Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001989
UniProt IDP46531
Primary gene name(s)NOTCH1
Synonym gene name(s)TAN1
Protein nameNeurogenic locus notch homolog protein 1
Protein functionFunctions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain, NICD it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4+ and CD8+ cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone, SVZ niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile, sensory cilia at the left-right organiser, LRO. {ECO:0000269|PubMed:20616313}.
Subcellular locationCell membrane {ECO:0000250};
Single-pass type I membrane protein {ECO:0000250}.;
SUBCELLULAR LOCATION: Notch 1 intracellular domain: Nucleus {ECO:0000250}. Note=Following proteolytical processing NICD is translocated to the nucleus. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P46531
Gene Ontology
(Biological Process)
Complete annatation
animal organ regeneration [GO:0031100];
aortic valve morphogenesis [GO:0003180];
apoptotic process involved in embryonic digit morphogenesis [GO:1902263];
arterial endothelial cell differentiation [GO:0060842];
astrocyte differentiation [GO:0048708];
atrioventricular node development [GO:0003162];
atrioventricular valve morphogenesis [GO:0003181];
auditory receptor cell fate commitment [GO:0009912];
axonogenesis [GO:0007409];
branching morphogenesis of an epithelial tube [GO:0048754];
cardiac atrium morphogenesis [GO:0003209];
cardiac chamber formation [GO:0003207];
cardiac epithelial to mesenchymal transition [GO:0060317];
cardiac left ventricle morphogenesis [GO:0003214];
cardiac muscle cell proliferation [GO:0060038];
cardiac muscle tissue morphogenesis [GO:0055008];
cardiac right atrium morphogenesis [GO:0003213];
cardiac right ventricle formation [GO:0003219];
cardiac septum morphogenesis [GO:0060411];
cardiac vascular smooth muscle cell development [GO:0060948];
cardiac ventricle morphogenesis [GO:0003208];
cell differentiation in spinal cord [GO:0021515];
cell fate specification [GO:0001708];
cell migration involved in endocardial cushion formation [GO:0003273];
cellular response to follicle-stimulating hormone stimulus [GO:0071372];
cellular response to vascular endothelial growth factor stimulus [GO:0035924];
cilium assembly [GO:0060271];
collecting duct development [GO:0072044];
compartment pattern specification [GO:0007386];
coronary artery morphogenesis [GO:0060982];
coronary vein morphogenesis [GO:0003169];
determination of left/right symmetry [GO:0007368];
distal tubule development [GO:0072017];
embryonic hindlimb morphogenesis [GO:0035116];
endocardial cell differentiation [GO:0060956];
endocardial cushion morphogenesis [GO:0003203];
endocardium development [GO:0003157];
endocardium morphogenesis [GO:0003160];
endoderm development [GO:0007492];
epithelial to mesenchymal transition [GO:0001837];
epithelial to mesenchymal transition involved in endocardial cushion formation [GO:0003198];
forebrain development [GO:0030900];
foregut morphogenesis [GO:0007440];
glomerular mesangial cell development [GO:0072144];
growth involved in heart morphogenesis [GO:0003241];
hair follicle morphogenesis [GO:0031069];
heart development [GO:0007507];
heart looping [GO:0001947];
heart trabecula morphogenesis [GO:0061384];
humoral immune response [GO:0006959];
immune response [GO:0006955];
inflammatory response to antigenic stimulus [GO:0002437];
interleukin-4 secretion [GO:0072602];
in utero embryonic development [GO:0001701];
keratinocyte differentiation [GO:0030216];
left/right axis specification [GO:0070986];
liver development [GO:0001889];
lung development [GO:0030324];
mesenchymal cell development [GO:0014031];
mitral valve formation [GO:0003192];
negative regulation of anoikis [GO:2000811];
negative regulation of auditory receptor cell differentiation [GO:0045608];
negative regulation of BMP signaling pathway [GO:0030514];
negative regulation of calcium ion-dependent exocytosis [GO:0045955];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of catalytic activity [GO:0043086];
negative regulation of cell migration involved in sprouting angiogenesis [GO:0090051];
negative regulation of cell proliferation [GO:0008285];
negative regulation of cell-substrate adhesion [GO:0010812];
negative regulation of endothelial cell chemotaxis [GO:2001027];
negative regulation of glial cell proliferation [GO:0060253];
negative regulation of myoblast differentiation [GO:0045662];
negative regulation of myotube differentiation [GO:0010832];
negative regulation of neurogenesis [GO:0050768];
negative regulation of oligodendrocyte differentiation [GO:0048715];
negative regulation of ossification [GO:0030279];
negative regulation of osteoblast differentiation [GO:0045668];
negative regulation of photoreceptor cell differentiation [GO:0046533];
negative regulation of pro-B cell differentiation [GO:2000974];
negative regulation of stem cell differentiation [GO:2000737];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
neural tube development [GO:0021915];
neuronal stem cell population maintenance [GO:0097150];
Notch signaling involved in heart development [GO:0061314];
Notch signaling pathway [GO:0007219];
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation [GO:0003270];
oligodendrocyte differentiation [GO:0048709];
pericardium morphogenesis [GO:0003344];
positive regulation of aorta morphogenesis [GO:1903849];
