SitesBLAST

R257 (= R256) mutation to C: Sodium-independent binding affinity for proline.
C281 (≠ T280) 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 (≠ S339) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (≠ S344) 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 (= R371) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.

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)
23% identity, 86% coverage: 9:434/498 of query aligns to 32:494/662 of P11170

query
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P11170

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C255 (vs. gap) modified: Disulfide link with 608
Q457 (≠ S397) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
T460 (≠ W400) mutation to W: Decreased affinity for glucose and phlorizin.

Sites not aligning to the query:

608 modified: Disulfide link with 255

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
25% identity, 73% coverage: 9:371/498 of query aligns to 15:410/602 of 7wmvA

query
sites
7wmvA

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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 (≠ D54), H66 (≠ M59), L70 (= L63), I81 (≠ L79), F84 (≠ L82), L257 (≠ V232), M266 (≠ L241), L269 (≠ W243), T270 (≠ G244), Y273 (= Y247), W274 (≠ F248)

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: 436, 437, 440, 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)
25% identity, 73% coverage: 9:371/498 of query aligns to 32:427/664 of P13866

query
sites
P13866

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M
x
K

T
x
L

V
x
M

T
x
P

I
x
M

I
x
F

G
x
I

A
x
M

L
x
V

A
x
M

T
x
P

G
|
G

L
x
M

V
x
I

G
x
S

-
x
R

I
|
I

A
x
L

Y
|
Y

A
x
T

N
x
E

K
|
K

F
x
I

G
x
A

M
x
C

K
x
V

L
x
V

-
x
P

S
|
S

D
x
E

P
x
C

E
|
E

T
x
K

I
x
Y

F
x
C

-
x
G

-
x
T

-
x
K

-
x
V

-
x
G

-
x
C

-
x
T

-
x
N

I
|
I

V
x
A

F
x
Y

S
x
P

E
x
T

L
|
L

L
x
V

F
x
V

H
x
E

P
x
L

L
x
M

I
x
P

S
x
N

G
|
G

-
x
L

-
x
R

-
x
G

F
x
L

L
x
M

L
|
L

A
x
S

A
x
V

I
x
M

L
|
L

A
|
A

A
x
S

I
x
L

M
|
M

S
|
S

T
x
S

I
x
L

S
x
T

S
|
S

Q
x
I

L
x
F

L
x
N

V
x
S

S
x
A

S
|
S

S
x
T

S
x
L

L
x
F

T
|
T

E
x
M

D
|
D

I
|
I

Y
|
Y

R
x
A

T
x
K

L
x
V

S

-

K
x
R

K
|
K

Q
x
R

A
|
A

S
|
S

E
|
E

Q
x
K

E
|
E

M
x
L

V
x
M

K
x
I

M
x
A

G
|
G

R
|
R

N51 (≠ S27) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
W67 (≠ P43) mutation to A: Strong reduction in D-glucose transporter activity.
S77 (= S53) mutation to A: Loss of activity.
H83 (≠ M59) 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 (= R116) to W: in GGM; loss of activity
S159 (= S141) to P: in GGM; loss of activity
A166 (≠ G148) to T: in GGM; about 90% reduction in activity
D204 (= D186) mutation to A: Loss of activity.
N248 (vs. gap) modified: carbohydrate, N-linked (GlcNAc...) asparagine; mutation to Q: Loss of N-glycosylation.
C255 (vs. gap) modified: Disulfide link with 511
W276 (≠ L234) to L: in GGM; about 95% reduction in activity
T287 (≠ G244) 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 (= Y247) 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 (≠ F248) mutation to A: Loss of D-glucose transporter activity.
C292 (≠ G249) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
Q295 (≠ H252) to R: in GGM; loss of activity
R300 (= R256) to S: in GGM; loss of activity
A304 (≠ I260) to V: in GGM; impairs trafficking to the plasma membrane
K321 (≠ M277) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
C345 (≠ M300) modified: Disulfide link with 351
C351 (≠ P305) modified: Disulfide link with 345
C355 (≠ F309) modified: Disulfide link with 361
C361 (vs. gap) modified: Disulfide link with 355
N363 (vs. gap) mutation to A: Loss of water permeation.
L369 (= L315) to S: in GGM; loss of activity
R379 (vs. gap) to Q: in GGM; loss of activity
A388 (= A331) to V: in GGM; loss of activity
S396 (= S339) mutation to A: Loss of activity.
F405 (≠ L348) to S: in GGM; loss of activity
A411 (≠ R354) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
G426 (= G370) to R: in GGM; loss of activity

