Disease relevance of PCOLCE

• Recently, sequencing of a human expressed sequence tag, which maps near the primary open angle glaucoma region on chromosome 3q21, showed it to encode a novel protein with only 43% identity with PCPE but with a similar domain structure [1].
• Nobiletin and PCPE give efficacious antiproliferation effects on B16 mouse melanoma cell with IC50 values 88.6 microM and 62.96 microg/mL, respectively, by the MTT test [2].

High impact information on PCOLCE

• Mammalian Tolloid-like 1 Binds Procollagen C-proteinase Enhancer Protein 1 and Differs from Bone Morphogenetic Protein 1 in the Functional Roles of Homologous Protein Domains [3].
• Further studies showed that PCPE-1 had no effect on the ability of BMP-1 to cleave chordin [4].
• Procollagen C-proteinase enhancer (PCOLCE) proteins are extracellular matrix proteins that enhance the activities of procollagen C-proteinases by binding to the C-propeptide of procollagen I [5].
• PCOLCE proteins are built of three structural modules, consisting of two CUB domains followed by a C-terminal netrin-like (NTR) domain [5].
• Low resolution structure determination shows procollagen C-proteinase enhancer to be an elongated multidomain glycoprotein [6].

Biological context of PCOLCE

• The human enhancer gene, PCOLCE, is localized to 7q21.3-->q22, the same chromosomal region containing the type I collagen alpha 2 chain gene, COL1A2 [7].
• PCPE2 is shown to be a glycoprotein that differs markedly in the nature of its glycosylation from that of PCPE1 [1].
• These data also indicate that PCOLCE is located within a 10- to 15-cM region of conserved synteny between human chromosome 7 and mouse chromosome 5 [8].
• In contrast, the association/dissociation kinetics of intact procollagen molecules on immobilized PCPE were relatively slow, corresponding to a dissociation constant of 1 nM [9].
• N-terminal sequences of the inhibitor matched amino acid sequences within the C-terminal domain of a protein known as procollagen C-terminal proteinase enhancer (PCPE) [10].

Anatomical context of PCOLCE

• Consistent with a possible role in leiomyomata, PCOLCE is shown to be expressed at relatively high levels in uterus [11].

Associations of PCOLCE with chemical compounds

• PCPE2 is also shown to have markedly stronger affinity for heparin than PCPE1, which may account for higher affinities for cell layers [1].
• Comparison of the N-terminal domain of TIMP with CT-PCPE revealed that both contained six cysteine residues [10].
• The mixtures PC with CO, both in the presence of 2 and 5 mM calcium, and PCPE with CO at 2 mM calcium concentration had surface properties significantly better than those of ALEC and Exosurf and equivalent to those of Survanta [12].
• Crude extracts from citrus peel (C. unshiu Marc.) were extracted with 95% ethanol and fractionated by petroleum ether (PCPE) [13].

Regulatory relationships of PCOLCE

• Substrate-specific modulation of a multisubstrate proteinase. C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1 [14].
• Purified CT-PCPE inhibited MMP-2 with an IC(50) value much greater than that of TIMP-2 [10].

Other interactions of PCOLCE

• The PCPE molecule consists of two CUB domains followed by a C-terminal NTR (netrin-like) domain [6].
• The NTR module: domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases [15].

Analytical, diagnostic and therapeutic context of PCOLCE

• Here we evaluate by reverse-transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization the expression and deletion status of PCOLCE in a series of karyotyped uterine leiomyomata [16].
• To determine the molecular mechanism of PCPE activity, the interactions of the recombinant protein with the procollagen molecule as well as with its isolated C-propeptide domain were studied using surface plasmon resonance (BIAcore) technology [9].
• In order to obtain structural insights into the function of PCPE, the recombinant protein was characterized by a range of biophysical techniques, including analytical ultracentrifugation, transmission electron microscopy, and small angle x-ray scattering [6].

References