positive regulation of apoptotic process [GO:0043065];
positive regulation of astrocyte differentiation [GO:0048711];
positive regulation of BMP signaling pathway [GO:0030513];
positive regulation of cardiac muscle cell proliferation [GO:0060045];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of endothelial cell differentiation [GO:0045603];
positive regulation of epithelial cell proliferation [GO:0050679];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of JAK-STAT cascade [GO:0046427];
positive regulation of keratinocyte differentiation [GO:0045618];
positive regulation of neuroblast proliferation [GO:0002052];
positive regulation of Notch signaling pathway [GO:0045747];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061419];
positive regulation of transcription of Notch receptor target [GO:0007221];
positive regulation of viral genome replication [GO:0045070];
prostate gland epithelium morphogenesis [GO:0060740];
pulmonary valve morphogenesis [GO:0003184];
regulation of epithelial cell proliferation involved in prostate gland development [GO:0060768];
regulation of extracellular matrix assembly [GO:1901201];
regulation of somitogenesis [GO:0014807];
regulation of transcription, DNA-templated [GO:0006355];
regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation [GO:0003256];
response to corticosteroid [GO:0031960];
response to lipopolysaccharide [GO:0032496];
response to muramyl dipeptide [GO:0032495];
secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development [GO:0060528];
skeletal muscle cell differentiation [GO:0035914];
somatic stem cell division [GO:0048103];
spermatogenesis [GO:0007283];
sprouting angiogenesis [GO:0002040];
tissue regeneration [GO:0042246];
transcription initiation from RNA polymerase II promoter [GO:0006367];
tube formation [GO:0035148];
vasculogenesis involved in coronary vascular morphogenesis [GO:0060979];
venous endothelial cell differentiation [GO:0060843];
ventricular septum morphogenesis [GO:0060412];
ventricular trabecula myocardium morphogenesis [GO:0003222]
Gene Ontology
(Molecular Function)
Complete annatation
calcium ion binding [GO:0005509];
chromatin DNA binding [GO:0031490];
core promoter binding [GO:0001047];
enzyme binding [GO:0019899];
enzyme inhibitor activity [GO:0004857];
receptor activity [GO:0004872];
sequence-specific DNA binding [GO:0043565];
transcriptional activator activity, RNA polymerase II transcription factor binding [GO:0001190];
transcription factor activity, sequence-specific DNA binding [GO:0003700]
Gene Ontology
(Cellular Component)
Complete annatation
acrosomal vesicle [GO:0001669];
adherens junction [GO:0005912];
apical plasma membrane [GO:0016324];
cell surface [GO:0009986];
cytosol [GO:0005829];
endoplasmic reticulum membrane [GO:0005789];
extracellular region [GO:0005576];
Golgi membrane [GO:0000139];
integral component of membrane [GO:0016021];
MAML1-RBP-Jkappa- ICN1 complex [GO:0002193];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
receptor complex [GO:0043235]
Protein-protein interaction110913
Phylogenetic treeP46531
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. CD30.7781255638798720.0321298185647290.0689633473949865
AZA vs. DISU0.02492521383440640.9216260891970510.994889252656529
AZA vs. IL70.06007121770535120.7547544427972310.999311006273513
AZA vs. SAHA-0.3939910871169770.1068443122079220.415953296028466
DISU vs. CD3-0.7657459614783810.04711917327793180.10299803045121
DISU vs. IL70.02593533074695690.9180164244971080.984743323281206
DISU vs. SAHA-0.4159866028171610.1547590275423270.506267268089952
DMSO vs. AZA0.05278803979833720.7528694369363291
DMSO vs. CD3-0.7377710986785670.03393314764654110.069466349951779
DMSO vs. DISU0.02576104294649990.9159301155933250.988576460318632
DMSO vs. IL70.01502948626895870.9333782770913930.98672467966686
DMSO vs. SAHA-0.4515106658798970.0560089597065220.269809054938304
HIV vs. Mock in Activation0.4849889238759860.503065647090940.999983755607037
HIV vs. Mock in Latency-0.08068568383948410.6255427135832440.999834320637052
IL7 vs. CD3-0.7127064359394070.05345893739396360.116107573968186
SAHA vs. CD3-1.194851986725090.001219226821784440.00423651099937548
SAHA vs. IL7-0.4567933808123290.06126013112542230.209907659702037
(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) FALSE
(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 0.354288 0.00728417
(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
0.88 0.756 0.658 0.649 0.85
(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
1PB5 NMR - A=1446-1480.
1TOZ NMR - A=411-526.
1YYH X-ray 1.9Å A/B=1872-2114.
2F8X X-ray 3.2Å K=1872-2126.
2F8Y X-ray 1.5Å A/B=1905-2126.
2HE0 X-ray 1.9Å A/B=1872-2114.
2VJ3 X-ray 2.6Å A=411-526.
3ETO X-ray 2.0Å A/B=1446-1733.
3I08 X-ray 3.2Å A/C=1446-1664# B/D=1665-1733.
3L95 X-ray 2.1Å X/Y=1448-1728.
3NBN X-ray 3.4Å B/E=1872-2126.
3V79 X-ray 3.8Å K=1872-2126# R=1759-1777.
4CUD X-ray 1.8Å A=411-526.
4CUE X-ray 3.0Å A=411-526.
4CUF X-ray 2.2Å A=411-526.
4D0E X-ray 1.6Å A=411-526.
4D0F X-ray 2.8Å A=411-526.
5FM9 X-ray 2.9Å A=140-294.
5FMA X-ray 2.4Å A/B=142-294.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 upregulates 24162774

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa04320 Dorso-ventral axis formation - Homo sapiens (human)
hsa04330 Notch signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa05020 Prion diseases - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)