Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008368
UniProt IDQ8IUQ4
Primary gene name(s)SIAH1
Synonym gene name(s)HUMSIAH
Protein nameE3 ubiquitin-protein ligase SIAH1
Protein functionE3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation, ELL2, MYB, POU2AF1, PML and RBBP8, a cell surface receptor, DCC, the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules, KLF10/TIEG1 and NUMB, an antiapoptotic protein, BAG1, a microtubule motor protein, KIF22, a protein involved in synaptic vesicle function in neurons, SYP, a structural protein, CTNNB1 and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid, NO generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. {ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.
Subcellular locationCytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8IUQ4
Gene Ontology
(Biological Process)
Complete annatation
anatomical structure morphogenesis [GO:0009653];
apoptotic process [GO:0006915];
axon guidance [GO:0007411];
cell cycle [GO:0007049];
cellular protein metabolic process [GO:0044267];
nervous system development [GO:0007399];
neuron apoptotic process [GO:0051402];
positive regulation of apoptotic process [GO:0043065];
positive regulation of intrinsic apoptotic signaling pathway [GO:2001244];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein catabolic process [GO:0030163];
protein destabilization [GO:0031648];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
spermatogenesis [GO:0007283];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
protein C-terminus binding [GO:0008022];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
beta-catenin destruction complex [GO:0030877];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early endosome [GO:0005769];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction112372
Phylogenetic treeQ8IUQ4
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.142284928813140.6669716316926380.758915629840816
AZA vs. DISU0.1403041423564830.585243474334630.955158276076142
AZA vs. IL7-0.003114136332704610.9874805562949930.999311006273513
AZA vs. SAHA0.2536316075748230.3083363373013890.680638712090254
DISU vs. CD3-0.01563604131546150.965875020789460.978590399896604
DISU vs. IL7-0.1520638745178610.5524211843531230.854079828029172
DISU vs. SAHA0.1151076988849860.6967619144269710.910532306883434
DMSO vs. AZA0.06088468306993080.7274698730071891
DMSO vs. CD3-0.09327132974895030.7723661307713240.837849025046496
DMSO vs. DISU-0.0811965182381380.7432435853223440.969179039562928
DMSO vs. IL7-0.05680564937593940.7596085932155220.951841190064606
DMSO vs. SAHA0.1861680414857030.4380126054412420.771178501939832
HIV vs. Mock in Activation-0.0501557289606410.9360992049770460.999983755607037
HIV vs. Mock in Latency-0.0868038176762010.6094148787332240.999834320637052
IL7 vs. CD3-0.1378442410902210.6705994444122640.774792689378051
SAHA vs. CD30.08658005488712490.8075495311170510.862981208330582
SAHA vs. IL70.2533239908485720.3069595467990930.556009157468099
(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 0.591412 0.482252
(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
2A25 X-ray 2.2Å A=90-282.
4C9Z X-ray 1.9Å A/B=91-282.
4CA1 X-ray 1.5Å A/B=91-282.
4I7B X-ray 3.0Å A/C=90-282.
4I7C X-ray 2.8Å A/C=90-282.
4I7D X-ray 2.4Å A/C=90-282.
4X3G X-ray 2.3Å A/B=91-282.

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
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
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