Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001940
UniProt IDP19838
Primary gene name(s)NFKB1
Synonym gene name(s)unknown
Protein nameNuclear factor NF-kappa-B p105 subunit
Protein functionNF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor, I-kappa-B family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases, IKKs in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. {ECO:0000269|PubMed:15485931}.
Subcellular locationNucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor, I-kappa-B.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P19838
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cellular response to dsRNA [GO:0071359];
cellular response to interleukin-1 [GO:0071347];
cellular response to interleukin-6 [GO:0071354];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to mechanical stimulus [GO:0071260];
cellular response to nicotine [GO:0071316];
cellular response to peptide hormone stimulus [GO:0071375];
Fc-epsilon receptor signaling pathway [GO:0038095];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
membrane protein intracellular domain proteolysis [GO:0031293];
negative regulation of apoptotic process [GO:0043066];
negative regulation of calcidiol 1-monooxygenase activity [GO:0010956];
negative regulation of cellular protein metabolic process [GO:0032269];
negative regulation of cholesterol transport [GO:0032375];
negative regulation of gene expression [GO:0010629];
negative regulation of inflammatory response [GO:0050728];
negative regulation of interleukin-12 biosynthetic process [GO:0045083];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of vitamin D biosynthetic process [GO:0010957];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of hyaluronan biosynthetic process [GO:1900127];
positive regulation of lipid storage [GO:0010884];
positive regulation of macrophage derived foam cell differentiation [GO:0010744];
positive regulation of miRNA metabolic process [GO:2000630];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of type I interferon production [GO:0032481];
response to muscle stretch [GO:0035994];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
transcription from RNA polymerase II promoter [GO:0006366]
Gene Ontology
(Molecular Function)
Complete annatation
actinin binding [GO:0042805];
chromatin binding [GO:0003682];
identical protein binding [GO:0042802];
protein heterodimerization activity [GO:0046982];
regulatory region DNA binding [GO:0000975];
RNA polymerase II distal enhancer sequence-specific DNA binding [GO:0000980];
RNA polymerase II regulatory region sequence-specific DNA binding [GO:0000977];
transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0001205];
transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding [GO:0001227];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
transcription regulatory region DNA binding [GO:0044212];
transcription regulatory region sequence-specific DNA binding [GO:0000976]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
I-kappaB/NF-kappaB complex [GO:0033256];
mitochondrion [GO:0005739];
neuron projection [GO:0043005];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction110857
Phylogenetic treeP19838
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is also observed
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. CD32.179367631855631.74456782353616e-102.92807641830033e-09
AZA vs. DISU0.0837529934859430.7404102777235110.974754980471983
AZA vs. IL70.2995291991312830.1197487452501050.881838177568205
AZA vs. SAHA-0.01621450384485470.9470112447606240.989286818491585
DISU vs. CD3-2.108433363671892.25291132416316e-083.23124503334306e-07
DISU vs. IL70.2070288553273920.411255225679520.770145655542703
DISU vs. SAHA-0.09869680147572720.7347271584746740.922756083780985
DMSO vs. AZA0.009301634814137410.955747684850321
DMSO vs. CD3-2.18382604565935.94285731736477e-119.76326559281355e-10
DMSO vs. DISU-0.07694074244770850.7523409414594320.969857060964769
DMSO vs. IL70.2977662842593720.0980459393851880.572516350121018
DMSO vs. SAHA-0.0318258436084560.8925857892574860.974245912143042
HIV vs. Mock in Activation0.2122247804882420.7331220816383410.999983755607037
HIV vs. Mock in Latency-0.2568119751397430.1200832563823520.999834320637052
IL7 vs. CD3-1.871703393171311.78436111442082e-082.54452933563529e-07
SAHA vs. CD3-2.220543119899891.85527282425824e-092.92213399709857e-08
SAHA vs. IL7-0.3192105695916840.1900587206592430.420388137229263
(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 -0.043975 0.812093
(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
0.983 1.145 1.202 1.33 1.098
(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
DB01041 Thalidomide approved, investigational, withdrawn yes antagonist
DB01411 Pranlukast approved unknown other/unknown
DB05212 HE3286 investigational unknown unknown
DB05451 P54 investigational unknown unknown
DB05464 NOX-700 investigational unknown unknown
DB05471 SGN-30 investigational unknown unknown
DB05767 HMPL-004 investigational unknown unknown
DB05487 CC-8490 investigational unknown unknown
DB08814 Triflusal approved yes antagonist
DB00945 Acetylsalicylic acid approved, vet_approved unknown antagonist

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1MDI NMR - B=55-67.
1MDJ NMR - B=55-67.
1MDK NMR - B=55-67.
1NFI X-ray 2.7Å B/D=248-354.
1SVC X-ray 2.6Å P=2-365.
2DBF NMR - A=806-893.
2O61 X-ray 2.8Å B=40-352.
3GUT X-ray 3.5Å B/D/F/H=41-352.