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)
451 Q→A: Strong reduction in water permeation.
452 L→A: Loss of water permeation.
454 D→A: Has no effect on water permeation.
457 Q→A: Loss of D-glucose transporter activity.; Q→C: Strong reduction in D-glucose transporter activity.
460 T→A: Loss of D-glucose transporter activity.
470 V → N: in GGM; about 90% reduction in activity; requires 2 nucleotide substitutions
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)
23% identity, 85% coverage: 9:432/498 of query aligns to 32:492/659 of Q9NY91

query
sites
Q9NY91

L

I

A

V

I

I

Y

Y

F

F

I

L

A

V

M

V

L

M

A

A

I

V

G

G

L

L

F

W

A

A

Y

M

R

L

K

K

S

T

T

N

D

R

-

G

D

T

V

I

S

G

G

G

Y

F

I

F

L

L

G

A

G

G

R

R

Q

D

V

M

S

A

P

W

H

W

V

P

T

M

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D

N

M

I

S

G

G

S

W

N

M

H

L

Y

M

V

G

G

L

L

P

A

G

G

A

T

M

G

F

A

L

A

V

S

G

G

F

V

E

A

T

T

L

V

Y

T

I

F

A

E

L

W

G

T

L

S

I

V

G

M

A

L

L

L

I

I

N

L

Y

G

L

W

V

I

V

F

A

V

P

P

K

-

L

-

R

-

V

I

Y

Y

T

-

E

-

V

I

A

K

D

S

N

G

A

V

L

M

T

T

I

M

P

P

E

E

F

Y

F

L

A

K

K

K

R

R

F

F

G

G

-

G

-

E

Q

R

A

L

D

Q

N

V

S

Y

I

L

R

S

I

I

I

L

A

S

A

L

A

F

I

I

I

C

V

V

I

V

F

-

T

-

L

L

Y

L

T

I

S

S

A

A

G

D

L

I

V

F

A

A

G

G

G

A

K

I

L

F

F

I

E

K

S

L

A

A

F

L

G

G

L

L

N

D

Y

L

D

Y

I

L

G

A

L

I

V

F

V

I

T

L

L

L

A

A

V

M

V

T

V

A

S

V

Y

Y

T

T

L

T

G

G

F

L

L

A

A

S

V

V

S

I

L

Y

T

T

D

D

F

T

V

L

Q

Q

G

T

C

I

I

I

M

M

F

L

V

I

-

G

A

S

L

F

V

I

L

L

V

M

P

G

F

F

V

A

-

F

-

N

-

E

-

V

-

G

A

G

Y

Y

Q

E

E

S

F

F

T

T

-

E

-

K

-

Y

-

V

-

N

-

A

-

T

-

P

-

S

-

V

S

E

A

G

D

D

R

N

M

L

M

T

N

I

F

S

A

A

Y

S

Q

C

S

Y

I

T

P

P

H

R

-

A

-

D

-

S

-

F

-

H

-

I

F

F

T

R

D

D

A

A

M

V

Q

T

-

G

N

D

V

I

T

P

L

W

L

P

G

G

L

I

I

I

S

F

S

G

L

M

S

P

-

I

W

T

G

A

L

L

G

W

Y

Y

F

W

G

C

Q

T

P

N

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

C

I

G

R

K

S

D

V

M

A

S

D

H

I

V

K

K

T

A

A

A

-

C

-

I

-

M

-

C

-

A

-

Y

-

L

-

K

-

L

-

P

-

M

-

F

-

L

-

M

-

V

-

M

-

P

-

G

-

M

-

I

R

S

R

R

I

I

G

L

I

Y

S

T

W

D

M

M

T

V

V

A

T

C

I

V

G

P

A

S

L

E

A

C

T

V

G

K

L

H

V

C

G

G

I

V

A

D

Y

V

A

G

N

C

K

T

F

-

G

-

M

-

K

N

L

Y

S

A

D

Y

P

P

E

T

T

M

I

V

F

L

I

-

V

-

F

-

S

-

E

E

L

L

L

M

F

P

H

Q

P

G

L

L

I

-

S

R

G

G

F

L

L

M

L

L

A

S

A

V

I

M

L

L

A

A

A

S

I

L

M

M

S

S

T

S

I

L

S

T

S

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

S

L

L

F

T

T

E

I

D

D

I

L

Y

Y

R

-

T

T

L

K

S

M

K

R

K

K

Q

Q

A

A

S

S

E

E

Q

K

E

E

M

L

V

L

K

I

M

A

G

G

R

R

Y

I

G

F

V

V

A

L

G

L

V

L

A

T

I

V

V

V

A

S

-

I

-

V

-

W

-

V

T

P

L

L

L

V

A

Q

L

V

D

S

R

Q

S

N

N

G

S

Q

I

L

L

I

S

H

L

Y

V

T

S
x
E

N

S

A

I

W

S

A

S

G

Y

F

L

G

G

A

P

F

I

G

A

P

A

L

V

V

F

L

V

F

L

S

A

L

I

Y

F

K

C

A

K

N

R

L

V

T

N

H

E

K

Q

A

G

A

A

I

F

A

W

G

G

I

L

I

M

S

V

G

G

E457 (≠ S397) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
24% identity, 74% coverage: 2:371/498 of query aligns to 2:407/590 of 8hg7A

query
sites
8hg7A

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A
|
A

S
|
S

D
x
N

M
x
I

S
x
G

G

S

W
x
G

M
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

-

T

-

G

-

A

-

S

A

G

M

L

F

A

L

V

V

A

G

G

F

F

E
|
