Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003667
UniProt IDQ9UKV5
Primary gene name(s)AMFR
Synonym gene name(s)RNF45
Protein nameE3 ubiquitin-protein ligase AMFR
Protein functionE3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation, ERAD. The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. {ECO:0000269|PubMed:10456327, ECO:0000269|PubMed:11724934, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:19103148}.
Subcellular locationEndoplasmic reticulum membrane {ECO:0000269|PubMed:11724934};
Multi-pass membrane protein {ECO:0000269|PubMed:11724934}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UKV5
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
endoplasmic reticulum unfolded protein response [GO:0030968];
ERAD pathway [GO:0036503];
ER-associated ubiquitin-dependent protein catabolic process [GO:0030433];
learning or memory [GO:0007611];
movement of cell or subcellular component [GO:0006928];
positive regulation of protein binding [GO:0032092];
protein autoubiquitination [GO:0051865];
protein K48-linked ubiquitination [GO:0070936];
protein oligomerization [GO:0051259];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
signal transduction [GO:0007165];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
BAT3 complex binding [GO:1904288];
chaperone binding [GO:0051087];
ligase activity [GO:0016874];
protein binding, bridging [GO:0030674];
receptor activity [GO:0004872];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase activity involved in ERAD pathway [GO:1904264];
ubiquitin-protein transferase activity [GO:0004842];
ubiquitin-specific protease binding [GO:1990381];
ubiquitin-ubiquitin ligase activity [GO:0034450];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
dendrite [GO:0030425];
Derlin-1 retrotranslocation complex [GO:0036513];
endoplasmic reticulum membrane [GO:0005789];
growth cone [GO:0030426];
Hrd1p ubiquitin ligase ERAD-M complex [GO:0000838];
integral component of endoplasmic reticulum membrane [GO:0030176];
integral component of membrane [GO:0016021];
membrane [GO:0016020];
neuronal cell body [GO:0043025];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
protein complex [GO:0043234]
Protein-protein interaction106764
Phylogenetic treeQ9UKV5
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. CD30.09877616203964410.7629174073495130.83584221388803
AZA vs. DISU0.01972055710604910.9381977707071610.995660176982638
AZA vs. IL7-0.1702768915131960.3778818955339310.999311006273513
AZA vs. SAHA0.3838996899805890.1175551578194310.436555443918997
DISU vs. CD3-0.09064493299720050.8034999293630270.865139852515591
DISU vs. IL7-0.1991880780977170.4311969422326590.784778413123502
DISU vs. SAHA0.3653154622825050.2170815654368130.591724290076658
DMSO vs. AZA-0.06281924142757430.7091812090897471
DMSO vs. CD3-0.174840292417340.5846547024144140.682988763327633
DMSO vs. DISU-0.08485701375924490.7292933131757350.965871143368065
DMSO vs. IL7-0.09998511364784990.5798694125668290.906883522682505
DMSO vs. SAHA0.4406287340423770.0633264108312990.290000710312521
HIV vs. Mock in Activation0.01112522121714460.9857360356215680.999983755607037
HIV vs. Mock in Latency-0.04611854871955910.7807416141626360.999834320637052
IL7 vs. CD3-0.2616125063228190.4159777032766450.552921676085794
SAHA vs. CD30.2600287043997490.462746522557770.574620790699009
SAHA vs. IL70.5504890644949680.02504625147731140.116204122735916
(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 -0.194124 0.170463
(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
0.984 1.408 1.122 1.044 1.194
(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
2EJS NMR - A=452-502.
2LVN NMR - C=453-504.
2LVO NMR - C=453-504.
2LVP NMR - C=453-504.
2LVQ NMR - D=453-504.
2LXH NMR - C=313-393.
2LXP NMR - B=574-600# C=327-384.
3FSH X-ray 2.7Å C=574-601.
3H8K X-ray 1.8Å B=573-600.
3TIW X-ray 1.8Å C/D=622-640.
4G3O X-ray 1.6Å A=456-498.
4LAD X-ray 2.3Å B=313-393# B=574-600.

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
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)