SitesBLAST

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)
29% identity, 82% coverage: 38:425/474 of query aligns to 58:495/662 of P11170

query
sites
P11170

Y

F

F

F

L

L

A

A

G

G

G

R

G

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M

S

V

W

W

I

W

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S

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F

M

A

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S

N

N

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I

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G

A

S

E

G

Q

H

I

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V

G

G

M

L

N

A

G

G

-

T

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G

-

A

A

A

Q

S

T

G

L

I

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A

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A

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W

G

W

F

E

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W

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I

C255 (≠ R216) modified: Disulfide link with 608
Q457 (= Q387) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
T460 (≠ N390) mutation to W: Decreased affinity for glucose and phlorizin.

Sites not aligning to the query:

608 modified: Disulfide link with 255

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
26% identity, 81% coverage: 38:423/474 of query aligns to 58:493/659 of Q9NY91

query
sites
Q9NY91

Y

F

F

F

L

L

A

A

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A

W

W

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E457 (≠ Q387) 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)
27% identity, 78% coverage: 47:417/474 of query aligns to 36:456/585 of 7slaA

query
sites
7slaA

W
|
W

I

W

V

P

V

I

A

G

G

A

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S

L

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M

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N

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W

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D

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Y

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W

W

binding cholesterol hemisuccinate: W36 (= W47), S277 (≠ K261), Y288 (≠ V272)

Sites not aligning to the query:

binding cholesterol hemisuccinate: 554, 558, 561

7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
27% identity, 78% coverage: 47:417/474 of query aligns to 35:455/582 of 7sl8A

