SitesBLAST
Comparing 17328 FitnessBrowser__Keio:17328 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)
P07117 Sodium/proline symporter; Proline carrier; Proline permease; Propionate transporter from Escherichia coli (strain K12) (see 4 papers)
27% identity, 97% coverage: 9:478/483 of query aligns to 8:480/502 of P07117
- R257 (= R259) mutation to C: Sodium-independent binding affinity for proline.
- C281 (≠ L283) mutation to S: Does not affect proline uptake activity. Confers resistance to N-ethylmaleimide. Na(+)-dependent proline binding activity is similar to wild-type carrier.
- C344 (≠ A338) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
- C349 (≠ S343) mutation to S: Does not affect proline uptake activity. Sensitive to N-ethylmaleimide. Na(+)-dependent proline binding activity is similar to wild-type carrier.
- R376 (≠ A371) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
24% identity, 88% coverage: 9:432/483 of query aligns to 32:492/659 of Q9NY91
- E457 (≠ G402) 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)
26% identity, 74% coverage: 6:363/483 of query aligns to 6:401/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ Y56), G59 (≠ S60), H60 (≠ S61), G63 (= G64), L64 (≠ G65), T67 (≠ A68), F78 (≠ I82), E79 (≠ Q83), V266 (≠ T240), S267 (= S241), W271 (≠ L245), K301 (≠ V280)
- binding sodium ion: A53 (= A54), I56 (= I57), G57 (≠ S58), A369 (= A331), S372 (= S334), S373 (≠ T335)
Sites not aligning to the query:
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: 433, 437
- binding : 568, 571, 572, 575, 576, 579, 580
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
26% identity, 74% coverage: 6:363/483 of query aligns to 6:401/586 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 (≠ Y56), H60 (≠ S61), G63 (= G64), L64 (≠ G65), V75 (≠ L79), F78 (≠ I82), E79 (≠ Q83), V266 (≠ T240), S267 (= S241), Y270 (≠ V244)
Sites not aligning to the query:
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
26% identity, 74% coverage: 6:363/483 of query aligns to 6:401/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (≠ Y56), G59 (≠ S60), H60 (≠ S61), G63 (= G64), L64 (≠ G65), E79 (≠ Q83), V266 (≠ T240), S267 (= S241), Y270 (≠ V244), W271 (≠ L245), K301 (≠ V280)
- binding sodium ion: A53 (= A54), S54 (≠ T55), I56 (= I57), G57 (≠ S58), A369 (= A331), S372 (= S334), S373 (≠ T335)
Sites not aligning to the query:
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: 433, 437
- binding : 579, 583, 584, 587, 588
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
26% identity, 74% coverage: 6:363/483 of query aligns to 6:401/586 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 (≠ Y56), G59 (≠ S60), H60 (≠ S61), G63 (= G64), L64 (≠ G65), F78 (≠ I82), E79 (≠ Q83), S267 (= S241), W271 (≠ L245)
- binding sodium ion: A53 (= A54), S54 (≠ T55), I56 (= I57), G57 (≠ S58), A369 (= A331), S372 (= S334), S373 (≠ T335)
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: 433, 434, 437, 506
- binding : 575, 579, 580, 583, 584
8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
26% identity, 74% coverage: 6:363/483 of query aligns to 6:401/586 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 (≠ Y56), H60 (≠ S61), G63 (= G64), L64 (≠ G65), T67 (≠ A68), V75 (≠ L79), F78 (≠ I82), E79 (≠ Q83), V137 (= V141), V266 (≠ T240), S267 (= S241), W271 (≠ L245)
- binding sodium ion: A53 (= A54), I56 (= I57), G57 (≠ S58), A369 (= A331), S372 (= S334), S373 (≠ T335)
Sites not aligning to the query:
- binding (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol: 433, 437
- binding : 575, 576, 579, 580, 583, 584
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)
26% identity, 74% coverage: 6:363/483 of query aligns to 26:421/672 of P31639
- V95 (≠ L79) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F98 (≠ I82) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
- V157 (= V141) mutation to A: Decreases D-glucose transporter activity.
- L283 (vs. gap) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
Sites not aligning to the query:
- 453 F→A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
25% identity, 87% coverage: 9:426/483 of query aligns to 13:454/582 of 7sl8A
Sites not aligning to the query:
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
25% identity, 87% coverage: 9:426/483 of query aligns to 14:455/585 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)
24% identity, 88% coverage: 9:432/483 of query aligns to 32:492/662 of P11170
- C255 (≠ A230) modified: Disulfide link with 608
- Q457 (vs. gap) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (≠ L398) 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)
24% identity, 88% coverage: 9:435/483 of query aligns to 32:495/656 of Q9ET37
- E457 (≠ G402) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
25% identity, 87% coverage: 9:426/483 of query aligns to 15:469/602 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 (≠ Y56), H66 (≠ S61), L70 (vs. gap), I81 (≠ L74), F84 (vs. gap), L257 (≠ I233), M266 (≠ F242), L269 (= L245), T270 (≠ V246), Y273 (≠ G249), W274 (≠ V250), F436 (≠ I392), D437 (≠ I393), Q440 (vs. gap)
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)
25% identity, 87% coverage: 9:426/483 of query aligns to 32:486/664 of P13866
- N51 (≠ S28) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (≠ G45) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (≠ T55) mutation to A: Loss of activity.
