GenomeNet

Database: UniProt
Entry: Q9UM11
LinkDB: Q9UM11
Original site: Q9UM11 
ID   FZR1_HUMAN              Reviewed;         496 AA.
AC   Q9UM11; O75869; Q86U66; Q96NW8; Q9UI96; Q9ULH8; Q9UM10; Q9UNQ1; Q9Y2T8;
DT   03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2003, sequence version 2.
DT   17-JUN-2020, entry version 194.
DE   RecName: Full=Fizzy-related protein homolog;
DE            Short=Fzr;
DE   AltName: Full=CDC20-like protein 1;
DE   AltName: Full=Cdh1/Hct1 homolog;
DE            Short=hCDH1;
GN   Name=FZR1; Synonyms=CDH1, FYR, FZR, KIAA1242;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Parathyroid adenoma;
RX   PubMed=9811605; DOI=10.1016/s0960-9822(07)00510-6;
RA   Kramer E.R., Gieffers C., Hoelzl G., Hengstschlaeger M., Peters J.-M.;
RT   "Activation of the human anaphase-promoting complex by proteins of the
RT   CDC20/Fizzy family.";
RL   Curr. Biol. 8:1207-1210(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RA   Kotani S., Oyamatu T., Todokoro K.;
RT   "Human homologue of Fizzy-related protein.";
RL   Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RA   Sudo T., Saya H.;
RT   "Identification of a human homolog of the Drosophila fizzy-related
RT   protein.";
RL   Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=12797865; DOI=10.1042/bj20030600;
RA   Zhou Y., Ching Y.-P., Ng R.W.M., Jin D.-Y.;
RT   "Differential expression, localization and activity of two alternatively
RT   spliced isoforms of human APC regulator CDH1.";
RL   Biochem. J. 374:349-358(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA   Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:337-345(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   FUNCTION, AND INTERACTION WITH APC/C.
RX   PubMed=9734353; DOI=10.1016/s1097-2765(00)80126-4;
RA   Fang G., Yu H., Kirschner M.W.;
RT   "Direct binding of CDC20 protein family members activates the anaphase-
RT   promoting complex in mitosis and G1.";
RL   Mol. Cell 2:163-171(1998).
RN   [10]
RP   PHOSPHORYLATION.
RX   PubMed=10459014; DOI=10.1083/jcb.146.4.791;
RA   Kotani S., Tanaka H., Yasuda H., Todokoro K.;
RT   "Regulation of APC activity by phosphorylation and regulatory factors.";
RL   J. Cell Biol. 146:791-800(1999).
RN   [11]
RP   INTERACTION WITH MAD2L2.
RX   PubMed=11459825; DOI=10.1101/gad.897901;
RA   Pfleger C.M., Salic A., Lee E., Kirschner M.W.;
RT   "Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel
RT   mechanism for regulating Cdh1.";
RL   Genes Dev. 15:1759-1764(2001).
RN   [12]
RP   INTERACTION WITH MAD2L2.
RX   PubMed=11459826; DOI=10.1101/gad.898701;
RA   Chen J., Fang G.;
RT   "MAD2B is an inhibitor of the anaphase-promoting complex.";
RL   Genes Dev. 15:1765-1770(2001).
RN   [13]
RP   INTERACTION WITH NINL.
RX   PubMed=17403670; DOI=10.1074/jbc.m701350200;
RA   Wang Y., Zhan Q.;
RT   "Cell cycle-dependent expression of centrosomal ninein-like protein in
RT   human cells is regulated by the anaphase-promoting complex.";
RL   J. Biol. Chem. 282:17712-17719(2007).
RN   [14]
RP   FUNCTION, PHOSPHORYLATION, DEPHOSPHORYLATION BY CDC14, AND MUTAGENESIS OF
RP   SER-40; THR-121; SER-151 AND SER-163.
RX   PubMed=18662541; DOI=10.1016/j.cell.2008.05.043;
RA   Bassermann F., Frescas D., Guardavaccaro D., Busino L., Peschiaroli A.,
RA   Pagano M.;
RT   "The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response
RT   checkpoint.";
RL   Cell 134:256-267(2008).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32; SER-36; SER-138; SER-146
RP   AND SER-151, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-151, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [18]
RP   FUNCTION, AND INTERACTION WITH USP37.
