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Official Full Name
aminoacyl tRNA synthetase complex-interacting multifunctional protein 1
The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20.
AIMP1; aminoacyl tRNA synthetase complex-interacting multifunctional protein 1; p43; EMAP2; SCYE1; EMAPII; aminoacyl tRNA synthase complex-interacting multifunctional protein 1; OTTHUMP00000161877; OTTHUMP00000161878; OTTHUMP00000219673; ARS-interacting multifunctional protein 1; endothelial monocyte-activating polypeptide 2; multisynthase complex auxiliary component p43; endothelial-monocyte activating polypeptide II; multisynthetase complex auxiliary component p43; small inducible cytokine subfamily E, member 1 (endothelial monocyte-activating); HLD3; p43, AIMP1, EMAP2, EMAP-2, EMAPII, EMAP-II; wu:fa95a05; zgc:154081

The amino-tRNA synthetase complex (MSC) is expressed in almost all mammalian cells, and the aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), it participates in the composition of MSC as a non-enzymatic accessory protein. MSC contains 8 different aminoacyl-tRNA synthetase (ARS) and 3 non-enzymatic factors (AIMP1, AIMP2, and AIMP3).

AIMP1 is a polypeptide with a relative molecular mass of 35 000 and containing 312 amino acids. It forms a complex with the glutamine tRNA synthetase, lysyl tRNA synthetase, and arginyl tRNA synthetase via the N-terminus of the 72nd amino acid. Then it plays a biological role. AIMP1 is thought to be at the center of the giant complex MSC, which plays an important role in the overall structure and function of the MSC, as well as the stability of other components in the MSC. As an auxiliary component of MSC, AIMP1 has an oligonucleotide-binding region at the C-terminus of the 95th amino acid that can interact with tRNA.

In vivo studies of AIMP1 gene-deficient animals revealed that AIMP1 gene-deficient mice had no abnormalities in anatomy compared with normal mice, but their body size was significantly reduced, the mortality rate was increased, and symptoms of severe autoimmune diseases were manifested. At the same time, such mice also have collagen reduction, wound healing slowdown, blood sugar lowering, muscle atrophy, motor dysfunction and the like. This evidence suggests that AIMP1 may have complex biological functions. The diverse biological functions of AIMP1 depend on its distribution in the cell and the specific biological components that interact with it.

The Role of AIMP1 on Specific Cells

AIMP1 can exert different functions through its different amino acid domains, and the proliferation of fibroblasts can be promoted through the 6 to 46 amino acid domains. Studies have confirmed that AIMP1 may be involved in the process of wound healing. When the skin of the mouse was traumatized, the level of AIMP1 near the wounded area was significantly increased; and the AIMP1 gene-deficient mice showed a decrease in collagen and delayed healing compared with normal mice, while overexpression of AIMP1 reversed the above phenomenon, suggesting that AIMP1 play an important role in wound healing.

AIMP1 plays an important role in the regulation of neovascularization. However, AIMP1 levels are different, which may have a diametrically opposite effect on the regulation of neovascularization. At lower levels, AIMP1 exhibits a pro-apoptotic effect that promotes neovascularization by activating extracellular signal-regulated kinase 1 /2, which in turn enhances matrix metalloproteinase-9-mediated endothelial cell migration. At a higher level, AIMP1 can inhibit angiogenesis by activating caspase 3 and c-Jun N-terminal kinase pathways to promote vascular endothelial cell apoptosis. Studies have also shown that AIMP1 can also inhibit the binding of adenosine triphosphate synthase to angiogenesis inhibitory proteins through EMALPⅡ, thereby inhibiting neovascularization.

AIMP1 can be released extracellularly as a secreted protein. Kim et al. found that AIMP1 stimulates the expression of many inflammatory factors by activating mitogen-activated protein kinase and nuclear factor-κB (NF-κB), such as macrophage inflammatory protein 1, monocyte-like Protein 1, tumor necrosis factor-α (TNF-α), interleukin (IL) family, etc., thereby AIMP1 can promote inflammation. Bronkhorst et al. also found a link between AIMP1 and mononuclear macrophages in the study of ocular melanoma. In macrophages and bone marrow-derived dendritic cells, AIMP1 induces IL-12 expression via NF-κB, which in turn participates in a type 1 helper T cell-mediated immune response.

