Some important erythrocyte membrane proteins
| Protein . | Molecular mass, kDa* . | Monomers per cell† × 10−3 . | Oligomeric state . | Oligomers in ankyrin complex . | Oligomers in actin junction complex . | Functions in mature erythrocyte membranes . | |
|---|---|---|---|---|---|---|---|
| Complex . | Unit cell‡ . | Complex and unit cell‡ . | |||||
| β-Actin | 41.6 | 500 | Oligomer (∼14) | 1 | Forms ∼37-nm long filaments that serve as a molecular junction in the membrane skeleton. Binds spectrin with the aid of protein 4.1R. Binds tropomyosin, tropomodulin, adducin, dematin, and chorein. | ||
| α-Adducin | 81.0 | 30 | Heterodimer/ tetramer | 1 (dimer) | Caps the fast-growing (barbed) end of actin and recruits spectrin to nearby sites on actin. Links actin junction to band 3, Glut1, and maybe stomatin. Binds chorein. | ||
| β-Adducin | 80.7 | 30 | |||||
| Aldolase A | 39.4 | 20 | Tetramer | <1 | <1 | <1 | Forms glycolytic complex on band 3 with PFK, enolase, G3PD, PK, and LDH. |
| Ankyrin-1§ | 206.0 | 124 ± 11 | Monomer | 1 | 3 | Attaches β-spectrin and the membrane skeleton to band 3 and to protein 4.2 and RhAG in the ankyrin-linked band 3 complex. | |
| Band 3 (SLC4A1) | 101.8 | 1200 | Dimer or tetramer | 2 (dimer) | 6 (dimer) | 1-6 (dimer) | Anion-exchange channel (especially HCO3− and Cl−) with the aid of CAII and CAIV. Forms membrane complexes with GPA, GPB, the Rh complex, Glut1, stomatin, and other proteins that are linked to spectrin via ankyrin-1 and protein 4.2, and linked to the actin junctional complex via protein 4.1R, protein 4.2, p55, adducin, and Glut1. Binds peroxiredoxin. Forms a glycolytic metabolon with G3PD, PFK, PGK, aldolase, LDH, and PK. Binds deoxyhemoglobin. Carries Ii and many other blood group antigens. |
| CAII | 29.1 | 100 | Unknown | Attaches to the outside (CAIV) and inside (CAII) surfaces of band 3, the HCO3− channel. Catalyzes interconversion of CO2 and HCO3−, which aids in HCO3− transport and CO2 elimination. | |||
| CAIV | 33.1 | Unknown | Unknown | ||||
| CD44 | 37.1 | 6-10 | Unknown | <1 | Binds to protein 4.1R and maybe to ankyrin. Multifunctional protein in nonerythroid cells. Function in the red cell is unknown. | ||
| CD47 | 33.3 | 17 | Monomer | <1 | <1 | Binds to protein 4.2 and to the Rh complex (RhAG/RhD/RhCE) within the ankyrin-linked band 3 complex. Inhibits phagocytosis. | |
| DARC/Duffy | 35.6 | 6-13 | Unknown | <1 | Chemokine receptor. Carries the Duffy (Fy) blood group antigen. Receptor for Plasmodium vivax. Function in normal red cell unknown. | ||
| Dematin | 43.1/45.5 | 130 | Monomer or trimer? | 3 (if monomer) 1 (if trimer) | Binds and bundles actin filaments. Facilitates spectrin-actin binding. Helps attach actin to the membrane via Glut1. | ||
| G3PD | 35.9 | 500 | Tetramer | 1 | 3 | 1-3 | Forms glycolytic metabolon on band 3 with aldolase, PFK, enolase, PK, and LDH. |
| Glut1 | 54.1 | 200-700 | Dimer and tetramer | ? | ? | 1-6 (dimer) | Transports glucose. Transports l-dehydroascorbic acid when bound to stomatin. Links actin to the membrane via interactions with dematin, adducin, and band 3. |
| GPA | 14.3 | 1000 | Homo or heterodimer | 2 | 6 | 1-6 | Binds band 3 in the ankyrin-linked band 3 complex, and maybe to RhAG. May facilitate band 3 transfer to the membrane. Carries MNSsU blood group antigens and much of the red cell’s negative surface charge. |
| GPB | 7.7 | 170-250 | |||||
| GPC | 13.8 | 143 | Monomer? Homo or heterodimer? | 6 | Links actin junctional complex to membrane via interactions with protein 4.1R, p55, and band 3. Carries Gerbich blood group antigens. | ||
