TFG (TRK-fused gene) is localised at endoplasmic reticulum (ER) exit sites and modulates ER export []. It may function at the ER/ERGIC interface to locally concentrate COPII-coated transport carriers and link exit sites on the ER to ERGIC membranes []. It is also an inhibitory regulator of the ubiquitin-proteasome system [, ]. Mutations in the TFG gene cause Okinawa hereditary motor and sensory neuropathy (HMSNO) []and spastic paraplegia 57, autosomal recessive (SPG57) [].
Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family arefound in all domains of life and are generally involved in important RNA-processing tasks. Lsm13-16 homologues share a domain organisation consisting ofa divergent N-terminal Lsm domain and a central or C-terminal consensus motifDFDF-x(7)-F. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box [].The FFD box and TFG box are two other strongly conserved sequence motifs(Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG respectively) contained in Lsm13-15, but not Lsm16, homologues. They succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature [].This entry represents the TGF box.
This is the PB1 domain found in TFG protein (TRK-fused gene), an oncogenic gene product first identified as a fusion partner to nerve growth factor tyrosine kinase receptor TrkA/NTRK1 []and subsequently found as an oncogenic fusion gene in various cancers [, ]. TFG is localised at endoplasmic reticulum (ER) exit sites and modulates ER export []. It may function at the ER/ERGIC interface to locally concentrate COPII-coated transport carriers and link exit sites on the ER to ERGIC membranes []. It is also a an inhibitory regulator of the ubiquitin-proteasome system [].The PB1 domain is a modular domain mediating specific protein-protein interaction in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development and cell polarity. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster []. The PB1 domain of TFG represent a type I/II domain.
Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family arefound in all domains of life and are generally involved in important RNA-processing tasks. Lsm13-16 homologues share a domain organisation consisting ofa divergent N-terminal Lsm domain and a central or C-terminal consensus motifDFDF-x(7)-F. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box [].The FFD box and TFG box are two other strongly conserved sequence motifs(Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG respectively) contained in Lsm13-15, but not Lsm16, homologues. They succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature [].This entry represents the FFD box.
Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family arefound in all domains of life and are generally involved in important RNA-processing tasks. Lsm13-16 homologs share a domain organisation consisting ofa divergent N-terminal Lsm domain and a central or C-terminal consensus motifDFDF-x(7)-F closely preceded and followed by further phenylalanines andcharged aspartates/glutamates and arginines/lysines/histidines. The variableseven-residue tract of this consensus motif usually contains an asparagine atthe third or fourth position except of one sequence where the asparagine isreplaced by a glycine. In few other sequences, the DFDF box is replaced by aDYDF or EFDF box []. The DFDF domain is a heterodimerization domain, whichadopts a helical conformation upon binding. It folds into twoconsecutive alpha helices that are preceded and connected by the FDF and arelated FDK sequence [].Two other strongly conserved FFD box and TFG box sequence motifs Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG contained inLsm13-15, but not Lsm16, homologs succeed the DFDF-x(7)-F motif and are alsopredicted to be of helical nature [].This entry represents the DFDF domain.