Figure 1. Schematic representation of the role of AIMP1 in dedifferentiated/degenerated chondrocytes. (Ahn, et al. 2016)

AIMP1 is abundant in secretory glands such as mouse pancreas and salivary glands. Erik found that under conditions of hypoglycemia, pancreas AIMP1 from up-regulation, in turn, stimulate the pancreatic α cells to release the glucagon, which is an important hormone regulating glucose. Overexpression of AIMP1 can increase plasma glucose and glucagon levels. In addition, AIMP1 may regulate blood sugar by promoting the breakdown of liver glycogen and fat. In contrast, plasma levels of glucose, glucagon, insulin, and fatty acids in AIMP1-deficient mice were lower than in normal mice. Therefore, it is speculated that AIMP1 plays an important role in maintaining blood glucose homeostasis. Since glucose is an important source of energy for the brain, hypoglycemia is thought to be life-threatening, so the role of AIMP1 in regulating blood glucose homeostasis is important.

Interaction of AIMP1 with Specific Proteins

gp96 is an important component of protein interaction with AIMP1 and is a member of the 90 families of heat shock proteins. gp69 contains a C-terminal endoplasmic reticulum retention signal peptide sequence that interacts with AIMP1 to regulate the binding of gp96 to the endoplasmic reticulum retention signal peptide receptor, thereby controlling the retention of endoplasmic reticulum gp96 in immune tolerance. The adjustment works. Since gp96 is expressed on the surface of immune cells, it is often associated with congenital and acquired immunity. Gp96 has a range of functional domains, including nucleotide-bound adenosine triphosphatase regions, acidic domains, and dimeric domains. Kim et al. found that AIMP1 interacts with the dimeric domain of gp96 to promote binding between gp96 dimer and KDEL dimer.

CD23 is a low-affinity receptor for immunoglobulin E, which can also be isolated from the cell surface to form a water-soluble CD23 protein. In immune cells, such as macrophage 1 monocytes and human peripheral blood mononuclear cells, CD23, as a receptor for AIMP1, is involved in mediating cell migration and also regulates the secretion of AIMP1-related TNF-α, forming a positive feedback regulation chain, thereby amplifying the regulation of TNF-α-related inflammation. Hong et al. found that although the C-terminal EMMPI domain of IMP1 is not involved in CD23-mediated responses, the binding of the central region of AIMP1 to CD23 is an important part of its role as a cytokine.

Smad ubiquitination regulatory factor (Smurf) 2 AIMP1 is an important component of negative feedback regulation of transforming growth factor beta (TGF-β) signaling pathway, which binds to protein-mediated Smurf2 and its structure tends to be stable. David et al. showed that Smurf1 and Smurf2 and HECT (homologous to E6APC-terminus)-type E3 ubiquitin ligases regulate TGF-β and bone morphogenetic protein signaling pathways. Although the effect of Smurf2 on the TGF-β signaling pathway appears to be contradictory, it can either enhance the TGF-β signaling pathway by down-regulating nuclear inhibitory factors or inhibit the TGF-β signaling pathway by down-regulating receptor levels. However, this contradictory effect can be explained by its different positions. The nuclear Smurf2 enhances the TGF-β signaling pathway, while the cytoplasmic Smurf2 inhibits this positive effect.


  1. Kim, M. S., Song, J. H., Cohen, E. P., Cho, D., & Kim, T. S. (2017). Aminoacyl trna synthetase--interacting multifunctional protein 1 activates nk cells via macrophages in vitro and in vivo. Journal of Immunology, 198(10), 4140.
  2. Bronkhorst, I. H., Jehs, T. M., Dijkgraaf, E. M., Luyten, G. P., Pa, V. D. V., & Sh, V. D. B., et al. (2014). Effect of hypoxic stress on migration and characteristics of monocytes in uveal melanoma. Jama Ophthalmology, 132(5), 614.
  3. Erik, G. (2016). Glucose control of glucagon secretion—‘there’s a brand-new gimmick every year’:. Upsala Journal of Medical Sciences, 121(2), 120-132.
  4. Kim, M. S., Kim, S., & Myung, H. (2014). Degradation of aimp1/p43 induced by hepatitis c virus e2 leads to upregulation of tgf-β signaling and increase in surface expression of gp96. Plos One, 9(5), e96302.
  5. Hong, S. H., Jin, G. C., Kang, J. Y., Lim, D. S., Kim, C. H., & Lee, S. W., et al. (2015). The antibody atliximab attenuates collagen-induced arthritis by neutralizing aimp1, an inflammatory cytokine that enhances osteoclastogenesis. Biomaterials, 44, 45-54.
  6. David, D., Jagadeeshan, S., Hariharan, R., Nair, A. S., & Pillai, R. M. (2014). Smurf2 e3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a cnksr2 dependent manner. Cell Div., 9(1), 2.
  7. Ahn, J., Kumar, H., Cha, B. H., Park, S., Arai, Y., & Han, I., et al. (2016). Aimp1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing tgf-β signal. Cell Death & Disease, 7(2), e2099.

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