RX   PubMed=21596315; DOI=10.1016/j.molcel.2011.03.027;
RA   Huang X., Summers M.K., Pham V., Lill J.R., Liu J., Lee G.,
RA   Kirkpatrick D.S., Jackson P.K., Fang G., Dixit V.M.;
RT   "Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and
RT   promote S phase entry.";
RL   Mol. Cell 42:511-523(2011).
RN   [19]
RP   ACETYLATION AT LYS-69 AND LYS-159, DEACETYLATION BY SIRT2, AND INTERACTION
RP   WITH SIRT2.
RX   PubMed=22014574; DOI=10.1016/j.ccr.2011.09.004;
RA   Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X., Li C.,
RA   Veenstra T.D., Li B., Yu H., Ji J., Wang X.W., Park S.H., Cha Y.I.,
RA   Gius D., Deng C.X.;
RT   "SIRT2 maintains genome integrity and suppresses tumorigenesis through
RT   regulating APC/C activity.";
RL   Cancer Cell 20:487-499(2011).
RN   [20]
RP   INTERACTION WITH MAK, AND PHOSPHORYLATION.
RX   PubMed=21986944; DOI=10.1038/onc.2011.464;
RA   Wang L.Y., Kung H.J.;
RT   "Male germ cell-associated kinase is overexpressed in prostate cancer cells
RT   and causes mitotic defects via deregulation of APC/C(CDH1).";
RL   Oncogene 31:2907-2918(2012).
RN   [21]
RP   INTERACTION WITH HECW2.
RX   PubMed=24163370; DOI=10.1074/jbc.m113.472076;
RA   Lu L., Hu S., Wei R., Qiu X., Lu K., Fu Y., Li H., Xing G., Li D., Peng R.,
RA   He F., Zhang L.;
RT   "The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting
RT   complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the
RT   metaphase to anaphase transition.";
RL   J. Biol. Chem. 288:35637-35650(2013).
RN   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133; SER-138 AND SER-151, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [23]
RP   FUNCTION, AND INTERACTION WITH RBBP8/CTIP.
RX   PubMed=25349192; DOI=10.15252/embj.201489017;
RA   Lafranchi L., de Boer H.R., de Vries E.G., Ong S.E., Sartori A.A.,
RA   van Vugt M.A.;
RT   "APC/C(Cdh1) controls CtIP stability during the cell cycle and in response
RT   to DNA damage.";
RL   EMBO J. 33:2860-2879(2014).
RN   [24] {ECO:0000244|PDB:4UI9}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH APC/C,
RP   SUBUNIT, MUTAGENESIS OF SER-40; ARG-47; ARG-52; THR-121; SER-151 AND
RP   SER-163, AND REGION.
RX   PubMed=26083744; DOI=10.1038/nature14471;
RA   Chang L., Zhang Z., Yang J., McLaughlin S.H., Barford D.;
RT   "Atomic structure of the APC/C and its mechanism of protein
RT   ubiquitination.";
RL   Nature 522:450-454(2015).
CC   -!- FUNCTION: Substrate-specific adapter for the anaphase promoting
CC       complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex.
CC       Associates with the APC/C in late mitosis, in replacement of CDC20, and
CC       activates the APC/C during anaphase and telophase. The APC/C remains
CC       active in degrading substrates to ensure that positive regulators of
CC       the cell cycle do not accumulate prematurely. At the G1/S transition
CC       FZR1 is phosphorylated, leading to its dissociation from the APC/C.
CC       Following DNA damage, it is required for the G2 DNA damage checkpoint:
CC       its dephosphorylation and reassociation with the APC/C leads to the
CC       ubiquitination of PLK1, preventing entry into mitosis. Acts as an
CC       adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for
CC       ubiquitination and subsequent proteasomal degradation. Through the
CC       regulation of RBBP8/CtIP protein turnover, may play a role in DNA
CC       damage response, favoring DNA double-strand repair through error-prone
CC       non-homologous end joining (NHEJ) over error-free, RBBP8-mediated
CC       homologous recombination (HR) (PubMed:25349192).
