - Synthetic construct Homo sapiens clone IMAGE:100071748; CCSB006019_01 fizzy/cell division cycle 20 related 1 (Drosophila) (FZR1) gene, encodes complete protein.
KJ893893 - Synthetic construct Homo sapiens clone ccsbBroadEn_03287 FZR1 gene, encodes complete protein.
AF080397 - Homo sapiens fizzy-related protein homolog (FZR) mRNA, complete cds.
BT007115 - Homo sapiens Fzr1 protein mRNA, complete cds.
AB013462 - Homo sapiens mRNA for Fzr1, complete cds.
AB013463 - Homo sapiens mRNA for Fzr2, complete cds.
AF433157 - Homo sapiens CDC20-like 1b mRNA, complete cds.
AF102508 - Homo sapiens fizzy-related protein mRNA, partial cds.
DQ591748 - Homo sapiens piRNA piR-58860, complete sequence.
BC111760 - Homo sapiens cDNA clone IMAGE:40027097.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04110 - Cell cycle
hsa04120 - Ubiquitin mediated proteolysis
hsa04914 - Progesterone-mediated oocyte maturation

Reactome (by CSHL, EBI, and GO)

Protein Q9UM11 (Reactome details) participates in the following event(s):

R-HSA-174251 Phosphorylation of Cdh1 by Cyclin B1:Cdc2
R-HSA-174124 Dephosphorylation of phospho-Cdh1
R-HSA-174070 Association of Cdh1 with the APC/C
R-HSA-174139 Dissociation of phospho-Cdh1 from the APC/C complex
R-HSA-188371 Association of Cyclin A:Cdk2 with Cdh1
R-HSA-3788708 CDKN1A (p21) prevents association of Cyclin A:Cdk2 with Cdh1
R-HSA-3788725 Cdh1:APC/C complex binds EHMT1:EHMT2
R-HSA-174097 Association of Emi1 with Cdh1
R-HSA-187948 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2
R-HSA-174088 Association of cell cycle proteins with the APC/C:Cdh1 complex
R-HSA-174057 Multiubiquitination of APC/C-associated Cdh1
R-HSA-174079 Phosphorylation of Cdh1 by Cyclin A:Cdk2
R-HSA-3788705 CDKN1A (p21) prevents phosphorylation of Cdh1 by Cyclin A:Cdk2
R-HSA-3788724 Cdh1:APC/C ubiquitinates EHMT1 and EHMT2
R-HSA-174174 Phosphorylation of the Emi1 DSGxxS degron by Plk1
R-HSA-174122 Phosphorylation of the Emi1 DSGxxS degron by Cyclin B:Cdc2
R-HSA-174195 Ubiquitination of cell cycle proteins targeted by the APC/C:Cdh1complex
R-HSA-69015 Cytoplasmic phosphorylated Cdc6 is ubiquitinated by the anaphase-promoting complex
R-HSA-174209 Phosphorylated Emi1 binds the beta-TrCP in the SCF complex
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-174159 Ubiquitination of Emi1 by SCF-beta-TrCP
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-2559583 Cellular Senescence
R-HSA-176417 Phosphorylation of Emi1
R-HSA-69242 S Phase
R-HSA-453276 Regulation of mitotic cell cycle
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-2262752 Cellular responses to stress
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-69052 Switching of origins to a post-replicative state
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-1640170 Cell Cycle
R-HSA-69239 Synthesis of DNA
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-69306 DNA Replication
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: CDH1, FYR, FZR, FZR_HUMAN, KIAA1242, NM_001136198, NP_001129670, O75869, Q86U66, Q96NW8, Q9UI96, Q9ULH8, Q9UM10, Q9UM11, Q9UNQ1, Q9Y2T8
UCSC ID: uc010dtk.2
RefSeq Accession: NM_001136198
Protein: Q9UM11 (aka FZR_HUMAN)
CCDS: CCDS12109.1, CCDS45916.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001136198.1
exon count: 13CDS single in 3' UTR: no RNA size: 3446
ORF size: 1491CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3182.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.