SitesBLAST

Comparing Ga0059261_1623 FitnessBrowser__Korea:Ga0059261_1623 to proteins with known functional sites using BLASTp with E ≤ 0.001.

Found 20 (the maximum) hits to proteins with known functional sites

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
49% identity, 92% coverage: 45:549/549 of query aligns to 20:508/512 of 3dh4A

• binding beta-D-galactopyranose: Q40 (= Q65), Y58 (= Y83), E59 (= E84), S62 (≠ A87), A224 (= A255), N225 (= N256), Y228 (= Y259), W229 (= W260), K259 (= K290), F389 (= F423), Q393 (= Q427)
• binding sodium ion: I36 (= I61), A326 (= A340), S329 (≠ A343)

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
32% identity, 82% coverage: 8:456/549 of query aligns to 5:466/586 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 (= N60), H60 (≠ Q65), G63 (= G68), L64 (≠ M69), T67 (≠ S72), V75 (≠ I80), F78 (≠ Y83), E79 (= E84), A82 (= A87), V137 (≠ S141), V266 (≠ A255), S267 (≠ N256), Y270 (= Y259), W271 (= W260), K301 (= K290), F433 (= F423), D434 (≠ Q424), Q437 (= Q427)

Sites not aligning to the query:

• 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: 506

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)
32% identity, 82% coverage: 8:456/549 of query aligns to 25:486/672 of P31639

• V95 (≠ I80) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
• F98 (≠ Y83) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
• V157 (≠ S141) mutation to A: Decreases D-glucose transporter activity.
• L283 (≠ M252) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
• F453 (= F423) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
32% identity, 82% coverage: 8:456/549 of query aligns to 11:469/602 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 (= N60), H66 (≠ Q65), L70 (≠ M69), I81 (= I80), F84 (≠ Y83), E85 (= E84), A88 (= A87), D256 (= D241), L257 (= L242), M266 (= M252), L269 (≠ A255), T270 (≠ N256), Y273 (= Y259), W274 (= W260), K304 (= K290), F436 (= F423), D437 (≠ Q424), Q440 (= Q427)

Sites not aligning to the query:

• 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: 508

7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
32% identity, 82% coverage: 8:456/549 of query aligns to 10:455/585 of 7slaA

• binding cholesterol hemisuccinate: W36 (= W49), S277 (= S277), Y288 (≠ F288)

Sites not aligning to the query:

• binding cholesterol hemisuccinate: 554, 558, 561

7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
32% identity, 82% coverage: 8:456/549 of query aligns to 9:454/582 of 7sl8A

• binding cholesterol: W35 (= W49), G280 (≠ K281), Y287 (≠ F288)

Sites not aligning to the query:

• binding cholesterol: 551, 554, 555, 558

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)
32% identity, 82% coverage: 8:456/549 of query aligns to 28:486/664 of P13866

• N51 (≠ S27) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
• W67 (= W49) mutation to A: Strong reduction in D-glucose transporter activity.
• S77 (≠ A59) mutation to A: Loss of activity.
• H83 (≠ Q65) 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 (= R117) to W: in GGM; loss of activity
• S159 (≠ T140) to P: in GGM; loss of activity
• A166 (≠ S147) to T: in GGM; about 90% reduction in activity
• D204 (= D185) mutation to A: Loss of activity.
• N248 (≠ T221) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
• C255 (≠ F228) modified: Disulfide link with 511
• W276 (≠ G244) to L: in GGM; about 95% reduction in activity
• T287 (≠ N256) 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 (= Y259) 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 (= W260) mutation to A: Loss of D-glucose transporter activity.
• C292 (≠ G261) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
• Q295 (= Q264) to R: in GGM; loss of activity
• R300 (= R269) to S: in GGM; loss of activity
• A304 (= A273) to V: in GGM; impairs trafficking to the plasma membrane
• K321 (= K290) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
• C345 (≠ L311) 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 (≠ M321) to S: in GGM; loss of activity
• R379 (≠ L330) to Q: in GGM; loss of activity
• A388 (= A339) to V: in GGM; loss of activity
• S396 (= S347) mutation to A: Loss of activity.
• F405 (= F356) to S: in GGM; loss of activity
• A411 (= A362) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
• G426 (= G397) to R: in GGM; loss of activity
• Q451 (= Q421) mutation to A: Strong reduction in water permeation.
• L452 (≠ A422) mutation to A: Loss of water permeation.
• D454 (≠ Q424) mutation to A: Has no effect on water permeation.
• Q457 (= Q427) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
• T460 (≠ S430) mutation to A: Loss of D-glucose transporter activity.
• V470 (≠ I440) to N: in GGM; requires 2 nucleotide substitutions; about 90% reduction in activity

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.

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
29% identity, 82% coverage: 8:458/549 of query aligns to 28:488/659 of Q9NY91

• E457 (≠ Q427) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation
32% identity, 75% coverage: 42:455/549 of query aligns to 19:443/564 of 7ynjA