PCSK1
Proprotein Convertase Subtilisin/Kexin Type 1
Gene Information Card
| Symbol | PCSK1 |
|---|---|
| Full Name | Proprotein Convertase Subtilisin/Kexin Type 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q15 |
| NCBI Gene ID | 5122 ncbi.nlm.nih.gov/gene/5122 |
| Ensembl ID | ENSG00000175426 |
| UniProt ID | P29120 |
| OMIM ID | 162150 |
| HGNC ID | 8743 |
| Aliases | PC1, PC3, SPC3, NEC1, BMIQ12 |
Description
PCSK1 encodes proprotein convertase 1 (PC1/PC3), a calcium-dependent serine endoprotease that cleaves precursor proteins at paired basic amino acid sites. It is primarily expressed in neuroendocrine tissues and is essential for the processing of prohormones such as proinsulin, proopiomelanocortin (POMC), proglucagon, and prothyrotropin-releasing hormone. Loss-of-function mutations cause monogenic obesity and proprotein convertase deficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity, early-onset, susceptibility to | Loss-of-function variants impair prohormone processing, leading to hyperphagia and energy imbalance | PMID: 16444270, ClinVar |
| Proprotein convertase 1/3 deficiency | Biallelic loss-of-function mutations cause severe malabsorptive diarrhea, obesity, hypogonadotropic hypogonadism, and reactive hypoglycemia | OMIM #600955 |
| Type 2 diabetes | Impaired proinsulin processing due to reduced PC1 activity contributes to hyperproinsulinemia and beta-cell dysfunction | PMID: 11416922 |
| Cushing disease | Altered POMC processing in pituitary adenomas may involve dysregulated PC1 expression | PMID: 16882749 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Pancreas | 8.3 | Medium |
| Pituitary | 15.2 | High |
| Adrenal gland | 6.1 | Low |
| Small intestine | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.1 | Neuroblastoma cell line |
| INS-1 | 18.4 | Rat insulinoma, high expression |
| AtT-20 | 22.0 | Mouse pituitary corticotroph |
| HEK293 | 0.5 | Very low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.661G>A (p.Gly221Arg) | Missense | <0.01% | Loss of function; associated with obesity |
| c.814C>T (p.Arg272*) | Nonsense | <0.01% | Truncation; loss of catalytic activity |
| c.1204C>T (p.Arg402*) | Nonsense | <0.01% | Truncation; causes PC1/3 deficiency |
| c.2002G>A (p.Glu668Lys) | Missense | <0.01% | Impaired proinsulin processing |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function, reducing or abolishing enzymatic activity, leading to impaired prohormone processing.
Gain of Function (GOF)
No gain-of-function mutations have been described in PCSK1.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by dimerizing with wild-type PC1, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Proinsulin processing (Reactome: R-HSA-264876)
• POMC processing (Reactome: R-HSA-209776)
• Glucagon-like peptide-1 processing (Reactome: R-HSA-381771)
• Regulation of appetite and energy homeostasis (KEGG: hsa04930)
Protein Summary
Proprotein convertase 1 (PC1) is a 753-amino-acid protein with a signal peptide, prodomain, catalytic domain, P domain, and C-terminal tail. It is synthesized as a zymogen and undergoes autocatalytic cleavage in the endoplasmic reticulum and Golgi. The active enzyme localizes to secretory granules and processes prohormones at dibasic sites. PC1 is critical for the maturation of insulin, POMC-derived peptides (ACTH, beta-endorphin), and other neuroendocrine precursors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCSK1 Knockout HEK293 Cell Line | EDJ-KQ4651 | Human | 5122 | Details Get a Quote |
| PCSK1N Knockout HEK293 Cell Line | EDJ-KQ8769 | Human | 27344 | Details Get a Quote |
| PCSK1N Knockout A-549 Cell Line | EDJ-KQ35034 | Human | 27344 | Details Get a Quote |
| PCSK1 Knockout HeLa Cell Line | EDJ-KQ28583 | Human | 5122 | Details Get a Quote |
| PCSK1N Knockout HeLa Cell Line | EDJ-KQ56064 | Human | 27344 | Details Get a Quote |
| PCSK1 Knockout A-549 Cell Line | EDJ-KQ62583 | Human | 5122 | Details Get a Quote |
| PCSK1 Knockout HCT 116 Cell Line | EDJ-KQ71052 | Human | 5122 | Details Get a Quote |
| PCSK1N Knockout HCT 116 Cell Line | EDJ-KQ73007 | Human | 27344 | Details Get a Quote |
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