query
sites
7sl8A

W
|
W

I

W

V

P

V

I

A

G

G

A

S

S

L

L

M

F

M

A

T

S

N

N

I

I

S

G

A

S

E

G

Q

H

I

F

V

I

G

G

M

L

N

A

G

G

-

T

-

G

-

A

A

A

Q

S

T

G

L

L

L

A

V

V

A

G

W

G

W

F

E

E

I

W

A

N

A

A

A

L

I

V

G

L

L

L

I

L

I

V

L

L

A

G

K

W

W

V

L

F

I

V

P

P

I

I

Y

Y

Y

I

R

K

Y

A

N

G

C

V

T

V

T

T

T

M

T

P

E

E

L

Y

L

L

E

R

R

K

K

R

Y

F

Q

G

D

G

K

Q

G

R

I

I

R

Q

A

V

M

Y

V

L

S

S

L

V

L

L

F

S

M

L

L

F

G

L

Y

Y

A

I

F

F

I

T

L

K

L

I

P

S

V

V

V

D

L

I

Y

F

T

S

G

G

S

A

L

I

F

F

M

I

K

N

S

L

M

A

F

L

G

G

L

W

S

N

I

L

S

Y

V

L

T

S

V

I

L

-

A

-

I

I

I

L

F

L

A

L

V

A

V

I

G

T

A

A

I

L

Y

Y

A

T

I

I

F

T

G

G

L

L

R

A

A

A

I

V

A

I

I

Y

S

T

D

D

T

T

L

L

N

Q

G

T

L

L

-

I

-

M

-

L

-

I

-

G

G

A

L

L

I

I

L

L

M

M

G

G

L

F

A

A

V

F

S

H

Y

E

L

V

A

G

M

G

H

Y

A

D

-

A

-

F

V

M

D

E

W

K

D

Y

L

M

S

K

G

A

I

I

P

P

L

-

E

-

R

-

L

-

T

T

L

I

I

V

G

S

D

D

S

G

Q

N

S

T

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

-

F

-

R

-

D

-

P

-

L

-

T

-

G

D

D

I

L

P

P

W

W

S

P

T

G

L

F

L

I

T

F

G

G

M

L

I

T

F

I

I

L

Q

A

I

L

F

W

Y

Y

W

W

G

C

T

T

N

D

M

Q

V

V

I

I

T

V

Q

Q

R

R

A

C

L

L

A

A

K

K

S

N

V

M

K

S

E

H

A

V

Q

K

K
x
G

G

G

L

C

Y

I

A

L

A

A

V

G

V
x
Y

M

L

K

K

L

L

I

L

I

P

P

M

V

F

I

I

V

M

V

V

L

M

P

P

G

G

I

M

V

I

A

S

F

R

K

I

L

L

Y

F

G

P

D

D

-

K

-

V

-

A

-

C

-

V

-

P

-

S

-

E

-

C

-

E

-

K

-

Y

-

C

-

G

-

T

-

K

V

V

G

G

-

C

-

T

D

N

V

I

A

A

Y

Y

G

P

K

T

L

L

V

V

G

V

D

E

L

L

L

M

P

P

S

N

W

G

L

L

S

R

G

G

A

L

F

M

A

L

A

A

V

V

I

M

A

L

G

A

A

A

V

L

L

M

S

S

F

L

N

T

S

S

C

I

L

F

N

N

S

S

A

A

A

S

A

T

L

L

Y

F

T

T

C

M

D

D

I

I

H

Y

Q

A

N

K

Y

V

I

R

N

K

-

R

-

A

A

S

D

E

A

K

D

E

V

L

R

M

K

I

I

V

G

G

S

R

R

L

V

F

A

V

L

L

L

F

F

L

T

V

L

V

I

V

S

S

V

I

A

A

L

W

V

I

P

P

L

I

F

V

-

Q

-

S

A

A

R

Q

S

S

E

G

S

Q

I

L

I

F

A

D

L

Y

L

I

Q

Q

Q

S

L

V

N

S

G

S

L

Y

Y

L

S

A

M

P

P

P

V

V

L

A

A

A

A

V

F

F

I

L

C

L

A

A

L

I

V

F

F

W

K

K

N

R

V

V

S

N

A

E

K

Q

A

G

I

A

K

F

W

W

binding cholesterol: W35 (= W47), G280 (≠ K265), Y287 (≠ V272)

Sites not aligning to the query:

binding cholesterol: 551, 554, 555, 558

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
27% identity, 80% coverage: 38:417/474 of query aligns to 41:470/602 of 7wmvA

