Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000971
UniProt IDP04626
Primary gene name(s)ERBB2
Synonym gene name(s)HER2, MLN19, NEU, NGL
Protein nameReceptor tyrosine-protein kinase erbB-2
Protein functionProtein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules, MTs. Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}.
Subcellular locationIsoform 1: Cell membrane;
Single-pass type I membrane protein. Cytoplasm, perinuclear region. Nucleus. Note=Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1.;
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. Nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P04626
Gene Ontology
(Biological Process)
Complete annatation
cell proliferation [GO:0008283];
cell surface receptor signaling pathway [GO:0007166];
cellular response to epidermal growth factor stimulus [GO:0071364];
cellular response to growth factor stimulus [GO:0071363];
enzyme linked receptor protein signaling pathway [GO:0007167];
ERBB2 signaling pathway [GO:0038128];
heart development [GO:0007507];
MAPK cascade [GO:0000165];
motor neuron axon guidance [GO:0008045];
myelination [GO:0042552];
negative regulation of immature T cell proliferation in thymus [GO:0033088];
neuromuscular junction development [GO:0007528];
oligodendrocyte differentiation [GO:0048709];
peripheral nervous system development [GO:0007422];
phosphatidylinositol 3-kinase signaling [GO:0014065];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of cell adhesion [GO:0045785];
positive regulation of cell growth [GO:0030307];
positive regulation of epithelial cell proliferation [GO:0050679];
positive regulation of GTPase activity [GO:0043547];
positive regulation of MAP kinase activity [GO:0043406];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of protein targeting to membrane [GO:0090314];
positive regulation of transcription from RNA polymerase III promoter [GO:0045945];
positive regulation of transcription from RNA polymerase I promoter [GO:0045943];
positive regulation of translation [GO:0045727];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
regulation of angiogenesis [GO:0045765];
regulation of cell motility [GO:2000145];
regulation of ERK1 and ERK2 cascade [GO:0070372];
regulation of microtubule-based process [GO:0032886];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066];
signal transduction [GO:0007165];
transcription, DNA-templated [GO:0006351];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169];
wound healing [GO:0042060]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
ErbB-3 class receptor binding [GO:0043125];
identical protein binding [GO:0042802];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
protein C-terminus binding [GO:0008022];
protein dimerization activity [GO:0046983];
protein heterodimerization activity [GO:0046982];
protein phosphatase binding [GO:0019903];
protein tyrosine kinase activity [GO:0004713];
Ras guanyl-nucleotide exchange factor activity [GO:0005088];
receptor signaling protein tyrosine kinase activity [GO:0004716];
RNA polymerase I core binding [GO:0001042];
transmembrane receptor protein tyrosine kinase activity [GO:0004714];
transmembrane signaling receptor activity [GO:0004888]
Gene Ontology
(Cellular Component)
Complete annatation
apical plasma membrane [GO:0016324];
basolateral plasma membrane [GO:0016323];
cytoplasm [GO:0005737];
cytoplasmic vesicle [GO:0031410];
endosome membrane [GO:0010008];
integral component of membrane [GO:0016021];
myelin sheath [GO:0043209];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
receptor complex [GO:0043235]
Protein-protein interaction108376
Phylogenetic treeP04626
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. CD3-0.3971883424424830.2400230546865960.351191592958134
AZA vs. DISU-0.2610207113437890.3749362424050610.89822839898246
AZA vs. IL7-0.2250742416213770.2796004231333970.999311006273513
AZA vs. SAHA0.1129798229433330.7427207771302780.928724429237811
DISU vs. CD30.1231530891363430.7480330113910850.824805573832237
DISU vs. IL70.02397359106809550.9377594037774430.988606234491045
DISU vs. SAHA0.3747332059224360.4202345091456850.773964840197313
DMSO vs. AZA-0.02440372815696940.8950289496946671
DMSO vs. CD30.3581066274854390.2778246153002620.386466096906597
DMSO vs. DISU0.2332437969648890.4192746430339510.876834425551157
DMSO vs. IL7-0.1923029013541920.3248197127863330.801285742145962
DMSO vs. SAHA0.1320657646222940.6986180312672790.908668271137394
HIV vs. Mock in Activation0.1202774227309670.8501136119241030.999983755607037
HIV vs. Mock in Latency-0.06028354606079710.7305026970649590.999834320637052
IL7 vs. CD30.1778248445903950.592674669974640.710112032174309
SAHA vs. CD30.4856656790089160.1987566821813090.300578344252115
SAHA vs. IL70.3344302489319230.3461798527250120.595630076472644
(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 -0.326205 0.0108507
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01259 Lapatinib approved, investigational yes antagonist
DB00072 Trastuzumab approved, investigational yes antibody
DB04988 IGN311 investigational unknown unknown
DB05007 XL647 investigational unknown unknown
DB05773 Trastuzumab emtansine approved yes antibody
DB06366 Pertuzumab approved yes antibody
DB08916 Afatinib approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1MFG X-ray 1.2Å B=1247-1255.
1MFL X-ray 1.8Å B=1247-1255.
1MW4 NMR - B=1135-1144.
1N8Z X-ray 2.5Å C=23-629.
1OVC Model - A=737-1031.
1QR1 X-ray 2.4Å C/F=654-662.
1S78 X-ray 3.2Å A/B=23-646.
2A91 X-ray 2.5Å A=22-530.
2JWA NMR - A/B=641-684.
2KS1 NMR - A=641-684.
2L4K NMR - B=1135-1144.
2N2A NMR - A/B=644-700.
3BE1 X-ray 2.9Å A=23-646.
3H3B X-ray 2.4Å A/B=23-214.
3MZW X-ray 2.9Å A=23-646.
3N85 X-ray 3.2Å A=23-646.
3PP0 X-ray 2.2Å A/B=703-1009.
3RCD X-ray 3.2Å A/B/C/D=713-1028.
3WLW X-ray 3.0Å A/B=23-586.
3WSQ X-ray 3.5Å A=23-586.
4GFU X-ray 2.0Å F=1246-1252.
4HRL X-ray 2.5Å C=24-219.
4HRM X-ray 3.2Å A/C=24-219.
4HRN X-ray 2.6Å C/D=529-625.

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
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04020 Calcium signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05230 Central carbon metabolism in cancer - Homo sapiens (human)