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 paper)
36% identity, 94% coverage: 5:534/564 of query aligns to 25:570/672 of P31639
- V95 (≠ M74) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F98 (≠ W77) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
- V157 (= V134) mutation to A: Decreases D-glucose transporter activity.
- L283 (≠ S250) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (≠ Y418) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.
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 6 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
- 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; mutation to A: Has no effect on water permeability.
- Q295 (= Q262) to R: in GGM; loss of activity
- 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
- 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
- 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
- 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
- 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
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)
Q9Y289 Sodium-dependent multivitamin transporter; Na(+)-dependent multivitamin transporter; hSMVT; Solute carrier family 5 member 6 from Homo sapiens (Human) (see 10 papers)
24% identity, 67% coverage: 84:460/564 of query aligns to 110:466/635 of Q9Y289
- R123 (= R97) to L: in SMVTD; reduced membrane localization; impaired biotin transport
- S128 (≠ T102) mutation to A: No effect on biotin transport.
- N138 (= N112) mutation to A: Reduced protein levels. Decrease in biotin transport.
- C144 (≠ I122) mutation to A: No effect on biotin transport.
- Y162 (≠ F143) to C: in COMNB; no effect on membrane localization
- C187 (≠ T169) mutation to A: No effect on biotin transport.
- S242 (≠ M229) mutation to A: No effect on biotin transport.
- S283 (= S270) mutation to A: No effect on protein levels or membrane localization.
- T286 (≠ N273) mutation to A: Resistant to phorbol 12-myristate 13-acetate (PMA)-induced inhibition of biotin transport. No effect on protein levels or membrane localization.
- C294 (≠ T281) mutation to A: Reduced membrane localization. Decrease in biotin transport (decreased Vmax, no change in Km).; mutation C->S,M: Decrease in biotin transport.
- C309 (≠ L296) mutation to A: No effect on biotin transport.
- C358 (≠ G351) mutation to A: No effect on biotin transport.
- T366 (≠ S359) mutation to A: No effect on biotin transport.
- R400 (≠ I391) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
- C410 (≠ I401) mutation to A: No effect on biotin transport.
- S429 (≠ Q422) to G: in COMNB; no effect on membrane localization
- C443 (≠ L437) mutation to A: No effect on biotin transport.
- C450 (≠ R444) mutation to A: No effect on biotin transport.
Sites not aligning to the query:
- 68 C→A: No effect on biotin transport.
- 78 T→A: Reduced membrane localization. Decrease in biotin transport.
- 94:635 natural variant: Missing (in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778)
- 104 C→A: No effect on biotin transport.
- 481 S → F: in dbSNP:rs1395
- 489 N→A: Slight decrease in protein levels. Decrease in biotin transport.
- 498 N→A: No effect on biotin transport.
- 534 N→A: No effect on biotin transport.
- 567:635 mutation Missing: Loss of biotin transport. Loss of membrane localization.
- 570:635 mutation Missing: Loss of biotin transport. Loss of membrane localization.
- 575:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
- 577 C→A: No effect on biotin transport.
- 583 C→A: No effect on biotin transport.
- 584:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
- 600:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
- 612:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
- 616:635 mutation Missing: Loss of apical membrane localization in polarized cells. Basolateral localization in polarized cells.
- 620:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.
- 624:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.
- 627 T→A: No effect on biotin transport.
- 628 mutation C->A,S: Decrease in biotin transport.
- 632:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.
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