query
sites
7wmvA

Y

F

F

F

L

L

A

A

G

G

G

R

G

S

L

M

S

V

W

W

I

W

V

P

V

I

A

G

G

A

S

S

L

L

M

F

M

A

T

S

N
|
N

I

I

S

G

A

S

E

G

Q
x
H

I

F

V

V

G

G

M
x
L

N

A

G

G

-

T

-

G

-

A

A

A

Q

S

T

G

L

I

L

A

V
x
I

A

G

W

G

W
x
F

E
|
E

I

W

A

N

A
|
A

A

L

I

V

G

L

L

V

I

V

L

L

A

G

K

W

W

L

L

F

I

V

P

P

I

I

Y

Y

Y

I

R

K

Y

A

N

G

C

V

T

V

T

T

T

M

T

P

E

E

L

Y

L

L

E

R

R

K

K

R

Y

F

Q

G

D

G

K

Q

G

R

I

I

R

Q

A

V

M

Y

V

L

S

S

L

L

F

S

M

L

L

L

G

L

Y

Y

A

I

F

F

I

T

L

K

L

I

P

S

V

A

V

D

L

I

Y

F

T

S

G

G

S

A

L

I

F

F

M

I

K

N

S

L

M

A

F

L

G

G

L

L

S

N

I

L

S

Y

V

L

T

A

V

I

L

F

A

L

I

L

F

-

A

-

V

A

V

I

G

T

A

A

I

L

Y

Y

A

T

I

I

F

T

G

G

L

L

R

A

A

A

I

V

A

I

I

Y

S

T

D

D

T

T

L

L

N

Q

G

T

L

V

G

I

L

M

I

L

L

V

M

G

G

S

L

L

A

I

V

L

S

T

Y

G

L

F

A

A

M

F

H

H

A

E

V

V

D

G

-

G

W

Y

D

D

-

A

-

F

-

M

-

E

-

K

-

Y

L

M

S

K

G

A

I

I

P

P

L

-

E

-

R

-

L

-

T

T

L

I

I

V

G

S

D

D

S

G

Q

N

S

T

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

-

F

-

R

-

D

-

P

-

L

-

T

-

G

D
|
D

I
x
L

P

P

W

W

S

P

T

G

L

F

L

I

T

F

G

G

M
|
M

I

S

F

I

I
x
L

Q
x
T

I

L

F

W

Y
|
Y

W
|
W

G

C

T

T

N

D

M

Q

V

V

I

I

T

V

Q

Q

R

R

A

C

L

L

A

S

A

A

K

K

S

N

V

M

K

S

E

H

A

V

Q

K

K

G

G

G

L

C

Y

I

A

L

A

C

V

G

V

Y

M

L

K
|
K

L

L

I

M

I

P

P

M

V

F

I

I

V

M

V

V

L

M

P

P

G

G

I

M

V

I

A

S

F

R

K

I

L

L

Y

Y

G

T

D

E

-

K

-

I

-

A

-

C

-

V

-

P

-

S

-

E

-

C

-

E

-

K

-

Y

-

C

-

G

-

T

-

K

V

V

G

G

-

C

-

T

D

N

V

I

A

A

Y

Y

G

P

K

T

L

L

V

V

G

V

D

E

L

L

L

M

P

P

S

N

W

G

L

L

S

R

G

G

A

L

F

M

A

L

A

S

V

V

I

M

A

L

G

A

A

S

V

L

L

M

S

S

F

L

N

T

S

S

C

I

L

F

N

N

S

S

A

A

A

S

A

T

L

L

Y

F

T

T

C

M

D

D

I

I

H

Y

Q

-

N

-

Y

-

I

-

N

-

A

-

D

-

A

A

D

K

V

V

R

R

K

K

I

R

G

A

S

S

R

E

V

K

A

E

L

L

-

M

-

I

-

A

-

G

-

R

L

L

F

F

T

I

L

L

-

V

-

L

-

I

-

G

I

I

S

S

V

I

A

A

L

W

V

V

P

P

L

I

F

V

-

Q

-

S

A

A

R

Q

S

S

E

G

S

Q

I

L

I
x
F

A
x
D

L

Y

L

I

Q
|
Q

Q

S

L

I

N

T

G

S

L

Y

Y

L

S

G

M

P

P

P

V

I

L

A

A

A

A

V

F

F

I

L

C

L

A

A

L

I

V

F

F

W

K

K

N

R

V

V

S

N

A

E

K

P

A

G

I

A

K

F

W

W

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 (= N58), H66 (≠ Q63), L70 (≠ M67), I81 (≠ V75), F84 (≠ W78), E85 (= E79), A88 (= A82), D256 (= D226), L257 (≠ I227), M266 (= M236), L269 (≠ I239), T270 (≠ Q240), Y273 (= Y243), W274 (= W244), K304 (= K274), F436 (≠ I383), D437 (≠ A384), Q440 (= Q387)

Sites not aligning to the query:

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: 508

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)
27% identity, 80% coverage: 38:417/474 of query aligns to 58:487/664 of P13866

