Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.
1. A pharmaceutical composition, comprising a physiologically acceptable carrier and a fusion polypeptide, wherein the fusion polypeptide comprises a histidyl-tRNA synthetase (HRS) polypeptide fused to an Fc fragment, wherein the HRS polypeptide consists of a sequence that has at least 95% identity along its length to SEQ ID NO: 6, comprises a WHEP domain, and lacks a functional aminoacylation domain.
2. The pharmaceutical composition of claim 1 , wherein the HRS polypeptide consists of a sequence that has at least 98% identity along its length to SEQ ID NO: 6.
3. The pharmaceutical composition of claim 1 , wherein the N-terminal region of the HRS reference polypeptide is truncated by 1, 2, or 3 amino acids.
4. A method of treating an inflammatory lung disease in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of any one of claims 1 - 3 .
5. The method of claim 4 , wherein the lung disease is selected from asthma, autoimmune pulmonary inflammation, and scleroderma.
6. The method of claim 4 , comprising reducing cell migration of monocytes/macrophages in the subject in need thereof.
7. A method of treating an inflammatory granulomatous disorder in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of any one of claims 1 - 3 .
8. A cell-based assay system comprising a cell line that expresses a binding partner of a histidyl-tRNA synthetase (HRS) polypeptide, and a pharmaceutical composition of any one of claims 1 - 3 , wherein the binding partner is cellular protein that associates with the HRS polypeptide.
9. The cell-based assay of claim 8 , wherein the cell line is genetically engineered to express the binding partner.
10. (Previously Presented The cell-based assay of claim 8 , wherein the cell line is selected from COS cells, CHO cells, HEK293 cells, and Hela cells.
11. The cell-based assay of claim 8 , which is adapted for high-throughput screening (HTS).