SitesBLAST
Comparing CA265_RS06755 FitnessBrowser__Pedo557:CA265_RS06755 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)
3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
48% identity, 92% coverage: 46:542/542 of query aligns to 21:508/512 of 3dh4A
7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
33% identity, 82% coverage: 5:448/542 of query aligns to 8:468/602 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 (= H65), L70 (≠ M69), I81 (= I80), F84 (≠ Y83), L257 (= L244), M266 (≠ L254), L269 (≠ N257), T270 (≠ N258), Y273 (= Y261), W274 (= W262), F436 (≠ Y416), D437 (≠ Q417), Q440 (= Q420)
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, 82% coverage: 5:448/542 of query aligns to 25:485/664 of P13866
- N51 (≠ K31) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
- W67 (= W49) mutation to A: Strong reduction in D-glucose transporter activity.
- S77 (= S59) mutation to A: Loss of activity.
- H83 (= H65) 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 (= D184) mutation to A: Loss of activity.
- N248 (≠ S227) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
- C255 (vs. gap) modified: Disulfide link with 511
- W276 (≠ G246) to L: in GGM; about 95% reduction in activity
- T287 (≠ N258) 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 (= Y261) 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 (= W262) mutation to A: Loss of D-glucose transporter activity.
- C292 (≠ G263) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
- Q295 (= Q266) to R: in GGM; loss of activity
- R300 (= R271) to S: in GGM; loss of activity
- A304 (= A275) to V: in GGM; impairs trafficking to the plasma membrane
- K321 (= K291) 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 (≠ S316) modified: Disulfide link with 345
- C355 (≠ D320) modified: Disulfide link with 361
- C361 (≠ K326) modified: Disulfide link with 355
- N363 (≠ D328) mutation to A: Loss of water permeation.
- L369 (= L334) to S: in GGM; loss of activity
- R379 (≠ K343) to Q: in GGM; loss of activity
- A388 (= A352) to V: in GGM; loss of activity
- S396 (≠ G360) mutation to A: Loss of activity.
- F405 (= F369) to S: in GGM; loss of activity
- A411 (≠ K375) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
- G426 (= G391) to R: in GGM; loss of activity
- Q451 (= Q414) mutation to A: Strong reduction in water permeation.
- L452 (≠ V415) mutation to A: Loss of water permeation.
- D454 (≠ Q417) mutation to A: Has no effect on water permeation.
- Q457 (= Q420) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
- T460 (≠ V423) mutation to A: Loss of D-glucose transporter activity.
- V470 (≠ I433) 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.
Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
31% identity, 82% coverage: 2:448/542 of query aligns to 21:485/659 of Q9NY91
- E457 (≠ Q420) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.
7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
34% identity, 82% coverage: 5:448/542 of query aligns to 7:454/585 of 7slaA
Sites not aligning to the query:
7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
34% identity, 82% coverage: 5:448/542 of query aligns to 6:453/582 of 7sl8A
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)
32% identity, 82% coverage: 5:448/542 of query aligns to 25:485/662 of P11170
- C255 (≠ L222) modified: Disulfide link with 608
- Q457 (= Q420) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
- T460 (≠ V423) 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)
33% identity, 82% coverage: 5:448/542 of query aligns to 25:485/656 of Q9ET37
- E457 (≠ Q420) 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, 82% coverage: 5:448/542 of query aligns to 7:447/566 of 7yniA
- binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: H51 (= H65), E70 (= E84), L248 (≠ N257), Y252 (= Y261), F415 (≠ Y416), Q419 (= Q420)
Sites not aligning to the query:
8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
30% identity, 81% coverage: 8:448/542 of query aligns to 5:465/582 of 8hezA
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (= N60), G59 (≠ E64), H60 (= H65), G63 (= G68), L64 (≠ M69), T67 (≠ S72), F78 (≠ Y83), E79 (= E84), V266 (≠ N257), S267 (≠ N258), W271 (= W262), K301 (= K291), F433 (≠ Y416), Q437 (= Q420)