query
sites
P13866

Y

F

F

F

L

L

A

A

G

G

G

R

G

S

L

M

S

V

W
|
W

I

W

V

P

V

I

A

G

G

A

S

S

L

L

M

F

M

A

T
x
S

N

N

I

I

S

G

A

S

E

G

Q
x
H

I

F

V

V

G

G

M

L

N

A

G

G

-

T

-

G

-

A

A

A

Q

S

T

G

L

I

L

A

V

I

A

G

W

G

W

F

E

E

I

W

A

N

A

A

A

L

I

V

G

L

L

V

I

V

L

L

A

G

K

W

W

L

L

F

I

V

P

P

I

I

Y

Y

Y

I

R

K

Y

A

N

G

C

V

T

V

T

T

T

M

T

P

E

E

L

Y

L

L

E

R

R

K

K
x
R

Y

F

Q

G

D

G

K

Q

G

R

I

I

R

Q

A

V

M

Y

V

L

S

S

L

L

F

S

M

L

L

L

G

L

Y

Y

A

I

F

F

I

T

L

K

L

I

P
x
S

V

A

V

D

L

I

Y

F

T

S

G

G

S
x
A

L

I

F

F

M

I

K

N

S

L

M

A

F

L

G

G

L

L

S

N

I

L

S

Y

V

L

T

A

V

I

L

F

A

L

I

L

F

-

A

-

V

A

V

I

G

T

A

A

I

L

Y
|
Y

A
x
T

I
|
I

F
x
T

G
|
G

L
|
L

R
x
A

A
|
A

I
x
V

A
x
I

I
x
Y

S
x
T

D
|
D

T
|
T

L
|
L

N
x
Q

G
x
T

L
x
V

G
x
I

L
x
M

I
x
L

L
x
V

M
x
G

G
x
S

L
|
L

A
x
I

V
x
L

S
x
T

Y
x
G

L
x
F

A
|
A

M
x
F

H
|
H

A
x
E

V
|
V

D
x
G

-
x
G

W
x
Y

D
|
D

-
x
A

-
x
F

-
x
M

-
x
E

-
x
K

-
x
Y

L
x
M

S
x
K

G
x
A

I
|
I

P
|
P

L

-

E

-

R

-

L

-

T
|
T

L
x
I

I
x
V

G
x
S

D
|
D

S
x
G

Q
x
N

S
x
T

-
x
T

-
x
F

-
x
Q

-
x
E

-
x
K

-
x
C

-
x
Y

-
x
T

-
x
P

-
x
R

-
x
A

-
x
D

-
x
S

-
x
F

-
x
H

-
x
I

-
x
F

-
x
R

-
x
D

-
x
P

-
x
L

-
x
T

-
x
G

D
|
D

I
x
L

P
|
P

W
|
W

S
x
P

T
x
G

L
x
F

L
x
I

T
x
F

G
|
G

M
|
M

I
x
S

F
x
I

I
x
L

Q
x
T

I
x
L

F
x
W

Y
|
Y

W
|
W

G
x
C

T
|
T

N
x
D

M
x
Q

V
|
V

I
|
I

T
x
V

Q
|
Q

R
|
R

A
x
C

L
|
L

A
x
S

A
|
A

K
|
K

S
x
N

V
x
M

K
x
S

E
x
H

A
x
V

Q
x
K

K
x
G

G
|
G

L
x
C

Y
x
I

A
x
L

A
x
C

V
x
G

V
x
Y

M
x
L

K
|
K

L
|
L

I
x
M

I
x
P

P
x
M

V
x
F

I
|
I

V
x
M

V
|
V

L
x
M

P
|
P

G
|
G

I
x
M

V
x
I

A
x
S

F
x
R

K
x
I

L
|
L

Y
|
Y

G
x
T

D
x
E

-
x
K

-
x
I

-
x
A

-
x
C

-
x
V

-
x
P

-
x
S

-
x
E

-
x
C

-
x
E

-
x
K

-
x
Y

-
x
C

-
x
G

-
x
T

-
x
K

V
|
V

G
|
G

-
x
C

-
x
T

D
x
N

V
x
I

A
|
A

Y
|
Y

G
x
P

K
x
T

L
|
L

V
|
V

G
x
V

D
x
E

L
|
L

L
x
M

P
|
P

S
x
N

W
x
G

L
|
L

S
x
R

G
|
G

A
x
L

F
x
M

A
x
L

A
x
S

V
|
V

I
x
M

A
x
L

G
x
A

A
x
S

V
x
L

L
x
M

S
|
S

F
x
L

N
x
T

S
|
S

C
x
I

L
x
F

N
|
N

S
|
S

A
|
A

A
x
S

A
x
T

L
|
L

Y
x
F

T
|
T

C
x
M

D
|
D

I
|
I

H
x
Y

Q

-

N

-

Y

-

I

-

N

-

A

-

D

-

A
|
A

D
x
K

V
|
V

R
|
R

K
|
K

I
x
R

G
x
A

S
|
S

R
x
E

V
x
K

A
x
E

L
|
L

-
x
M

-
x
I

-
x
A

-
x
G

-
x
R

L
|
L

F
|
F

T
x
I

L
|
L

-
x
V

-
x
L

-
x
I

-
x
G

I
|
I

S
|
S

V
x
I

A
|
A

L
x
W

V
|
