8.A.90 The Uroplakin 2/3 (UPK2/3) Family
Uroplakins are a widespread group of vertebrate integral membrane proteins that belong to two different families: UPK1a and UPK1b belong to the large tetraspanin (TSPAN) gene family (see TC# 8.A.40.7), and UPK3a, UPK3b, UPK3c, UPK3d, UPK2a and UPK2b form the UPK2/3 tetraspanin-associated family. Uroplakins may have first appeared in vertebrates. Chicote et al. 2017 provided evidence that the UPK2/3 family originated by gene duplication and domain loss from a protoPTPRQ-like basal deuterostome gene. PTPRQs are members of the subtype R3 tyrosine phosphatase receptor (R3 PTPR) family, which are characterized by having a unique modular composition of extracellular fibronectin (FN3) repeats, a transmembrane helix, and a single intra- cytoplasmic phosphotyrosine phophatase (PTP) domain.The possibility of a deuterostome protoPTPRQ-like gene as an ancestor of the UPK2/3 family by gene duplication and loss of its PTP and fibronectin (FN3) domains, excluding the one closest to the transmembrane helix, is based on the following: (i) phylogenetic analyses, (ii) the existence of an identical intron/exon gene pattern between UPK2/3 and the corresponding genetic region in R3 PTPRs, (iii) the conservation of cysteine patterns and protein motifs between UPK2/3 and PTPRQ proteins and, (iv) the existence in tunicates, the closest organisms to vertebrates, of two sequences related to PTPRQ; one with the full subtype R3 modular characteristic and another without the PTP domain but with a short cytoplasmic tail with some sequence similarity to that of UPK3a (Chicote et al. 2017).
Uroplakin 2, UPK2, of 184 aas and 2 or 3 TMSs, 1 or 2 N-terminal and 1 C-terminal. UPK2 is a component of the asymmetric unit membrane
(AUM), a highly specialized biomembrane elaborated by terminally
differentiated urothelial cells. May play a role in
regulating the assembly of the AUM which regulates channel activities (see 8.A.40.1.1) (Chicote et al. 2017).
UPK2 of Homo sapiens
UPK2 of 179 aas and 1 - 3 TMSs, possibly 0, 1 or 2 TMSs N-terminal and 1 C-terminal.
UPK2 of Salmo salar (Atlantic salmon)
UPK2 of 188 aas and 2 TMSs, one N-terminal and one C-terminal
UPK2 of Lepisosteus oculatus (Spotted gar)
Uroplakin 3a (UKP3a) of 287 aas and 2 probable TMSs, one N-terminal and one C-terminal (Chicote et al. 2017).
UKP3a of Homo sapiens
Uroplakin 3b, UPK3B, of 320 aas
UPK3b of Homo sapiens
Uroplakin 3c, UPK3C, of 263 aas and 2 TMSs, one N-terminal and one C-terminal.
UPK3c of Homo sapiens