- H83 (≠ S61) 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 (= A147) to T: in GGM; about 90% reduction in activity
- D204 (= D185) 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 (≠ S235) to L: in GGM; about 95% reduction in activity
- T287 (≠ V246) 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 (≠ G249) 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 (≠ V250) mutation to A: Loss of D-glucose transporter activity.
- C292 (≠ I251) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
- Q295 (≠ P254) to R: in GGM; loss of activity
- R300 (= R259) to S: in GGM; loss of activity
- A304 (≠ Y263) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (≠ V280) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
- C345 (≠ A296) modified: Disulfide link with 351
- C351 (vs. gap) modified: Disulfide link with 345
- C355 (vs. gap) modified: Disulfide link with 361
- C361 (≠ V303) modified: Disulfide link with 355
- N363 (≠ D305) mutation to A: Loss of water permeation.
- L369 (= L311) to S: in GGM; loss of activity
- R379 (≠ A321) to Q: in GGM; loss of activity
- A388 (= A330) to V: in GGM; loss of activity
- S396 (≠ A338) mutation to A: Loss of activity.
- F405 (≠ I347) to S: in GGM; loss of activity
- A411 (≠ L353) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G378) to R: in GGM; loss of activity
- Q451 (≠ E390) mutation to A: Strong reduction in water permeation.
- L452 (≠ M391) mutation to A: Loss of water permeation.
- D454 (≠ I393) mutation to A: Has no effect on water permeation.
- Q457 (vs. gap) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (≠ L398) mutation to A: Loss of D-glucose transporter activity.
- V470 (= V406) 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.
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
25% identity, 74% coverage: 6:363/483 of query aligns to 13:397/588 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 (≠ T51), A49 (= A54), S50 (≠ T55), G53 (≠ S58), D177 (= D185), T181 (≠ G189), R276 (= R259), S369 (≠ T335)
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)
25% identity, 71% coverage: 13:357/483 of query aligns to 24:373/643 of Q92911
- A102 (≠ G95) natural variant: A -> P
- H226 (≠ L217) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (≠ Q228) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ T240) 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 (≠ S241) 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
7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation (see paper)
25% identity, 74% coverage: 6:363/483 of query aligns to 1:379/564 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)
23% identity, 83% coverage: 33:435/483 of query aligns to 56:466/635 of Q9Y289
- C68 (≠ G45) mutation to A: No effect on biotin transport.
- T78 (= T55) mutation to A: Reduced membrane localization. Decrease in biotin transport.
- C104 (≠ M81) mutation to A: No effect on biotin transport.
- R123 (= R104) to L: in SMVTD; reduced membrane localization; impaired biotin transport
- S128 (≠ T109) mutation to A: No effect on biotin transport.
- N138 (≠ Q119) mutation to A: Reduced protein levels. Decrease in biotin transport.
- C144 (≠ L126) mutation to A: No effect on biotin transport.
- Y162 (≠ I144) to C: in COMNB; no effect on membrane localization
- C187 (≠ I169) mutation to A: No effect on biotin transport.
- S242 (≠ Q228) mutation to A: No effect on biotin transport.
- S283 (= S262) mutation to A: No effect on protein levels or membrane localization.
- T286 (≠ D265) 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 (vs. gap) 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 (≠ T277) mutation to A: No effect on biotin transport.
- C358 (≠ A327) mutation to A: No effect on biotin transport.
- T366 (= T335) mutation to A: No effect on biotin transport.
- R400 (≠ A371) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
- C410 (≠ L381) mutation to A: No effect on biotin transport.
- S429 (≠ L398) to G: in COMNB; no effect on membrane localization
- C443 (≠ V412) mutation to A: No effect on biotin transport.
- C450 (≠ R419) 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.
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
23% identity, 87% coverage: 9:426/483 of query aligns to 14:448/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (≠ S61), E70 (vs. gap), L248 (= L245), Y252 (≠ G249), F415 (≠ I392), Q419 (vs. gap)
Sites not aligning to the query:
3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
27% identity, 78% coverage: 51:426/483 of query aligns to 30:422/512 of 3dh4A
Query Sequence
>17328 FitnessBrowser__Keio:17328
MQLEVILPLVAYLVVVFGISVYAMRKRSTGTFLNEYFLGSRSMGGIVLAMTLTATYISAS
SFIGGPGAAYKYGLGWVLLAMIQLPAVWLSLGILGKKFAILARRYNAVTLNDMLFARYQS
RLLVWLASLSLLVAFVGAMTVQFIGGARLLETAAGIPYETGLLIFGISIALYTAFGGFRA
SVLNDTMQGLVMLIGTVVLLIGVVHAAGGLSNAVQTLQTIDPQLVTPQGADDILSPAFMT
SFWVLVCFGVIGLPHTAVRCISYKDSKAVHRGIIIGTIVVAILMFGMHLAGALGRAVIPD
LTVPDLVIPTLMVKVLPPFAAGIFLAAPMAAIMSTINAQLLQSSATIIKDLYLNIRPDQM
QNETRLKRMSAVITLVLGALLLLAAWKPPEMIIWLNLLAFGGLEAVFLWPLVLGLYWERA
NAKGALSAMIVGGVLYAVLATLNIQYLGFHPIVPSLLLSLLAFLVGNRFGTSVPQATVLT
TDK
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