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

HIV Partner Interaction Type PubMed
nucleocapsid downregulates 19884766
Envelope surface glycoprotein gp120 interacts with 16001969
21826700
22528837
23251686
8870842
9621091
Vpr regulated by 24225433
Nef inhibits 1527859
1527859
15638726
2038069815827086
16429138
Tat activates 10393859
2207714010400814
2124288810799874
11299302
220771401505523
1583734
7494249
7729429
7800480
8615004
8676466
8709193
9525916
9566873
10384093
10644726
11511100
11704662
17376917
18070983
18216101
18670233
18840709
18971284
18976975
19066594
19132086
19812265
20138641
20139419
20172044
21242888
22077140
22211660
22229121
22435562
22618514
23132857
2488641618070983
18160848
18710415
19287189
2013932219387490
19479051
20631305
22406815
22450687
25164676
25879536
7859743
91101468113688
8207793
8627654
8724035
9278385
9510190
9730685
9792375
10384093
10446807
10480634
10580107
10644332
10671224
11044099
11160671
11241736
11385624
11522182
11579140
11827962
11833470
12167619
12427593
12473373
12482669
12485413
15258149
17334226
18160848
18538010
18692180
21172429
Envelope transmembrane glycoprotein gp41 activates 22341466
2370597222341466
23705972
Tat activated by 18336259
23803414
Envelope surface glycoprotein gp120 inhibits 7957556
Vpr interacts with 9560267
16243842
19275588
Nef modulates 26375588
Vpr involves 26270987
26270987
26270987
26270987
Nef binds 22534017
Envelope surface glycoprotein gp120 relocalizes 21712995
23251686
Vpr inhibits 16429131
2300184923001849
25620704
9334723
15725353
15780175
15817944
19275583
20380700
nucleocapsid enhances 10704334
Tat cooperates with 20336759
Tat induces acetylation of 18329615
Nef downregulates 8151786
8178481
24187576
Tat regulated by 11704662
20139322
Envelope surface glycoprotein gp120 upregulates 15103018
Tat downregulates 19884766
Nef activates 12396456
12419805
12574335
14597672
15258149
16237100
18621011
20380698
23986795
24187576
25525794
25529283
2562070418621011
21845735
21886773
23774506
25620704
Vpr activates 10775602
10775602
12444143
12444143
16305395
16429131
2300184920145198
23547379
24912525
9560267
16305395
Vpu modulates 26375588
Tat enhances 22187158
22187158
22435562
Envelope surface glycoprotein gp120 cooperates with 20051532
Nef interacts with 24658403
Tat recruits 9566873
14657027
16697675
23803414
Asp interacts with 8289399
22569184
Tat acetylates 11739381
18329615
21242888
22077140
22435562
HIV-1 virus replication enhanced by expression of human gene 18976975
19460752
Tat interacts with 17197380
17266559
17312171
22593154
24244375
8834464
10207088
21242888
capsid interacts with 24196705
24196714
Vpu inhibits 11278695
11278695
11696595
12973300
14561767
18672082
20012522
23468625
23831603
2582753123221546
2446521023552418
25620704
retropepsin cleaves 2017258
7742037
8790371
8997639
Vpr downregulates 9334723
15142381
16429131
20380700
Nef enhances 25620704
Tat binds 7690421
7838536
10225209
Vpr regulates 9334723
9560267
10775602
12444143
15142381
15725353
15780175
15817944
16305395
19275583
19275588
23001849
25620704
Envelope surface glycoprotein gp120 activates 11959143
1510301816554660
18203956
19319745
19736361
21190575
2325168621712995
24043886
8621941
8814265
9235945
102355098870842
Vpr enhances 26401039
Envelope surface glycoprotein gp120 requires 21945445

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01523 Antifolate resistance - Homo sapiens (human)
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05146 Amoebiasis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)
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