SitesBLAST
Comparing 5209833 FitnessBrowser__PV4:5209833 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)
52% identity, 92% coverage: 42:519/519 of query aligns to 19:508/512 of 3dh4A
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
33% identity, 83% coverage: 6:434/519 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 (= N58), H66 (≠ Q63), L70 (≠ M67), I81 (= I78), F84 (≠ Y81), L257 (≠ M238), M266 (≠ L250), L269 (≠ M253), T270 (≠ N254), Y273 (= Y257), W274 (= W258), F436 (= F401), D437 (≠ Q402), Q440 (= Q405)
Sites not aligning to the query:
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)
33% identity, 83% coverage: 6:434/519 of query aligns to 28:486/664 of P13866
- N51 (≠ K29) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (= W47) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (= S57) mutation to A: Loss of activity.
- H83 (≠ Q63) 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 (≠ T138) to P: in GGM; loss of activity
- A166 (≠ G145) to T: in GGM; about 90% reduction in activity
- D204 (= D183) mutation to A: Loss of activity.
- N248 (= N234) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (vs. gap) modified: Disulfide link with 511
- W276 (vs. gap) to L: in GGM; about 95% reduction in activity
- T287 (≠ N254) 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 (≠ G259) 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 (= A271) 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 (vs. gap) modified: Disulfide link with 345
- C355 (vs. gap) modified: Disulfide link with 361
- C361 (≠ S311) modified: Disulfide link with 355
- N363 (≠ D313) mutation to A: Loss of water permeation.
- L369 (≠ M319) to S: in GGM; loss of activity
- R379 (≠ K328) to Q: in GGM; loss of activity
- A388 (= A337) to V: in GGM; loss of activity
- S396 (= S345) mutation to A: Loss of activity.
- F405 (= F354) to S: in GGM; loss of activity
- A411 (= A360) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G375) to R: in GGM; loss of activity
- Q451 (= Q399) mutation to A: Strong reduction in water permeation.
- L452 (≠ A400) mutation to A: Loss of water permeation.
- D454 (≠ Q402) mutation to A: Has no effect on water permeation.
- Q457 (= Q405) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (= T408) mutation to A: Loss of D-glucose transporter activity.
- V470 (≠ I418) 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.
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
31% identity, 83% coverage: 6:434/519 of query aligns to 9:454/582 of 7sl8A
Sites not aligning to the query:
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
31% identity, 83% coverage: 6:434/519 of query aligns to 10:455/585 of 7slaA
Sites not aligning to the query:
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
30% identity, 82% coverage: 6:433/519 of query aligns to 28:485/659 of Q9NY91
- E457 (≠ Q405) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
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, 83% coverage: 6:434/519 of query aligns to 28:486/662 of P11170
- C255 (vs. gap) modified: Disulfide link with 608
- Q457 (= Q405) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (= T408) mutation to W: Decreased affinity for glucose and phlorizin.
Sites not aligning to the query:
- 608 modified: Disulfide link with 255
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
32% identity, 82% coverage: 6:433/519 of query aligns to 5:465/586 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 (≠ E62), H60 (≠ Q63), G63 (= G66), L64 (≠ M67), F78 (≠ Y81), E79 (= E82), S267 (≠ N254), W271 (= W258), F433 (= F401), D434 (≠ Q402), Q437 (= Q405)
- binding sodium ion: A53 (= A56), S54 (= S57), I56 (= I59), G57 (≠ S60), A369 (= A338), S372 (= S341), S373 (= S342)
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)
32% identity, 82% coverage: 6:433/519 of query aligns to 5:465/586 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 (≠ Q63), G63 (= G66), L64 (≠ M67), T67 (≠ S70), V75 (≠ I78), F78 (≠ Y81), E79 (= E82), V137 (≠ A139), V266 (≠ M253), S267 (≠ N254), W271 (= W258), F433 (= F401), Q437 (= Q405)
- binding sodium ion: A53 (= A56), I56 (= I59), G57 (≠ S60), A369 (= A338), S372 (= S341), S373 (= S342)
Sites not aligning to the query:
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
32% identity, 83% coverage: 6:434/519 of query aligns to 5:466/582 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 (≠ E62), H60 (≠ Q63), G63 (= G66), L64 (≠ M67), T67 (≠ S70), F78 (≠ Y81), E79 (= E82), V266 (≠ M253), S267 (≠ N254), W271 (= W258), K301 (= K288), F433 (= F401), Q437 (= Q405)
- binding sodium ion: A53 (= A56), I56 (= I59), G57 (≠ S60), A369 (= A338), S372 (= S341), S373 (= S342)
Sites not aligning to the query:
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
32% identity, 83% coverage: 6:434/519 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 (= N58), H60 (≠ Q63), G63 (= G66), L64 (≠ M67), V75 (≠ I78), F78 (≠ Y81), E79 (= E82), V266 (≠ M253), S267 (≠ N254), Y270 (= Y257), F433 (= F401), D434 (≠ Q402), Q437 (= Q405)
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
32% identity, 83% coverage: 6:434/519 of query aligns to 5:466/590 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 (≠ E62), H60 (≠ Q63), G63 (= G66), L64 (≠ M67), E79 (= E82), V266 (≠ M253), S267 (≠ N254), Y270 (= Y257), W271 (= W258), K301 (= K288), F433 (= F401), Q437 (= Q405)
- binding sodium ion: A53 (= A56), S54 (= S57), I56 (= I59), G57 (≠ S60), A369 (= A338), S372 (= S341), S373 (= S342)
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)
32% identity, 83% coverage: 6:434/519 of query aligns to 25:486/672 of P31639
- V95 (≠ I78) 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 (≠ A139) mutation to A: Decreases D-glucose transporter activity.
