| Structural highlights
Function
MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.RECK_MOUSE Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28803732). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (PubMed:26658478, PubMed:28803732). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7 (By similarity). ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (By similarity). Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity (PubMed:11747814). Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP) (PubMed:11747814).[UniProtKB:O95980][1] [2] [3]
Publication Abstract from PubMed
Five small protein domains, the CC-domains, at the N terminus of the RECK protein, play essential roles in signaling by WNT7A and WNT7B in the context of central nervous system angiogenesis and blood-brain barrier formation and maintenance. We have determined the structure of CC domain 4 (CC4) at 1.65-A resolution and find that it folds into a compact four-helix bundle with three disulfide bonds. The CC4 structure, together with homology modeling of CC1, reveals the surface locations of critical residues that were shown in previous mutagenesis studies to mediate GPR124 binding and WNT7A/WNT7B recognition and signaling. Surprisingly, sequence and structural homology searches reveal no other cell-surface or secreted domains in vertebrates that resemble the CC domain, a pattern that is in striking contrast to other ancient and similarly sized domains, such as Epidermal Growth Factor, Fibronectin Type 3, Immunoglobulin, and Thrombospondin type 1 domains, which are collectively present in hundreds of proteins.
Structure of the RECK CC domain, an evolutionary anomaly.,Chang TH, Hsieh FL, Smallwood PM, Gabelli SB, Nathans J Proc Natl Acad Sci U S A. 2020 Jun 15. pii: 2006332117. doi:, 10.1073/pnas.2006332117. PMID:32541044[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C, Noda M. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell. 2001 Dec 14;107(6):789-800. PMID:11747814 doi:10.1016/s0092-8674(01)00597-9
- ↑ de Almeida GM, Yamamoto M, Morioka Y, Ogawa S, Matsuzaki T, Noda M. Critical roles for murine Reck in the regulation of vascular patterning and stabilization. Sci Rep. 2015 Dec 11;5:17860. PMID:26658478 doi:10.1038/srep17860
- ↑ Cho C, Smallwood PM, Nathans J. Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation. Neuron. 2017 Aug 30;95(5):1056-1073.e5. PMID:28803732 doi:10.1016/j.neuron.2017.07.031
- ↑ Chang TH, Hsieh FL, Smallwood PM, Gabelli SB, Nathans J. Structure of the RECK CC domain, an evolutionary anomaly. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15104-15111. PMID:32541044 doi:10.1073/pnas.2006332117
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