E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A

V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

-

P

-

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

V

A

T

L

L

L

G

G

L

L

I

T

S

I

S
x
V

L
x
S

S

G

W

W

G

-

L

-

G

-

Y
|
Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W
x
K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

I

I

V

A

F

Y

S

P

E

R

L

L

L

V

F

V

H

K

P

L

L

M

-

P

-

N

-

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

A
|
A

I

L

M

M

S
|
S

T
x
S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyl-oxane-3,4,5-triol: N55 (≠ D54), G59 (≠ W58), H60 (≠ M59), G63 (= G62), L64 (= L63), E79 (= E73), V266 (≠ S240), S267 (≠ L241), Y270 (= Y247), W271 (≠ F248), K301 (≠ W276)
binding sodium ion: A53 (= A52), S54 (= S53), I56 (≠ M55), G57 (≠ S56), A369 (= A332), S372 (= S335), S373 (≠ T336)

Sites not aligning to the query:

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
24% identity, 74% coverage: 2:371/498 of query aligns to 2:407/586 of 7vsiA

query
sites
7vsiA

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D
x
N

M

I

S

G

G

S

W

G

M
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

-

T

-

G

-

A

-

S

A

G

M

L

F

A

L
x
V

V

A

G

G

F
|
F

E
|
E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A

V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L

L

I

T

S

I

S
x
V

L
x
S

S

G

W

W

G

-

L

-

G

-

Y
|
Y

F

W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W

K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

I

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

F

C

S

S

E

N

L

I

L

A

F

Y

H

P

P

R

L

L

I

V

-

V

-

K

-

L

-

M

-

P

-

N

-

G

-

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

I

L

M

M

S

S

T

S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

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 (≠ D54), H60 (≠ M59), G63 (= G62), L64 (= L63), V75 (≠ L69), F78 (= F72), E79 (= E73), V266 (≠ S240), S267 (≠ L241), Y270 (= Y247)

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: 433, 434, 437

8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
24% identity, 74% coverage: 2:371/498 of query aligns to 2:407/586 of 8hdhA

query
sites
8hdhA

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A
|
A

S
|
S

D
x
N

M
x
I

S
x
G

G

S

W
x
G

M
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

-

T

-

G

-

A

-

S

A

G

M

L

F

A

L

V

V

A

G

G

F
|
F

E
|
E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A

V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L

L

I

T

S

I

S

V

L
x
S

S

G

W

W

G

-

L

-

G

-

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W

K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

I

I

V

A

F

Y

S

P

E

R

L

L

L

V

F

V

H

K

P

L

L

M

-

P

-

N

-

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

A
|
A

I

L

M

M

S
|
S

T
x
S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

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 (≠ D54), G59 (≠ W58), H60 (≠ M59), G63 (= G62), L64 (= L63), F78 (= F72), E79 (= E73), S267 (≠ L241), W271 (≠ F248)
binding sodium ion: A53 (= A52), S54 (= S53), I56 (≠ M55), G57 (≠ S56), A369 (= A332), S372 (= S335), S373 (≠ T336)

Sites not aligning to the query:

8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
24% identity, 74% coverage: 2:371/498 of query aligns to 2:407/586 of 8hb0A

query
sites
8hb0A

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A
|
A

S

S

D
x
N

M
x
I

S
x
G

G

S

W

G

M
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

-
x
T

-

G

-

A

-

S

A

G

M

L

F

A

L
x
V

V

A

G

G

F
|
F

E
|
E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A
x
V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L

