SitesBLAST
Comparing 349883 FitnessBrowser__Btheta:349883 to proteins with known functional sites using BLASTp with E ≤ 0.001.
Or try Sites on a Tree, PaperBLAST, Conserved Domains, or compare to all protein structures
Found 20 (the maximum) hits to proteins with known functional sites (download)
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
36% identity, 91% coverage: 2:514/564 of query aligns to 25:549/659 of Q9NY91
- E457 (≠ Q422) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
35% identity, 99% coverage: 5:564/564 of query aligns to 5:581/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N54), G59 (≠ E58), H60 (= H59), G63 (= G62), L64 (= L63), T67 (≠ A66), F78 (≠ W77), E79 (= E78), V266 (≠ I253), S267 (≠ G254), W271 (= W258), K301 (= K288), F433 (≠ Y418), Q437 (= Q422)
- binding sodium ion: A53 (= A52), I56 (= I55), G57 (= G56), A369 (= A355), S372 (= S358), S373 (= S359)
- binding : L568 (≠ V550), M571 (≠ L553), A572 (= A554), V575 (≠ A558), F576 (= F559), G579 (≠ Y562), F580 (= F563)
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
35% identity, 99% coverage: 5:564/564 of query aligns to 5:585/586 of 8hdhA
- binding (2~{S},3~{R},4~{R},5~{S},6~{R})-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl]-4-methyl-phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N54), G59 (≠ E58), H60 (= H59), G63 (= G62), L64 (= L63), F78 (≠ W77), E79 (= E78), S267 (≠ G254), W271 (= W258), F433 (≠ Y418), D434 (≠ T419), Q437 (= Q422), Y506 (≠ W491)
- binding sodium ion: A53 (= A52), S54 (= S53), I56 (= I55), G57 (= G56), A369 (= A355), S372 (= S358), S373 (= S359)
- binding : M575 (≠ L553), V579 (≠ A558), F580 (= F559), G583 (≠ Y562), F584 (= F563)
8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
35% identity, 99% coverage: 5:564/564 of query aligns to 5:585/586 of 8hb0A
- binding (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N54), H60 (= H59), G63 (= G62), L64 (= L63), T67 (≠ A66), V75 (≠ M74), F78 (≠ W77), E79 (= E78), V137 (= V134), V266 (≠ I253), S267 (≠ G254), W271 (= W258), F433 (≠ Y418), Q437 (= Q422)
- binding sodium ion: A53 (= A52), I56 (= I55), G57 (= G56), A369 (= A355), S372 (= S358), S373 (= S359)
- binding : M575 (≠ L553), A576 (= A554), V579 (≠ A558), F580 (= F559), G583 (≠ Y562), F584 (= F563)
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
35% identity, 99% coverage: 5:564/564 of query aligns to 5:585/586 of 7vsiA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N54), H60 (= H59), G63 (= G62), L64 (= L63), V75 (≠ M74), F78 (≠ W77), E79 (= E78), V266 (≠ I253), S267 (≠ G254), Y270 (= Y257), F433 (≠ Y418), D434 (≠ T419), Q437 (= Q422)
Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
35% identity, 95% coverage: 2:534/564 of query aligns to 25:570/656 of Q9ET37
- E457 (≠ Q422) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
35% identity, 99% coverage: 5:564/564 of query aligns to 5:589/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (= N54), G59 (≠ E58), H60 (= H59), G63 (= G62), L64 (= L63), E79 (= E78), V266 (≠ I253), S267 (≠ G254), Y270 (= Y257), W271 (= W258), K301 (= K288), F433 (≠ Y418), Q437 (= Q422)
- binding sodium ion: A53 (= A52), S54 (= S53), I56 (= I55), G57 (= G56), A369 (= A355), S372 (= S358), S373 (= S359)
- binding : M579 (≠ L553), V583 (≠ A558), F584 (= F559), G587 (≠ Y562), F588 (= F563)
P31639 Sodium/glucose cotransporter 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter; Solute carrier family 5 member 2 from Homo sapiens (Human) (see 2 papers)
36% identity, 94% coverage: 5:534/564 of query aligns to 25:570/672 of P31639
- A73 (= A52) binding Na(+)
- S74 (= S53) mutation to A: Impairs phlorizin binding and its inhibition on glucose uptake.
