SitesBLAST
Comparing CA265_RS19720 FitnessBrowser__Pedo557:CA265_RS19720 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)
47% identity, 92% coverage: 48:558/558 of query aligns to 21:508/512 of 3dh4A
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
31% identity, 83% coverage: 1:463/558 of query aligns to 19:498/659 of Q9NY91
- E457 (≠ Q422) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
31% identity, 80% coverage: 7:452/558 of query aligns to 8:470/602 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 (= N62), H66 (≠ Q67), L70 (≠ M71), I81 (= I82), F84 (≠ Y85), L257 (≠ I244), M266 (= M256), L269 (≠ V259), T270 (≠ N260), Y273 (= Y263), W274 (= W264), F436 (= F418), D437 (≠ Q419), Q440 (= Q422)
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)
31% identity, 80% coverage: 7:452/558 of query aligns to 25:487/664 of P13866
- N51 (≠ K33) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (= W51) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (= S61) mutation to A: Loss of activity.
- H83 (≠ Q67) 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 (= R119) to W: in GGM; loss of activity
- S159 (≠ T142) to P: in GGM; loss of activity
- A166 (= A149) to T: in GGM; about 90% reduction in activity
- D204 (= D186) mutation to A: Loss of activity.
- N248 (≠ Y221) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (≠ A228) modified: Disulfide link with 511
- W276 (≠ L246) to L: in GGM; about 95% reduction in activity
- T287 (≠ N260) 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 (= Y263) 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 (= W264) mutation to A: Loss of D-glucose transporter activity.
- C292 (≠ G265) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
- Q295 (= Q268) to R: in GGM; loss of activity
- R300 (= R273) to S: in GGM; loss of activity
- A304 (= A277) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (= K293) 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 (≠ S318) modified: Disulfide link with 345
- C355 (≠ Q322) modified: Disulfide link with 361
- C361 (≠ P328) modified: Disulfide link with 355
- N363 (≠ R330) mutation to A: Loss of water permeation.
- L369 (= L335) to S: in GGM; loss of activity
- R379 (≠ K344) to Q: in GGM; loss of activity
- A388 (= A353) to V: in GGM; loss of activity
- S396 (≠ G361) mutation to A: Loss of activity.
- F405 (= F370) to S: in GGM; loss of activity
- A411 (≠ K376) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G392) to R: in GGM; loss of activity
- Q451 (≠ G417) mutation to A: Strong reduction in water permeation.
- L452 (vs. gap) mutation to A: Loss of water permeation.
- D454 (≠ Q419) mutation to A: Has no effect on water permeation.
- Q457 (= Q422) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (= T425) mutation to A: Loss of D-glucose transporter activity.
- V470 (≠ M435) 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, 80% coverage: 7:452/558 of query aligns to 6:455/582 of 7sl8A
Sites not aligning to the query:
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
31% identity, 80% coverage: 7:452/558 of query aligns to 7:456/585 of 7slaA
Sites not aligning to the query:
Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
30% identity, 83% coverage: 3:463/558 of query aligns to 21:498/656 of Q9ET37
- E457 (≠ Q422) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
32% identity, 80% coverage: 7:452/558 of query aligns to 2:467/586 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 (= N62), G59 (≠ E66), H60 (≠ Q67), G63 (= G70), L64 (≠ M71), F78 (≠ Y85), E79 (= E86), S267 (≠ N260), W271 (= W264), F433 (= F418), D434 (≠ Q419), Q437 (= Q422)
- binding sodium ion: A53 (= A60), S54 (= S61), I56 (= I63), G57 (≠ S64), A369 (= A354), S372 (≠ A357), S373 (= S358)
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, 80% coverage: 7:452/558 of query aligns to 2:467/586 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 (= N62), H60 (≠ Q67), G63 (= G70), L64 (≠ M71), T67 (≠ S74), V75 (≠ I82), F78 (≠ Y85), E79 (= E86), V137 (≠ S143), V266 (= V259), S267 (≠ N260), W271 (= W264), F433 (= F418), Q437 (= Q422)
- binding sodium ion: A53 (= A60), I56 (= I63), G57 (≠ S64), A369 (= A354), S372 (≠ A357), S373 (= S358)
Sites not aligning to the query:
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
32% identity, 80% coverage: 7:452/558 of query aligns to 2:467/586 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 (= N62), H60 (≠ Q67), G63 (= G70), L64 (≠ M71), V75 (≠ I82), F78 (≠ Y85), E79 (= E86), V266 (= V259), S267 (≠ N260), Y270 (= Y263), F433 (= F418), D434 (≠ Q419), Q437 (= Q422)
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, 81% coverage: 2:452/558 of query aligns to 16:487/672 of P31639
- V95 (≠ I82) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F98 (≠ Y85) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
- V157 (≠ S143) mutation to A: Decreases D-glucose transporter activity.