CC       {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315,
CC       ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: The unphosphorylated form interacts with APC/C during mitosis
CC       (PubMed:26083744, PubMed:9734353). Interacts with NINL
CC       (PubMed:17403670). Interacts (in complex with the anaphase promoting
CC       complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation
CC       (PubMed:11459825, PubMed:11459826). Interacts with SIRT2 and USP37
CC       (PubMed:21596315, PubMed:22014574). Interacts (via WD repeats) with MAK
CC       (PubMed:21986944). Interacts with RBBP8/CtIP; this interaction leads to
CC       RBBP8 proteasomal degradation (PubMed:25349192). Interacts with HECW2
CC       (PubMed:24163370). {ECO:0000269|PubMed:11459825,
CC       ECO:0000269|PubMed:11459826, ECO:0000269|PubMed:17403670,
CC       ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:21986944,
CC       ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:24163370,
CC       ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:26083744,
CC       ECO:0000269|PubMed:9734353}.
CC   -!- INTERACTION:
CC       Q9UM11; P30260: CDC27; NbExp=12; IntAct=EBI-724997, EBI-994813;
CC       Q9UM11; Q9HAW4: CLSPN; NbExp=4; IntAct=EBI-724997, EBI-1369377;
CC       Q9UM11; Q9UI95: MAD2L2; NbExp=2; IntAct=EBI-724997, EBI-77889;
CC       Q9UM11; P20794: MAK; NbExp=7; IntAct=EBI-724997, EBI-3911321;
CC       Q9UM11; O75943: RAD17; NbExp=2; IntAct=EBI-724997, EBI-968231;
CC       Q9UM11; P31350: RRM2; NbExp=2; IntAct=EBI-724997, EBI-2339245;
CC       Q9UM11; Q8IXJ6-2: SIRT2; NbExp=2; IntAct=EBI-724997, EBI-5240785;
CC       Q9UM11; Q13309: SKP2; NbExp=2; IntAct=EBI-724997, EBI-456291;
CC       Q9UM11; P40337: VHL; NbExp=2; IntAct=EBI-724997, EBI-301246;
CC       Q9UM11; P40337-1: VHL; NbExp=2; IntAct=EBI-724997, EBI-3504450;
CC       Q9UM11; P40337-3: VHL; NbExp=2; IntAct=EBI-724997, EBI-301270;
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9UM11-1; Sequence=Displayed;
CC       Name=2; Synonyms=CDH1alpha, Fzr1;
CC         IsoId=Q9UM11-2; Sequence=VSP_008504;
CC       Name=3; Synonyms=CDH1beta, Fzr2;
CC         IsoId=Q9UM11-3; Sequence=VSP_008503, VSP_008504;
CC   -!- TISSUE SPECIFICITY: Isoform 2 is expressed at high levels in heart,
CC       liver, spleen and some cancer cell lines whereas isoform 3 is expressed
CC       only at low levels in these tissues. {ECO:0000269|PubMed:12797865}.
CC   -!- PTM: Acetylated. Deacetylated by SIRT2 at Lys-69 and Lys-159;
CC       deacetylation enhances the interaction of FZR1 with CDC27, leading to
CC       activation of anaphase promoting complex/cyclosome (APC/C).
CC       {ECO:0000269|PubMed:22014574}.
CC   -!- PTM: Phosphorylated during mitosis, probably by maturation promoting
CC       factor (MPF), leading to its dissociation of the APC/C. Following DNA
CC       damage, it is dephosphorylated by CDC14B in G2 phase, leading to its
CC       reassociation with the APC/C, and allowing an efficient G2 DNA damage
CC       checkpoint. Phosphorylated by MAK. {ECO:0000269|PubMed:10459014,
CC       ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21986944}.
CC   -!- MISCELLANEOUS: [Isoform 2]: Major. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 3]: Minor. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the WD repeat CDC20/Fizzy family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD26623.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305};
CC       Sequence=AAD26624.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC       Sequence=BAA86556.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
DR   EMBL; AF102508; AAD26624.1; ALT_SEQ; mRNA.
DR   EMBL; AF102507; AAD26623.1; ALT_SEQ; mRNA.
DR   EMBL; AB013462; BAA86954.1; -; mRNA.
DR   EMBL; AB013463; BAA86955.1; -; mRNA.
DR   EMBL; AF080397; AAF20266.1; -; mRNA.
DR   EMBL; AF083810; AAD52030.1; -; mRNA.
DR   EMBL; AF433157; AAL28117.1; -; mRNA.
DR   EMBL; BT007115; AAP35779.1; -; mRNA.