L

I

T

S

I

S
x
V

L
x
S

S

G

W

W

G

-

L

-

G

-

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W

K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

I

I

V

A

F

Y

S

P

E

R

L

L

L

V

F

V

H

K

P

L

L

M

-

P

-

N

-

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

A
|
A

I

L

M

M

S
|
S

T
x
S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

binding (2R,3R,4S,5S,6R)-2-[3-[(4-cyclopropylphenyl)methyl]-4-fluoranyl-indol-1-yl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ D54), H60 (≠ M59), G63 (= G62), L64 (= L63), T67 (vs. gap), V75 (≠ L69), F78 (= F72), E79 (= E73), V137 (≠ A142), V266 (≠ S240), S267 (≠ L241), W271 (≠ F248)
binding sodium ion: A53 (= A52), I56 (≠ M55), G57 (≠ S56), A369 (= A332), S372 (= S335), S373 (≠ T336)

Sites not aligning to the query:

8hezA Structure of human sglt2-map17 complex with dapagliflozin (see paper)
24% identity, 74% coverage: 2:371/498 of query aligns to 2:407/582 of 8hezA

query
sites
8hezA

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A
|
A

S

S

D
x
N

M
x
I

S
x
G

G

S

W
x
G

M
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

-
x
T

-

G

-

A

-

S

A

G

M

L

F

A

L

V

V

A

G

G

F
|
F

E
|
E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A

V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L

L

I

T

S

I

S
x
V

L
x
S

S

G

W

W

G

-

L

-

G

-

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W
x
K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

-

R

-

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

I

I

V

A

F

Y

S

P

E

R

L

L

L

V

F

V

H

K

P

L

L

M

-

P

-

N

-

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

A
|
A

I

L

M

M

S
|
S

T
x
S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[(4-ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ D54), G59 (≠ W58), H60 (≠ M59), G63 (= G62), L64 (= L63), T67 (vs. gap), F78 (= F72), E79 (= E73), V266 (≠ S240), S267 (≠ L241), W271 (≠ F248), K301 (≠ W276)
binding sodium ion: A53 (= A52), I56 (≠ M55), G57 (≠ S56), A369 (= A332), S372 (= S335), S373 (≠ T336)

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: 433, 437
binding : 568, 571, 572, 575, 576, 579, 580

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, 74% coverage: 2:371/498 of query aligns to 22:427/672 of P31639

query
sites
P31639

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

-

M

Y

C

R

R

K

T

S

N

T

R

D

G

D

T

V

V

S

G

G

G

Y

Y

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

V

P

W

H

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D

N

M

I

S

G

G

S

W

G

M

H

L

F

M

V

G

G

L

L

P

A

G

G

-

T

-

G

-

A

-

S

A

G

M

L

F

A

L
x
V

V

A

G

G

F
|
F

E

E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A
x
V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

T

-

F

C

V

I

I

M

L

F

G

V

G

A

A

L

C

V

I

L

L

V

M

P

G

F

Y

V

A

A

F

Y

H

Q

E

-

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

-

V

-

S

E

E

F

D

T

P

S

A

A

V

D

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L
|
L

I

T

S

I

S

V

L

S

S

G

W

W

G

-

L

-

G

-

Y

Y

F

W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W

K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

I

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

F

C

S

S

E

N

L

I

L

A

F

Y

H

P

P

R

L

L

I

V

-

V

-

K

-

L

-

M

-

P

-

N

-

G

-

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

I

L

M

M

S

S

T

S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

V95 (≠ L69) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (= F72) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
V157 (≠ A142) mutation to A: Decreases D-glucose transporter activity.
L283 (= L237) mutation to M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.

Sites not aligning to the query:

453 F→A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.

7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
25% identity, 53% coverage: 107:371/498 of query aligns to 95:396/585 of 7slaA

