SitesBLAST
Comparing 17739 b3679 predicted transporter (NCBI) to proteins with known functional sites using BLASTp with E ≤ 0.001.
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Found 20 (the maximum) hits to proteins with known functional sites (download)
3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
31% identity, 73% coverage: 39:456/571 of query aligns to 19:437/512 of 3dh4A
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
27% identity, 75% coverage: 2:431/571 of query aligns to 8:463/602 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 (= N55), H66 (≠ Q60), L70 (= L64), I81 (≠ V75), F84 (≠ W78), L257 (= L242), M266 (≠ L251), L269 (≠ V254), T270 (≠ N255), Y273 (= Y258), W274 (= W259), F436 (≠ Y404), D437 (≠ S405), Q440 (≠ K408)
Sites not aligning to the query:
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
26% identity, 78% coverage: 2:449/571 of query aligns to 25:502/659 of Q9NY91
- E457 (≠ K408) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
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)
27% identity, 75% coverage: 2:431/571 of query aligns to 25:480/664 of P13866
- N51 (≠ D28) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (≠ A44) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (≠ T54) mutation to A: Loss of activity.
- H83 (≠ Q60) 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 (= R112) to W: in GGM; loss of activity
- S159 (≠ V137) to P: in GGM; loss of activity
- A166 (= A142) to T: in GGM; about 90% reduction in activity
- D204 (= D190) mutation to A: Loss of activity.
- N248 (vs. gap) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (≠ L224) modified: Disulfide link with 511
- W276 (≠ I244) to L: in GGM; about 95% reduction in activity
- T287 (≠ N255) 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 (= Y258) 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 (= W259) mutation to A: Loss of D-glucose transporter activity.
- C292 (= C260) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
- Q295 (= Q263) to R: in GGM; loss of activity
- R300 (= R268) to S: in GGM; loss of activity
- A304 (≠ S272) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (= K289) 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 (vs. gap) modified: Disulfide link with 345
- C355 (vs. gap) modified: Disulfide link with 361
- C361 (vs. gap) modified: Disulfide link with 355
- N363 (≠ D314) mutation to A: Loss of water permeation.
- L369 (= L320) to S: in GGM; loss of activity
- R379 (≠ V330) to Q: in GGM; loss of activity
- A388 (≠ G339) to V: in GGM; loss of activity
- S396 (≠ G347) mutation to A: Loss of activity.
- F405 (= F356) to S: in GGM; loss of activity
- A411 (≠ R362) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G378) to R: in GGM; loss of activity
- Q451 (vs. gap) mutation to A: Strong reduction in water permeation.
- L452 (= L403) mutation to A: Loss of water permeation.
- D454 (≠ S405) mutation to A: Has no effect on water permeation.
- Q457 (≠ K408) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (≠ N411) mutation to A: Loss of D-glucose transporter activity.
- V470 (≠ I421) to N: in GGM; about 90% reduction in activity; requires 2 nucleotide substitutions
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)
- 499 R → H: in GGM; impairs trafficking to the plasma membrane; decreases the sugar affinity
- 511 modified: Disulfide link with 255
- 517 modified: Disulfide link with 522
- 522 modified: Disulfide link with 517
- 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.