DR   EMBL; AC005787; AAC62835.1; -; Genomic_DNA.
DR   EMBL; AC005786; AAC62836.1; -; Genomic_DNA.
DR   EMBL; AB033068; BAA86556.1; ALT_INIT; mRNA.
DR   EMBL; BC013413; AAH13413.1; -; mRNA.
DR   CCDS; CCDS12109.1; -. [Q9UM11-2]
DR   CCDS; CCDS45916.1; -. [Q9UM11-1]
DR   CCDS; CCDS45917.1; -. [Q9UM11-3]
DR   RefSeq; NP_001129669.1; NM_001136197.1. [Q9UM11-3]
DR   RefSeq; NP_001129670.1; NM_001136198.1. [Q9UM11-1]
DR   RefSeq; NP_057347.2; NM_016263.3. [Q9UM11-2]
DR   RefSeq; XP_005259630.1; XM_005259573.4. [Q9UM11-1]
DR   PDB; 4UI9; EM; 3.60 A; R=1-496.
DR   PDB; 5L9T; EM; 6.40 A; R=1-496.
DR   PDB; 5L9U; EM; 6.40 A; R=1-496.
DR   PDBsum; 4UI9; -.
DR   PDBsum; 5L9T; -.
DR   PDBsum; 5L9U; -.
DR   SMR; Q9UM11; -.
DR   BioGRID; 119489; 196.
DR   DIP; DIP-38700N; -.
DR   ELM; Q9UM11; -.
DR   IntAct; Q9UM11; 59.
DR   MINT; Q9UM11; -.
DR   STRING; 9606.ENSP00000378529; -.
DR   iPTMnet; Q9UM11; -.
DR   PhosphoSitePlus; Q9UM11; -.
DR   BioMuta; FZR1; -.
DR   DMDM; 37537753; -.
DR   jPOST; Q9UM11; -.
DR   MassIVE; Q9UM11; -.
DR   PaxDb; Q9UM11; -.
DR   PeptideAtlas; Q9UM11; -.
DR   PRIDE; Q9UM11; -.
DR   ProteomicsDB; 85167; -. [Q9UM11-1]
DR   ProteomicsDB; 85168; -. [Q9UM11-2]
DR   ProteomicsDB; 85169; -. [Q9UM11-3]
DR   Antibodypedia; 11031; 332 antibodies.
DR   DNASU; 51343; -.
DR   Ensembl; ENST00000313639; ENSP00000321800; ENSG00000105325. [Q9UM11-3]
DR   Ensembl; ENST00000395095; ENSP00000378529; ENSG00000105325. [Q9UM11-1]
DR   Ensembl; ENST00000441788; ENSP00000410369; ENSG00000105325. [Q9UM11-2]
DR   Ensembl; ENST00000652521; ENSP00000498659; ENSG00000105325. [Q9UM11-2]
DR   GeneID; 51343; -.
DR   KEGG; hsa:51343; -.
DR   UCSC; uc002lxt.3; human. [Q9UM11-1]
DR   CTD; 51343; -.
DR   DisGeNET; 51343; -.
DR   EuPathDB; HostDB:ENSG00000105325.13; -.
DR   GeneCards; FZR1; -.
DR   HGNC; HGNC:24824; FZR1.
DR   HPA; ENSG00000105325; Low tissue specificity.
DR   MIM; 603619; gene.
DR   neXtProt; NX_Q9UM11; -.
DR   OpenTargets; ENSG00000105325; -.
DR   PharmGKB; PA134896003; -.
DR   eggNOG; KOG0305; Eukaryota.
DR   eggNOG; ENOG410XQ8I; LUCA.
DR   GeneTree; ENSGT00950000183104; -.
DR   HOGENOM; CLU_014831_4_2_1; -.
DR   InParanoid; Q9UM11; -.
DR   KO; K03364; -.
DR   OMA; WSERGHQ; -.
DR   OrthoDB; 1220675at2759; -.
DR   PhylomeDB; Q9UM11; -.
DR   TreeFam; TF101066; -.
DR   Reactome; R-HSA-174084; Autodegradation of Cdh1 by Cdh1:APC/C.
DR   Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1.
DR   Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR   Reactome; R-HSA-176407; Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
DR   Reactome; R-HSA-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR   Reactome; R-HSA-176417; Phosphorylation of Emi1.
