Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002782
UniProt IDQ9HAU4
Primary gene name(s)SMURF2
Synonym gene name(s)unknown
Protein nameE3 ubiquitin-protein ligase SMURF2
Protein functionE3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level. {ECO:0000269|PubMed:11389444, ECO:0000269|PubMed:12717440}.
Subcellular locationNucleus {ECO:0000269|PubMed:12717440}. Cytoplasm {ECO:0000269|PubMed:12717440}. Cell membrane {ECO:0000269|PubMed:12717440}. Membrane raft {ECO:0000269|PubMed:12717440}. Note=Cytoplasmic in the presence of SMAD7. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9HAU4
Gene Ontology
(Biological Process)
Complete annatation
BMP signaling pathway [GO:0030509];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of trophoblast cell migration [GO:1901165];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of transforming growth factor beta receptor signaling pathway [GO:0017015];
ubiquitin-dependent protein catabolic process [GO:0006511];
ubiquitin-dependent SMAD protein catabolic process [GO:0030579];
Wnt signaling pathway, planar cell polarity pathway [GO:0060071]
Gene Ontology
(Molecular Function)
Complete annatation
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
SMAD binding [GO:0046332];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane raft [GO:0045121];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
ubiquitin ligase complex [GO:0000151]
Protein-protein interaction122265
Phylogenetic treeQ9HAU4
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. CD3-1.014015756471240.002278627090329220.00740799557925842
AZA vs. DISU0.1191434640572690.6547396270257750.960165885571217
AZA vs. IL7-0.2113668418409390.4103767174218180.999311006273513
AZA vs. SAHA-0.1514875858062510.5357132082232920.840860067232937
DISU vs. CD31.118986711627960.002717138061089090.00974034224324777
DISU vs. IL7-0.3386230000780040.2299035707240090.613198218093494
DISU vs. SAHA-0.2705652470004420.3544807493507590.731618684842216
DMSO vs. AZA-0.01657944559735710.9391208026801851
DMSO vs. CD30.9811010543598480.00245426477789890.00745734144393846
DMSO vs. DISU-0.1390316869307410.5716769706108560.930565127144697
DMSO vs. IL7-0.1869447114280610.4255024581671120.856015213243108
DMSO vs. SAHA-0.1420700412486870.5480686159756460.837552434736256
HIV vs. Mock in Activation-0.1433741594532810.8180488543001550.999983755607037
HIV vs. Mock in Latency-0.06408463449172070.6994632352051040.999834320637052
IL7 vs. CD30.8126616419795420.01235278097722410.0354047285928312
SAHA vs. CD30.8349485104606340.01995257017005960.0459974349797763
SAHA vs. IL70.05455057123895930.8288467881178670.926073770549515
(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) TRUE
(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 0.200958 0.244614
(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
205596_s_at 1.38 No downregulated in CD8+ cells

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
1ZVD X-ray 2.1Å A=369-748.
2DJY NMR - A=297-333.
2JQZ NMR - A=10-140.
2KXQ NMR - A=250-333.
2LTZ NMR - A=297-333.

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
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04350 TGF-beta signaling pathway - Homo sapiens (human)