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2.A.22.6.3
B(O)AT1 or BOAT (SLC6A19; Hartnup's disease protein) is a kidney and intestinal apical membrane epithelial transporter for Na+-dependent, Cl--independent reabsorption of neutral amino acids. Many neutral L-amino acids bind with ~0.5 mM affinities; Leu is the preferred substrate, but all large, neutral, non-aromatic, L-amino acids bind to this transporter. Uptake of leucine is sodium-dependent. In contrast to other members of the neurotransmitter transporter family, this one does not appear to be chloride-dependent.  Activity is enhanced by collectrin (Tmem27), a collecting duct transmembrane (1 TMS) glycoprotein (Q9HBJ8) (Danilczyk et al., 2006). The mouse orthologue is (Q9D687) (Broer et al., 2004; 2008) which is deficient due to mutation(s) in its structural gene, and it forms a complex with collectrin and the brush border carboxypeptidase angiotensin-converting enzyme 2 (ACE2; Q9BYF1). Mutations in Hartnup disorder protein, such as B0AT1(R240Q), decrease complex formation (Kraut and Sachs 2005) and lead to neutral aminoaciduria and in some cases pellagra-like symptoms (Kowalczuk et al., 2008; Singer et al. 2012).  Collectrin is expressed at high levels in the simple embryonic kidney (the pronephros) of amphibians such as Xenopus  (McCoy et al. 2008). ACE2 plays an important role in amino acid transport by acting as a binding partner of SLC6A19 in  the intestine, regulating its trafficking, expression on the cell surface and catalytic activity (Kowalczuk et al. 2008, Camargo et al. 2009). ACE2 is also the cellular receptor for SARS-CoV and SARS-CoV-2 ( causitive agent of COVID-19). Yan et al. 2020 presented cryoEM structures of full-length human ACE2 in the presence of B0AT1 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 angstroms. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues (Yan et al. 2020).

Accession Number:Q695T7
Protein Name:Sodium-dependent neutral amino acid transporter B(0)
Length:634
Molecular Weight:71110.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Na+, Cl-, Neutral amino acids

Cross database links:

RefSeq: NP_001003841.1   
Entrez Gene ID: 340024   
Pfam: PF00209   
OMIM: 234500  phenotype
608893  gene
KEGG: hsa:340024    hsa:340024   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005328 F:neurotransmitter:sodium symporter activity
GO:0006836 P:neurotransmitter transport
GO:0005886 C:plasma membrane
GO:0015175 F:neutral amino acid transmembrane transporter activity
GO:0006865 P:amino acid transport
GO:0006811 P:ion transport
GO:0007584 P:response to nutrient
GO:0055085 P:transmembrane transport

References (7)

[1] “Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder.”  Kleta R.et.al.   15286787
[2] “Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.”  Seow H.F.et.al.   15286788
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder.”  Kleta R.et.al.   15286787
[5] “Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19.”  Seow H.F.et.al.   15286788
[6] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[7] “Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters.”  Broer S.et.al.   19033659
Structure:
6M17   6M18   6M1D     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MVRLVLPNPG LDARIPSLAE LETIEQEEAS SRPKWDNKAQ YMLTCLGFCV GLGNVWRFPY 
61:	LCQSHGGGAF MIPFLILLVL EGIPLLYLEF AIGQRLRRGS LGVWSSIHPA LKGLGLASML 
121:	TSFMVGLYYN TIISWIMWYL FNSFQEPLPW SDCPLNENQT GYVDECARSS PVDYFWYRET 
181:	LNISTSISDS GSIQWWMLLC LACAWSVLYM CTIRGIETTG KAVYITSTLP YVVLTIFLIR 
241:	GLTLKGATNG IVFLFTPNVT ELAQPDTWLD AGAQVFFSFS LAFGGLISFS SYNSVHNNCE 
301:	KDSVIVSIIN GFTSVYVAIV VYSVIGFRAT QRYDDCFSTN ILTLINGFDL PEGNVTQENF 
361:	VDMQQRCNAS DPAAYAQLVF QTCDINAFLS EAVEGTGLAF IVFTEAITKM PLSPLWSVLF 
421:	FIMLFCLGLS SMFGNMEGVV VPLQDLRVIP PKWPKEVLTG LICLGTFLIG FIFTLNSGQY 
481:	WLSLLDSYAG SIPLLIIAFC EMFSVVYVYG VDRFNKDIEF MIGHKPNIFW QVTWRVVSPL 
541:	LMLIIFLFFF VVEVSQELTY SIWDPGYEEF PKSQKISYPN WVYVVVVIVA GVPSLTIPGY 
601:	AIYKLIRNHC QKPGDHQGLV STLSTASMNG DLKY