SitesBLAST
Comparing 349869 BT0341 Na+/glucose cotransporter (NCBI ptt file) 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)
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
30% identity, 95% coverage: 2:498/523 of query aligns to 1:549/582 of 7sl8A
Sites not aligning to the query:
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
31% identity, 92% coverage: 2:482/523 of query aligns to 2:518/585 of 7slaA
Sites not aligning to the query:
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)
31% identity, 84% coverage: 2:440/523 of query aligns to 20:497/662 of P11170
- C255 (vs. gap) modified: Disulfide link with 608
- Q457 (= Q398) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (≠ L401) 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)
30% identity, 92% coverage: 2:482/523 of query aligns to 3:532/602 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 (= N58), H66 (≠ M63), L70 (≠ S67), I81 (≠ S78), F84 (≠ Y81), L257 (≠ F231), M266 (≠ Y240), L269 (≠ M243), T270 (≠ G244), Y273 (≠ F247), W274 (= W248), F436 (= F394), D437 (≠ N395), Q440 (= Q398), H508 (= H458)
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)
30% identity, 92% coverage: 2:482/523 of query aligns to 20:549/664 of P13866
- N51 (≠ K31) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (= W47) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (≠ T57) mutation to A: Loss of activity.
- H83 (≠ M63) 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 (= R115) to W: in GGM; loss of activity
- S159 (≠ A138) to P: in GGM; loss of activity
- A166 (≠ G145) to T: in GGM; about 90% reduction in activity
- D204 (≠ N183) mutation to A: Loss of activity.
- N248 (vs. gap) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (vs. gap) modified: Disulfide link with 511
- W276 (= W233) to L: in GGM; about 95% reduction in activity
- T287 (≠ G244) 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 (≠ F247) 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 (= W248) mutation to A: Loss of D-glucose transporter activity.
- C292 (= C249) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
- Q295 (= Q252) to R: in GGM; loss of activity
- R300 (≠ P257) to S: in GGM; loss of activity
- A304 (= A261) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (= K278) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
- C345 (≠ L299) 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 (vs. gap) mutation to A: Loss of water permeation.
- L369 (≠ M309) to S: in GGM; loss of activity
- R379 (≠ V319) to Q: in GGM; loss of activity
- A388 (= A328) to V: in GGM; loss of activity
- S396 (= S336) mutation to A: Loss of activity.
- F405 (= F345) to S: in GGM; loss of activity
- A411 (≠ V351) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G367) to R: in GGM; loss of activity
- Q451 (≠ N392) mutation to A: Strong reduction in water permeation.
- L452 (= L393) mutation to A: Loss of water permeation.
- D454 (≠ N395) mutation to A: Has no effect on water permeation.
- Q457 (= Q398) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (≠ L401) mutation to A: Loss of D-glucose transporter activity.
- V470 (= V411) to N: in GGM; about 90% reduction in activity; requires 2 nucleotide substitutions
- R499 (≠ T431) to H: in GGM; impairs trafficking to the plasma membrane; decreases the sugar affinity
- C511 (≠ L443) modified: Disulfide link with 255
- C517 (≠ Q452) modified: Disulfide link with 522
- C522 (≠ A455) 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.
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
30% identity, 82% coverage: 7:433/523 of query aligns to 25:492/659 of Q9NY91
- E457 (≠ Q398) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
31% identity, 79% coverage: 13:426/523 of query aligns to 8:465/586 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 (= N58), G59 (≠ S62), H60 (≠ M63), G63 (≠ A66), L64 (≠ S67), F78 (≠ Y81), E79 (≠ A82), S267 (≠ G244), W271 (= W248), F433 (= F394), D434 (≠ N395), Q437 (= Q398)
- binding sodium ion: A53 (≠ G56), S54 (≠ T57), I56 (≠ V59), G57 (= G60), A369 (= A329), S372 (= S332), S373 (≠ T333)
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)
31% identity, 79% coverage: 13:426/523 of query aligns to 8:465/586 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 (= N58), H60 (≠ M63), G63 (≠ A66), L64 (≠ S67), T67 (≠ A70), V75 (≠ S78), F78 (≠ Y81), E79 (≠ A82), V137 (≠ L139), V266 (≠ M243), S267 (≠ G244), W271 (= W248), F433 (= F394), Q437 (= Q398)
