KEGG   PATHWAY: hsa04064Help
Entry
hsa04064                    Pathway                                

Name
NF-kappa B signaling pathway - Homo sapiens (human)
Description
Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or byproducts of bacterial and viral infections. This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its  degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK-independent and rely on phosphorylation of IkappaB-alpha on Tyr42 or on Ser residues in IkappaB-alpha PEST domain. The non-canonical pathway is triggered by particular members of the TNFR superfamily, such as lymphotoxin-beta (LT-beta) or BAFF. It involves NIK and IKK-alpha-mediated p100 phosphorylation and processing to p52, resulting in nuclear translocation of p52/RelB heterodimers.
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
NF-kappa B signaling pathway
hsa04064

All organismsOrtholog table
Drug
D04690  
Lenercept (USAN/INN)
D05263  
Onercept (USAN/INN)
D05393  
Pegsunercept (USAN)
D08866  
Baminercept (USAN/INN)
D08877  
Briobacept (USAN)
D09347  
Fostamatinib (USAN)
D09348  
Fostamatinib disodium (USAN)
D09692  
Veliparib (USAN/INN)
D09730  
Olaparib (JAN/INN)
D09913  
Iniparib (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
3932  
LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
7535  
ZAP70; zeta-chain (TCR) associated protein kinase 70kDa [KO:K07360] [EC:2.7.10.2]
27040  
LAT; linker for activation of T cells [KO:K07362]
5335  
PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
5588  
PRKCQ; protein kinase C, theta [KO:K18052] [EC:2.7.11.13]
6850  
SYK; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
4067  
LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
29760  
BLNK; B-cell linker [KO:K07371]
695  
BTK; Bruton agammaglobulinemia tyrosine kinase [KO:K07370] [EC:2.7.10.2]
5336  
PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
84433  
CARD11; caspase recruitment domain family, member 11 [KO:K07367]
8915  
BCL10; B-cell CLL/lymphoma 10 [KO:K07368]
10892  
MALT1; mucosa associated lymphoid tissue lymphoma translocation gene 1 [KO:K07369] [EC:3.4.22.-]
3553  
IL1B; interleukin 1, beta [KO:K04519]
3554  
IL1R1; interleukin 1 receptor, type I [KO:K04386]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
3654  
IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
51135  
IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
7189  
TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
7124  
TNF; tumor necrosis factor [KO:K03156]
7132  
TNFRSF1A; tumor necrosis factor receptor superfamily, member 1A [KO:K03158]
8737  
RIPK1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
8717  
TRADD; TNFRSF1A-associated via death domain [KO:K03171]
7186  
TRAF2; TNF receptor-associated factor 2 [KO:K03173]
7188  
TRAF5; TNF receptor-associated factor 5 [KO:K09849]
329  
BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
330  
BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
23586  
DDX58; DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 [KO:K12646] [EC:3.6.3.14]
7706  
TRIM25; tripartite motif containing 25 [KO:K10652] [EC:6.3.2.19]
3929  
LBP; lipopolysaccharide binding protein [KO:K05399]
929  
CD14; CD14 molecule [KO:K04391]
7099  
TLR4; toll-like receptor 4 [KO:K10160]
23643  
LY96; lymphocyte antigen 96 [KO:K05400]
114609  
TIRAP; toll-interleukin 1 receptor (TIR) domain containing adaptor protein [KO:K05403]
353376  
TICAM2; toll-like receptor adaptor molecule 2 [KO:K05409]
148022  
TICAM1; toll-like receptor adaptor molecule 1 [KO:K05842]
959  
CD40LG; CD40 ligand [KO:K03161]
958  
CD40; CD40 molecule, TNF receptor superfamily member 5 [KO:K03160]
7187  
TRAF3; TNF receptor-associated factor 3 [KO:K03174]
8600  
TNFSF11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
8792  
TNFRSF11A; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
4049  
LTA; lymphotoxin alpha [KO:K05468]
4050  
LTB; lymphotoxin beta (TNF superfamily, member 3) [KO:K03157]
8740  
TNFSF14; tumor necrosis factor (ligand) superfamily, member 14 [KO:K05477]
4055  
LTBR; lymphotoxin beta receptor (TNFR superfamily, member 3) [KO:K03159]
9020  
MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
6885  
MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
