Pathways & interactions
Short name: PRY
Overlapping homologous superfamilies
PRY is a domain associated with SPRY domains. The SPRY domain (IPR003877) is of unknown function however distant homologues are domains in butyrophilin/marenostrin/pyrin. Ca2+-release from the sarcoplasmic or endoplasmic reticulum, the intracellular Ca2+ store, is mediated by the ryanodine receptor (RyR) and/or the inositol trisphosphate receptor (IP3R).
The proteins identified by the PRY domain, clearly fall into 3 sets which can be defined by their combination of signatures:
- This group contains an immunoglobulin domain N-terminal to the PRY and butyrophilin domains. Butyrophilins are glycoproteins that are expressed on the apical surfaces of secretory cells in lactating mammary tissue and which may function in the secretion of milk-fat droplets.
- This group contain a RING-finger domain N-terminal to the PRY domain. The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc, and is probably involved in mediating protein-protein interactions. There are two different variants, the C3HC4-type and a C3H2C3-type, which is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as 'RING-H2 finger' is not found associated with this group of proteins.
This set of proteins are described as TRIM (TRIpartite Motif) family members and are involved in cellular compartmentalisation [PMID: 11331580]. The TRIM family sequences are defined by a Ring finger domain, a B-box type1 (B1) and a B-box type 2 (B2) followed by a coiled-coil (CC) region [PMID: 1412709]. Genes belonging to this family are implicated in a variety of processes such as development and cell growth and are involved in human disease.
Many of these proteins, if not all of those with the PRY domain have a number of C-terminal signatures, SPRY, RFP-like (B30.2) and butyrophilin domain. The B30.2-like domain is a well conserved C-terminal domain of 160-170 amino acids which is found in nuclear and cytoplasmic proteins, as well as transmembrane and secreted proteins. The function of the B30.2-like domain is not known, but the cytoplasmic B30.2-like domain of butyrophilin has been shown to interact with xanthine oxidase [PMID: 9866204].
The third set of proteins have the C-terminal signatures but have no N-terminal RING-finger or immunoglobulin domain signatures. These proteins have not been functionally described.