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
30% identity, 75% coverage: 2:431/571 of query aligns to 2:460/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N55), G59 (≠ E59), H60 (≠ Q60), G63 (= G63), L64 (= L64), T67 (≠ Q67), F78 (≠ W78), E79 (= E79), V266 (= V254), S267 (≠ N255), W271 (= W259), K301 (= K289), F433 (≠ Y404), Q437 (≠ K408)
- binding sodium ion: A53 (≠ L53), I56 (≠ L56), G57 (≠ S57), A369 (= A340), S372 (= S343), S373 (≠ T344)
Sites not aligning to the query:
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
30% identity, 75% coverage: 2:431/571 of query aligns to 2:460/586 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 (= N55), H60 (≠ Q60), G63 (= G63), L64 (= L64), V75 (= V75), F78 (≠ W78), E79 (= E79), V266 (= V254), S267 (≠ N255), Y270 (= Y258), F433 (≠ Y404), D434 (≠ S405), Q437 (≠ K408)
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
30% identity, 75% coverage: 2:431/571 of query aligns to 2:460/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (= N55), G59 (≠ E59), H60 (≠ Q60), G63 (= G63), L64 (= L64), E79 (= E79), V266 (= V254), S267 (≠ N255), Y270 (= Y258), W271 (= W259), K301 (= K289), F433 (≠ Y404), Q437 (≠ K408)
- binding sodium ion: A53 (≠ L53), S54 (≠ T54), I56 (≠ L56), G57 (≠ S57), A369 (= A340), S372 (= S343), S373 (≠ T344)
Sites not aligning to the query:
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
30% identity, 75% coverage: 2:431/571 of query aligns to 2:460/586 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 (= N55), G59 (≠ E59), H60 (≠ Q60), G63 (= G63), L64 (= L64), F78 (≠ W78), E79 (= E79), S267 (≠ N255), W271 (= W259), F433 (≠ Y404), D434 (≠ S405), Q437 (≠ K408)
- binding sodium ion: A53 (≠ L53), S54 (≠ T54), I56 (≠ L56), G57 (≠ S57), A369 (= A340), S372 (= S343), S373 (≠ T344)
Sites not aligning to the query:
- 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: 506
- binding : 575, 579, 580, 583, 584
8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
30% identity, 75% coverage: 2:431/571 of query aligns to 2:460/586 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 (= N55), H60 (≠ Q60), G63 (= G63), L64 (= L64), T67 (≠ Q67), V75 (= V75), F78 (≠ W78), E79 (= E79), V137 (≠ I136), V266 (= V254), S267 (≠ N255), W271 (= W259), F433 (≠ Y404), Q437 (≠ K408)
- binding sodium ion: A53 (≠ L53), I56 (≠ L56), G57 (≠ S57), A369 (= A340), S372 (= S343), S373 (≠ T344)
Sites not aligning to the query:
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
28% identity, 69% coverage: 40:431/571 of query aligns to 32:449/585 of 7slaA
Sites not aligning to the query:
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
28% identity, 69% coverage: 40:431/571 of query aligns to 31:448/582 of 7sl8A
Sites not aligning to the query:
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)
30% identity, 75% coverage: 2:431/571 of query aligns to 22:480/672 of P31639
- V95 (= V75) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F98 (≠ W78) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
- V157 (≠ I136) mutation to A: Decreases D-glucose transporter activity.
- L283 (= L251) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (≠ Y404) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.
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)
26% identity, 75% coverage: 2:431/571 of query aligns to 25:480/662 of P11170
- C255 (≠ I235) modified: Disulfide link with 608
- Q457 (≠ K408) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (≠ N411) mutation to W: Decreased affinity for glucose and phlorizin.
Sites not aligning to the query:
- 608 modified: Disulfide link with 255
Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
26% identity, 83% coverage: 2:474/571 of query aligns to 25:522/656 of Q9ET37
- E457 (≠ K408) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
29% identity, 75% coverage: 2:431/571 of query aligns to 9:456/588 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 (= S50), A49 (≠ L53), S50 (≠ T54), G53 (≠ S57), D177 (= D190), T181 (≠ G194), R276 (= R268), S369 (≠ T344)
Sites not aligning to the query:
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
26% identity, 69% coverage: 40:431/571 of query aligns to 31:442/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (≠ Q60), E70 (= E79), L248 (≠ V254), Y252 (= Y258), F415 (≠ Y404), Q419 (≠ K408)
Sites not aligning to the query:
7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation (see paper)
29% identity, 69% coverage: 37:431/571 of query aligns to 19:438/564 of 7ynjA
Sites not aligning to the query:
Q9Y289 Sodium-dependent multivitamin transporter; Na(+)-dependent multivitamin transporter; hSMVT; Solute carrier family 5 member 6 from Homo sapiens (Human) (see 10 papers)
25% identity, 72% coverage: 37:445/571 of query aligns to 61:465/635 of Q9Y289
- C68 (≠ A44) mutation to A: No effect on biotin transport.
