Introduction

During the subsequent decades sources of energy for transport other than hydrolysis of ATP were discovered (light in halobacteria, oxidative decarboxylation in various bacteria, terminal oxidation of substances in inner mitochondrial and chloroplast membranes, etc.), something that has led to a mushrooming of transport systems and attempts to classify them appropriately. In parallel with this research, and sometimes even preceding it, went the discoveries of selective channels in cell membranes, such as would permit the passage of Na⁺, K⁺ and Ca²⁺ ions across nerve plasma membranes and a number of intracellular membranes in other types of cells, without any energy supply being required and hence no accumulation of such ions against their electrochemical potential gradient being achieved.

Quite apart from those transport mechanisms a great many pathways were discovered that not only did not require energy coupling but that were either fully or in great measure nonselective, some of them even proceeding in the absence of proteins. Thus, in the 1990s it was possible to draft a classification system of transport mechanisms that looks as shown below.

• 1. Nonspecific permeation
  • 1.1 through hydrophobic domains of membranes
       (various small, medium-sized and large lipophilic molecules)
  • 1.2 through water-filled pores; some permanently opened, such as the complement complex, bacteriocins, defensins, polyene antibiotics; some opening only after a stimulus, such as connexons between adjacent cells
       (virtually all solutes up to a certain size)
  • 1.3 through true pores in the lipid bilayer, as are transiently formed at higher temperature and with applied transmembrane electric potential
       (all solutes, including macromolecules ("electroporation"))
  • 1.4 via non-receptor endocytosis in membrane vesicles
       (all solutes present in extracellular aqueous medium)
• 2. Specific transport
  • 2.1 through selective channels
    • 2.1.1 nongated, such as porins in bacterial, outer mitochondrial and chloroplast membranes, aquaporins in most cells
         (cations, anions, water; also nonelectrolytes)
    • 2.1.2 electrically or potential-gated, such as nerve and muscle-cell channels involved in action potential generation and propagation
         (Na⁺, K⁺, Ca²⁺)
    • 2.1.3 chemically or ligand-gated, such as the various hormone receptor-channels
         (cations)
    • 2.1.4 mechanically or stress-gated, such as channels in blood capillary walls and inner ear hair cells
         (cations, especially K⁺)
  • 2.2 on specific carriers
    • 2.2.1 through mediated (or facilitated) diffusion
         (monosaccharides in animal, noninsulin-dependent tissues, some yeast cells)
    • 2.2.2 by primary active transport
      • 2.2.2.1 driven by ATP or diphosphate hydrolysis by P-type, F-type and ABC-type ATPases in all cells
           (cations, anions, amino acids, sugars, xenobiotics)
      • 2.2.2.2 driven by oxidation reactions, in bacterial, inner mitochondrial and chloroplast membranes
           (H⁺, Na⁺)
      • 2.2.2.3 driven by light absorption, in halobacteria
           (H⁺, Cl^-)
      • 2.2.2.4 driven by decarboxylation, in bacteria
           (Na⁺)
      • 2.2.2.5 driven by methyl transfer, some methanobacteria
           (Na⁺)
    • 2.2.3. by secondary active transport
    • 2.2.3.1 of symport type, using H⁺, Na⁺ and, exceptionally, K⁺ as driving ion, in bacterial, fungal, plant and animal cells, net charge transporting
         (various nonelectrolytes, mainly nutrients)
    • 2.2.3.2 of antiport type, electrically silent, in a variety of cells
         (anions, cations, often in combination)
    • 2.2.3.3 of antiport type, net charge transporting, in outer mitochondrial membranes
         (ADP/ATP)
  • 2.3 by group translocation, mainly in Gram-positive and Gram-negative bacteria, in brain tissue
       (mono- and disaccharides; amino acids)
  • 2.4 by receptor-mediated pinocytosis
    • 2.4.1 by endocytosis, mainly in animal cells
         (ferritransferrin)
    • 2.4.2 by exocytosis, mainly in fungal and animal cells
         (hormones)

In contrast with transport proteins, enzymes have been classified in accordance with the recommendations of the Enzyme Commission of the International Union of Biochemistry, the first classification system having appeared in 1961. This was long before protein sequence data became available. Enzyme classification is based solely on the reaction catalyzed. It was assumed that proteins of similar catalytic function would be related and that they should be grouped together.