- I76 (= I55) binding Na(+)
- V95 (≠ M74) mutation to I: Strong reduction in D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
- F98 (≠ W77) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes empagliflozin binding and its inhibition on glucose uptake. Impairs phlorizin binding and its inhibition on glucose uptake.
- V157 (= V134) mutation to A: Decreases D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
- D201 (≠ S185) mutation to A: Impairs phlorizin binding and its inhibition on glucose uptake.
- L283 (≠ S250) mutation to M: Strong reduction in D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
- A389 (= A355) binding Na(+)
- S392 (= S358) binding Na(+)
- S393 (= S359) binding Na(+)
- F453 (≠ Y418) mutation to A: Slightly decreases D-glucose transporter activity. Impairs empagliflozin binding and its inhibition on glucose uptake. Impairs phlorizin binding and its inhibition on glucose uptake.
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
36% identity, 100% coverage: 2:563/564 of query aligns to 7:576/585 of 7slaA
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
36% identity, 100% coverage: 2:563/564 of query aligns to 6:573/582 of 7sl8A
P11170 Sodium/glucose cotransporter 1; Na(+)/glucose cotransporter 1; High affinity sodium-glucose cotransporter; Solute carrier family 5 member 1 from Oryctolagus cuniculus (Rabbit) (see 2 papers)
37% identity, 87% coverage: 2:494/564 of query aligns to 25:529/662 of P11170
- C255 (vs. gap) modified: Disulfide link with 608
- Q457 (= Q422) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (≠ Q425) mutation to W: Decreased affinity for glucose and phlorizin.
Sites not aligning to the query:
- 608 modified: Disulfide link with 255
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
36% identity, 91% coverage: 2:514/564 of query aligns to 8:532/602 of 7wmvA
- binding N-[2-(dimethylamino)ethyl]-2-methyl-2-[4-[4-[[2-methyl-5-[(2S,3R,4R,5S,6R)-6-methylsulfanyl-3,4,5-tris(oxidanyl)oxan-2-yl]phenyl]methyl]phenyl]butanoylamino]propanamide: N61 (= N54), H66 (= H59), L70 (= L63), I81 (≠ M74), F84 (≠ W77), L257 (≠ F241), M266 (≠ S250), L269 (≠ I253), T270 (≠ G254), Y273 (= Y257), W274 (= W258), F436 (≠ Y418), D437 (≠ T419), Q440 (= Q422), H508 (≠ N490)
P13866 Sodium/glucose cotransporter 1; Na(+)/glucose cotransporter 1; High affinity sodium-glucose cotransporter; Solute carrier family 5 member 1 from Homo sapiens (Human) (see 7 papers)
36% identity, 91% coverage: 2:514/564 of query aligns to 25:549/664 of P13866
- N51 (≠ K27) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (= W43) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (= S53) mutation to A: Loss of activity.
- H83 (= H59) mutation to L: Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and C-290.; mutation to Q: Loss of D-glucose transporter activity.
- R135 (= R110) to W: in GGM; loss of activity
- S159 (≠ A133) to P: in GGM; loss of activity; dbSNP:rs933026071
- A166 (≠ G140) to T: in GGM; about 90% reduction in activity
- D204 (≠ S185) mutation to A: Loss of activity.
- N248 (≠ D227) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (vs. gap) modified: Disulfide link with 511
- W276 (= W243) to L: in GGM; about 95% reduction in activity
- T287 (≠ G254) mutation to A: Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with L-83 and C-290.; mutation to N: Loss of D-glucose transporter activity. Has strict selectivity for D-galactose.; mutation T->S,A: Has normal D-glucose and D-galactose transporter activity.
- Y290 (= Y257) mutation to C: Loss of D-galactose transporter activity. Has strict selectivity for D-glucose. Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and L-83.
- W291 (= W258) mutation to A: Loss of D-glucose transporter activity.
- C292 (= C259) to Y: in GGM; loss of activity; dbSNP:rs765502638; mutation to A: Has no effect on water permeability.