| GPD | 11.5 | 82 | |||||
| Kell | 82.8 | 3-18 | Heterodimer with Kx | <1 | The Kx/Kell complex may reside in the actin-linked band 3 complex. Kell carries the Kell blood group antigen. Kx probably has an undiscovered transport function. | ||
| Kx | 50.9 | Unknown | Heterodimer with Kell | <1 | |||
| Lu/BCAM | 64.3 | 1.5-8 | Unknown | Adhesion molecule that carries the Lu blood group antigen. Binds to α-spectrin. | |||
| LW glycoprotein/ ICAM4 | 27.0 | 3-5 | Monomer | <1 | <1 | ICAM that carries the LW blood group antigen. Interacts with RhAG/RhD/RhCE and probably resides in the ankyrin-linked band 3 complex. | |
| p55/Palmitoylated membrane protein 1 | 52.3 | 80 | Dimer? | 1 | Links actin junctional complex to membrane via interactions with some protein 4.1R and GPC/D molecules. Heavily palmitoylated. May contribute to organization of lipid rafts. | ||
| Peroxiredoxin 2 | 21.8 | 200 | Dimer or decamer | ? | ? | ? | Abundant antioxidant protein that is partially linked to band 3 on the membrane. Also binds stomatin and activates the calcium ion–dependent potassium ion (Gardos) channel. |
| PFK (liver) | 85.0 | 6 | Heterotetramer | <1 | <1 | <1 | Forms glycolytic metabolon on band 3 with aldolase, G3PD, enolase, PK, and LDH. |
| PFK (muscle) | 85.2 | ||||||
| Protein 4.1R | 66.4 | ∼240 | Monomer | 6 | Binds to both β-spectrin and actin and greatly strengthens the spectrin-actin interaction. Links actin to the membrane via interactions with GPC/D, p55, and band 3. Competes with ankyrin for binding to band 3. | ||
| Protein 4.2 | 79.8/76.9 | ∼280 | Monomer? | 2 | 6 | 1 | Binds to band 3, ankyrin, and CD47 in the ankyrin-linked band 3 complex. Also binds to the EF hand domain of α-spectrin. |
| RhAG | 44.2 | 100-200 | Heterotrimer of RhAG, RhD, and RhCE? | 1 | 3 | The RhAG/RhD/RhCE trimer binds to CD47, LW, ankyrin, CD47, and GPB in the ankyrin-linked band 3 complex. RhAG transports NH3/NH4+ and maybe CO2. | |
| RhCE | 45.4 | 100-200 | |||||
| RhD | 45.1 | 100-200 | |||||
| α-Spectrin | 280.0 | 242 | Heterodimer/ tetramer/oligomer | 2 (dimer) | 6 (dimer) | 6 (dimer) | Cross-links actin filaments into a hexagonal lattice at the tail end with the help of protein 4.1R, adducin, and dematin. Binds protein 4.2 via the α-spectrin EF hand domain. Self-associates into tetramers and oligomers and binds to ankyrin-1 and Lu/BCAM at the head end. |
| β-Spectrin | 246.4 | 242 | |||||
| Stomatin | 31.7 | 200-400? | Oligomer (9-12)? | ? | ? | 1 | Binds to Glut1 and converts it into an ascorbic acid transporter. Also binds band 3, adducin, and peroxiredoxin. Located in lipid rafts. |
| Tropomodulin 1 | 40.6 | 30 | Monomer | 1 | Caps slow-growing (pointed) end of actin. Binds TM, which strengthens capping. | ||
| Tropomyosin 1 (α-TM) | 32.9 | 140 | Homodimer | 2 | Binds to and stabilizes actin filaments in a magnesium ion–dependent manner. May help specify actin filament lengths in the red cell. | ||
| Tropomyosin 3 (γ-TM) | 32.9 | ||||||
| Protein . | Molecular mass, kDa* . | Monomers per cell† × 10−3 . | Oligomeric state . | Oligomers in ankyrin complex . | Oligomers in actin junction complex . | Functions in mature erythrocyte membranes . | |
|---|---|---|---|---|---|---|---|
| Complex . | Unit cell‡ . | Complex and unit cell‡ . | |||||
| β-Actin | 41.6 | 500 | Oligomer (∼14) | 1 | Forms ∼37-nm long filaments that serve as a molecular junction in the membrane skeleton. Binds spectrin with the aid of protein 4.1R. Binds tropomyosin, tropomodulin, adducin, dematin, and chorein. | ||