- binding sodium ion: A53 (= A58), I56 (= I61), G57 (≠ S62), A369 (= A353), S372 (≠ A356), S373 (= S357)
Sites not aligning to the query:
8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
30% identity, 81% coverage: 8:448/542 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 (= N60), G59 (≠ E64), H60 (= H65), G63 (= G68), L64 (≠ M69), F78 (≠ Y83), E79 (= E84), S267 (≠ N258), W271 (= W262), F433 (≠ Y416), D434 (≠ Q417), Q437 (= Q420)
- binding sodium ion: A53 (= A58), S54 (= S59), I56 (= I61), G57 (≠ S62), A369 (= A353), S372 (≠ A356), S373 (= S357)
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)
30% identity, 81% coverage: 8:448/542 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 (= N60), H60 (= H65), G63 (= G68), L64 (≠ M69), T67 (≠ S72), V75 (≠ I80), F78 (≠ Y83), E79 (= E84), V137 (≠ S141), V266 (≠ N257), S267 (≠ N258), W271 (= W262), F433 (≠ Y416), Q437 (= Q420)
- binding sodium ion: A53 (= A58), I56 (= I61), G57 (≠ S62), A369 (= A353), S372 (≠ A356), S373 (= S357)
Sites not aligning to the query:
7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
30% identity, 81% coverage: 8:448/542 of query aligns to 5:465/586 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 (= N60), H60 (= H65), G63 (= G68), L64 (≠ M69), V75 (≠ I80), F78 (≠ Y83), E79 (= E84), V266 (≠ N257), S267 (≠ N258), Y270 (= Y261), F433 (≠ Y416), D434 (≠ Q417), Q437 (= Q420)
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)
30% identity, 81% coverage: 8:448/542 of query aligns to 25:485/672 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 (= L254) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
- F453 (≠ Y416) 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)
30% identity, 81% coverage: 8:448/542 of query aligns to 5:465/590 of 8hg7A
- binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (= N60), G59 (≠ E64), H60 (= H65), G63 (= G68), L64 (≠ M69), E79 (= E84), V266 (≠ N257), S267 (≠ N258), Y270 (= Y261), W271 (= W262), K301 (= K291), F433 (≠ Y416), Q437 (= Q420)
- binding sodium ion: A53 (= A58), S54 (= S59), I56 (= I61), G57 (≠ S62), A369 (= A353), S372 (≠ A356), S373 (= S357)
Sites not aligning to the query:
8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
30% identity, 81% coverage: 8:448/542 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 (= S55), A49 (= A58), S50 (= S59), G53 (≠ S62), D177 (= D184), T181 (≠ V188), R276 (= R271), S369 (= S357)
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, 75% coverage: 42:448/542 of query aligns to 19:443/564 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)
25% identity, 83% coverage: 8:456/542 of query aligns to 6:436/480 of 5nv9A
- binding sodium ion: A52 (= A58), T53 (≠ S59), L55 (≠ I61), S56 (= S62), V174 (≠ I180), D178 (= D184), A335 (= A353), S338 (≠ A356), S338 (≠ A356), S339 (= S357), S341 (≠ A359), S342 (≠ G360)
- binding N-acetyl-beta-neuraminic acid: T54 (≠ N60), S56 (= S62), I58 (≠ E64), T59 (≠ H65), G77 (≠ Y83), Q78 (≠ E84), R131 (≠ N138), F239 (≠ L254)
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)
23% identity, 80% coverage: 6:439/542 of query aligns to 14:436/643 of Q92911
- A102 (= A95) natural variant: A -> P
- H226 (= H229) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
- D237 (≠ L244) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
- Y242 (vs. gap) 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 (vs. gap) 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)
22% identity, 80% coverage: 7:437/542 of query aligns to 13:431/610 of Q8N695
- V193 (= V188) to I: in dbSNP:rs1709189
- F251 (≠ W255) 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.
Query Sequence
>CA265_RS06755 FitnessBrowser__Pedo557:CA265_RS06755
MNHLSAFDYAVFLMYFVIVSAYGYWVYRSKKKKRTDTKDYFLAEGSLTWWAIGASIIASN
ISAEHFIGMSGSGFAMGLAIASYEWMAAATLIIVAIFFLPIYIKNKIYTMPQFLSNRYNN
TVSTLMAVFWLLVYVFVNLTSIFFLGAIAIETITGVPFNICIIFLAIFSAIITLGGMKVI
GYTDVIQVFVLVAGGLITCYMALKLVSEKLDAPSVLASLPLLRSEASDHFHMIFSKGDKF
YNELPGIAVLVGGLWINNLNYWGCNQYIVQRALGADLKTGRNGLIFAAFLKLLIPVIVVI
PGIAAYVLYQRGYFHSEMLDAAGVVKPDHAYPVLMNLLPAGIKGLAFAALTAAIVASLAG
KCNSIATIFTLDIYKKFIKPEASETRLVSVGRWSVVIASLIAIIIAPALRSFDQVYQFIQ
EYVGFISPGVFAIFLLGFFWKKTTSRAALTAALLTIPLSTLFKFLPAVTNGAIAPIPFLN
RMSWVFMIIIGLMIVVTLTDPKSKDNPQGLEIDSSMFKVTPAFTIASVMICGILAALYTV
FW
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