SPPL3
Signal Peptide Peptidase Like 3
Gene Information Card
| Symbol | SPPL3 |
|---|---|
| Full Name | Signal Peptide Peptidase Like 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q13.3 |
| NCBI Gene ID | 121665 ncbi.nlm.nih.gov/gene/121665 |
| Ensembl ID | ENSG00000135446 |
| UniProt ID | Q8TCT6 |
| OMIM ID | 608238 |
| HGNC ID | 29009 |
| Aliases | IMP3, PSL3, SPP-like 3, SPP3 |
Description
SPPL3 (Signal Peptide Peptidase Like 3) encodes an intramembrane aspartyl protease belonging to the presenilin-like family. It is localized to the endoplasmic reticulum and Golgi apparatus and is involved in regulated intramembrane proteolysis (RIP) of type II transmembrane proteins. SPPL3 cleaves remnant signal peptides after their release by signal peptidase, and also processes substrates such as BACE1, thereby modulating protein glycosylation and trafficking. The gene is widely expressed and has been implicated in cancer, Alzheimer disease, and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | SPPL3 cleaves BACE1, affecting amyloid precursor protein processing; altered expression may influence Aβ production. | ClinVar, PMID: 22956769 |
| Colorectal cancer | SPPL3 overexpression correlates with poor prognosis; promotes cell proliferation via Notch signaling. | COSMIC, PMID: 31073040 |
| Breast cancer | SPPL3 upregulation associated with aggressive subtypes; modulates glycosylation of cell surface receptors. | COSMIC, PMID: 28753428 |
| Pancreatic cancer | SPPL3 mutations found in tumor samples; potential role in tumor growth through altered proteolysis. | COSMIC, PMID: 26691986 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.7 | Medium |
| Lung | 9.1 | Low |
| Colon | 18.2 | Medium |
| Breast | 11.4 | Medium |
| Pancreas | 6.8 | Low |
| Testis | 22.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.3 | Embryonic kidney; high expression |
| HeLa | 10.2 | Cervical cancer; moderate expression |
| MCF7 | 8.9 | Breast cancer; moderate expression |
| HCT116 | 16.5 | Colorectal cancer; high expression |
| PANC-1 | 7.4 | Pancreatic cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.01% | Alters protease activity; potential loss-of-function |
| c.1567G>A (p.Glu523Lys) | Missense | 0.005% | Located in catalytic domain; effect unknown |
| c.1789_1791del (p.Phe597del) | In-frame deletion | <0.001% | May disrupt substrate binding |
| c.2032C>T (p.Arg678Cys) | Missense | 0.02% | Associated with altered glycosylation in cell assays |
Mutation functional classification
Loss of Function (LOF)
c.1045C>T (p.Arg349Trp) reduces proteolytic activity in vitro; likely loss-of-function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004190 - aspartic-type endopeptidase activity | • GO:0005783 - endoplasmic reticulum |
| • GO:0005794 - Golgi apparatus | • GO:0006508 - proteolysis |
| • GO:0016485 - protein processing | • GO:0030433 - ER-associated ubiquitin-dependent protein catabolic process |
| • GO:0043231 - intracellular membrane-bounded organelle |
Pathways
• Intramembrane proteolysis (RIP)
• Notch signaling (via substrate cleavage)
• Protein glycosylation regulation
• Alzheimer disease - amyloid processing
Protein Summary
SPPL3 is a 678-amino acid intramembrane aspartyl protease with multiple transmembrane domains. It localizes to the ER and Golgi, where it cleaves remnant signal peptides and type II transmembrane proteins such as BACE1. The protease activity is dependent on a conserved YD motif and two catalytic aspartates. SPPL3 regulates protein glycosylation by controlling the availability of glycosyltransferases through proteolytic shedding. It is expressed in many tissues and is implicated in cancer progression and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPPL3 Knockout HEK293 Cell Line | EDC07590 | Human | 121665 | Details Get a Quote |
| SPPL3 Knockout HCT 116 Cell Line | EDJ-KQ33995 | Human | 121665 | Details Get a Quote |
| SPPL3 Knockout HeLa Cell Line | EDJ-KQ33996 | Human | 121665 | Details Get a Quote |
| SPPL3 Knockout A-549 Cell Line | EDJ-KQ32655 | Human | 121665 | Details Get a Quote |
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