V

P
|
P

L
x
I

F
x
V

-
x
Q

-
x
S

A
|
A

R
x
Q

S
|
S

E
x
G

S
x
Q

I
x
L

I
x
F

A
x
D

L
x
Y

L
x
I

Q
|
Q

Q
x
S

L
x
I

N
x
T

G
x
S

L
x
Y

Y
x
L

S
x
G

M
x
P

P
|
P

V
x
I

L
x
A

A
|
A

A
x
V

F
|
F

I
x
L

C
x
L

A
|
A

L
x
I

V
x
F

F
x
W

K
|
K

N
x
R

V
|
V

S
x
N

A
x
E

K
x
P

A
x
G

I
x
A

K
x
F

W
|
W

W67 (= W47) mutation to A: Strong reduction in D-glucose transporter activity.
S77 (≠ T57) mutation to A: Loss of activity.
H83 (≠ Q63) 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 (≠ K112) to W: in GGM; loss of activity
S159 (≠ P136) to P: in GGM; loss of activity
A166 (≠ S143) to T: in GGM; about 90% reduction in activity
D204 (= D183) mutation to A: Loss of activity.
N248 (≠ Q224) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
C255 (vs. gap) modified: Disulfide link with 511
W276 (= W229) to L: in GGM; about 95% reduction in activity
T287 (≠ Q240) 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 (= Y243) 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 (= W244) mutation to A: Loss of D-glucose transporter activity.
C292 (≠ G245) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
Q295 (≠ M248) to R: in GGM; loss of activity
R300 (= R253) to S: in GGM; loss of activity
A304 (= A257) to V: in GGM; impairs trafficking to the plasma membrane
K321 (= K274) 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 (vs. gap) modified: Disulfide link with 345
C355 (vs. gap) modified: Disulfide link with 361
C361 (vs. gap) modified: Disulfide link with 355
N363 (≠ D297) mutation to A: Loss of water permeation.
L369 (= L303) to S: in GGM; loss of activity
R379 (≠ S313) to Q: in GGM; loss of activity
A388 (≠ G322) to V: in GGM; loss of activity
S396 (= S330) mutation to A: Loss of activity.
F405 (≠ Y339) to S: in GGM; loss of activity
A411 (= A352) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
G426 (vs. gap) to R: in GGM; loss of activity
Q451 (≠ S381) mutation to A: Strong reduction in water permeation.
L452 (≠ I382) mutation to A: Loss of water permeation.
D454 (≠ A384) mutation to A: Has no effect on water permeation.
Q457 (= Q387) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
T460 (≠ N390) mutation to A: Loss of D-glucose transporter activity.
V470 (≠ A400) to N: in GGM; requires 2 nucleotide substitutions; about 90% reduction in activity

Sites not aligning to the query:

51 N → S: in GGM; slightly decreased activity; dbSNP:rs17683011
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.

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
27% identity, 80% coverage: 38:417/474 of query aligns to 35:467/586 of 7vsiA