- Q295 (= Q262) to R: in GGM; loss of activity; dbSNP:rs779428134
- R300 (= R267) to S: in GGM; loss of activity
- A304 (≠ G271) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (= K288) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
- C345 (vs. gap) modified: Disulfide link with 351
- C351 (≠ G314) modified: Disulfide link with 345
- C355 (≠ L318) modified: Disulfide link with 361
- C361 (≠ N327) modified: Disulfide link with 355
- N363 (≠ D329) mutation to A: Loss of water permeation.
- L369 (= L335) to S: in GGM; loss of activity
- R379 (≠ K345) to Q: in GGM; loss of activity; dbSNP:rs747215838
- A388 (= A354) to V: in GGM; loss of activity
- S396 (= S362) mutation to A: Loss of activity.
- F405 (= F371) to S: in GGM; loss of activity
- A411 (≠ K377) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G392) to R: in GGM; loss of activity; dbSNP:rs1304151494
- Q451 (≠ V416) mutation to A: Strong reduction in water permeation.
- L452 (= L417) mutation to A: Loss of water permeation.
- D454 (≠ T419) mutation to A: Has no effect on water permeation.
- Q457 (= Q422) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (≠ Q425) mutation to A: Loss of D-glucose transporter activity.
- V470 (≠ A435) to N: in GGM; about 90% reduction in activity; requires 2 nucleotide substitutions
- R499 (= R464) to H: in GGM; impairs trafficking to the plasma membrane; decreases the sugar affinity; dbSNP:rs927157864
- C511 (≠ E476) modified: Disulfide link with 255
- C517 (≠ F482) modified: Disulfide link with 522
- C522 (≠ Y487) modified: Disulfide link with 517
Sites not aligning to the query:
- 191:664 natural variant: Missing (in GGM; loss of activity)
- 379:664 natural variant: Missing (in GGM; loss of activity)
- 615 H → Q: in GGM; slightly decreased activity; dbSNP:rs33954001
- 641 W→A: Slightly reduced D-glucose transporter activity.
- 660:661 HA→WG: Loss of D-glucose transporter activity.
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
35% identity, 96% coverage: 5:547/564 of query aligns to 12:559/588 of 8hinA
- binding 1-[2-[(2S,3R,4S,5S,6R)-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-4,6-bis(oxidanyl)phenyl]-3-(4-hydroxyphenyl)propan-1-one: S46 (= S49), A49 (= A52), S50 (= S53), G53 (= G56), D177 (≠ S185), T181 (= T189), R276 (= R267), S369 (= S359)
Sites not aligning to the query:
7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation (see paper)
34% identity, 99% coverage: 7:564/564 of query aligns to 2:563/564 of 7ynjA
- binding methyl alpha-D-glucopyranoside: H42 (= H59), E61 (= E78), Y248 (= Y257), F411 (≠ Y418), Q415 (= Q422), S418 (≠ Q425)
- binding : L550 (≠ V550), M553 (≠ L553), V557 (≠ A558), F558 (= F559), G561 (≠ Y562), F562 (= F563)
Sites not aligning to the query:
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
37% identity, 84% coverage: 39:514/564 of query aligns to 31:503/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (= H59), E70 (= E78), L248 (≠ I253), Y252 (= Y257), F415 (≠ Y418), Q419 (= Q422)
Sites not aligning to the query:
3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
34% identity, 75% coverage: 38:462/564 of query aligns to 19:433/512 of 3dh4A
Q92911 Sodium/iodide cotransporter; Na(+)/I(-) cotransporter; Natrium iodide transporter; Sodium-iodide symporter; Na(+)/I(-) symporter; Solute carrier family 5 member 5 from Homo sapiens (Human) (see 3 papers)
24% identity, 68% coverage: 5:389/564 of query aligns to 16:385/643 of Q92911
- A102 (≠ G88) natural variant: A -> P
- H226 (≠ D227) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (= D238) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ F241) Required for homodimerization; mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471. Loss of iodide transport activity; when associated with F-535.
- T243 (≠ P242) Required for homodimerization; mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471.
Sites not aligning to the query:
- 471 Required for homodimerization; Q→A: No effect on localization to the cell membrane, iodide transport activity and homodimerization. Significant loss of homodimerization; when associated with A-242 or A243.