| α-Adducin | 81.0 | 30 | Heterodimer/ tetramer | 1 (dimer) | Caps the fast-growing (barbed) end of actin and recruits spectrin to nearby sites on actin. Links actin junction to band 3, Glut1, and maybe stomatin. Binds chorein. | ||
| β-Adducin | 80.7 | 30 | |||||
| Aldolase A | 39.4 | 20 | Tetramer | <1 | <1 | <1 | Forms glycolytic complex on band 3 with PFK, enolase, G3PD, PK, and LDH. |
| Ankyrin-1§ | 206.0 | 124 ± 11 | Monomer | 1 | 3 | Attaches β-spectrin and the membrane skeleton to band 3 and to protein 4.2 and RhAG in the ankyrin-linked band 3 complex. | |
| Band 3 (SLC4A1) | 101.8 | 1200 | Dimer or tetramer | 2 (dimer) | 6 (dimer) | 1-6 (dimer) | Anion-exchange channel (especially HCO3− and Cl−) with the aid of CAII and CAIV. Forms membrane complexes with GPA, GPB, the Rh complex, Glut1, stomatin, and other proteins that are linked to spectrin via ankyrin-1 and protein 4.2, and linked to the actin junctional complex via protein 4.1R, protein 4.2, p55, adducin, and Glut1. Binds peroxiredoxin. Forms a glycolytic metabolon with G3PD, PFK, PGK, aldolase, LDH, and PK. Binds deoxyhemoglobin. Carries Ii and many other blood group antigens. |
| CAII | 29.1 | 100 | Unknown | Attaches to the outside (CAIV) and inside (CAII) surfaces of band 3, the HCO3− channel. Catalyzes interconversion of CO2 and HCO3−, which aids in HCO3− transport and CO2 elimination. | |||
| CAIV | 33.1 | Unknown | Unknown | ||||
| CD44 | 37.1 | 6-10 | Unknown | <1 | Binds to protein 4.1R and maybe to ankyrin. Multifunctional protein in nonerythroid cells. Function in the red cell is unknown. | ||
| CD47 | 33.3 | 17 | Monomer | <1 | <1 | Binds to protein 4.2 and to the Rh complex (RhAG/RhD/RhCE) within the ankyrin-linked band 3 complex. Inhibits phagocytosis. | |
| DARC/Duffy | 35.6 | 6-13 | Unknown | <1 | Chemokine receptor. Carries the Duffy (Fy) blood group antigen. Receptor for Plasmodium vivax. Function in normal red cell unknown. | ||
| Dematin | 43.1/45.5 | 130 | Monomer or trimer? | 3 (if monomer) 1 (if trimer) | Binds and bundles actin filaments. Facilitates spectrin-actin binding. Helps attach actin to the membrane via Glut1. | ||
| G3PD | 35.9 | 500 | Tetramer | 1 | 3 | 1-3 | Forms glycolytic metabolon on band 3 with aldolase, PFK, enolase, PK, and LDH. |
| Glut1 | 54.1 | 200-700 | Dimer and tetramer | ? | ? | 1-6 (dimer) | Transports glucose. Transports l-dehydroascorbic acid when bound to stomatin. Links actin to the membrane via interactions with dematin, adducin, and band 3. |
| GPA | 14.3 | 1000 | Homo or heterodimer | 2 | 6 | 1-6 | Binds band 3 in the ankyrin-linked band 3 complex, and maybe to RhAG. May facilitate band 3 transfer to the membrane. Carries MNSsU blood group antigens and much of the red cell’s negative surface charge. |
| GPB | 7.7 | 170-250 | |||||
| GPC | 13.8 | 143 | Monomer? Homo or heterodimer? | 6 | Links actin junctional complex to membrane via interactions with protein 4.1R, p55, and band 3. Carries Gerbich blood group antigens. | ||
| GPD | 11.5 | 82 | |||||
| Kell | 82.8 | 3-18 | Heterodimer with Kx | <1 | The Kx/Kell complex may reside in the actin-linked band 3 complex. Kell carries the Kell blood group antigen. Kx probably has an undiscovered transport function. | ||
| Kx | 50.9 | Unknown | Heterodimer with Kell | <1 | |||
| Lu/BCAM | 64.3 | 1.5-8 | Unknown | Adhesion molecule that carries the Lu blood group antigen. Binds to α-spectrin. | |||
| LW glycoprotein/ ICAM4 | 27.0 | 3-5 | Monomer | <1 | <1 | ICAM that carries the LW blood group antigen. Interacts with RhAG/RhD/RhCE and probably resides in the ankyrin-linked band 3 complex. | |