DR   Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR   Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR   Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR   Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q9UM11; -.
DR   SIGNOR; Q9UM11; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 51343; 84 hits in 796 CRISPR screens.
DR   ChiTaRS; FZR1; human.
DR   GeneWiki; FZR1; -.
DR   GenomeRNAi; 51343; -.
DR   Pharos; Q9UM11; Tbio.
DR   PRO; PR:Q9UM11; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9UM11; protein.
DR   Bgee; ENSG00000105325; Expressed in testis and 203 other tissues.
DR   ExpressionAtlas; Q9UM11; baseline and differential.
DR   Genevisible; Q9UM11; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0010997; F:anaphase-promoting complex binding; IEA:InterPro.
DR   GO; GO:0097027; F:ubiquitin-protein transferase activator activity; IEA:InterPro.
DR   GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; IDA:UniProtKB.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR   GO; GO:0090344; P:negative regulation of cell aging; IEA:Ensembl.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:UniProtKB.
DR   GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IDA:UniProtKB.
DR   GO; GO:0070979; P:protein K11-linked ubiquitination; TAS:UniProtKB.
DR   GO; GO:0040020; P:regulation of meiotic nuclear division; IEA:Ensembl.
DR   GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; TAS:Reactome.
DR   GO; GO:0072425; P:signal transduction involved in G2 DNA damage checkpoint; IDA:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR   DisProt; DP01524; -.
DR   Gene3D; 2.130.10.10; -; 1.
DR   InterPro; IPR024977; Apc4_WD40_dom.
DR   InterPro; IPR033010; Cdc20/Fizzy.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR001680; WD40_repeat.
DR   InterPro; IPR019775; WD40_repeat_CS.
DR   InterPro; IPR017986; WD40_repeat_dom.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   PANTHER; PTHR19918; PTHR19918; 1.
DR   Pfam; PF12894; ANAPC4_WD40; 1.
DR   Pfam; PF00400; WD40; 3.
DR   SMART; SM00320; WD40; 6.
DR   SUPFAM; SSF50978; SSF50978; 1.
DR   PROSITE; PS00678; WD_REPEATS_1; 2.
DR   PROSITE; PS50082; WD_REPEATS_2; 3.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW   Cytoplasm; DNA damage; DNA repair; Mitosis; Nucleus; Phosphoprotein;
KW   Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT   CHAIN           1..496
FT                   /note="Fizzy-related protein homolog"
FT                   /id="PRO_0000051001"
FT   REPEAT          182..222
FT                   /note="WD 1"
FT   REPEAT          227..266
FT                   /note="WD 2"
FT   REPEAT          269..306
FT                   /note="WD 3"
FT   REPEAT          311..350
FT                   /note="WD 4"
FT   REPEAT          353..395
FT                   /note="WD 5"
FT   REPEAT          397..438
FT                   /note="WD 6"
FT   REPEAT          441..480
FT                   /note="WD 7"
FT   REGION          47..52
FT                   /note="Involved in APC/FZR1 E3 ubiquitin-protein ligase
FT                   complex activity"
FT                   /evidence="ECO:0000269|PubMed:26083744"
FT   MOD_RES         32
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         36
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332"
FT   MOD_RES         69
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000269|PubMed:22014574"
FT   MOD_RES         133
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   MOD_RES         138
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         146
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648"
FT   MOD_RES         151
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:23186163"
FT   MOD_RES         159
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000269|PubMed:22014574"
FT   VAR_SEQ         130..218
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12797865, ECO:0000303|Ref.2"
FT                   /id="VSP_008503"
FT   VAR_SEQ         481..483
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10574462,
FT                   ECO:0000303|PubMed:12797865, ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:9811605, ECO:0000303|Ref.2,
FT                   ECO:0000303|Ref.3, ECO:0000303|Ref.6"
FT                   /id="VSP_008504"
FT   MUTAGEN         40
FT                   /note="S->A: Constitutively active; when associated with A-
FT                   121; A-151 and A-163. Does not affect APC/FZR1 E3
FT                   ubiquitin-protein ligase complex activity; when associated
FT                   with A-121; A-151 and A-163. Decreases APC/FZR1 E3
FT                   ubiquitin-protein ligase complex activity; when associated
FT                   with A-121 and A-151. Decreases APC/FZR1 E3 ubiquitin-
FT                   protein ligase complex activity; when associated with A-121
FT                   and A-163."
