FICD
FIC Domain Containing Protein: A Key Regulator of Protein AMPylation and DeAMPylation
Gene Information Card
| Symbol | FICD |
|---|---|
| Full Name | FIC Domain Containing Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.23 |
| NCBI Gene ID | 11153 ncbi.nlm.nih.gov/gene/11153 |
| Ensembl ID | ENSG00000111247 |
| UniProt ID | Q9BVA6 |
| OMIM ID | 610093 |
| HGNC ID | 16978 |
| Aliases | HYPE, UNQ3031/PRO9859 |
Description
FICD (FIC Domain Containing Protein), also known as HYPE, is a bifunctional enzyme that catalyzes both AMPylation (adenylylation) and deAMPylation of target proteins. It plays a critical role in the unfolded protein response (UPR) by regulating the activity of BiP (HSPA5), a key ER chaperone. FICD-mediated AMPylation of BiP inhibits its ATPase activity, while deAMPylation restores it, thereby modulating ER stress signaling. The gene is located on chromosome 12q24.23 and is expressed in multiple tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type 1 (HSAN1) | Missense mutations in FICD (e.g., p.Arg371His) impair deAMPylation activity, leading to dysregulated BiP function and ER stress in neurons. | ClinVar, OMIM |
| Cancer (various types) | Somatic mutations and altered expression of FICD may influence tumor cell survival under ER stress. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 10.2 | Medium |
| Testis | 15.8 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 9.5 | Medium expression |
| SH-SY5Y | 11.0 | Medium expression |
| HepG2 | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1112G>A (p.Arg371His) | Missense | Rare | Impairs deAMPylation activity, associated with HSAN1 |
| c.1015C>T (p.Arg339Trp) | Missense | Rare | Unknown functional effect, reported in ClinVar |
| c.1246G>A (p.Glu416Lys) | Missense | Somatic | Found in colorectal cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
p.Arg371His reduces deAMPylation activity, leading to BiP hyper-AMPylation and ER stress.
Gain of Function (GOF)
Not well characterized; some somatic mutations may enhance AMPylation.
Dominant Negative (DN)
p.Arg371His may act dominant-negative by disrupting FICD dimerization or substrate interaction.
View complete mutation data：
Gene Ontology (GO)
| • AMPylase activity | • deAMPylase activity |
| • ATP binding | • protein adenylyltransferase activity |
| • response to endoplasmic reticulum stress | • protein folding in endoplasmic reticulum |
Pathways
• Unfolded protein response (UPR)
• ER stress signaling
• Protein AMPylation
Protein Summary
FICD is a 458-amino acid protein containing an N-terminal transmembrane domain and a C-terminal FIC domain. It localizes to the endoplasmic reticulum (ER) membrane. The FIC domain catalyzes the transfer of AMP from ATP to target proteins (AMPylation), primarily BiP. FICD also possesses deAMPylation activity, allowing it to reverse this modification. This bifunctionality is essential for fine-tuning BiP activity during ER stress. Structural studies show that FICD forms a dimer and its activity is regulated by auto-AMPylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FICD Knockout HEK293 Cell Line | EDJ-KQ7306 | Human | 11153 | Details Get a Quote |
| FICD Knockout A-549 Cell Line | EDJ-KQ32355 | Human | 11153 | Details Get a Quote |
| FICD Knockout HCT 116 Cell Line | EDJ-KQ32356 | Human | 11153 | Details Get a Quote |
| FICD Knockout HeLa Cell Line | EDJ-KQ32357 | Human | 11153 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
