Table 2.
List of known atypical chemokines (ACKs), their “hijacked”*chemokine receptors, other receptors, and intracellular interaction partners.
| Atypical chemokine (ACK) | Engaged receptor(s)****** | Intracellular binding partner(s) (if any) |
|---|---|---|
| MIF | CXCR2, CXCR4, CXCR7 CD74** |
CSN5/JAB1, peroxiredoxin (PRX), thioredoxin (TRX), p53, AIF, mutSOD1, p115 |
| MIF-2 |
CXCR4 (?)*** CD74** |
Unknown |
| HMGB1/CXCL12 | CXCR4 (via formation of a heterodimer with CXCL12) TLR2/4, RAGE |
Chromatin, DNA |
| Thioredoxin | Unknown**** | Various redox proteins with active disulfides |
| β-Defensins | ||
| HBD1 HBD2 HBD3 MBD4 MBD14 |
CCR6 CCR2 CXCR4, CCR6, CCR2 CCR2 CCR6, CCR2 |
N/A |
| HNP-1/CCL5 | CCR5 (via formation of a heterodimer with CCL5) | N/A |
| Aminoacyl-tRNA synthetases (AaaRS) | ||
| TyrRS EMAP-II/p43-C-domain TrpRS HisRS AsnRS |
CXCR1 CXCR1 CXCR1, CXCR3 CCR5 CCR3 |
Various interactions with the ribosomal protein/rRNA machinery |
| LL37/Cramp-1 | FPR2 | N/A |
| Serum amyoid A (SAA) | FPR2 TLR2 |
N/A |
| Viral chemokine mimics***** | ||
| HIV gp120 v-MIP |
CXCR4, CCR5 CXCR4 |
N/A |
The utilization of chemokine receptors by mediators that do not formally belong to the structural class of classical chemokines, is also referred to as “molecular hijacking,” emphasizing the binding between an ACK and a classical chemokine receptor of the CC or CXC subclasses.
CD74 is not a non-chemokine receptor and is often referred to as the cognate MIF receptor.
While experimental evidence is yet missing, it has been speculated that MIF-2 may interact with CXCR4 but not CXCR2 due to the lack of a pseudo-ELR motif.
It has been suspected that thioredoxin elicits monocyte chemotaxis via engaging a chemokine receptor, but this receptor has yet remained elusive (69).
There are numerous examples of “viral chemokine mimicry” mechanisms, involving mimicry of host chemokine receptors or ligands, e.g., to facilitate viral entry into host immune cells. Here, we only list HIVgp120 and viral MIP (vMIP) as prototypical examples; others are summarized in recent reviews, e.g., (75–79).
For other references see main text.