- 525 A→F: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Loss of iodide transport activity; when associated with A-242.
- 536 T → Q: requires 2 nucleotide substitutions
- 556 S → Q: requires 2 nucleotide substitutions
B4EZY7 Sodium/sialic acid symporter SiaT; Na(+)-coupled sialic acid symporter; Sialic acid transporter from Proteus mirabilis (strain HI4320) (see paper)
26% identity, 80% coverage: 7:459/564 of query aligns to 22:445/496 of B4EZY7
- A56 (= A52) binding Na(+)
- T58 (≠ N54) mutation to A: 2-fold increase in Neu5Ac transport.
- L59 (≠ I55) binding Na(+)
- S60 (≠ G56) mutation to A: Abolishes Neu5Ac transport.
- T63 (≠ H59) mutation to A: Abolishes Neu5Ac transport.
- Q82 (≠ E78) mutation to D: Abolishes Neu5Ac transport.
- R135 (≠ K131) mutation to E: Abolishes Neu5Ac transport.
- D182 (≠ S185) binding Na(+); mutation to A: Abolishes Neu5Ac transport.
- A339 (= A355) binding Na(+)
- S342 (= S358) binding Na(+); binding Na(+); mutation to A: Abolishes Neu5Ac transport.
- S343 (= S359) binding Na(+); mutation to A: Abolishes Neu5Ac transport.
- S345 (≠ A361) binding Na(+); mutation to A: Reduces Neu5Ac transport.
- S346 (= S362) binding Na(+); mutation to A: Slightly increases Neu5Ac transport.
5nv9A Substrate-bound outward-open state of a na+-coupled sialic acid symporter reveals a novel na+-site (see paper)
26% identity, 80% coverage: 7:459/564 of query aligns to 18:437/480 of 5nv9A
- binding sodium ion: A52 (= A52), T53 (≠ S53), L55 (≠ I55), S56 (≠ G56), V174 (= V181), D178 (≠ S185), A335 (= A355), S338 (= S358), S338 (= S358), S339 (= S359), S341 (≠ A361), S342 (= S362)
- binding N-acetyl-beta-neuraminic acid: T54 (≠ N54), S56 (≠ G56), I58 (≠ E58), T59 (≠ H59), G77 (≠ W77), Q78 (≠ E78), R131 (≠ K131), F239 (= F255)
Query Sequence
>349883 FitnessBrowser__Btheta:349883
MEALDWLVIGVFFLALIGIIVWVVRQKQNDSADYFLGGRDATWLAIGASIFASNIGSEHL
IGLAGAGASSGMAMAHWEIQGWMILILGWVFVPFYSRSMVYTMPEFLERRYNPQSRTILS
VISLVSYVLTKVAVTVYAGGLVFQQVFGIKELWGIDFFWIAAIGLVVLTALYTIFGGMKS
VLYTSVLQTPILLLGSLIILVLGFKELGGWDEMMRVCGAVTVNDYGDTMTNLIRSNDDAN
FPWLGALIGSAIIGFWYWCTDQFIVQRVLSGKNEKEARRGTIFGAYLKLLPVFLFLIPGM
IAFALHQKYIGAGGEGFLPMLANGTANADAAFPTLVAKLLPAGVKGLVVCGILAALMSSL
ASLFNSSAMLFTIDFYKRFRPETPEKKLVGIGQIATVVIVILGILWIPIMRSVGDVLYTY
LQDVQSVLAPGIAAAFLLGICWKRTSAQGGMWGLIAGMIIGLTRLGAKVYYSNAGEVADS
TFKYLFYDMNWLFFCGWMFLFCIIVVIVVSLATEAPTAEKIQGLVFGTATKEQKAATRAS
WDHWDIIHTVIILAITGAFYWYFW
Or try a new SitesBLAST search
SitesBLAST's Database
SitesBLAST's database includes
(1) SwissProt
entries with experimentally-supported functional features;
and (2) protein structures with bound ligands, from the
BioLip database.
by Morgan Price,
Arkin group
Lawrence Berkeley National Laboratory