- L283 (≠ M256) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (= F418) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.
8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
32% identity, 80% coverage: 7:452/558 of query aligns to 2:467/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (= N62), G59 (≠ E66), H60 (≠ Q67), G63 (= G70), L64 (≠ M71), E79 (= E86), V266 (= V259), S267 (≠ N260), Y270 (= Y263), W271 (= W264), K301 (= K293), F433 (= F418), Q437 (= Q422)
- binding sodium ion: A53 (= A60), S54 (= S61), I56 (= I63), G57 (≠ S64), A369 (= A354), S372 (≠ A357), S373 (= S358)
Sites not aligning to the query:
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
32% identity, 80% coverage: 7:452/558 of query aligns to 2:467/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N62), G59 (≠ E66), H60 (≠ Q67), G63 (= G70), L64 (≠ M71), T67 (≠ S74), F78 (≠ Y85), E79 (= E86), V266 (= V259), S267 (≠ N260), W271 (= W264), K301 (= K293), F433 (= F418), Q437 (= Q422)
- binding sodium ion: A53 (= A60), I56 (= I63), G57 (≠ S64), A369 (= A354), S372 (≠ A357), S373 (= S358)
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, 82% coverage: 3:458/558 of query aligns to 21:493/662 of P11170
- C255 (≠ A228) modified: Disulfide link with 608
- Q457 (= Q422) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (= T425) mutation to W: Decreased affinity for glucose and phlorizin.
Sites not aligning to the query:
- 608 modified: Disulfide link with 255
7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
30% identity, 80% coverage: 7:452/558 of query aligns to 7:449/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (≠ Q67), E70 (= E86), L248 (≠ V259), Y252 (= Y263), F415 (= F418), Q419 (= Q422)
Sites not aligning to the query:
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
31% identity, 81% coverage: 2:452/558 of query aligns to 3:463/588 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 (= S57), A49 (= A60), S50 (= S61), G53 (≠ S64), D177 (= D186), T181 (≠ V190), R276 (= R273), S369 (= S358)
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, 79% coverage: 12:452/558 of query aligns to 2:445/564 of 7ynjA
Sites not aligning to the query:
5nv9A Substrate-bound outward-open state of a na+-coupled sialic acid symporter reveals a novel na+-site (see paper)
26% identity, 79% coverage: 11:451/558 of query aligns to 4:429/480 of 5nv9A
- binding sodium ion: A52 (= A60), T53 (≠ S61), L55 (≠ I63), S56 (= S64), V174 (≠ I182), D178 (= D186), A335 (= A354), S338 (≠ A357), S338 (≠ A357), S339 (= S358), S341 (≠ A360), S342 (≠ G361)
- binding N-acetyl-beta-neuraminic acid: T54 (≠ N62), S56 (= S64), I58 (≠ E66), T59 (≠ Q67), G77 (≠ Y85), Q78 (≠ E86), R131 (≠ N140), F239 (≠ M256)
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)
25% identity, 81% coverage: 10:462/558 of query aligns to 14:454/610 of Q8N695
- V193 (= V190) to I: in dbSNP:rs1709189
- F251 (≠ W257) 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.
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, 77% coverage: 10:441/558 of query aligns to 16:436/643 of Q92911
- A102 (= A97) natural variant: A -> P
- H226 (= H231) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (= D239) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (≠ I244) 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 (≠ D245) 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
Query Sequence
>CA265_RS19720 FitnessBrowser__Pedo557:CA265_RS19720
MKNNLLDTKDYIVFAIYFVIVAAYGLYIYNKKKSASTGSKDYFLAEGSLTWWAIGASLIA
SNISAEQFIGMSGSGFKMGLAIATYEWMAALTLVIVAVFFIPVYLKNKIATMPQFLHQRY
NGTVAMIMAVFWLLLYVVVNLTSILYLGALAVSSISGFDLTFCMYAIAAFAIVITLGGMK
VIGYTDVIQVFFLILGGLATTYLALNLVSTHYGTSGIFEGYSLMTSKASEHFHMILKPDN
ENYIDLPGLSVLVGGMWIVNLNYWGCNQYITQRALGADLKTARGGILFAAFLKLLMPIIV
VLPGIAAYVLYKDGAFQSEMLQDGSVNPDRAYPVLLNLLPAGLKGLSFAALTAAVVASLA
GKANSIATIFTLDIYKKVLKTDASEKNLVFTGKIAVVVAMVLGVVIAPYLGIDKKGGFQY
IQEYTGFVSPGIFAMFILGFFWKRATSNAALFATVGGFGLSLLLKVLPTWTDLSWLSGMG
FSVKNGVGVYEIPFLDRMGFVFVFCVIGMVIISLFENRNGVNPKGLEIDSKMFKTTTGFA
VGSLIIIGLLVALYSVYW
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