PF20917

Asparaginal-tRNA synthetase, N-terminal domain

Pfam entry
Member databasePfam
Pfam typedomain
Short nameAsnRS_N
Author Lazaro Pinto Beatriz;0000-0001-6837-2941 Chuguransky S;0000-0002-0520-0736 Bateman A;0000-0002-6982-4660
Sequence Ontology0000417

Description

This domain is found at the N-terminal domain of the eukaryotic protein Asparaginal-tRNA synthetase (AsnRS, also known as NARS1). AsnRS is essential for protein translation and has been related to autoimmune and neurological diseases. Unlike its bacterial homologs, this protein has a conserved N-terminal extension (this entry) connected by an unstructured tether to the part of the enzyme that has homologues within eukaryotes and prokaryotes: an anticodon-binding domain (Pfam:PF01336), a hinge region (HR), and a catalytic domain (Pfam:PF00152). This domain folds into two alpha-helices and three beta-strands form a parallel/antiparallel mixed beta-sheet and has a characteristic lysine-rich helical motif that interacts with tRNA. It also shows chemokine activity through its interaction with C-C chemokine receptor 3 (CCR3) and the promotion of NRS-CCR3-mediated proinflammatory signaling [1-3].

References

1. De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects. Manole A, Efthymiou S, O'Connor E, Mendes MI, Jennings M, Maroofian R, Davagnanam I, Mankad K, Lopez MR, Salpietro V, Harripaul R, Badalato L, Walia J, Francklyn CS, Athanasiou-Fragkouli A, Sullivan R, Desai S, Baranano K, Zafar F, Rana N, Ilyas M, Horga A, Kara M, Mattioli F, Goldenberg A, Griffin H, Piton A, Henderson LB, Kara B, Aslanger AD, Raaphorst J, Pfundt R, Portier R, Shinawi M, Kirby A, Christensen KM, Wang L, Rosti RO, Paracha SA, Sarwar MT, Jenkins D; SYNAPS Study Group, Ahmed J, Santoni FA, Ranza E, Iwaszkiewicz J, Cytrynbaum C, Weksberg R, Wentzensen IM, Guillen Sacoto MJ, Si Y, Telegrafi A, Andrews MV, Baldridge D, Gabriel H, Mohr J, Oehl-Jaschkowitz B, Debard S, Senger B, Fischer F, van Ravenwaaij C, Fock AJM, Stevens SJC, Bahler J, Nasar A, Mantovani JF, Manzur A, Sarkozy A, Smith DEC, Salomons GS, Ahmed ZM, Riazuddin S, Riazuddin S, Usmani MA, Seibt A, Ansar M, Antonarakis SE, Vincent JB, Ayub M, Grimmel M, Jelsig AM, Hjortshoj TD, Karstensen HG, Hummel M, Haack TB, Jamshidi Y, Distelmaier F, Horvath R, Gleeson JG, Becker H, Mandel JL, Koolen DA, Houlden H. Am J Hum Genet 107, 311-324, (2020). View articlePMID: 32738225

2. Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity. Park JS, Park MC, Lee KY, Goughnour PC, Jeong SJ, Kim HS, Kim HJ, Lee BJ, Kim S, Han BW. Int J Biol Macromol 120, 835-845, (2018). View articlePMID: 30171954

3. A hybrid structural model of the complete Brugia malayi cytoplasmic asparaginyl-tRNA synthetase. Crepin T, Peterson F, Haertlein M, Jensen D, Wang C, Cusack S, Kron M. J. Mol. Biol. 405, 1056-69, (2011). View articlePMID: 21134380

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