Alternative titles; symbols
HGNC Approved Gene Symbol: SRP9
Cytogenetic location: 1q42.12 Genomic coordinates (GRCh38): 1:225,777,826-225,790,464 (from NCBI)
SRP9 is a component of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of proteins to the endoplasmic reticulum. SRP9 and SRP14 (600708) together make up the Alu domain of the SRP (summary by Hsu et al., 1995).
Short interspersed elements (SINEs) are ubiquitous repetitive DNAs that occur in the genomes of many, if not all, mammals. In humans the most common of the SINEs are the approximately 1 million Alu sequences that comprise as much as 5% of genomic DNA. The progenitor of the human Alu repeat may be 7SL RNA, which is a component of the signal recognition particle. Some Alu repeats are transcribed and the noncoding RNA is predicted to form secondary structures. Most primate Alu sequences are dimeric, with 2 nonidentical motifs, and contain RNA polymerase III internal promoters followed by a poly(A) tail. Alu-mediated homologous recombination has been implicated in a variety of genetic disorders as have Alu sequence insertions. Some Alu transcripts are converted by 3-prime processing to a poly(A)-, monomeric species known as small cytoplasmic (sc) Alu RNA. The 'Alu domain' of SRP consists of 2 proteins referred to as SRP9 (9 kD) and SRP14 (600708) and the Alu-homologous region of 7SL RNA. Information on SRP9 and SRP14 has been obtained from the study of the genes in the dog and mouse, respectively. The human and mouse SRP14 proteins are about 90% identical (Chang et al., 1994). Hsu et al. (1995) cloned the human SRP9 cDNA and showed that the predicted protein was approximately 96% similar to its canine homolog. Further, when SRP9 was translated in vitro together with SRP14, Hsu et al. (1995) found that Alu RNA-binding activity was reconstituted and that scAlu RNA, 7SL RNA, and artificial transcripts that included Alu sequence motifs were all bound with similar affinity.
For information on a signal recognition particle database, see Larsen et al. (1998).
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, SRP14 (600708), SRP19 (182175), SRP54 (604857), 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 constitute the Alu domain of 7S, 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).
Crystal Structure
Weichenrieder et al. (2000) reported 2 crystal structures of the heterodimer SRP9/14 bound either to the 5-prime domain or to a construct containing both 5-prime and 3-prime domains of the SRP RNA.
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.
Gross (2014) mapped the SRP9 gene to chromosome 1q42.12 based on an alignment of the SRP9 sequence (GenBank BC008443) with the genomic sequence (GRCh38).
Chang, D. Y., Nelson, B., Bilyeu, T., Hsu, K., Darlington, G. J., Maraia, R. J. A human Alu RNA-binding protein whose expression is associated with accumulation of small cytoplasmic Alu RNA. Molec. Cell. Biol. 14: 3949-3959, 1994. [PubMed: 8196634] [Full Text: https://doi.org/10.1128/mcb.14.6.3949-3959.1994]
Gross, M. B. Personal Communication. Baltimore, Md. 7/28/2014.
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]
Hsu, K., Chang, D.-Y., Maraia, R. J. Human signal recognition particle (SRP) Alu-associated protein also binds Alu interspersed repeat sequence RNAs: characterization of human SRP9. J. Biol. Chem. 270: 10179-10186, 1995. [PubMed: 7730321] [Full Text: https://doi.org/10.1074/jbc.270.17.10179]
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]
Weichenrieder, O., Wild, K., Strub, K., Cusack, S. Structure and assembly of the Alu domain of the mammalian signal recognition particle. Nature 408: 167-173, 2000. [PubMed: 11089964] [Full Text: https://doi.org/10.1038/35041507]