- L283 (= L250) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (= F401) 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)
31% identity, 82% coverage: 6:433/519 of query aligns to 12:461/588 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 (= A56), S50 (= S57), G53 (≠ S60), D177 (= D183), T181 (≠ V187), R276 (= R267), S369 (= S342)
Sites not aligning to the query:
Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
29% identity, 83% coverage: 6:434/519 of query aligns to 28:486/656 of Q9ET37
- E457 (≠ Q405) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
31% identity, 83% coverage: 6:434/519 of query aligns to 10:448/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (≠ Q63), E70 (= E82), L248 (≠ M253), Y252 (= Y257), F415 (= F401), Q419 (= Q405)
Sites not aligning to the query:
7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation (see paper)
31% identity, 76% coverage: 40:433/519 of query aligns to 19:443/564 of 7ynjA
Sites not aligning to the query:
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, 91% coverage: 6:475/519 of query aligns to 16:491/643 of Q92911
- A102 (≠ G93) natural variant: A -> P
- H226 (= H225) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (≠ H236) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ P241) 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 (≠ G242) 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.
- Q471 (≠ P455) Required for homodimerization; mutation to 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.
Sites not aligning to the query:
- 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)
25% identity, 62% coverage: 5:326/519 of query aligns to 5:305/480 of 5nv9A
- binding sodium ion: A52 (= A56), T53 (≠ S57), L55 (≠ I59), S56 (= S60), V174 (= V179), D178 (= D183)
- binding N-acetyl-beta-neuraminic acid: T54 (≠ N58), S56 (= S60), I58 (≠ E62), T59 (≠ Q63), G77 (≠ Y81), Q78 (≠ E82), R131 (≠ N136), F239 (≠ L250)
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, 80% coverage: 30:445/519 of query aligns to 53:468/635 of Q9Y289
- C68 (≠ W47) mutation to A: No effect on biotin transport.
- T78 (≠ S57) mutation to A: Reduced membrane localization. Decrease in biotin transport.
- C104 (≠ W83) mutation to A: No effect on biotin transport.
- R123 (≠ K102) to L: in SMVTD; reduced membrane localization; impaired biotin transport
- S128 (≠ T107) mutation to A: No effect on biotin transport.
- N138 (≠ D117) mutation to A: Reduced protein levels. Decrease in biotin transport.
- C144 (vs. gap) mutation to A: No effect on biotin transport.
- Y162 (≠ W142) to C: in COMNB; no effect on membrane localization
- C187 (≠ S167) mutation to A: No effect on biotin transport.
- S242 (≠ I229) mutation to A: No effect on biotin transport.
- S283 (≠ A270) mutation to A: No effect on protein levels or membrane localization.
- T286 (≠ S273) 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 (≠ A285) 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 (≠ L293) mutation to A: No effect on biotin transport.
- C358 (≠ A334) mutation to A: No effect on biotin transport.
- T366 (≠ S342) mutation to A: No effect on biotin transport.
- R400 (= R376) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
- C410 (≠ A386) mutation to A: No effect on biotin transport.
- S429 (≠ Q405) to G: in COMNB; no effect on membrane localization
- C443 (≠ L420) mutation to A: No effect on biotin transport.
- C450 (≠ R427) 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.
Query Sequence
>5209833 FitnessBrowser__PV4:5209833
MLETLDIGILLVYALGLLGLALWISRQDKRHERDTKDYFLAGKALPWWAIGASLIASNIS
AEQIIGMSGSGYAIGLAIASYEWMAAITLILVGKYMLPIFIKNEIYTMPQYLEQRFDKRV
KTTLALFWLSVYILVNLTAVLWLGGLAIETVAGIDWLYGMVFLALFSLAYSLYGGLKAVA
YTDIIQVVLLIFGGLLLSYLALDRVADGQGVLAGFDRLSSALPEHFEMILSQSNPHYMSL
PGISVLVGGLWIMNISYWGFNQYIIQRALAAKSVAEAQKGIAFAAYLKLLMPLIVVLPGI
AAVLLYPGLESPDQAYPSMMALMPAGVKGLVFAALVAAIVSSLASMTNSISTIFTMDIYA
MLRPAKSEGHYVLVGRLSSLISLLIALVMAQPLLGEFEQAFQYIQEFTGVFTPGIVVIFL
TGMFWRRATSQGALAAALGSAIFSFGLRFYWPELPFMDRIGLVFLLCLALSVLVSLMGRS
LEEGASVALGGVSFKTGRAFNVSALGVVVILNFLYVTWW
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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