10454  
TAB1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
23118  
TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
257397  
TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
10673  
TNFSF13B; tumor necrosis factor (ligand) superfamily, member 13b [KO:K05476]
115650  
TNFRSF13C; tumor necrosis factor receptor superfamily, member 13C [KO:K05151]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
51588  
PIAS4; protein inhibitor of activated STAT, 4 [KO:K16065] [EC:6.3.2.-]
7329  
UBE2I; ubiquitin-conjugating enzyme E2I [KO:K10577] [EC:6.3.2.19]
472  
ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
55367  
PIDD1; p53-induced death domain protein 1 [KO:K10130]
23085  
ERC1; ELKS/RAB6-interacting/CAST family member 1 [KO:K16072]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
8837  
CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
331  
XIAP; X-linked inhibitor of apoptosis [KO:K04725]
598  
BCL2L1; BCL2-like 1 [KO:K04570]
596  
BCL2; B-cell CLL/lymphoma 2 [KO:K02161]
7185  
TRAF1; TNF receptor-associated factor 1 [KO:K03172]
597  
BCL2A1; BCL2-related protein A1 [KO:K02162]
4791  
NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100) [KO:K04469]
3576  
CXCL8; chemokine (C-X-C motif) ligand 8 [KO:K10030]
7128  
TNFAIP3; tumor necrosis factor, alpha-induced protein 3 [KO:K11859] [EC:6.3.2.19 3.4.19.12]
5743  
PTGS2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) [KO:K11987] [EC:1.14.99.1]
6351  
CCL4; chemokine (C-C motif) ligand 4 [KO:K12964]
9560  
CCL4L2; chemokine (C-C motif) ligand 4-like 2 [KO:K12964]
388372  
CCL4L1; chemokine (C-C motif) ligand 4-like 1 [KO:K12964]
7412  
VCAM1; vascular cell adhesion molecule 1 [KO:K06527]
5328  
PLAU; plasminogen activator, urokinase [KO:K01348] [EC:3.4.21.73]
1457  
CSNK2A1; casein kinase 2, alpha 1 polypeptide [KO:K03097] [EC:2.7.11.1]
1459  
CSNK2A2; casein kinase 2, alpha prime polypeptide [KO:K03097] [EC:2.7.11.1]
1460  
CSNK2B; casein kinase 2, beta polypeptide [KO:K03115]
5971  
RELB; v-rel avian reticuloendotheliosis viral oncogene homolog B [KO:K09253]
6357  
CCL13; chemokine (C-C motif) ligand 13 [KO:K16595]
6363  
CCL19; chemokine (C-C motif) ligand 19 [KO:K05512]
6366  
CCL21; chemokine (C-C motif) ligand 21 [KO:K16062]
6387  
CXCL12; chemokine (C-X-C motif) ligand 12 [KO:K10031]
3383  
ICAM1; intercellular adhesion molecule 1 [KO:K06490]
142  
PARP1; poly (ADP-ribose) polymerase 1 [KO:K10798] [EC:2.4.2.30]
2920  
CXCL2; chemokine (C-X-C motif) ligand 2 [KO:K05505]
4616  
GADD45B; growth arrest and DNA-damage-inducible, beta [KO:K04402]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
C01245  
D-myo-Inositol 1,4,5-trisphosphate
Reference
  Authors
Oeckinghaus A, Hayden MS, Ghosh S
  Title
Crosstalk in NF-kappaB signaling pathways.
  Journal
Nat Immunol 12:695-708 (2011)
Reference
  Authors
Gloire G, Piette J
  Title
Redox regulation of nuclear post-translational modifications during NF-kappaB activation.
  Journal
Antioxid Redox Signal 11:2209-22 (2009)
Reference
  Authors
Perkins ND
  Title
Integrating cell-signalling pathways with NF-kappaB and IKK function.
  Journal
Nat Rev Mol Cell Biol 8:49-62 (2007)
Reference
  Authors
Lindstrom TM, Bennett PR
  Title
The role of nuclear factor kappa B in human labour.
  Journal
Reproduction 130:569-81 (2005)
Reference
  Authors
Razani B, Reichardt AD, Cheng G
  Title
Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives.
  Journal
Immunol Rev 244:44-54 (2011)
Reference
  Authors
Sun SC
  Title
Non-canonical NF-kappaB signaling pathway.
  Journal
Cell Res 21:71-85 (2011)
Reference
  Authors
Neumann M, Naumann M
  Title
Beyond IkappaBs: alternative regulation of NF-kappaB activity.
  Journal
FASEB J 21:2642-54 (2007)
Reference
  Authors
Verhelst K, Carpentier I, Beyaert R
  Title
Regulation of TNF-induced NF-kappaB activation by different cytoplasmic ubiquitination events.
  Journal
Cytokine Growth Factor Rev 22:277-86 (2011)
Reference
  Authors
Rickert RC, Jellusova J, Miletic AV
  Title
Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
  Journal
Immunol Rev 244:115-33 (2011)
Reference
  Authors
Naude PJ, den Boer JA, Luiten PG, Eisel UL
  Title
Tumor necrosis factor receptor cross-talk.
