Aβ1 Aα1 Aβ2
rBAT-ED --DWWQEGPMYQIYPRSFKDSNKDGNGDLKGIQDKLDYITALNIKTVWITSFYKSSLKDF 173
2ZE0 KKTWWKEGVAYQIYPRSFMDANGDGIGDLRGIIEKLDYLVELGVDIVWICPIYRSPNADN 61
**:** ******** *:* ** ***:** :****:. *.:. *** .:*:*. *
Aα2 Aβ3 Bα1
rBAT-ED RYGVEDFREVDPIFGTMEDFENLVAAIHDKGLKLIIDFIPNHTSDKHIWFQLSRT-RTGK 232
2ZE0 GYDISDYYAIMDEFGTMDDFDELLAQAHRRGLKVILDLVINHTSDEHPWFIESRSSRDNP 121
*.:.*: : ****:**::*:* * :***:*:*:: *****:* ** **: .
Bα2 Bβ1 Bβ2
rBAT-ED YTDYYIWHDCTHENGKTIPPNNWLSVYGNSSWHFDEVRNQCYFHQFMKEQPDLNFRNPDV 292
2ZE0 KRDWYIWRDGKDG----REPNNWESIFGGSAWQYDERTGQYYLHIFDVKQPDLNWENSEV 177
*:***:* .. **** *::*.*:*::** .* *:* * :*****:.*.:*
Aα3 Aβ4 Aα4
rBAT-ED QEEIKEILRFWLTKGVDGFSLDAVKFLLEAKHLRDEI--QVNKTQIPDTVTQYSELYHDF 350
2ZE0 RQALYEMVNWWLDKGIDGFRIDAISHIKKKPGLPDLPLKYVPSFAGHMNQPGIMEYLREL 241
:: : *::.:** **:*** :**:..: : * * * . . . * :::
Aβ5 Aα5 Aβ6
rBAT-ED TTTQVGMHDIVRSFRQTMDQYSTEPGRYRFMGTEAYAESIDRTVMYYGLPFIQEADFPFN 410
2ZE0 KEQTFARY-DIMTVGEANG---VTVDEAEQWVGEE-NGVFNMIFQFEHLGL------287
. .. : : :. :: . . .. . * :: . : * :
Aα6 Aβ7 Aα7
rBAT-ED NYLSMLDTVSGNSVYEVITSWMENMPEGKWPNWMIGGPDSSRLTSRLGNQ------YVNV 464
2ZE0 --WERRASIDVRRLKRTLTKWQKGLENRGWNALFLENHDLPRSVSTWGNDRDYWAESAKA 344
. ::. . : ..:*.* :.: : * :: . * .* .* **: .:.
Aβ8
rBAT-ED MNMLLFTLPGTPITYYGEEIGMGNIVAANLNESYDINT------LRSKSPMQWDNSS 515
2ZE0 LGALYFFMQGTPFIYQGQEIGMTNVRFDDIRDYRDVSALRIIWKTGRDNSRTPMQWSGAS 424
:. * * : ***: * *:**** *: ::.: *:.: .*::****..:*
Aα8 Cβ1
rBAT-ED NAGFSEASNTWLPTNSDYHTVNVDVQKTQPRSALKLYQDLSLLHANELLLNRGWFCHLR- 574
2ZE0 NAGFTTG-TPWIKVNENYRTINVEAERRDPNSVWSFYRQMIQLRKANELFVYGTYDLLLE 483
****: . ..*: .*.:*:*:**:.:: :*.*. .:*::: *: : *: * : *
Cβ2 Cβ3 Cβ4 Cβ5 Cβ6
rBAT-ED NDSHYVVYTRELDGIDRIFIVVLNFGESTLLNLHNMISGLPA-KIRIRLSTNSADKGSKV 633
2ZE0 NHPSIYAYTRTLGRD-RALVVVNLSDRPSLYRYD---GFRLQSSDLALSNYPVR---PHK 536
*.. .*** *. * ::** ...:* ...... :
Cβ7 Cβ8
rBAT-ED DTSGIFLDKGEGLIFEHNTKNLLHRQTAFRDRCFVSNRACYSSVLNILYTSC 685
2ZE0 NATRFKLKPYEARVYIWKE------555
::: : *. *. :: :
Supplementary Figure 2. Structural alignment of human rBAT ectodomain (ED-rBAT) and GH13 a-glucosidase. This glucosidase is from the deep-sea bacterium Geobacillus sp. (PDBID: 2ZE0). This alignment has been obtained using MODELLER together with other homologous structures (PDBIDs: 2ZIC, 3GBD, 1UOK, 1M53 and 2DH2). The characteristic secondary structure elements are highlighted in the a-glucosidase sequence and labeled with the correspondent domain (A, B or C), a-helix (blue) or b-strand (green) and the order in the domain. The location of reported cystinuria missense mutations are highlighted in red in the ED-rBAT sequence, except for two mutations (Leu89Pro and Ile105Arg) that are in the TM segment. The last 33 rBAT residues are excluded from the structural alignment. *Identical residues in the aligned proteins. :Similar residues in the aligned proteins.