title: Structural and functional conservation of CLEC-2 with the species-specific regulation of transcript expression in evolution.
abstract: CLEC-2 was first identified by sequence similarity to C-type lectin-like molecules with immune functions and has been reported as a receptor for the platelet-aggregating snake venom toxin rhodocytin and the endogenous sialoglycoprotein podoplanin. Recent researches indicate that CLEC-2-deficient mice were lethal at the embryonic stage associated with disorganized and blood-filled lymphatic vessels and severe edema. In view of a necessary role of CLEC-2 in the individual development, it is of interest to investigate its phylogenetic homology and highly conserved functional regions. In this work, we reported that CLEC-2 from different species holds with an extraordinary conservation by sequence alignment and phylogenetic tree analysis. The functional structures including N-linked oligosaccharide sites and ligand-binding domain implement a structural and functional conservation in a variety of species. The glycosylation sites (N120 and N134) are necessary for the surface expression CLEC-2. CLEC-2 from different species possesses the binding activity of mouse podoplanin. Nevertheless, the expression of CLEC-2 is regulated with a species-specific manner. The alternative splicing of pre-mRNA, a regulatory mechanism of gene expression, and the binding sites on promoter for several key transcription factors vary between different species. Therefore, CLEC-2 shares high sequence homology and functional identity. However the transcript expression might be tightly regulated by different mechanisms in evolution.
authors: Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Lan
authors: L
authors: Wang
authors: Shifang
authors: S
authors: Ren
authors: Haiyan
authors: H
authors: Zhu
authors: Dongmei
authors: D
authors: Zhang
authors: Yuqing
authors: Y
authors: Hao
authors: Yuanyuan
authors: Y
authors: Ruan
authors: Lei
authors: L
authors: Zhou
authors: Chiayu
authors: C
authors: Lee
authors: Lin
authors: L
authors: Qiu
authors: Xiaojing
authors: X
authors: Yun
authors: Jianhui
authors: J
authors: Xie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D001792:Blood Platelets; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013045:Species Specificity; D000098853:Podoplanin
chemical_list: D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D012333:RNA, Messenger; C104778:CLEC2B protein, human; C490441:Pdpn protein, mouse; D000098853:Podoplanin