UBX domain-containing protein 8 is involved in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins, possibly by tethering VCP to the endoplasmic reticulum membrane [].
Tyrosine-protein phosphatase non-receptor type 22 (PTPN22) acts as negative regulator of T-cell receptor (TCR) signalling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signalling molecules [].Variations of the PTPN22 gene affects the susceptibility of systemic lupus erythematosus (SLE) [].
Tyrosine-protein phosphatase non-receptor type-4 (PTPN4, also known as PTPMEG) is a cytoplasmic protein-tyrosine phosphatase (PTP) thought to play a role in cerebellar function. PTPMEG-knockout mice have impaired memory formation and cerebellar long-term depression []. Tyrosine-protein phosphatase non-receptor type-3 (PTPN3/PTPH1) is a membrane-associated PTP implicated in regulating tyrosine phosphorylation of growth factor receptors, p97 VCP (valosin-containing protein, or Cdc48 in Saccharomyces cerevisiae), and HBV (Hepatitis B Virus) gene expression; it is mutated in a subset of colon cancers []. PTPN3 and PTPN4 contain an N-terminal FERM domain, a middle PDZ domain, and a C-terminal phosphatase domain. Tyrosine-protein phosphatase 1/PTP1 from nematodes is also included in this entry. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. Like most other ERM members they have a phosphoinositide-binding site in their FERM domain. The FERM C domain is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [, ].
