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Protein

Fizzy-related protein homolog

Gene

FZR1

Organism
Homo sapiens (Human)
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.3 Publications

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

Complete GO annotation...

Keywords - Biological processi

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

Enzyme and pathway databases

ReactomeiR-HSA-174084. Autodegradation of Cdh1 by Cdh1:APC/C.
R-HSA-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-176407. Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
R-HSA-176408. Regulation of APC/C activators between G1/S and early anaphase.
R-HSA-176417. Phosphorylation of Emi1.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9UM11.
SIGNORiQ9UM11.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Fizzy-related protein homolog
Short name:
Fzr
Alternative name(s):
CDC20-like protein 1
Cdh1/Hct1 homolog
Short name:
hCDH1
Gene namesi
Name:FZR1
Synonyms:CDH1, FYR, FZR, KIAA1242
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:24824. FZR1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40S → A: Constitutively active; when associated with A-121; A-151 and A-163. 1 Publication1
Mutagenesisi121T → A: Constitutively active; when associated with A-40; A-151 and A-163. 1 Publication1
Mutagenesisi151S → A: Constitutively active; when associated with A-40; A-121 and A-163. 1 Publication1
Mutagenesisi163S → A: Constitutively active; when associated with A-40; A-121 and A-151. 1 Publication1

Organism-specific databases

DisGeNETi51343.
OpenTargetsiENSG00000105325.
PharmGKBiPA134896003.

Polymorphism and mutation databases

BioMutaiFZR1.
DMDMi37537753.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000510011 – 496Fizzy-related protein homologAdd BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32PhosphothreonineCombined sources1
Modified residuei36PhosphoserineCombined sources1
Modified residuei69N6-acetyllysine1 Publication1
Modified residuei133PhosphoserineCombined sources1
Modified residuei138PhosphoserineCombined sources1
Modified residuei146PhosphoserineCombined sources1
Modified residuei151PhosphoserineCombined sources1
Modified residuei159N6-acetyllysine1 Publication1

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).1 Publication
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.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ9UM11.
PeptideAtlasiQ9UM11.
PRIDEiQ9UM11.

PTM databases

iPTMnetiQ9UM11.
PhosphoSitePlusiQ9UM11.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000105325.
CleanExiHS_CDH1.
ExpressionAtlasiQ9UM11. baseline and differential.
GenevisibleiQ9UM11. HS.

Organism-specific databases

HPAiHPA043536.

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 SIRT2 and USP37. Interacts (via WD repeats) with MAK.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC27P302608EBI-724997,EBI-994813
CLSPNQ9HAW44EBI-724997,EBI-1369377
MAD2L2Q9UI952EBI-724997,EBI-77889
MAKP207947EBI-724997,EBI-3911321
RAD17O759432EBI-724997,EBI-968231
RRM2P313502EBI-724997,EBI-2339245
SIRT2Q8IXJ6-22EBI-724997,EBI-5240785
SKP2Q133092EBI-724997,EBI-456291
VHLP403372EBI-724997,EBI-301246
VHLP40337-12EBI-724997,EBI-3504450
VHLP40337-32EBI-724997,EBI-301270

Protein-protein interaction databases

BioGridi119489. 139 interactors.
DIPiDIP-38700N.
IntActiQ9UM11. 29 interactors.
MINTiMINT-1415280.
STRINGi9606.ENSP00000378529.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UI9electron microscopy3.60R1-496[»]
5L9Uelectron microscopy6.40R1-496[»]
ProteinModelPortaliQ9UM11.
SMRiQ9UM11.
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
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0305. Eukaryota.
ENOG410XQ8I. LUCA.
GeneTreeiENSGT00860000133834.
HOVERGENiHBG001024.
InParanoidiQ9UM11.
KOiK03364.
OMAiIEKSHNQ.
OrthoDBiEOG091G06FJ.
PhylomeDBiQ9UM11.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UM11-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDQDYERRLL RQIVIQNENT MPRVTEMRRT LTPASSPVSS PSKHGDRFIP
60 70 80 90 100
SRAGANWSVN FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL
110 120 130 140 150
GAGIEKVQDP QTEDRRLQPS TPEKKGLFTY SLSTKRSSPD 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 AEQLSSGSRD 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 VKWESVSVLN LFTRIR
Length:496
Mass (Da):55,179
Last modified:October 3, 2003 - v2
Checksum:iF6C8FDAF81D8103A
GO
Isoform 2 (identifier: Q9UM11-2) [UniParc]FASTAAdd to basket
Also known as: CDH1alpha, Fzr1

The sequence of this isoform differs from the canonical sequence as follows:
     481-483: Missing.

Note: Major.
Show »
Length:493
Mass (Da):54,766
Checksum:i7C6A947EBB8A6D5C
GO
Isoform 3 (identifier: Q9UM11-3) [UniParc]FASTAAdd to basket
Also known as: CDH1beta, Fzr2

The sequence of this isoform differs from the canonical sequence as follows:
     130-218: Missing.
     481-483: Missing.