  Journal
FEBS J 278:888-98 (2011)
Reference
  Authors
Grivennikov SI, Kuprash DV, Liu ZG, Nedospasov SA
  Title
Intracellular signals and events activated by cytokines of the tumor necrosis factor superfamily: From simple paradigms to complex mechanisms.
  Journal
Int Rev Cytol 252:129-61 (2006)
Reference
  Authors
Wada T, Nakashima T, Hiroshi N, Penninger JM
  Title
RANKL-RANK signaling in osteoclastogenesis and bone disease.
  Journal
Trends Mol Med 12:17-25 (2006)
Reference
  Authors
Schulze-Luehrmann J, Ghosh S
  Title
Antigen-receptor signaling to nuclear factor kappa B.
  Journal
Immunity 25:701-15 (2006)
Reference
  Authors
Weil R, Israel A
  Title
T-cell-receptor- and B-cell-receptor-mediated activation of NF-kappaB in lymphocytes.
  Journal
Curr Opin Immunol 16:374-81 (2004)
Reference
  Authors
Siebenlist U, Brown K, Claudio E
  Title
Control of lymphocyte development by nuclear factor-kappaB.
  Journal
Nat Rev Immunol 5:435-45 (2005)
Reference
  Authors
Lucas PC, McAllister-Lucas LM, Nunez G
  Title
NF-kappaB signaling in lymphocytes: a new cast of characters.
  Journal
J Cell Sci 117:31-9 (2004)
Reference
  Authors
Khan WN
  Title
B cell receptor and BAFF receptor signaling regulation of B cell homeostasis.
  Journal
J Immunol 183:3561-7 (2009)
Reference
  Authors
Vallabhapurapu S, Karin M
  Title
Regulation and function of NF-kappaB transcription factors in the immune system.
  Journal
Annu Rev Immunol 27:693-733 (2009)
Reference
  Authors
Hacker H, Karin M
  Title
Regulation and function of IKK and IKK-related kinases.
  Journal
Sci STKE 2006:re13 (2006)
Reference
  Authors
Sabatel H, Pirlot C, Piette J, Habraken Y
  Title
Importance of PIKKs in NF-kappaB activation by genotoxic stress.
  Journal
Biochem Pharmacol 82:1371-83 (2011)
Reference
  Authors
Miyamoto S
  Title
Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
  Journal
Cell Res 21:116-30 (2011)
Reference
  Authors
Brzoska K, Szumiel I
  Title
Signalling loops and linear pathways: NF-kappaB activation in response to genotoxic stress.
  Journal
Mutagenesis 24:1-8 (2009)
Reference
  Authors
Wu ZH, Miyamoto S
  Title
Many faces of NF-kappaB signaling induced by genotoxic stress.
  Journal
J Mol Med (Berl) 85:1187-202 (2007)
Reference
  Authors
Maelfait J, Beyaert R
  Title
Emerging role of ubiquitination in antiviral RIG-I signaling.
  Journal
Microbiol Mol Biol Rev 76:33-45 (2012)
Reference
  Authors
Ware CF
  Title
Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways.
  Journal
Immunol Rev 223:186-201 (2008)
Reference
  Authors
Schneider K, Potter KG, Ware CF
  Title
Lymphotoxin and LIGHT signaling pathways and target genes.
  Journal
Immunol Rev 202:49-66 (2004)
Reference
  Authors
Remouchamps C, Boutaffala L, Ganeff C, Dejardin E
  Title
Biology and signal transduction pathways of the Lymphotoxin-alphabeta/LTbetaR system.
  Journal
Cytokine Growth Factor Rev 22:301-10 (2011)
Reference
  Authors
Liu S, Chen ZJ
  Title
Expanding role of ubiquitination in NF-kappaB signaling.
  Journal
Cell Res 21:6-21 (2011)
Reference
  Authors
Skaug B, Jiang X, Chen ZJ
  Title
The role of ubiquitin in NF-kappaB regulatory pathways.
  Journal
Annu Rev Biochem 78:769-96 (2009)
Reference
  Authors
Wertz IE, Dixit VM
  Title
Signaling to NF-kappaB: regulation by ubiquitination.
  Journal
Cold Spring Harb Perspect Biol 2:a003350 (2010)
Reference
  Authors
Karin M, Lin A
  Title
NF-kappaB at the crossroads of life and death.
  Journal
Nat Immunol 3:221-7 (2002)
Reference
  Authors
Lin A, Karin M
  Title
NF-kappaB in cancer: a marked target.
  Journal
Semin Cancer Biol 13:107-14 (2003)
KO pathway
 

DBGET integrated database retrieval system