HGNC Approved Gene Symbol: SRP19
Cytogenetic location: 5q22.2 Genomic coordinates (GRCh38): 5:112,861,287-112,898,371 (from NCBI)
SRP19 has an essential role in the assembly of the signal recognition particle (SRP), a universally conserved ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to cellular membranes. SRP19 binds to free SRP RNA already in the nucleolus, a prerequisite for the binding of SRP54 (604857) to helix 8 of SRP RNA in eukaryotes (summary by Wild et al., 2001).
By screening a liver cDNA library with an anti-SRP19 probe, Lingelbach et al. (1988) isolated a human SRP19 cDNA encoding a 144-amino acid protein. Sequence analysis showed that SRP19 contains a very basic C-terminal domain of 7 lysine residues interrupted by 2 glycine residues. Northern blot analysis revealed expression of a 0.9 kb transcript in HeLa cells. SDS-PAGE analysis showed that SRP19 is expressed as a 19-kD protein, identical in size to canine SRP19. Functional analysis determined that the SRP19 protein binds to 7SL RNA in canine pancreas.
Groden et al. (1991) determined that the SRP19 gene consists of 5 exons.
In 2 small nested deletions of 100 to 260 kb identified by Joslyn et al. (1991) in patients with adenomatous polyposis coli (APC; 175100), Groden et al. (1991) identified 3 genes in a span of about 100 kb on chromosome 5. One of these was DP1 (125265); a second was the gene that is mutant in APC, called by them DP2.5 (611731). The third was a gene which was found to have the same sequence as that of SRP19. Horii et al. (1993) discussed the occurrence of alternative splicing not only within the APC gene but also between the APC gene and the neighboring SRP19 gene.
The signal recognition particle (SRP) is a ribonucleoprotein complex that mediates the targeting of proteins to the endoplasmic reticulum (ER). The complex consists of a 7S (or 7SL) RNA and 6 different proteins, SRP9 (600707), SRP14 (600708), SRP19, SRP54, SRP68 (604858), and SRP72 (602122). The proteins are bound to the 7S RNA as monomers (SRP19 and SRP54) or heterodimers (SRP9/SRP14 and SRP68/SRP72). SRP9 and SRP14 bind to the Alu domain of the SRP, whereas the other 4 proteins belong to the S domain. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein (summary by Lingelbach et al., 1988).
For information on a signal recognition particle database, see Larsen et al. (1998).
Crystal Structure
Wild et al. (2001) reported the 1.8-angstrom resolution crystal structure of human SRP19 in complex with its primary binding site on helix 6 of SRP RNA, which consists of a stem-loop structure closed by an unusual GGAG tetraloop. Protein-RNA interactions are mediated by the specific recognition of a widened major groove and the tetraloop without any direct protein-base contacts and include a complex network of highly ordered water molecules. Wild et al. (2001) proposed a model of the assembly of the SRP core comprising SRP19, SRP54, and SRP RNA based on crystallographic and biochemical data.
Cryoelectron Microscopy
Halic et al. (2004) presented the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, determined to 12-angstrom resolution by cryoelectron microscopy, enabled Halic et al. (2004) to generate a molecular model of SRP in its functional conformation. The model showed how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation factor-binding site of the ribosome, explaining its elongation arrest activity.
The SRP19 gene maps to chromosome 5q21-q22, between the DP1 (125265) and APC (611731) genes (Groden et al., 1991).
Groden, J., Thliveris, A., Samowitz, W., Carlson, M., Gelbert, L., Albertsen, H., Joslyn, G., Stevens, J., Spirio, L., Robertson, M., Sargeant, L., Krapcho, K., Wolff, E., Burt, R., Hughes, J. P., Warrington, J., McPherson, J., Wasmuth, J., Le Paslier, D., Abderrahim, H., Cohen, D., Leppert, M., White, R. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66: 589-600, 1991. [PubMed: 1651174] [Full Text: https://doi.org/10.1016/0092-8674(81)90021-0]
Halic, M., Becker, T., Pool, M. R., Spahn, C. M. T., Grassucci, R. A., Frank, J., Beckmann, R. Structure of the signal recognition particle interacting with the elongation-arrested ribosome. Nature 427: 808-814, 2004. [PubMed: 14985753] [Full Text: https://doi.org/10.1038/nature02342]
Horii, A., Nakatsuru, S., Ichii, S., Nagase, H., Nakamura, Y. Multiple forms of the APC gene transcripts and their tissue-specific expression. Hum. Molec. Genet. 2: 283-287, 1993. [PubMed: 8388766] [Full Text: https://doi.org/10.1093/hmg/2.3.283]
Joslyn, G., Carlson, M., Thliveris, A., Albertsen, H., Gelbert, L., Samowitz, W., Groden, J., Stevens, J., Spirio, L., Robertson, M., Sargeant, L., Krapcho, K., Wolff, E., Burt, R., Hughes, J. P., Warrington, J., McPherson, J., Wasmuth, J., Le Paslier, D., Abderrahim, H., Cohen, D., Leppert, M., White, R. Identification of deletion mutations and three new genes at the familial polyposis locus. Cell 66: 601-613, 1991. [PubMed: 1678319] [Full Text: https://doi.org/10.1016/0092-8674(81)90022-2]
Larsen, N., Samuelsson, T., Swieb, C. The Signal Recognition Particle Database (SRPDB). Nucleic Acids Res. 26: 177-178, 1998. [PubMed: 9399828] [Full Text: https://doi.org/10.1093/nar/26.1.177]
Lingelbach, K., Zwieb, C., Webb, J., Marshallsay, C., Hoben, P., Walter, P., Dobberstein, B. Isolation and characterization of a cDNA clone encoding the 19 kDa protein of signal recognition particle (SRP): expression and binding to 7SL RNA. Nucleic Acids Res. 16: 9431-9442, 1988. [PubMed: 2460823] [Full Text: https://doi.org/10.1093/nar/16.20.9431]
Wild, K., Sinning, I., Cusack, S. Crystal structure of an early protein-RNA assembly complex of the signal recognition particle. Science 294: 598-601, 2001. [PubMed: 11641499] [Full Text: https://doi.org/10.1126/science.1063839]