In preparing a classification of transport proteins it would have been futile to design a system simply on the basis of specificity toward the substrate molecule or ion being transported. Since data on amino acid sequences of various proteins, including transport proteins, are becoming available and various new genomes are being sequenced at an unprecedented rate we are able to present a classification of such proteins that includes the advantages of the enzyme system in grouping various entries according to the type of reaction (i.e. of transport) but, lower in the hierarchy, bases the classification on sequence homology of the proteins involved. This has the advantage of clarifying, in the vast majority of cases, phylogenetic relationships between the various entries and justifies the designation of this type of classification as a phylogeny-based one. While several thousand of the presently known (and sequenced) transport proteins can be meaningfully classified according to the scheme outlined below there is an obvious lack of readily available information on their specificity. Therefore, several tables are attached to the general classification overview where transport proteins are grouped according to the molecule or ion they actually transport.

The presently employed classification uses a five-digit system where the first digit (a number) designates the CLASS of transport proteins, the second digit (a letter) designates the SUBCLASS, with both of these referring to the mechanism of translocation and/or the source of energy used for the process; the third digit (a number) specifies the transporter FAMILY and the fourth digit the SUBFAMILY, these hierarchical levels being defined and differentiated on the basis of their primary structure. (Where the term SUPERFAMILY occurs it refers simply to a large entity systematically at the level of families.) The fifth digit then designates a particular TRANSPORT PROTEIN.

The classification of proteins in the TC system used here (the TC standing for a Transport Commission properly a Transport Protein Panel, in analogy to the EC system for enzymes where an Enzyme Commission was instrumental) is shown in the following table where transport protein families and, where relevant, subfamilies are grouped in classes and subclasses, together with the abbreviation used in subsequent tables of this document.

Glossary of Terms used in Membrane Transport Work

Carrier older name for transporter (q.v.) which appears in some transport protein names.

Channel membrane protein (or an oligomeric cluster) involved in specific transport of ions or uncharged molecules down their chemical or electrochemical potential gradient. Most channels exist in two conformational states, open and closed. The opening can be accomplisahed (a) by a spreading electric field (potential-gated channels), (b) by binding a specific ligand (chemically gated channels), (c) by mechanical stress or strain (mechanically gated channels). When open, the specific site in the channel can transiently bind solutes from both sides of the membrane.

Exporter transporter which functions in the outward direction.

Facilitator designation for some transporters within the TC 2.A.1 and TC 2.A.4 families; not a generic term.

Importer transporter which functions in the inward direction.

Membrane potential electric potential difference across the membrane consisitng of static and dynamic components, its negative side being generally on the cytosolic (inner) face of the membrane; it is usually expressed in mV, with a negative sign.

Permease a historical term applied to some secondary active transporters; not to be applied to newly described transporters.

Pore membrane protein (usually an oligomeric structure) permitting nonspecific passage of solutes of different size ranges.

Symporter transporter which moves two chemical species in the same direction, at least one of them being ionic and driven by its electrochemical potential gradient.

Translocase a term occasionally applied to a transporter; its use is discouraged.

Transporter current name for membrane proteins showing a relatively high specificity and characterized by the fact that their binding site opens alternately to the one and to the other membrane side. They can either function without input of energy beyond the thermal movement (facilitated or mediated diffusion), or be driven by electrochemical potential gradients of H⁺ and Na⁺ (exceptionally of K⁺) - such processes are often termed secondary active transports, or by various exergonic chemical and photochemical reactions - these are called primary active transports. Transporters (occasionally called porters) are characterized by being able to transport solutes against their chemical or electrochemical potential gradient.

Uniporter transporter which mediates the movement of a single chemical species across the membrane.