hCHL2, a novel chordin-related gene, displays differential expression and complex alternative splicing in human tissues and during myoblast and osteoblast maturation.
Chordin-like cysteine-rich repeats (CRs) are conserved domains present in an expanding family of secreted proteins that associate with members of the TGF beta superfamily. In this study, we report the molecular cloning and characterization of CHL2 (chordin-like 2), a novel protein closely related to CHL (chordin-like). Both are members of the chordin family of proteins, and contain a signal peptide and three CR domains. We found that recombinant human CHL2 (hCHL2) protein is secreted and binds activin A, but not BMP-2, -4, or -6. Expression of hCHL2 mRNA and protein was detected in a variety of human tissues and is particularly abundant in the uterus. Extensive and complex alternative splicing of hCHL2 was observed in different tissues, resulting in several distinct protein isoforms that vary substantially in the presence of a signal peptide and their content of CR domains. Differential expression of CHL2 variants was observed during myoblast and osteoblast differentiation, implying a role for this gene in these physiological processes.
Oren
Anat
A
Compugen Ltd., 72 Pinchas Rosen St., Tel Aviv 69512, Israel.
Toporik
Amir
A
Biton
Sharon
S
Almogy
Nechama
N
Eshel
Dani
D
Bernstein
Jeanne
J
Savitsky
Kinneret
K
Rotman
Galit
G
D028341:Activins / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D017124:Conserved Sequence / Q000235:genetics; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C477338:CHRDL2 protein, human; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D007328:Insulin; D020033:Protein Isoforms; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; C499469:recombinant human bone morphogenetic protein-2; D028341:Activins; D012313:RNA; D028322:Inhibin-beta Subunits; D003545:Cysteine