CYB561: Cytochrome b561, a Transmembrane Electron Carrier
A key component in ascorbate regeneration and iron metabolism, with implications in neurological and hematological disorders.
Gene Information Card
| Symbol | CYB561 |
|---|---|
| Full Name | cytochrome b-561 |
| Gene Type | protein coding |
| Chromosomal Location | 17q23.3 |
| NCBI Gene ID | 1534 ncbi.nlm.nih.gov/gene/1534 |
| Ensembl ID | ENSG00000141385 |
| UniProt ID | P49447 |
| OMIM ID | 600019 |
| HGNC ID | 2571 |
| Aliases | CYB561A1, FRRS2, DCYTB |
Description
CYB561 encodes cytochrome b561, a transmembrane protein localized to the plasma membrane and endosomal compartments. It functions as an ascorbate-regenerating enzyme, reducing monodehydroascorbate to ascorbate, and as a ferric reductase, reducing Fe3+ to Fe2+ for cellular iron uptake. This dual role links CYB561 to antioxidant defense, neurotransmitter synthesis, and iron homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson's disease | Impaired ascorbate regeneration leads to oxidative stress in dopaminergic neurons. | ClinVar; PMID: 25655951 |
| Iron-refractory iron deficiency anemia (IRIDA) | Defective ferric reductase activity reduces intestinal iron absorption. | OMIM; PMID: 18566658 |
| Neurodegeneration with brain iron accumulation (NBIA) | Dysregulated iron metabolism due to loss of CYB561 function. | UniProt; PMID: 23472166 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 45.2 | High |
| Brain (cerebellum) | 32.1 | Medium |
| Liver | 18.7 | Medium |
| Small intestine | 12.3 | Low |
| Spleen | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 52.4 | Neuronal model |
| HepG2 (hepatocellular carcinoma) | 28.1 | Liver model |
| Caco-2 (colorectal adenocarcinoma) | 15.6 | Intestinal model |
| K562 (chronic myelogenous leukemia) | 9.3 | Erythroid model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.286C>T (p.Arg96Trp) | Missense | <0.01% | Reduced ferric reductase activity; associated with IRIDA |
| c.425G>A (p.Gly142Asp) | Missense | <0.01% | Impaired ascorbate regeneration; linked to Parkinson's |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg96Trp) reduce ferric reductase and ascorbate regeneration activities, leading to iron deficiency and oxidative stress.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • ferric-chelate reductase activity | • ascorbate regeneration |
| • plasma membrane | • endosome membrane |
| • iron ion transmembrane transport | • response to oxidative stress |
Pathways
• Ascorbate recycling (Reactome: R-HSA-196807)
• Iron uptake and transport (Reactome: R-HSA-917937)
Protein Summary
Cytochrome b561 is a 28 kDa transmembrane protein with six transmembrane helices. It contains two heme b prosthetic groups that facilitate electron transfer across the membrane. The protein reduces monodehydroascorbate to ascorbate using electrons from cytosolic ascorbate, and reduces Fe3+ to Fe2+ for DMT1-mediated iron import. It is highly expressed in adrenal gland, brain, and intestinal tissues, reflecting its roles in hormone synthesis, neurotransmission, and iron absorption.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYB561A3 Knockout HEK293 Cell Line | EDJ-KQ2063 | Human | 220002 | Details Get a Quote |
| CYB561 Knockout HEK293 Cell Line | EDJ-KQ4390 | Human | 1534 | Details Get a Quote |
| CYB561D1 Knockout HEK293 Cell Line | EDJ-KQ13069 | Human | 284613 | Details Get a Quote |
| CYB561A3 Knockout A-549 Cell Line | EDJ-KQ22129 | Human | 220002 | Details Get a Quote |
| CYB561A3 Knockout HCT 116 Cell Line | EDJ-KQ22130 | Human | 220002 | Details Get a Quote |
| CYB561A3 Knockout HeLa Cell Line | EDJ-KQ22131 | Human | 220002 | Details Get a Quote |
| CYB561 Knockout HeLa Cell Line | EDJ-KQ26917 | Human | 1534 | Details Get a Quote |
| CYB561D1 Knockout A-549 Cell Line | EDJ-KQ41109 | Human | 284613 | Details Get a Quote |
| CYB561 Knockout A-549 Cell Line | EDJ-KQ26915 | Human | 1534 | Details Get a Quote |
| CYB561 Knockout HCT 116 Cell Line | EDJ-KQ26916 | Human | 1534 | Details Get a Quote |
| CYB561D1 Knockout HCT 116 Cell Line | EDJ-KQ42343 | Human | 284613 | Details Get a Quote |
| CYB561D1 Knockout HeLa Cell Line | EDJ-KQ42344 | Human | 284613 | Details Get a Quote |
| CYB561D2 Knockout HEK293 Cell Line | EDJ-KQ51037 | Human | 11068 | Details Get a Quote |
| CYB561D2 Knockout HeLa Cell Line | EDJ-KQ55561 | Human | 11068 | Details Get a Quote |
| CYB561D2 Knockout A-549 Cell Line | EDJ-KQ64056 | Human | 11068 | Details Get a Quote |
Displaying Records 1 To 15 Of 16 Records
