1IVZ

Solution structure of the SEA domain from murine hypothetical protein homologous to human mucin 16

1IVZ の概要

• エントリーDOI: 10.2210/pdb1ivz/pdb
• 分子名称: hypothetical protein 1110008I14RIK (1 entity in total)
• 機能のキーワード: structural genomics, sea domain, mucin 16, riken structural genomics/proteomics initiative, rsgi, unknown function
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14668.08

構造登録者

Maeda, T.,Inoue, M.,Kigawa, T.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2002-04-02, 公開日: 2002-10-02, 最終更新日: 2023-12-27)

主引用文献

Maeda, T.,Inoue, M.,Koshiba, S.,Yabuki, T.,Aoki, M.,Nunokawa, E.,Seki, E.,Matsuda, T.,Motoda, Y.,Kobayashi, A.,Hiroyasu, F.,Shirouzu, M.,Terada, T.,Hayami, N.,Ishizuka, Y.,Shinya, N.,Tatsuguchi, A.,Yoshida, M.,Hirota, H.,Matsuo, Y.,Tani, K.,Arakawa, T.,Carninci, P.,Kawai, J.,Hayashizaki, Y.,Kigawa, T.,Yokoyama, S.
Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16)
J.Biol.Chem., 279:13174-13182, 2004

PubMed Abstract: Human CA125, encoded by the MUC16 gene, is an ovarian cancer antigen widely used for a serum assay. Its extracellular region consists of tandem repeats of SEA domains. In this study we determined the three-dimensional structure of the SEA domain from the murine MUC16 homologue using multidimensional NMR spectroscopy. The domain forms a unique alpha/beta sandwich fold composed of two alpha helices and four antiparallel beta strands and has a characteristic turn named the TY-turn between alpha1 and alpha2. The internal mobility of the main chain is low throughout the domain. The residues that form the hydrophobic core and the TY-turn are fully conserved in all SEA domain sequences, indicating that the fold is common in the family. Interestingly, no other residues are conserved throughout the family. Thus, the sequence alignment of the SEA domain family was refined on the basis of the three-dimensional structure, which allowed us to classify the SEA domains into several subfamilies. The residues on the surface differ between these subfamilies, suggesting that each subfamily has a different function. In the MUC16 SEA domains, the conserved surface residues, Asn-10, Thr-12, Arg-63, Asp-75, Asp-112, Ser-115, and Phe-117, are clustered on the beta sheet surface, which may be functionally important. The putative epitope (residues 58-77) for anti-MUC16 antibodies is located around the beta2 and beta3 strands. On the other hand the tissue tumor marker MUC1 has a SEA domain belonging to another subfamily, and its GSVVV motif for proteolytic cleavage is located in the short loop connecting beta2 and beta3.

PubMed: 14764598
DOI: 10.1074/jbc.M309417200

実験手法

SOLUTION NMR