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interleukin-12; cytotoxic lymphocyte maturation factor; NK cell stimulatory factor (IL12, IL-12)

Function: 1) synergy with IL-2 for NK cell activation 2) promotes differentiation of T-helper-1 cells. 3) induces production of IFN-gamma from T-helper-1 & NK cells 4) growth factor for activated T-cells & NK cells 5) enhances lytic activity of NK/lymphokine-activated NK cells Structure: - disulfide-bonded heterodimer (IL12A & IL12B) - NKSF is essentially a complex of cytokine & soluble receptor Compartment: secreted Pathology: - higher plasma levels of IL-12 p70 in cognitively intact older adults associated with a) less cognitive decline in persons with significant burden of beta-amyloid b) fewer neurofibrillary tangles [4]

Related

interleukin 12 (IL-12) in serum/plasma interleukin-12 receptor

General

interleukin multisubunit protein

Properties

COMPARTMENT: extracellular compartment SECRETED-BY: macrophage monocyte B lymphocyte SUBUNITS: interleukin-12 subunit alpha MOTIF: signal sequence {1-22} cysteine residue {C64} MODIFICATION: cysteine residue {C196} cysteine residue {C85} MODIFICATION: cysteine residue {C123} N-glycosylation site {N93} cysteine residue {C96} MODIFICATION: cysteine residue {C199 IN IL12B} N-glycosylation site {N107} cysteine residue {C123} MODIFICATION: cysteine residue {C85} cysteine residue {C196} MODIFICATION: cysteine residue {C64} interleukin-12 subunit beta MOTIF: signal sequence {1-22} immunoglobulin superfamily domain {23-106} MOTIF: cysteine residue {C50} MODIFICATION: cysteine residue {C90} cysteine residue {C90} MODIFICATION: cysteine residue {C50} cysteine residue {C131} MODIFICATION: cysteine residue {C142} N-glycosylation site {N135} cysteine residue {C142} MODIFICATION: cysteine residue {C131} cysteine residue {C170} MODIFICATION: cysteine residue {C193} cysteine residue {C193} MODIFICATION: cysteine residue {C170} cysteine residue {C199} MODIFICATION: cysteine residue {C96 IN IL12A} N-glycosylation site {N222} fibronectin type III domain or F3 module {235-327} MOTIF: cysteine residue {C300} MODIFICATION: cysteine residue {C327} cysteine residue {C327} MODIFICATION: cysteine residue {C300}

References

  1. Stern AS et al Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. PMID: 2204066 PNAS 87:6808 1990
  2. Gubler U et al Coexpression of two distinct genes is required to generate bioactive cytotoxic lymphocyte maturation factor. PNAS 88:4143 1991 PMID: 1674604
  3. Scott P IL-12: initiation cytokine for cell-mediated immunity Science 260:496 1993 PMID: 8097337
  4. George J Two Inflammatory Proteins Linked With Slower Cognitive Decline. Surprise finding ties plasma cytokine levels with Alzheimer's biomarkers and cognition. MedPage Today June 23, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/93257 - Yang HS, Zhang C, Carlyle BC et al Plasma IL-12/IFN-gamma axis predicts cognitive trajectories in cognitively unimpaired older adults. Alzheimer's & Dementia. 2021. June 23 PMID: 34160128 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12399

Components

interleukin-12 subunit alpha; IL-12A; cytotoxic lymphocyte maturation factor 35 kD subunit; CLMF p35; IL-12 subunit p35; NK cell stimulatory factor chain 1; NKSF1 (IL12A, NKSF1) interleukin-12 subunit beta; IL-12B; cytotoxic lymphocyte maturation factor 40 kD subunit; CLMF p40; IL-12 subunit p40; NK cell stimulatory factor chain 2; NKSF2 (IL12B NKSF2) interleukin-27 subunit beta; IL-27 subunit beta; IL-27B; Epstein-Barr virus-induced gene 3 protein; EBV-induced gene 3 protein (EBI3, IL27B)