SitesBLAST

R257 (= R276) mutation to C: Sodium-independent binding affinity for proline.
C281 (≠ F296) 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.

Sites not aligning to the query:

344 C→S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
349 C→S: Does not affect proline uptake activity. Sensitive to N-ethylmaleimide. Na(+)-dependent proline binding activity is similar to wild-type carrier.
376 mutation R->E,Q: No change in activity.; R→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)
26% identity, 28% coverage: 17:191/617 of query aligns to 26:204/643 of Q92911

query
sites
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, 29% coverage: 9:186/617 of query aligns to 27:209/672 of P31639

query
sites
P31639

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V95 (≠ G73) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (≠ Y76) 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.

8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
24% identity, 29% coverage: 9:186/617 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 (= L62), F78 (≠ Y76), E79 (≠ G79)
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, 29% coverage: 9:186/617 of query aligns to 7:189/586 of 8hb0A

query
sites
8hb0A

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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 (= L62), T67 (≠ I65), V75 (≠ G73), F78 (≠ Y76), E79 (≠ G79), 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

8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
24% identity, 29% coverage: 9:186/617 of query aligns to 7:189/590 of 8hg7A

query
sites
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 (= L62), E79 (≠ G79)
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

8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
24% identity, 29% coverage: 9:186/617 of query aligns to 7:189/582 of 8hezA

query
sites
8hezA

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P

D

Q

F

Y

V

L

G

R

D

K

R

R

Y

F

Y

G

S

G

D

R

T

R

A

I

R

R

L

L

-

Y

V

L

A

S

V

V

I

L

G

S

V

L

I

F

F

L

V

Y

S

I

F

F

T

T

Y

K

V

I

A

S

G

V

Q

D

M

M

R

F

G

S

V

G

G

A

I

V

V

F

F

I

S

Q

R

Q

F

A

L

L

Q

G

V

W

D

N

V

I

N

Y

T

A

G

S

V

V

L

I

I

A

G

L

M

L

G

G

I

I

V

T

F

M

F

I

Y

Y

S

T

V

V

L

T

G

G

M

L

K

A

G

A

I

L

T

M

Y

Y

T

T

Q

D

V

T

A

V

Q

Q

Y

T

V

F

V

V

M

I

I

L

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 (= L62), T67 (≠ I65), F78 (≠ Y76), E79 (≠ G79)
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

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
24% identity, 29% coverage: 9:186/617 of query aligns to 7:189/586 of 7vsiA

query
sites
7vsiA

L

L

F

V

V

I

G

A

I

A

S

Y

F

F

A

L

I

L

Y

V

I

I

G

G

I

V

A

G

L

L

W

W

A

S

K

M

A

C

-

R

-

T

-

N

-

R

G

G

S

T

T

V

K

G

D

G

F

Y

Y

F

V

L

A

A

G

G

G

R

G

S

V

M

H

V

P

W

V

W

A

P

N

V

G

G

M

A

A

S

T

L

A

F

A

A

D

S

W
x
N

M

I

S

G

A

S

A

G

S
x
H

F

F

I

V

S
x
G

L
|
L

A

A

G

G

I

T

I

G

S

A

F

A

K

S

G

G

S

L

D

A

G
x
V

S

A

A

G

Y
x
F

L

-

M

-

G
x
E

W

W

T

N

G

A

G

L

Y

F

V

V

-

V

-

L

L

L

A

G

M

W

L

L

L

F

A

A

P

P

Y

V

L

Y

R

L

K

T

F

A

G

G

K

V

F

I

T

T

V

M

P

P

D

Q

F

Y

V

L

G

R

D

K

R

R

Y

F

Y

G

S

G

D

R

T

R

A

I

R

R

L

L

-

Y

V

L

A

S

V

V

I

L

G

S

V

L

I

F

F

L

V

Y

S

I

F

F

T

T

Y

K

V

I

A

S

G

V

Q

D

M

M

R

F

G

S

V

G

G

A

I

V

V

F

F

I

S

Q

R

Q

F

A

L

L

Q

G

V

W

D

N

V

I

N

Y

T

A

G

S

V

V

L

I

I

A

G

L

M

L

G

G

I

I

V

T

F

M

F

I

Y

Y

S

T

V

V

L

T

G

G

M

L

K

A

G

A

I

L

T

M

Y

Y

T

T

Q

D

V

T

A

V

Q

Q

Y

T

V

F

V

V

M

I

I

L

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 (= L62), V75 (≠ G73), F78 (≠ Y76), E79 (≠ G79)

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

Query Sequence

>WP_013134570.1 NCBI__GCF_000092245.1:WP_013134570.1
MELQSLIYLFVGISFAIYIGIALWAKAGSTKDFYVAGGGVHPVANGMATAADWMSAASFI
SLAGIISFKGSDGSAYLMGWTGGYVLLAMLLAPYLRKFGKFTVPDFVGDRYYSDTARLVA
VIGVIFVSFTYVAGQMRGVGIVFSRFLQVDVNTGVLIGMGIVFFYSVLGGMKGITYTQVA
QYVVMIFAYMIPAIFLSLQVTDTFLPQLGIFNTTTFAFDDGVRVIPEGTYLLHALDTAVT
DLGFKAYTQPGNLWNTFMLTTALMLGTAGLPHVIVRFFTVPTVKDARVSAGWALVFIAIM
YTTISSVAAFSRVNLIKNVQNVEYKAFVNGEIEGNNGKWFKTWEHGGLLAWTDRNGDGKI
QYGPDAAFKGKPQFDGTKTGEYGERVTTNAVPATNSGKIENELYVDRDIMVLANPEIANL
PNWVIAFIAAGGLAAALSTAAGLLLVIASAISHDLMGQVIFKDSETGKSTLNEKTELMWA
RISAVVAICIAGYLGIHPPGFVAQVVAFAFGLAAAAFFPTIILGVFDKRMNKEGAIAGIL
TGLIFTFGYIIYFVFMGGDKANYLFGIAPTGIGTIGTILHLIVALVVSRMTPPPPQDIQD
LVERIRIPSGAGDAVDH

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