Function: Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4. Ref.16 Ref.17Isoform 1 may act as a scaffolding protein that anchors ion channels in the membrane. Ref.16 Ref.17Isoform 3 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells. Ref.16 Ref.17
Subunit structure: Homotetramer
Probable. According to Ref.19, the formation of a homotetrameric protein complex is not required for the chemo-attractant function. Isoform 3 interacts (via PDZ 3 domain) with PPP1R12A, PPP1R12B and PPP1R12C. Isoform 1 interacts with PPP1R12B. Isoform 3 interacts with GRIN2A. Isoform 3 interacts with GABPB1. Isoform 3 interacts (via PDZ 3 domain) with HDAC3. Isoform 1 interacts with GRIN2D, KCNJ10, KCNJ15 and CACNA1C
By similarity. Isoform 3 interacts with HTLV-1 tax. Ref.1 Ref.9 Ref.15 Ref.17
Subcellular location: Interleukin-16: Secreted Ref.12 Ref.15 Ref.16 Ref.17. Isoform 1: Cytoplasm
By similarity Ref.12 Ref.15 Ref.16 Ref.17. Isoform 3: Cytoplasm. Nucleus Ref.12 Ref.15 Ref.16 Ref.17.
Tissue specificity: Isoform 3 is expressed in hemopoietic tissues, such as resting T-cells, but is undetectable during active T-cell proliferation.
Induction: Isoform 3 is down-regulated in T-cells after TCR activation. Ref.13
Post-translational modification: Isoform 3 is synthesized as a chemo-attractant inactive precursor in hemopoietic tissues and is proteolytically cleaved by caspase-3 to yield IL-16. Ref.11
Sequence similarities: Contains 4 PDZ (DHR) domains.
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