| Structural highlights
Disease
[S6A19_HUMAN] Hartnup disease;Iminoglycinuria. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for hyperglycinuria. The disease may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families.
Function
[S6A19_HUMAN] Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells (PubMed:18424768, PubMed:18484095, PubMed:19185582, PubMed:26240152). This uptake is sodium-dependent and chloride-independent (PubMed:19185582, PubMed:15286788). Requires CLTRN in kidney or ACE2 in intestine for cell surface expression and amino acid transporter activity (PubMed:19185582, PubMed:18424768).[1] [2] [3] [4] [5] [ACE2_HUMAN] Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[6] [7] [8]
Publication Abstract from PubMed
Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious epidemic COVID-19. Here we present cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B(0)AT1, with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 A, with a local resolution of 3.5 A at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the Collectrin-like domain (CLD) of ACE2 mediating homo-dimerization. The RBD is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. These findings provide important insights to the molecular basis for coronavirus recognition and infection.
Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2.,Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q Science. 2020 Mar 4. pii: science.abb2762. doi: 10.1126/science.abb2762. PMID:32132184[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Seow HF, Broer S, Broer A, Bailey CG, Potter SJ, Cavanaugh JA, Rasko JE. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat Genet. 2004 Sep;36(9):1003-7. doi: 10.1038/ng1406. Epub 2004 Aug 1. PMID:15286788 doi:http://dx.doi.org/10.1038/ng1406
- ↑ Kowalczuk S, Broer A, Tietze N, Vanslambrouck JM, Rasko JE, Broer S. A protein complex in the brush-border membrane explains a Hartnup disorder allele. FASEB J. 2008 Aug;22(8):2880-7. doi: 10.1096/fj.08-107300. Epub 2008 Apr 18. PMID:18424768 doi:http://dx.doi.org/10.1096/fj.08-107300
- ↑ Azmanov DN, Kowalczuk S, Rodgers H, Auray-Blais C, Giguere R, Rasko JE, Broer S, Cavanaugh JA. Further evidence for allelic heterogeneity in Hartnup disorder. Hum Mutat. 2008 Oct;29(10):1217-21. doi: 10.1002/humu.20777. PMID:18484095 doi:http://dx.doi.org/10.1002/humu.20777
- ↑ Camargo SM, Singer D, Makrides V, Huggel K, Pos KM, Wagner CA, Kuba K, Danilczyk U, Skovby F, Kleta R, Penninger JM, Verrey F. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology. 2009 Mar;136(3):872-82. doi: 10.1053/j.gastro.2008.10.055. Epub, 2008 Oct 29. PMID:19185582 doi:http://dx.doi.org/10.1053/j.gastro.2008.10.055
- ↑ Fairweather SJ, Broer A, Subramanian N, Tumer E, Cheng Q, Schmoll D, O'Mara ML, Broer S. Molecular basis for the interaction of the mammalian amino acid transporters B0AT1 and B0AT3 with their ancillary protein collectrin. J Biol Chem. 2015 Oct 2;290(40):24308-25. doi: 10.1074/jbc.M115.648519. Epub 2015, Aug 3. PMID:26240152 doi:http://dx.doi.org/10.1074/jbc.M115.648519
- ↑ Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. PMID:10969042
- ↑ Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. PMID:10924499 doi:http://dx.doi.org/10.1074/jbc.M002615200
- ↑ Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID:14647384 doi:http://dx.doi.org/10.1038/nature02145
- ↑ Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 4. pii: science.abb2762. doi: 10.1126/science.abb2762. PMID:32132184 doi:http://dx.doi.org/10.1126/science.abb2762
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