query
sites
7vsiA

Y

Y

F

F

L

L

A

A

G

G

G

R

G

S

L

M

S

V

W

W

I

W

V

P

V

V

A

G

G

A

S

S

L

L

M

F

M

A

T

S

N
|
N

I

I

S

G

A

S

E

G

Q
x
H

I

F

V

V

G
|
G

M
x
L

N

A

G

G

-
x
T

-

G

-

A

A

A

Q

S

T

G

L

L

L

A

V
|
V

A

A

W

G

W
x
F

E
|
E

I

W

A

N

A
|
A

A

L

I

F

G

V

L

V

I

L

L

L

A

G

K

W

W

L

L

F

I

A

P

P

I

V

Y

Y

Y

L

R

T

Y

A

N

G

C

V

T

I

T

T

T

M

T

P

E

Q

L

Y

L

L

E

R

R

K

K

R

Y

F

Q

G

D

G

K

R

G

R

I

I

R

R

A

L

M

Y

V

L

S

S

L

V

L

L

F

S

M

L

L

F

G

L

Y

Y

A

I

F

F

I

T

L

K

L

I

P

S

V
|
V

V

D

L

M

Y

F

T

S

G

G

S

A

L

V

F

F

M

I

K

Q

S

Q

M

A

F

L

G

G

L

W

S

N

I

I

S

Y

V

A

T

S

V

V

L

I

A

A

I

L

F

-

A

-

V

G

V

I

G

T

A

M

I

I

Y

Y

A

T

I

V

F

T

G

G

L

L

R

A

A

A

I

L

A

M

I

Y

S

T

D

D

T

T

L

V

N

Q

-

T

-

F

-

V

-

I

-

L

G

G

L

G

G

A

L

C

I

I

L

L

M

M

G

G

L

Y

A

A

V

F

S

H

Y

E

L

V

A

G

M

G

H

Y

A

S

V

G

D

L

W

F

D

D

-

K

-

Y

-

L

-

G

-

A

L

A

S

T

G

S

I

L

P

T

L

V

E

S

R

E

L

D

T

P

L

A

I

V

G

G

D

N

S

I

Q

S

S

S

-

F

-

C

-

Y

-

R

-

P

-

R

-

P

-

D

-

S

-

Y

-

H

-

L

-

R

-

H

-

P

-

V

-

T

-

G

D

D

I

L

P

P

W

W

S

P

T

A

L

L

T

L

G

G

M

L

I

T

F

I

I
x
V

Q
x
S

I

G

F

W

Y
|
Y

W
|
W

G

C

T

S

N

D

M

Q

V

V

I

I

T

V

Q

Q

R

R

A

C

L

L

A

A

A

G

K

K

S

S

V

L

K

T

E

H

A

I

Q

K

K

A

G

G

L

C

Y

I

A

L

A

C

V

G

V

Y

M

L

K
|
K

L

L

I

T

I

P

P

M

V

F

I

L

V

M

V

V

L

M

P

P

G

G

I

M

V

I

A

S

F

R

K

I

L

L

Y

Y

G

P

D

D

-

E

-

V

-

A

-

C

-

V

-

P

-

E

-

V

-

C

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

V

C

G

S

D

N

V

I

A

A

Y

Y

G

P

K

R

L

L

V

V

G

V

D

K

L

L

L

M

P

P

S

N

W

G

L

L

S

R

G

G

A

L

F

M

A

L

A

A

V

V

I

M

A

L

G

A

A

A

V

L

L

M

S

S

F

L

N

A

S

S

C

I

L

F

N

N

S

S

A

S

A

T

L

L

Y

F

T

T

C

M

D

D

I

I

H

Y

Q

T

N

R

Y

L

I

R

N

P

-

R

-

A

A

G

D

D

A

R

D

E

V

L

R

L

K

L

I

V

G

G

S

R

R

L

V

W

A

V

L

V

L

F

F

I

T

V

L

V

I

V

S

S

V

V

A

A

L

W

V

L

P

P

L

V

F

V

-

Q

-

A

A

A

R

Q

S

G

E

G

S

Q

I

L

I
x
F

A
x
D

L

Y

L

I

Q
|
Q

Q

A

L

V

N

S

G

S

L

Y

Y

L

S

A

M

P

P

P

V

V

L

S

A

A

A

V

F

F

I

V

C

L

A

A

L

L

V

F

F

V

K

P

N

R

V

V

S

N

A

E

K

Q

A

G

I

A

K

F

W

W

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 (= N58), H60 (≠ Q63), G63 (= G66), L64 (≠ M67), T67 (vs. gap), V75 (= V75), F78 (≠ W78), E79 (= E79), A82 (= A82), V137 (= V137), V266 (≠ I239), S267 (≠ Q240), Y270 (= Y243), W271 (= W244), K301 (= K274), F433 (≠ I383), D434 (≠ A384), Q437 (= Q387)

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: 506

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)
27% identity, 80% coverage: 38:417/474 of query aligns to 55:487/672 of P31639

