Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0010955
UniProt IDQ9UM11
Primary gene name(s)FZR1
Synonym gene name(s)CDH1, FYR, FZR, KIAA1242
Protein nameFizzy-related protein homolog
Protein functionSubstrate-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. {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.
Subcellular locationIsoform 2: Nucleus.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UM11
Gene Ontology
(Biological Process)
Complete annatation
anaphase-promoting complex-dependent catabolic process [GO:0031145];
cell division [GO:0051301];
DNA repair [GO:0006281];
G2 DNA damage checkpoint [GO:0031572];
lens fiber cell differentiation [GO:0070306];
mitotic nuclear division [GO:0007067];
negative regulation of cell aging [GO:0090344];
negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle [GO:0051436];
positive regulation of cell proliferation [GO:0008284];
positive regulation of protein catabolic process [GO:0045732];
positive regulation of ubiquitin protein ligase activity [GO:1904668];
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition [GO:0051437];
protein K11-linked ubiquitination [GO:0070979];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of meiotic nuclear division [GO:0040020];
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle [GO:0051439]
Gene Ontology
(Molecular Function)
Complete annatation
ubiquitin-protein transferase activator activity [GO:0097027]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nuclear membrane [GO:0031965];
nucleoplasm [GO:0005654]
Protein-protein interaction119489
Phylogenetic treeQ9UM11
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.3394713499225930.304770433649620.423481144645254
AZA vs. DISU0.2192375275719690.3884571869793010.901416815967669
AZA vs. IL7-0.2793260967475690.149824971308350.917267178119725
AZA vs. SAHA0.2484122240444090.310958273076110.682838838043596
DISU vs. CD30.5462074291211290.1400961459144940.242965796799298
DISU vs. IL7-0.5083329566956110.04482469348222830.279980468876379
DISU vs. SAHA0.03181857476517430.9136967585218530.98055132615251
DMSO vs. AZA0.03036430235538390.8575371775871641
DMSO vs. CD30.3561194502115190.2721907329162380.380738476451544
DMSO vs. DISU-0.1914689339967840.4341026207883850.881898961348201
DMSO vs. IL7-0.3018712452788370.09604174523716380.567241000353004
DMSO vs. SAHA0.2134588179468830.3683296142243660.715993243386485
HIV vs. Mock in Activation0.3355920653757910.5919055576304320.999983755607037
HIV vs. Mock in Latency0.05452881452407690.7429604315748230.999834320637052
IL7 vs. CD30.0651697911808350.8415006706548810.897914456235383
SAHA vs. CD30.5647651540048040.1121697936973270.191193556201641
SAHA vs. IL70.5253038508303980.03262837131486630.138234982911831
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.238463 0.093397
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
4UI9 EM 3.6Å R=1-496.
5L9U EM 6.4Å R=1-496.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04110 Cell cycle - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)