Disease relevance of C5orf13

• P311, an 8-kDa polypeptide, was previously shown to be highly expressed in invasive glioma cells [1].
• To our knowledge, these studies are the first to implicate P311 in myofibroblast transformation, to demonstrate that transformation may occur independently of TGF-beta1, and to suggest that P311 may prevent fibrosis [2].
• Metallothionein mediates gene expression of 3.1 mRNA (PTZ17) related to epileptic seizure [3].
• Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection [4].
• Intriguingly, P311 gene expression was significantly decreased in lungs of individuals with emphysema compared with control subjects [5].

Psychiatry related information on C5orf13

• Together our data suggest that P311 expression is tightly regulated during the critical periods of alveolar formation, and that under pathologic conditions, its relative absence may contribute to failure of alveolar regeneration and lead to the development of human emphysema [5].

High impact information on C5orf13

• P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype [2].
• P311, also called PTZ17, was identified by suppressive subtraction hybridization as potentially involved in smooth muscle (SM) myogenesis [2].
• Dinucleotide repeat polymorphisms at the D4S126 and D4S114 loci [6].
• In vitro studies using antisense oligodeoxynucleotides and integrin activation confirmed the role of P311 in supporting migration of malignant glioma cells [4].
• One of the sequences overexpressed by the invasive cells showed 99% homology to the P311 gene, the protein product of which is reported to localize at focal adhesions [4].

Biological context of C5orf13

• We previously showed that P311, an intracellular protein involved in cell migration, is found in human wound myofibroblast precursors (proto-myofibroblasts) and myofibroblasts [7].
• Our studies therefore suggest that, by inducing RalA activity, P311 promotes a motile proto-myofibroblast and myofibroblast phenotype specifically adapted to rapidly populate the initial wound matrix [7].
• P311-induced ameboid migration depended on activation of the GTPase RalA and was reverted to mesenchymal-type migration by RalA RNA interference [7].
• P311 is constitutively serine-phosphorylated; decreased phosphorylation is observed in migration-activated glioma cells [1].
• The nucleotide sequence of NM31 (294 bp) was identical to the 3' region of 3.1 mRNA (PTZ 17), which is abundant in the embryonic mouse brain and is related to chemically induced seizures [3].

Anatomical context of C5orf13

• Furthermore, by binding to the TGF-beta1 latency associated protein (LAP), P311 induced NIH 3T3 cells to transform into non-fibrogenic myofibroblasts characterized by lack of TGF-beta1 production [7].
• Collectively, these results suggest a role for levels of P311 in regulating glioma motility and invasion through the reorganization of actin cytoskeleton at the cell periphery [1].
• Hence, reduced P311 expression in PCS piglets might contribute to atrophy through reduced muscle cell proliferation [8].
• To investigate a functional role of P311 in skeletal muscle, its full-length cDNA was over-expressed in murine C2C12 muscle cells, which resulted in enhanced cell proliferation with reduced myotube formation [8].

Associations of C5orf13 with chemical compounds

• Moreover, P311-induced cell migration was abrogated by inhibition of beta1 integrin function using TACbeta1A, a dominant-negative inhibitor of beta1 integrin signaling, suggesting that P311 acts downstream of beta1 signaling [1].
• The primary amino acid sequence of P311 indicates a putative serine phosphorylation site (S59) near the PEST domain [1].
• Consistent with a role for this gene in alveolar formation, inhibition of alveolization by dexamethasone treatment in vivo resulted in decreased expression of P311 [5].

Physical interactions of C5orf13

• Coimmunoprecipitation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis identified Filamin A as a binding partner of P311, and immunofluorescence studies showed that both proteins colocalized at the cell periphery [1].

Other interactions of C5orf13

• In Northern blots, an induction was confirmed for the new gene, DAP3 and PTZ-17 were down-regulated in some but not in all parallel experiments; however, basal level of H-NUC mRNA was too low to be detected in Northern blots [9].
• Four markers close to the HD gene: D4S111, D4S113, D4S114 and clone 417 are described here [10].
• However, we discovered that an herbal mixture, Saiko-keishi-to-ka shakuyaku (SK, TJ-960), showed regulatory function of gene expression such as increased expression of seizure-related gene PTZ-17, proto-oncogene c-fos and heat shock protein HSP 72 [11].

Analytical, diagnostic and therapeutic context of C5orf13

• Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility [1].
• 3. We have characterized a new locus, D4S114, identified by cloning the end of a NotI fragment resolved by pulsed-field gel electrophoresis [12].
• Quantitative real-time RT-PCR showed that the expression of P311 is developmentally regulated, with peak levels occurring during saccular and alveolar formation [5].

References