query
sites
P31639

Y

Y

F

F

L

L

A

A

G

G

G

R

G

S

L

M

S

V

W

W

I

W

V

P

V

V

A

G

G

A

S

S

L

L

M

F

M

A

T

S

N

N

I

I

S

G

A

S

E

G

Q

H

I

F

V

V

G

G

M

L

N

A

G

G

-

T

-

G

-

A

A

A

Q

S

T

G

L

L

L

A

V
|
V

A

A

W

G

W
x
F

E

E

I

W

A

N

A

A

A

L

I

F

G

V

L

V

I

L

L

L

A

G

K

W

W

L

L

F

I

A

P

P

I

V

Y

Y

Y

L

R

T

Y

A

N

G

C

V

T

I

T

T

T

M

T

P

E

Q

L

Y

L

L

E

R

R

K

K

R

Y

F

Q

G

D

G

K

R

G

R

I

I

R

R

A

L

M

Y

V

L

S

S

L

V

L

L

F

S

M

L

L

F

G

L

Y

Y

A

I

F

F

I

T

L

K

L

I

P

S

V
|
V

V

D

L

M

Y

F

T

S

G

G

S

A

L

V

F

F

M

I

K

Q

S

Q

M

A

F

L

G

G

L

W

S

N

I

I

S

Y

V

A

T

S

V

V

L

I

A

A

I

L

F

-

A

-

V

G

V

I

G

T

A

M

I

I

Y

Y

A

T

I

V

F

T

G

G

L

L

R

A

A

A

I

L

A

M

I

Y

S

T

D

D

T

T

L

V

N

Q

-

T

-

F

-

V

-

I

-

L

G

G

L

G

G

A

L

C

I

I

L

L

M

M

G

G

L

Y

A

A

V

F

S

H

Y

E

L

V

A

G

M

G

H

Y

A

S

V

G

D

L

W

F

D

D

-

K

-

Y

-

L

-

G

-

A

L

A

S

T

G

S

I

L

P

T

L

V

E

S

R

E

L

D

T

P

L

A

I

V

G

G

D

N

S

I

Q

S

S

S

-

F

-

C

-

Y

-

R

-

P

-

R

-

P

-

D

-

S

-

Y

-

H

-

L

-

R

-

H

-

P

-

V

-

T

-

G

D

D

I

L

P

P

W

W

S

P

T

A

L

L

T

L

G

G

M
x
L

I

T

F

I

I

V

Q

S

I

G

F

W

Y

Y

W

W

G

C

T

S

N

D

M

Q

V

V

I

I

T

V

Q

Q

R

R

A

C

L

L

A

A

A

G

K

K

S

S

V

L

K

T

E

H

A

I

Q

K

K

A

G

G

L

C

Y

I

A

L

A

C

V

G

V

Y

M

L

K

K

L

L

I

T

I

P

P

M

V

F

I

L

V

M

V

V

L

M

P

P

G

G

I

M

V

I

A

S

F

R

K

I

L

L

Y

Y

G

P

D

D

-

E

-

V

-

A

-

C

-

V

-

P

-

E

-

V

-

C

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

V

C

G

S

D

N

V

I

A

A

Y

Y

G

P

K

R

L

L

V

V

G

V

D

K

L

L

L

M

P

P

S

N

W

G

L

L

S

R

G

G

A

L

F

M

A

L

A

A

V

V

I

M

A

L

G

A

A

A

V

L

L

M

S

S

F

L

N

A

S

S

C

I

L

F

N

N

S

S

A

S

A

T

L

L

Y

F

T

T

C

M

D

D

I

I

H

Y

Q

T

N

R

Y

L

I

R

N

P

-

R

-

A

A

G

D

D

A

R

D

E

V

L

R

L

K

L

I

V

G

G

S

R

R

L

V

W

A

V

L

V

L

F

F

I

T

V

L

V

I

V

S

S

V

V

A

A

L

W

V

L

P

P

L

V

F

V

-

Q

-

A

A

A

R

Q

S

G

E

G

S

Q

I

L

I
x
F

A

D

L

Y

L

I

Q

Q

Q

A

L

V

N

S

G

S

L

Y

Y

L

S

A

M

P

P

P

V

V

L

S

A

A

A

V

F

F

I

V

C

L

A

A

L

L

V

F

F

V

K

P

N

R

V

V

S

N

A

E

K

Q

A

G

I

A

K

F

W

W

V95 (= V75) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (≠ W78) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
V157 (= V137) mutation to A: Decreases D-glucose transporter activity.
L283 (≠ M236) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F453 (≠ I383) mutation to A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.

7ynjA Structure of human sglt2-map17 complex bound with substrate amg in the occluded conformation
26% identity, 78% coverage: 47:417/474 of query aligns to 26:445/564 of 7ynjA

query
sites
7ynjA

W

W

I

W

V

P

V

V

A

G

G

A

S

S

L

L

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