SitesBLAST

R257 (= R267) mutation to C: Sodium-independent binding affinity for proline.
C281 (≠ F287) 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 (≠ G396) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (≠ I401) 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 (= R428) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.

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, 35% coverage: 6:204/567 of query aligns to 15:216/643 of Q92911

query
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Q92911

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A102 (= A88) natural variant: A -> P

Sites not aligning to the query:

226 mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
237 D→A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
242 Required for homodimerization; Y→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.
243 Required for homodimerization; T→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.
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

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)
24% identity, 31% coverage: 9:186/567 of query aligns to 27:209/672 of P31639

query
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P31639

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V95 (≠ L77) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (vs. gap) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
V157 (≠ G134) mutation to A: Decreases D-glucose transporter activity.

Sites not aligning to the query:

283 L→M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
453 F→A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
24% identity, 31% coverage: 9:186/567 of query aligns to 7:189/586 of 7vsiA

query
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7vsiA

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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 (≠ W53), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), V75 (≠ L77), F78 (vs. gap), E79 (vs. gap)

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: 266, 267, 270, 433, 434, 437

8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
24% identity, 31% coverage: 9:186/567 of query aligns to 7:189/590 of 8hg7A

query
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8hg7A

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binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (≠ W53), G59 (≠ A57), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), E79 (vs. gap)
binding sodium ion: A53 (= A51), S54 (≠ D52), I56 (≠ M54), G57 (≠ S55)

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: 266, 267, 270, 271, 301, 433, 437
binding sodium ion: 369, 372, 373
binding : 579, 583, 584, 587, 588

8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
24% identity, 31% coverage: 9:186/567 of query aligns to 7:189/586 of 8hdhA

query
sites
8hdhA

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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 (≠ W53), G59 (≠ A57), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), F78 (vs. gap), E79 (vs. gap)
binding sodium ion: A53 (= A51), S54 (≠ D52), I56 (≠ M54), G57 (≠ S55)

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: 267, 271, 433, 434, 437, 506
binding sodium ion: 369, 372, 373
binding : 575, 579, 580, 583, 584

8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
24% identity, 31% coverage: 9:186/567 of query aligns to 7:189/586 of 8hb0A

query
sites
8hb0A

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-

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binding (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ W53), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), T67 (≠ V69), V75 (≠ L77), F78 (vs. gap), E79 (vs. gap), V137 (≠ G134)
binding sodium ion: A53 (= A51), I56 (≠ M54), G57 (≠ S55)

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: 266, 267, 271, 433, 437
binding sodium ion: 369, 372, 373
binding : 575, 576, 579, 580, 583, 584

8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
24% identity, 31% coverage: 9:186/567 of query aligns to 7:189/582 of 8hezA

query
sites
8hezA

I

L

L

V

V

I

G

A

I

A

T

Y

F

F

A

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L

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Y

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-

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x
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x
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x
H

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x
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x
L

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binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ W53), G59 (≠ A57), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), T67 (≠ V69), F78 (vs. gap), E79 (vs. gap)
binding sodium ion: A53 (= A51), I56 (≠ M54), G57 (≠ S55)

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: 266, 267, 271, 301, 433, 437
binding sodium ion: 369, 372, 373
binding : 568, 571, 572, 575, 576, 579, 580

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
29% identity, 24% coverage: 367:503/567 of query aligns to 303:438/512 of 3dh4A

query
sites
3dh4A

A

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binding beta-D-galactopyranose: Q393 (≠ A454)
binding sodium ion: A326 (= A389), S329 (= S392)

Sites not aligning to the query:

binding beta-D-galactopyranose: 40, 58, 59, 62, 225, 229, 259
binding sodium ion: 36

Query Sequence

>WP_068330730.1 NCBI__GCF_001650345.1:WP_068330730.1
MDIQTWTFILVGITFALYIGIAIWARAGSTSEFYVAGGGVHPVANGMATAADWMSAASFI
SMAGIISFVGYDGGVYLMGWTGGYVLLALCLAPYLRKFGQFTVPDFIGERYYSKTARMVA
VFCAIFVSFTYVAGQMRGVGVVFARFLEVDINMGIIIGMGIVFFYAVLGGMKGITYTQVA
QYCVLIFAFMVPAIFTSLMMTGTPIPQIGFGSTLAGSETYLLERLDGLTQELGFTAYTDG
SKSMVDVFFICAALMVGTAGLPHVIIRFFTVPKVSDARVSAGWALVFIAVLYTTAPAVAA
FARVNMIDTINGPDMQGVAASEAPSWYQNWESTGLVSWEDKNGDGKMFYSGDERNEMNIN
RDIIVLASPELAQLPNWVVALLAAGGLAAALSTAAGLLLVISTSISHDLLKKGLKPDMTD
KQELMAARIGAAVAIVGAGYLGINPPGFVAQVVAFSFGLAAASFFPAIILGIFYKQMNKE
GAIAGMLTGITFTAAYIIYFKFINPAASTPENWLFGISPEGIGTLGMCLNFVVAIVVNKF
TAEVPTEVQDMVESIRYPKGAGAAHDH

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