FT                   /evidence="ECO:0000269|PubMed:18662541,
FT                   ECO:0000269|PubMed:26083744"
FT   MUTAGEN         47
FT                   /note="R->A: Inhibits APC/FZR1 E3 ubiquitin-protein ligase
FT                   complex activity."
FT                   /evidence="ECO:0000269|PubMed:26083744"
FT   MUTAGEN         52
FT                   /note="R->A: Inhibits APC/FZR1 E3 ubiquitin-protein ligase
FT                   complex activity."
FT                   /evidence="ECO:0000269|PubMed:26083744"
FT   MUTAGEN         121
FT                   /note="T->A: Constitutively active; when associated with A-
FT                   40; A-151 and A-163. Does not affect APC/FZR1 E3 ubiquitin-
FT                   protein ligase complex activity; when associated with A-40;
FT                   A-151 and A-163. Decreases APC/FZR1 E3 ubiquitin-protein
FT                   ligase complex activity; when associated with A-40 and A-
FT                   151. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex
FT                   activity; when associated with A-40 and A-163. Decreases
FT                   APC/FZR1 E3 ubiquitin-protein ligase complex activity; when
FT                   associated with A-151 and A-163."
FT                   /evidence="ECO:0000269|PubMed:18662541,
FT                   ECO:0000269|PubMed:26083744"
FT   MUTAGEN         151
FT                   /note="S->A: Constitutively active; when associated with A-
FT                   40; A-121 and A-163. Does not affect ubiquitination; when
FT                   associated with A-40; A-121 and A-163. Decreases
FT                   ubiquitination; when associated with A-40 and A-163.
FT                   Decreases ubiquitination; when associated with A-121 and A-
FT                   163."
FT                   /evidence="ECO:0000269|PubMed:18662541,
FT                   ECO:0000269|PubMed:26083744"
FT   MUTAGEN         163
FT                   /note="S->A: Constitutively active; when associated with A-
FT                   40; A-121 and A-151. Does not affect APC/FZR1 E3 ubiquitin-
FT                   protein ligase complex activity; when associated with A-40;
FT                   A-121 and A-151. Decreases APC/FZR1 E3 ubiquitin-protein
FT                   ligase complex activity; when associated with A-40 and A-
FT                   121. Decreases APC/FZR1 E3 ubiquitin-protein ligase complex
FT                   activity; when associated with A-121 and A-151. Decreases
FT                   ubiquitination; when associated with A-40 and A-151."
FT                   /evidence="ECO:0000269|PubMed:18662541,
FT                   ECO:0000269|PubMed:26083744"
FT   CONFLICT        259
FT                   /note="A -> S (in Ref. 3; AAF20266)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        275
FT                   /note="G -> W (in Ref. 3; AAF20266)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        326
FT                   /note="Q -> H (in Ref. 2; BAA86954/BAA86955)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        341
FT                   /note="N -> I (in Ref. 3; AAF20266)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   496 AA;  55179 MW;  F6C8FDAF81D8103A CRC64;
     MDQDYERRLL RQIVIQNENT MPRVTEMRRT LTPASSPVSS PSKHGDRFIP SRAGANWSVN
     FHRINENEKS PSQNRKAKDA TSDNGKDGLA YSALLKNELL GAGIEKVQDP QTEDRRLQPS
     TPEKKGLFTY SLSTKRSSPD DGNDVSPYSL SPVSNKSQKL LRSPRKPTRK ISKIPFKVLD
     APELQDDFYL NLVDWSSLNV LSVGLGTCVY LWSACTSQVT RLCDLSVEGD SVTSVGWSER
     GNLVAVGTHK GFVQIWDAAA GKKLSMLEGH TARVGALAWN AEQLSSGSRD RMILQRDIRT
     PPLQSERRLQ GHRQEVCGLK WSTDHQLLAS GGNDNKLLVW NHSSLSPVQQ YTEHLAAVKA
     IAWSPHQHGL LASGGGTADR CIRFWNTLTG QPLQCIDTGS QVCNLAWSKH ANELVSTHGY
     SQNQILVWKY PSLTQVAKLT GHSYRVLYLA MSPDGEAIVT GAGDETLRFW NVFSKTRSTK
     VKWESVSVLN LFTRIR
//
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