Written and maintained by CASRAI Editorial Board
Last updated
General reference information for researchers and laboratory staff; it is not medical advice.
Short answer: what the Fc domain of an antibody is
The Fc (fragment crystallizable) domain is the tail of an immunoglobulin G molecule: the lower hinge region plus the CH2 and CH3 heavy-chain domains. It does not bind antigen. It is the part that complement components and Fc receptors recognise, and, with the Fab arms, it is what a protease separates in the classic fragment preparations.
Definition and scope: Fc fragment, Fc portion, Fc region
“Fc fragment”, “Fc portion”, “Fc region” and “immunoglobulin Fc fragment” all name the same part of the molecule. In the IgG heavy chain, a variable domain (VH) and CH1 form the Fab arm together with the light chain, and the hinge sits between CH1 and CH2. “The part … formed by the lower hinge region and the CH2/CH3 domains is called Fc (fragment crystalline)” (Vidarsson, Dekkers and Rispens 2014, Frontiers in Immunology, read 2026-11-07). Each heavy chain contributes its own CH2 and CH3 segment, so the Fc is built from the paired heavy chains.
Antibody structure: how the Fc relates to Fab
An IgG is a glycoprotein of about 150,000 daltons built from two light and two heavy chains (Thermo Fisher Molecular Probes Handbook, antibody structure and classification, read 2026-11-07). The two Fab arms (fragment antigen binding) carry the antigen-binding sites, so “Fab antibody”, “Fab immunoglobulin” and “antibody Fab fragment” mean the antigen-binding arm of an immunoglobulin, not a separate antibody type. The hinge between CH1 and CH2 gives the Fab arms flexibility. The variable region sits at the tip of each Fab; the Fc is at the opposite end.
Fab vs Fc vs F(ab’)2: the fragment map
Enzymes split IgG at the hinge, which is how the fragments were first defined. Papain cuts in the hinge region to give two identical Fab fragments and one Fc fragment; pepsin gives a bivalent F(ab’)2 fragment that can still precipitate antigen (Thermo Fisher Handbook, read 2026-11-07). The exact cut position differs between sources and subclasses, so this page says only that papain cuts in or near the hinge.
| Fragment | How it is produced | What it contains | What it does |
|---|---|---|---|
| Intact IgG | Not cleaved | Two light and two heavy chains, about 150,000 daltons | Binds antigen and carries Fc functions |
| Fab | Papain digestion (two per IgG) | Light chain with VH and CH1 | Binds antigen |
| F(ab’)2 | Pepsin digestion | Two Fab arms joined through the hinge | Bivalent; can precipitate antigen |
| Fc | Papain digestion (one per IgG) | Lower hinge, CH2 and CH3 of the heavy chains | Glycosylated; complement and Fc-receptor recognition |
What does the Fc region do?
The Fc is glycosylated and carries the effector functions of the antibody, such as complement activation and binding to Fc receptors on macrophages and monocytes; it is also what distinguishes antibody classes (Thermo Fisher Handbook, read 2026-11-07). Vidarsson and colleagues map the receptor sites onto the domain:
- The CH2 residues closest to the hinge form overlapping binding sites for C1q and for the Fcγ receptors.
- The CH2-CH3 interface carries the binding site for the neonatal Fc receptor, FcRn.
- A conserved N-linked glycan at Asn297 sits at the CH2/CH3 interface.
Subclasses differ in the hinge as well as the Fc: the hinge is 15 amino acids in IgG1, 12 in IgG2 and IgG4, and up to 62 in IgG3 (Vidarsson et al. 2014).
How many kDa is an antibody? Molecular weight of a monoclonal antibody
An intact IgG is about 150 kDa (Thermo Fisher Handbook). Vidarsson et al. list about 146 kDa for IgG1, IgG2 and IgG4 and about 170 kDa for IgG3, which has the longest hinge. A monoclonal antibody of the IgG type therefore falls in this range unless it has been engineered or fused to another protein; the supplier’s datasheet states the value for a given product.
| IgG subclass | Approx. mass | Hinge length | Half-life reported |
|---|---|---|---|
| IgG1 | ~146 kDa | 15 amino acids | ~21 days |
| IgG2 | ~146 kDa | 12 amino acids | ~21 days |
| IgG3 | ~170 kDa | up to 62 amino acids | ~7 or ~21 days (by allotype) |
| IgG4 | ~146 kDa | 12 amino acids | ~21 days |
Source: Vidarsson, Dekkers and Rispens 2014, Table 1 and text, read 2026-11-07.
Where the Fc matters in the laboratory
Because the Fc is the effector end and the Fab is the antigen-binding end, reagent questions often come down to which end a method relies on. These are editorial readings of the structure above, not product instructions.
- Fragment-based reagents. A Fab or F(ab’)2 fragment lacks the Fc, so it cannot engage Fc receptors or complement through that region; pepsin-derived F(ab’)2 stays bivalent.
- Cell-based assays. Macrophages and monocytes carry receptors for the Fc, so an intact antibody can interact with such cells through its Fc as well as its Fab. See the CASRAI guides on FMO and isotype controls in flow cytometry and PBMC preparation and staining.
- Detection reagents. See primary and secondary antibodies and secondary antibodies for western blot.
- Therapeutic antibodies and clonal source. Antibodies raised against a therapeutic antibody are covered under anti-drug antibodies; clonal sources are compared in polyclonal vs monoclonal antibodies.
Common misunderstandings
- Fab and Fc are not two kinds of antibody. They are two parts of one immunoglobulin, defined originally by enzymatic digestion.
- The variable region is not the Fc. Antigen binding comes from the Fab arms.
- The antibody mass is not the Fc mass. The ~150 kDa figure is for the whole IgG, not for the Fc fragment.
- Subclasses are not interchangeable. IgG1 to IgG4 differ in hinge length and mass, and in effector behaviour.
Frequently asked questions
What is the Fc region of an antibody?
It is the tail of an immunoglobulin, formed by the lower hinge and the CH2 and CH3 domains, that binds Fc receptors and complement components rather than antigen.
What is the Fc part (or Fc portion) of an antibody?
The same thing as the Fc region and the Fc fragment: the fragment that remains, alongside two Fab fragments, after papain cleaves IgG in the hinge region.
How many kDa are antibodies?
An IgG antibody is about 150 kDa: about 146 kDa for IgG1, IgG2 and IgG4 and about 170 kDa for IgG3 in the figures cited above.
What is the molecular weight of a monoclonal antibody?
A monoclonal IgG is of the same order, roughly 146 to 150 kDa, unless it is engineered or fused to another protein. The product datasheet gives the exact value.
What is the structure of an antibody molecule?
Two light and two heavy chains form an IgG with two Fab arms (light chain with VH and CH1), a flexible hinge, and the Fc formed by the CH2 and CH3 domains of the heavy chains.
What is a Fab antibody fragment?
It is the antigen-binding arm of an immunoglobulin, released by papain digestion together with the Fc fragment.
