title: Identification and characterization of CPAMD8, a novel member of the complement 3/alpha2-macroglobulin family with a C-terminal Kazal domain.
abstract: We have identified and characterized a novel member of the complement 3/alpha(2)-macroglobulin (C3/alpha(2)M) family named CPAMD8 (complement 3 and pregnancy zone protein-like, alpha2-macroglobulin domain-containing 8). The gene maps to chromosome 19p13.2-p13.3 and spans approximately 130 kb. The gene partially overlaps with the protease-activated receptor-4 (PAR4) gene in the reverse orientation. The cDNA consists of 40 exons ( approximately 6 kb) and encodes a protein of 1885 amino acids. Similar to other proteins in this family, CPAMD8 contains a signal sequence, an RXXR processing site, and a thioester motif. In addition, CPAMD8 has a Kazal-type serine proteinase inhibitor/follistatin-like domain at the C-terminus. The intact CPAMD8 protein generated by in vitro transcription and translation resolved as a single band of about 200 kDa on SDS-PAGE. RT-PCR and immunoblot assays showed that CPAMD8 is expressed in a number of human tissues, most abundantly in the kidney, brain, and testis and at lower levels in heart, liver, and small intestine. CPAMD8 is also expressed in several types of cells in culture, in which it is proteolytically processed into two chains of about 70 and 130 kDa. The Kazal domain of CPAMD8 binds to heparin, and subcellular fractionation shows that CPAMD8 is membrane associated via ionic interaction. In response to immune stimulants, CPAMD8 expression is markedly up-regulated in cells in culture. Thus, CPAMD8 may, like other members of the C3/alpha(2)M family, function in innate immunity but in a localized manner.
authors.affiliation: The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Li
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Wu
authors.forename: Eva
authors.initials: E
authors.lastname: Engvall
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003001:Cloning, Molecular; D003176:Complement C3 / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000511:alpha-Macroglobulins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: C495374:CPAMD8 protein, human; D003176:Complement C3; D016207:Cytokines; D021382:Protein Sorting Signals; D000511:alpha-Macroglobulins; D014359:Trypsin Inhibitor, Kazal Pancreatic