- binding sodium ion: A53 (≠ G56), I56 (≠ V59), G57 (= G60), A369 (= A329), S372 (= S332), S373 (≠ T333)
Sites not aligning to the query:
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
31% identity, 79% coverage: 13:426/523 of query aligns to 8:465/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N58), G59 (≠ S62), H60 (≠ M63), G63 (≠ A66), L64 (≠ S67), T67 (≠ A70), F78 (≠ Y81), E79 (≠ A82), V266 (≠ M243), S267 (≠ G244), W271 (= W248), K301 (= K278), F433 (= F394), Q437 (= Q398)
- binding sodium ion: A53 (≠ G56), I56 (≠ V59), G57 (= G60), A369 (= A329), S372 (= S332), S373 (≠ T333)
Sites not aligning to the query:
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
31% identity, 79% coverage: 13:426/523 of query aligns to 8:465/586 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 (= N58), H60 (≠ M63), G63 (≠ A66), L64 (≠ S67), V75 (≠ S78), F78 (≠ Y81), E79 (≠ A82), V266 (≠ M243), S267 (≠ G244), Y270 (≠ F247), F433 (= F394), D434 (≠ N395), Q437 (= Q398)
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
31% identity, 79% coverage: 13:426/523 of query aligns to 8:465/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (= N58), G59 (≠ S62), H60 (≠ M63), G63 (≠ A66), L64 (≠ S67), E79 (≠ A82), V266 (≠ M243), S267 (≠ G244), Y270 (≠ F247), W271 (= W248), K301 (= K278), F433 (= F394), Q437 (= Q398)
- binding sodium ion: A53 (≠ G56), S54 (≠ T57), I56 (≠ V59), G57 (= G60), A369 (= A329), S372 (= S332), S373 (≠ T333)
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)
31% identity, 79% coverage: 13:426/523 of query aligns to 28:485/672 of P31639
- V95 (≠ S78) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F98 (≠ Y81) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
- V157 (≠ L139) mutation to A: Decreases D-glucose transporter activity.
- L283 (≠ Y240) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (= F394) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
30% identity, 79% coverage: 13:426/523 of query aligns to 15:461/588 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 (= S53), A49 (≠ G56), S50 (≠ T57), G53 (= G60), D177 (≠ N183), T181 (≠ M187), R276 (≠ P257), S369 (≠ T333)
Sites not aligning to the query:
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
29% identity, 81% coverage: 2:426/523 of query aligns to 2:447/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (≠ M63), E70 (≠ A82), L248 (≠ M243), Y252 (≠ F247), F415 (= F394), Q419 (= Q398)
Sites not aligning to the query:
7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation (see paper)
30% identity, 79% coverage: 13:426/523 of query aligns to 3:443/564 of 7ynjA
Sites not aligning to the query:
Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
28% identity, 83% coverage: 7:438/523 of query aligns to 25:497/656 of Q9ET37
- E457 (≠ Q398) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
29% identity, 73% coverage: 43:426/523 of query aligns to 20:421/512 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)
22% identity, 79% coverage: 10:423/523 of query aligns to 16:442/643 of Q92911
- A102 (= A93) natural variant: A -> P
- H226 (≠ A217) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (≠ N226) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ F231) 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 (≠ P232) 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, 83% coverage: 10:442/523 of query aligns to 14:458/610 of Q8N695
- V193 (≠ M187) to I: in dbSNP:rs1709189
- F251 (≠ W246) 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.
7sl9A Cryoem structure of smct1 (see paper)
26% identity, 69% coverage: 81:442/523 of query aligns to 67:437/497 of 7sl9A
Query Sequence
>349869 BT0341 Na+/glucose cotransporter (NCBI ptt file)
MHAKFLDTLDWGILIAYFLILIAIGIWASSKRKKGSSLFLAEHSLRWHHIGFSMWGTNVG
PSMLIASASAGFTTGIVSGNYAWYAFVFICLLAFVFAPRYLGSRVSTLPEFMGKRFGQST
RNILAWYTIVTILISWLALTLFAGGVLIRQVFDIPMWQSALILLIISAFFTMLGGLKAVA
YTNVYQMILLILVSAALAIVGIYKVGGISALTDAVPADFWNLFRPNDDTAFPWLPIILGY
PVMGVWFWCTDQSMVQPVLAAKSLKEGQLGTNFTGWLKILDVPLYILPGIICLALFPQLE
NPDEAYMTMVTHLFPVGMVGLVLAVLTAALVSTIGSALNALSTVFTMDIYVKKIRPQAKQ
KEIIRVGQVVTVAGALISVIITIAIDSIHGLNLFNVFQSVLGFIAPPMAAVFLFGVFWKR
TTTLAANAALTVGTVFSIGVGVLYLWVFPADQYSAWPHFMLLSFYLFVIIGIGMVVVGLL
DKTPQTAILNMEKIEEKPARIVLILWGLLIVTMIGLYIFFNGH
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