| 1996 |
Spc1p (yeast homolog of mammalian SPC12/SPCS1) co-purifies with the essential signal peptidase subunit Sec11p and genetically interacts with it; Spc1p is not required for cell growth or proteolytic processing of tested proteins but is important for efficient signal peptidase activity. A high-copy plasmid encoding Spc1p suppresses the conditional sec11 mutation, whereas Spc2p does not. |
Genetic epistasis (synthetic lethality, high-copy suppression of sec11 conditional mutant), co-purification biochemistry |
The Journal of biological chemistry |
High |
8663399 8910564
|
| 1996 |
Spc1p (SPCS1 yeast homolog) and Spc2p are both non-essential for signal peptidase activity individually; null mutations in each are synthetically lethal with a conditional sec11 mutation; however, they are functionally distinct — Spc1p (but not Spc2p) suppresses sec11 in high copy, while Spc2p (but not Spc1p) is required for signal peptidase activity at high temperatures. A double spc1Δ spc2Δ mutant grows well, indicating the signal peptidase complex missing both subunits retains activity in vivo. |
Yeast genetics (null mutants, synthetic lethality, high-copy suppression, temperature-sensitive growth assays) |
The Journal of biological chemistry |
High |
8910564
|
| 2013 |
SPCS1 interacts with HCV NS2 and E2; a trimeric complex of NS2, E2, and SPCS1 was detected by co-immunoprecipitation. Knockdown of SPCS1 reduced infectious HCV production and impaired the NS2–E2 interaction, but did not affect structural protein processing, cell entry, RNA replication, or virus release. This places SPCS1 as required for formation of the membrane-associated NS2–E2 assembly complex. |
Split-ubiquitin membrane yeast two-hybrid screen, siRNA knockdown, co-immunoprecipitation |
PLoS pathogens |
Medium |
24009510
|
| 2016 |
SPCS1 is specifically required for proper cleavage of flavivirus structural proteins (prM and E) and secretion of viral particles; loss of SPCS1 markedly reduces yield of all Flaviviridae tested (WNV, DENV, ZIKV, YFV, JEV, HCV) but does not impair alphavirus, bunyavirus, or rhabdovirus infection, nor surface expression or secretion of diverse host proteins. SPCS1 dependence is bypassed by replacing the native prM leader with a class I MHC antigen leader, indicating SPCS1 preferentially promotes processing of specific signal peptide cargo. |
Genome-wide CRISPR/Cas9 screen, genetic validation by KO, rescue with MHC leader sequence replacement, viral yield assays |
Nature |
High |
27383988
|
| 2018 |
SPCS1 interacts with JEV NS2B via two transmembrane domains of NS2B [NS2B(1-49) and NS2B(84-131)]; SPCS1 residues 91-169 (containing two transmembrane domains) mediate these interactions. Loss of SPCS1 impairs intracellular virion assembly and infectious JEV particle production but does not affect cell entry, RNA replication, or translation. Point mutations G12A, G37A, G47A in NS2B(1-49) and P112A in NS2B(84-131) weaken the SPCS1 interaction. |
siRNA knockdown, CRISPR knockout, co-immunoprecipitation, serial deletion and point mutagenesis |
Journal of virology |
High |
29593046
|
| 2021 |
Yeast Spc1 (SPCS1 homolog) negatively regulates signal peptidase-mediated processing of membrane proteins: loss of Spc1 enhances SPase cleavage of signal-anchored and transmembrane segments, while Spc1 overexpression reduces this processing. Spc1 co-immunoprecipitates with proteins carrying uncleaved signal-anchored or transmembrane segments, suggesting it protects TM segments from SPase action to sharpen substrate selection. |
In vivo SPase cleavage assay with modified signal sequences, deletion strains, overexpression, co-immunoprecipitation |
Journal of cell science |
High |
34125229
|
| 2021 |
SPCS1 is an essential Zika virus host factor in placental trophoblasts; CRISPR/Cas9 screen identified SPCS1 among ER membrane complex and signal peptide processing pathway factors required for ZIKV replication in this cell type. |
Pooled CRISPR/Cas9 screen in trophoblasts, validated SPCS1 KO |
Virus research |
Medium |
33577859
|
| 2022 |
Loss of SPCS1 specifically impairs SPC-mediated processing of the HCV E2-p7 junction (but not other SPC cleavage sites in the HCV polyprotein). Efficient E2-p7 separation, regardless of dependence on SPC processing, renders SPCS1 dispensable for HCV assembly. Structural modeling and MD simulations indicate that the structural rigidity of p7 N-terminal TM helix-1 causes intrinsically delayed E2-p7 processing, and SPCS1 facilitates this cleavage by enhancing presentation of the E2-p7 junction to the SPC active site. |
SPCS1 knockout/knockdown, SPC cleavage site mutagenesis, structural modeling, molecular dynamics simulations, viral infectivity assays |
PLoS pathogens |
Medium |
35130329
|
| 2025 |
SPCS1 interacts with rotavirus outer capsid protein VP7 (VP7 residue E256 identified as key binding site; E256R mutation abolishes interaction and reduces viral infectivity). Loss of SPCS1 leads to inefficient cleavage of the VP7 signal peptide, formation of abnormal viral particles by TEM, and severely impaired virion maturation and assembly, without affecting viral transcription, translation, or replication. |
Tandem affinity purification–mass spectrometry, CRISPR knockout, siRNA knockdown, site-directed mutagenesis (E256R), transmission electron microscopy, VP7 signal peptide cleavage assay |
PLoS pathogens |
High |
41860932
|
| 2025 |
SPCS1 mediates upregulation of HPV entry receptors CD151 and HSPG2 in keratinocytes downstream of T. vaginalis adhesion protein TvAP65; siRNA knockdown of SPCS1 alone reduced HPV infection by ~34% and abolished T. vaginalis-driven CD151/HSPG2 upregulation, defining a TvAP65–SPCS1–CD151/HSPG2 axis. |
siRNA screen of 12 TvAP65-interacting host molecules, siRNA knockdown of SPCS1, dual knockdown epistasis, HPV infection quantification, receptor expression measurement |
Infectious diseases of poverty |
Medium |
41199321
|