Disease relevance of OLFM4

• OLFM4 mRNA was highly expressed in pancreatic cancer tissues [1].
• On comparing paired samples, the expression of OLFM4 mRNA was observed to be elevated in 90, 69 and 85% of colon, breast and lung cancer tissues, respectively [2].
• Positivity for OLFM4 mRNA, defined as the mean + 2 SD in non-cancerous colon and breast tissues, was observed in 68 and 50% of the studied colon and breast cancer tissues [2].
• Unlike the well-studied class C ES beta-lactamase from Enterobacter cloacae GC1, the Omega-loop does not affect the active site conformation and the catalytic activity of CMY-10 [3].
• The fold of DAA is similar to that of the penicillin-recognizing proteins, especially d-alanyl-d-alanine-carboxypeptidase from Streptomyces R61, and class C beta-lactamase from Entereobacter cloacae strain GC1 [4].
• Our findings indicate that hGC-1 is involved in colon cancer adhesion and metastasis, and that hGC-1 may be a useful marker for tumor differentiation and progression of human colon carcinoma [5].

High impact information on OLFM4

• We show that the GCAP1(Y99C) mutant and native GCAP1 are highly effective in stimulation of photoreceptor GC1 [6].
• Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-beta-mediated cellular apoptosis and apoptosis-related gene expression [7].
• We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis [7].
• Taken together, our data suggest that GW112 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth [7].
• The 1560 nucleotides including the GC1 beta-lactamase gene were sequenced, and the amino acid sequence of the mature enzyme comprising 364 amino acids was deduced [8].

Chemical compound and disease context of OLFM4

• Using hGC-1 purified from baculovirus Sf9 cells we demonstrated that hGC-1 is a secreted glycoprotein containing N-linked carbohydrate chains and forms disulfide-bonded multimers [9].

Biological context of OLFM4

• Inhibition of OLFM4 mRNA expression by small interfering RNA did not promote apoptosis [1].
• Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic mucosa [10].
• In the GC2 phenotype, amino acid 420 is a lysine residue, and in the both common GC1 phenotypes, it is a threonine residue [11].
• The hGC-1 gene locus mapped to chromosome 13q14 [12].
• The 2861 bp cDNA clone of hGC-1 contained an open reading frame of 1530 nucleotides, translating into a protein of 510 amino acids with a signal peptide and six N-linked glycosylation motifs [12].

Anatomical context of OLFM4

• Of these, Reg 1alpha and GW112 were the dominant species and expression of these genes was confined to the crypt epithelium [10].
• Olfactomedin-like genes show characteristic tissue-restricted patterns of expression; the specific tissues expressing these genes differ among the family members. hGC-1 was strongly expressed in the prostate, small intestine, and colon, moderately expressed in the bone marrow and stomach, and not detectable in other tissues [12].
• This factor, which we have named GC1, is undetectable in nuclear extracts of non-rGH-producing rat fibroblast (Rat-2), or HeLa cells [13].

Associations of OLFM4 with chemical compounds

• CONCLUSIONS: Selective expression of Reg 1alpha and GW112 genes in the crypt epithelium of inflamed colonic mucosa suggests the important regulatory functions of these genes [10].
• In vitro translation and ex vivo expression showed hGC-1 to be an N-linked glycoprotein [12].
• However, cysteine residues at 83, 85, 246 and 437 are essential for secretion, and cysteine 226 is critical for hGC-1 multimer formation [9].
• The chemical complementation system was first shown to be able to distinguish between the wild-type (wt) class C beta-lactamase P99 and the clinically isolated extended-spectrum class C beta-lactamase GC1 in the presence of cefotaxime [14].

Physical interactions of OLFM4

• Induction of olfactomedin 4 (OLFM4(GW112/hGC-1)) in cancer cells was recently reported to have a novel antiapoptotic action via binding to the potent apoptosis inducer GRIM-19 [1].

Regulatory relationships of OLFM4

• 3. Together, our findings indicate that hGC-1 is primarily expressed as an extracellular olfactomedin-related glycoprotein during normal myeloid-specific lineage differentiation, suggesting the possibility of a matrix-related function for hGC-1 in differentiation [12].
• Olfactomedin 4 promotes S-phase transition in proliferation of pancreatic cancer cells [1].

Other interactions of OLFM4

• Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development [12].
• One clone specifically induced by G-CSF, hGC-1, was characterized [12].
• MIA and GW112 were overexpressed in 10 (25%) and 22 (55%) of 40 GC samples, and the overexpression of these two genes was associated with tumor stage, respectively [15].

Analytical, diagnostic and therapeutic context of OLFM4

• Since the discovery in 1977 that the GC1 gene could be resolved into two common subcomponents on an isoelectric focusing (IEF) gel, a large number of ethnic groups have been screened to analyze the extent of genetic variation in human populations [16].
• A class C beta-lactamase from a clinical isolate of Enterobacter cloacae strain GC1 with improved hydrolytic activity for oxyimino beta-lactam antibiotics has been analyzed by X-ray crystallography to 1.8 A resolution [17].

References