title: Extra domains in secondary transport carriers and channel proteins.
abstract: "Extra" domains in members of the families of secondary transport carrier and channel proteins provide secondary functions that expand, amplify or restrict the functional nature of these proteins. Domains in secondary carriers include TrkA and SPX domains in DASS family members, DedA domains in TRAP-T family members (both of the IT superfamily), Kazal-2 and PDZ domains in OAT family members (of the MF superfamily), USP, IIA(Fru) and TrkA domains in ABT family members (of the APC superfamily), ricin domains in OST family members, and TrkA domains in AAE family members. Some transporters contain highly hydrophilic domains consisting of multiple repeat units that can also be found in proteins of dissimilar function. Similarly, transmembrane alpha-helical channel-forming proteins contain unique, conserved, hydrophilic domains, most of which are not found in carriers. In some cases the functions of these domains are known. They may be ligand binding domains, phosphorylation domains, signal transduction domains, protein/protein interaction domains or complex carbohydrate-binding domains. These domains mediate regulation, subunit interactions, or subcellular targeting. Phylogenetic analyses show that while some of these domains are restricted to closely related proteins derived from specific organismal types, others are nearly ubiquitous within a particular family of transporters and occur in a tremendous diversity of organisms. The former probably became associated with the transporters late in the evolutionary process; the latter probably became associated with the carriers much earlier. These domains can be located at either end of the transporter or in a central region, depending on the domain and transporter family. These studies provide useful information about the evolution of extra domains in channels and secondary carriers and provide novel clues concerning function.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA.
authors.forename: Ravi D
authors.initials: RD
authors.lastname: Barabote
authors.forename: Dorjee G
authors.initials: DG
authors.lastname: Tamang
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Abeywardena
authors.forename: Neda S
authors.initials: NS
authors.lastname: Fallah
authors.forename: Jeffrey Yu Chung
authors.initials: JY
authors.lastname: Fu
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Lio
authors.forename: Pegah
authors.initials: P
authors.lastname: Mirhosseini
authors.forename: Ronnie
authors.initials: R
authors.lastname: Pezeshk
authors.forename: Sheila
authors.initials: S
authors.lastname: Podell
authors.forename: Marnae L
authors.initials: ML
authors.lastname: Salampessy
authors.forename: Mark D
authors.initials: MD
authors.lastname: Thever
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D006801:Humans; D007473:Ion Channels / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000737:chemistry
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D027361:Organic Anion Transporters; D014359:Trypsin Inhibitor, Kazal Pancreatic