Note: Minor.
Show »
Length:404
Mass (Da):44,874
Checksum:iA793194D88777035
GO

Sequence cautioni

The sequence AAD26623 differs from that shown. Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated
The sequence AAD26624 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence BAA86556 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti259A → S in AAF20266 (Ref. 3) Curated1
Sequence conflicti275G → W in AAF20266 (Ref. 3) Curated1
Sequence conflicti326Q → H in BAA86954 (Ref. 2) Curated1
Sequence conflicti326Q → H in BAA86955 (Ref. 2) Curated1
Sequence conflicti341N → I in AAF20266 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008503130 – 218Missing in isoform 3. 2 PublicationsAdd BLAST89
Alternative sequenceiVSP_008504481 – 483Missing in isoform 2 and isoform 3. 7 Publications3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102508 mRNA. Translation: AAD26624.1. Sequence problems.
AF102507 mRNA. Translation: AAD26623.1. Sequence problems.
AB013462 mRNA. Translation: BAA86954.1.
AB013463 mRNA. Translation: BAA86955.1.
AF080397 mRNA. Translation: AAF20266.1.
AF083810 mRNA. Translation: AAD52030.1.
AF433157 mRNA. Translation: AAL28117.1.
BT007115 mRNA. Translation: AAP35779.1.
AC005787 Genomic DNA. Translation: AAC62835.1.
AC005786 Genomic DNA. Translation: AAC62836.1.
AB033068 mRNA. Translation: BAA86556.1. Different initiation.
BC013413 mRNA. Translation: AAH13413.1.
CCDSiCCDS12109.1. [Q9UM11-2]
CCDS45916.1. [Q9UM11-1]
CCDS45917.1. [Q9UM11-3]
RefSeqiNP_001129669.1. NM_001136197.1. [Q9UM11-3]
NP_001129670.1. NM_001136198.1. [Q9UM11-1]
NP_057347.2. NM_016263.3. [Q9UM11-2]
XP_005259630.1. XM_005259573.4. [Q9UM11-1]
UniGeneiHs.413133.

Genome annotation databases

EnsembliENST00000313639; ENSP00000321800; ENSG00000105325. [Q9UM11-3]
ENST00000395095; ENSP00000378529; ENSG00000105325. [Q9UM11-1]
ENST00000441788; ENSP00000410369; ENSG00000105325. [Q9UM11-2]
GeneIDi51343.
KEGGihsa:51343.
UCSCiuc002lxt.3. human. [Q9UM11-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF102508 mRNA. Translation: AAD26624.1. Sequence problems.
AF102507 mRNA. Translation: AAD26623.1. Sequence problems.
AB013462 mRNA. Translation: BAA86954.1.
AB013463 mRNA. Translation: BAA86955.1.
AF080397 mRNA. Translation: AAF20266.1.
AF083810 mRNA. Translation: AAD52030.1.
AF433157 mRNA. Translation: AAL28117.1.
BT007115 mRNA. Translation: AAP35779.1.
AC005787 Genomic DNA. Translation: AAC62835.1.
AC005786 Genomic DNA. Translation: AAC62836.1.
AB033068 mRNA. Translation: BAA86556.1. Different initiation.
BC013413 mRNA. Translation: AAH13413.1.
CCDSiCCDS12109.1. [Q9UM11-2]
CCDS45916.1. [Q9UM11-1]
CCDS45917.1. [Q9UM11-3]
RefSeqiNP_001129669.1. NM_001136197.1. [Q9UM11-3]
NP_001129670.1. NM_001136198.1. [Q9UM11-1]
NP_057347.2. NM_016263.3. [Q9UM11-2]
XP_005259630.1. XM_005259573.4. [Q9UM11-1]
UniGeneiHs.413133.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UI9electron microscopy3.60R1-496[»]
5L9Uelectron microscopy6.40R1-496[»]
ProteinModelPortaliQ9UM11.
SMRiQ9UM11.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119489. 139 interactors.
DIPiDIP-38700N.
IntActiQ9UM11. 29 interactors.
MINTiMINT-1415280.
STRINGi9606.ENSP00000378529.

PTM databases

iPTMnetiQ9UM11.
PhosphoSitePlusiQ9UM11.

Polymorphism and mutation databases

BioMutaiFZR1.
DMDMi37537753.

Proteomic databases

PaxDbiQ9UM11.
PeptideAtlasiQ9UM11.
PRIDEiQ9UM11.

Protocols and materials databases

DNASUi51343.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000313639; ENSP00000321800; ENSG00000105325. [Q9UM11-3]
ENST00000395095; ENSP00000378529; ENSG00000105325. [Q9UM11-1]
ENST00000441788; ENSP00000410369; ENSG00000105325. [Q9UM11-2]
GeneIDi51343.
KEGGihsa:51343.
UCSCiuc002lxt.3. human. [Q9UM11-1]

Organism-specific databases

CTDi51343.
DisGeNETi51343.
GeneCardsiFZR1.
HGNCiHGNC:24824. FZR1.
HPAiHPA043536.
MIMi603619. gene.
neXtProtiNX_Q9UM11.
OpenTargetsiENSG00000105325.
PharmGKBiPA134896003.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0305. Eukaryota.
ENOG410XQ8I. LUCA.
GeneTreeiENSGT00860000133834.
HOVERGENiHBG001024.
InParanoidiQ9UM11.
KOiK03364.
OMAiIEKSHNQ.
OrthoDBiEOG091G06FJ.
PhylomeDBiQ9UM11.
TreeFamiTF101066.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-174084. Autodegradation of Cdh1 by Cdh1:APC/C.
R-HSA-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-176407. Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
R-HSA-176408. Regulation of APC/C activators between G1/S and early anaphase.
R-HSA-176417. Phosphorylation of Emi1.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiQ9UM11.
SIGNORiQ9UM11.

Miscellaneous databases

ChiTaRSiFZR1. human.
GeneWikiiFZR1.
GenomeRNAii51343.
PROiQ9UM11.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105325.
CleanExiHS_CDH1.
ExpressionAtlasiQ9UM11. baseline and differential.
GenevisibleiQ9UM11. HS.

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...

Entry informationi

Entry nameiFZR_HUMAN
AccessioniPrimary (citable) accession number: Q9UM11
Secondary accession number(s): O75869
, Q86U66, Q96NW8, Q9UI96, Q9ULH8, Q9UM10, Q9UNQ1, Q9Y2T8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 30, 2016
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.