title: The acquisition of novel N-glycosylation sites in conserved proteins during human evolution.
abstract: BACKGROUND
  N-linked protein glycosylation plays an important role in various biological processes, including protein folding and trafficking, and cell adhesion and signaling. The acquisition of a novel N-glycosylation site may have significant effect on protein structure and function, and therefore, on the phenotype.
  
  
  RESULTS
  We analyzed the human glycoproteome data set (2,534 N-glycosylation sites in 1,027 proteins) and identified 112 novel N-glycosylation sites in 91 proteins that arose in the human lineage since the last common ancestor of Euarchonta (primates and treeshrews). Three of them, Asn-196 in adipocyte plasma membrane-associated protein (APMAP), Asn-91 in cluster of differentiation 166 (CD166/ALCAM), and Asn-76 in thyroglobulin, are human-specific. Molecular evolutionary analysis suggested that these sites were under positive selection during human evolution. Notably, the Asn-76 of thyroglobulin might be involved in the increased production of thyroid hormones in humans, especially thyroxine (T4), because the removal of the glycan moiety from this site was reported to result in a significant decrease in T4 production.
  
  
  CONCLUSIONS
  We propose that the novel N-glycosylation sites described in this study may be useful candidates for functional analyses to identify innovative genetic modifications for beneficial phenotypes acquired in the human lineage.
authors: Dong Seon
authors: DS
authors: Kim
authors: Department of Life Science, Research Center for Biomolecules and Biosystems, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu 156-756, Seoul, Korea. hahny@cau.ac.kr.
authors: Yoonsoo
authors: Y
authors: Hahn
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D030562:Databases, Protein; D019143:Evolution, Molecular; D005326:Fetal Proteins / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D017510:Protein Folding; D021381:Protein Transport; D020543:Proteome / Q000032:analysis; D013954:Thyroglobulin / Q000737:chemistry / Q000378:metabolism; D013974:Thyroxine / Q000737:chemistry / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D006023:Glycoproteins; D020543:Proteome; D013954:Thyroglobulin; D013974:Thyroxine; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule
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