| p55/Palmitoylated membrane protein 1 | 52.3 | 80 | Dimer? | 1 | Links actin junctional complex to membrane via interactions with some protein 4.1R and GPC/D molecules. Heavily palmitoylated. May contribute to organization of lipid rafts. | ||
| Peroxiredoxin 2 | 21.8 | 200 | Dimer or decamer | ? | ? | ? | Abundant antioxidant protein that is partially linked to band 3 on the membrane. Also binds stomatin and activates the calcium ion–dependent potassium ion (Gardos) channel. |
| PFK (liver) | 85.0 | 6 | Heterotetramer | <1 | <1 | <1 | Forms glycolytic metabolon on band 3 with aldolase, G3PD, enolase, PK, and LDH. |
| PFK (muscle) | 85.2 | ||||||
| Protein 4.1R | 66.4 | ∼240 | Monomer | 6 | Binds to both β-spectrin and actin and greatly strengthens the spectrin-actin interaction. Links actin to the membrane via interactions with GPC/D, p55, and band 3. Competes with ankyrin for binding to band 3. | ||
| Protein 4.2 | 79.8/76.9 | ∼280 | Monomer? | 2 | 6 | 1 | Binds to band 3, ankyrin, and CD47 in the ankyrin-linked band 3 complex. Also binds to the EF hand domain of α-spectrin. |
| RhAG | 44.2 | 100-200 | Heterotrimer of RhAG, RhD, and RhCE? | 1 | 3 | The RhAG/RhD/RhCE trimer binds to CD47, LW, ankyrin, CD47, and GPB in the ankyrin-linked band 3 complex. RhAG transports NH3/NH4+ and maybe CO2. | |
| RhCE | 45.4 | 100-200 | |||||
| RhD | 45.1 | 100-200 | |||||
| α-Spectrin | 280.0 | 242 | Heterodimer/ tetramer/oligomer | 2 (dimer) | 6 (dimer) | 6 (dimer) | Cross-links actin filaments into a hexagonal lattice at the tail end with the help of protein 4.1R, adducin, and dematin. Binds protein 4.2 via the α-spectrin EF hand domain. Self-associates into tetramers and oligomers and binds to ankyrin-1 and Lu/BCAM at the head end. |
| β-Spectrin | 246.4 | 242 | |||||
| Stomatin | 31.7 | 200-400? | Oligomer (9-12)? | ? | ? | 1 | Binds to Glut1 and converts it into an ascorbic acid transporter. Also binds band 3, adducin, and peroxiredoxin. Located in lipid rafts. |
| Tropomodulin 1 | 40.6 | 30 | Monomer | 1 | Caps slow-growing (pointed) end of actin. Binds TM, which strengthens capping. | ||
| Tropomyosin 1 (α-TM) | 32.9 | 140 | Homodimer | 2 | Binds to and stabilizes actin filaments in a magnesium ion–dependent manner. May help specify actin filament lengths in the red cell. | ||
| Tropomyosin 3 (γ-TM) | 32.9 | ||||||
Ankyrin-1, erythrocyte ankyrin; BCAM, basal cell adhesion molecule; CAII, carbonic anhydrase II; CAIV, carbonic anhydrase IV; Cl−, chloride ion; CO2, carbon dioxide; G3PD, glyceraldehyde-3-phosphate dehydrogenase; HCO3−, bicarbonate; ICAM4, intercellular adhesion molecule 4; LDH, lactic dehydrogenase; Lu, Lutheran; NH3/NH4+, ammonia/ammonium ion; PFK, phosphofructokinase; PGK, phosphoglycerate kinase; PK, pyruvate kinase; TM, tropomyosin.
Size of the mature protein chain without any signal peptide, propeptides, or initiator methionine, but not including posttranslational modifications.
References for the numbers of copies of each protein are listed in the footnotes of Table 2 found in Lux6 . It must be emphasized that the numbers of many red cell membrane proteins are roughly estimated but not accurately measured, which affects the estimates of the composition of the ankyrin complex and actin junctional complex.
The unit cell is defined in Figure 8.
Data shown are for full-length ankyrin (band 2.1), the major isoform, except for the number of copies per cell, which includes the smaller isoforms: bands 2.2, 2.3, and 2.6.