- T78 (= T54) mutation to A: Reduced membrane localization. Decrease in biotin transport.
- C104 (≠ V80) mutation to A: No effect on biotin transport.
- R123 (≠ K99) to L: in SMVTD; reduced membrane localization; impaired biotin transport
- S128 (≠ T104) mutation to A: No effect on biotin transport.
- N138 (≠ D114) mutation to A: Reduced protein levels. Decrease in biotin transport.
- C144 (≠ I120) mutation to A: No effect on biotin transport.
- Y162 (= Y139) to C: in COMNB; no effect on membrane localization
- C187 (≠ G174) mutation to A: No effect on biotin transport.
- S242 (≠ I235) mutation to A: No effect on biotin transport.
- S283 (≠ A271) mutation to A: No effect on protein levels or membrane localization.
- T286 (≠ S274) 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 (≠ A286) 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 (≠ V297) mutation to A: No effect on biotin transport.
- C358 (≠ V336) mutation to A: No effect on biotin transport.
- T366 (= T344) mutation to A: No effect on biotin transport.
- R400 (≠ V377) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
- C410 (vs. gap) mutation to A: No effect on biotin transport.
- S429 (≠ Q409) to G: in COMNB; no effect on membrane localization
- C443 (≠ I423) mutation to A: No effect on biotin transport.
- C450 (≠ R430) mutation to A: No effect on biotin transport.
Sites not aligning to the query:
- 94:635 natural variant: Missing (in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778)
- 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.
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)
22% identity, 73% coverage: 12:429/571 of query aligns to 20:438/643 of Q92911
- A102 (= A90) natural variant: A -> P
- H226 (≠ A229) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (= D240) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ A246) 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 (≠ A247) 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
Q8N695 Sodium-coupled monocarboxylate transporter 1; Apical iodide transporter; Electrogenic sodium monocarboxylate cotransporter; Sodium iodide-related cotransporter; Solute carrier family 5 member 8 from Homo sapiens (Human) (see 3 papers)
24% identity, 56% coverage: 31:351/571 of query aligns to 41:359/610 of Q8N695
- V193 (≠ I195) to I: in dbSNP:rs1709189
- F251 (= F257) to V: in dbSNP:rs11834933
Sites not aligning to the query:
- 608 T→A: Loss of interaction with PDZK1.
- 608:610 PDZ-binding
- 610 L→A: Loss of interaction with PDZK1.
Query Sequence
>17739 b3679 predicted transporter (NCBI)
MNSLQILSFVGFTLLVAVITWWKVRKTDTGSQQGYFLAGRSLKAPVIAASLMLTNLSTEQ
LVGLSGQAYKSGMSVMGWEVTSAVTLIFLALIFLPRYLKRGIATIPDFLEERYDKTTRII
IDFCFLIATGVCFLPIVLYSGALALNSLFHVGESLQISHGAAIWLLVILLGLAGILYAVI
GGLRAMAVADSINGIGLVIGGLMVPVFGLIAMGKGSFMQGIEQLTTVHAEKLNSIGGPTD
PLPIGAAFTGLILVNTFYWCTNQGIVQRTLASKSLAEGQKGALLTAVLKMLDPLVLVLPG
LIAFHLYQDLPKADMAYPTLVNNVLPVPMVGFFGAVLFGAVISTFNGFLNSASTLFSMGI
YRRIINQNAEPQQLVTVGRKFGFFIAIVSVLVAPWIANAPQGLYSWMKQLNGIYNVPLVT
IIIMGFFFPRIPALAAKVAMGIGIISYITINYLVKFDFHFLYVLACTFCINVVVMLVIGF
IKPRATPFTFKDAFAVDMKPWKNVKIASIGILFAMIGVYAGLAEFGGYGTRWLAMISYFI
AAVVIVYLIFDSWRHRHDPAVTFTPDGKDSL
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