query
sites
7slaA

L

V

T

T

I

M

P

P

E

E

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

G

A

Q

D

R

N

I

S

Q

I

V

R

Y

I

L

I

S

A

V

A

L

A

S

I

L

I

F

V

L

I

Y

F

I

F

F

T

T

L

-

Y

K

T

I

S

S

A

V

G

D

L

I

V

F

A

S

G

G

G

A

K

I

L

F

F

I

E

N

S

L

A

A

F

L

G

G

L

W

N

N

Y

L

D

Y

I

L

G

S

L

I

V

I

V

L

T

L

L

L

A

A

V

I

V

T

V

A

S

L

Y

Y

T

T

L

I

L

T

G

G

F

L

L

A

A

A

V

V

S

I

L

Y

T

T

D

D

F

T

V

L

Q

Q

G

T

C

L

I

I

M

M

F

L

V

I

-

G

A

A

L

L

V

I

L

L

V

M

P

G

F

F

V

-

A

A

Y

F

Q

H

E

E

F

V

T

G

S

G

A

Y

D

D

R

A

M

F

M

M

N

E

F

K

A

Y

Y

M

Q

K

S

A

I

I

P

P

H

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

F

F

T

R

D

D

A

P

M

L

Q

T

-

G

N

D

V

L

T

P

L

W

L

P

G

G

L

F

I

I

S

F

S

G

L

L

S

T

-

I

W

L

G

A

L

L

G

W

Y

Y

F

W

G

C

Q

T

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

A

R

K

S

N

V

M

A

S

D

H

I

V

K

K

T

G

A

G

R

C

R

I

I

L

G

A

I

G

S
x
Y

W

L

M

K

T

L

V

L

T

P

I

M

I

F

G

I

A

M

L

V

A

M

T

P

G

G

L

M

V

I

G

S

-

R

I

I

A

L

Y

F

A

P

N

D

K

K

F

V

-

A

-

C

-

V

-

P

-

S

-

E

-

C

-

E

-

K

-

Y

-

C

G

G

M

T

K

K

L

V

S

G

D

C

P

T

E

N

T

I

I

A

F

Y

I

P

V

T

F

L

S

V

E

V

L

E

L

L

F

M

H

P

P

N

L

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

I

L

M

M

S

S

T

S

I

L

S

T

S

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

A

T

K

L

V

S

-

K

R

K

K

Q

R

A

A

S

S

E

E

Q

K

E

E

M

L

V

M

K

I

M

V

G

G

R

R

binding cholesterol hemisuccinate: Y288 (≠ S275)

Sites not aligning to the query:

binding cholesterol hemisuccinate: 36, 554

7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
25% identity, 53% coverage: 107:371/498 of query aligns to 94:395/582 of 7sl8A

query
sites
7sl8A

L

V

T

T

I

M

P

P

E

E

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

G

A

Q

D

R

N

I

S

Q

I

V

R

Y

I

L

I

S

A

V

A

L

A

S

I

L

I

F

V

L

I

Y

F

I

F

F

T

T

L

-

Y

K

T

I

S

S

A

V

G

D

L

I

V

F

A

S

G

G

G

A

K

I

L

F

F

I

E

N

S

L

A

A

F

L

G

G

L

W

N

N

Y

L

D

Y

I

L

G

S

L

I

V

I

V

L

T

L

L

L

A

A

V

I

V

T

V

A

S

L

Y

Y

T

T

L

I

L

T

G

G

F

L

L

A

A

A

V

V

S

I

L

Y

T

T

D

D

F

T

V

L

Q

Q

G

T

C

L

I

I

M

M

F

L

V

I

-

G

A

A

L

L

V

I

L

L

V

M

P

G

F

F

V

-

A

A

Y

F

Q

H

E

E

F

V

T

G

S

G

A

Y

D

D

R

A

M

F

M

M

N

E

F

K

A

Y

Y

M

Q

K

S

A

I

I

P

P

H

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

F

F

T

R

D

D

A

P

M

L

Q

T

-

G

N

D

V

L

T

P

L

W

L

P

G

G

L

F

I

I

S

F

S

G

L

L

S

T

-

I

W

L

G

A

L

L

G

W

Y

Y

F

W

G

C

Q

T

P

D

H

Q

I

V

I

I

V

V

-

Q

R

R

F

C

M

L

A

A

I

A

R

K

S

N

V

M

A

S

D

H

I

V

K

K

T
x
G

A

G

R

C

R

I

I

L

G

A

I

G

S
x
Y

W

L

M

K

T

L

V

L

T

P

I

M

I

F

G

I

A

M

L

V

A

M

T

P

G

G

L

M

V

I

G

S

-

R

I

I

A

L

Y

F

A

P

N

D

K

K

F

V

-

A

-

C

-

V

-

P

-

S

-

E

-

C

-

E

-

K

-

Y

-

C

G

G

M

T

K

K

L

V

S

G

D

C

P

T

E

N

T

I

I

A

F

Y

I

P

V

T

F

L

S

V

E

V

L

E

L

L

F

M

H

P

P

N

L

G

I

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

I

L

M

M

S

S

T

S

I

L

S

T

S

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

A

T

K

L

V

S

-

K

R

K

K

Q

R

A

A

S

S

E

E

Q

K

E

E

M

L

V

M

K

I

M

V

G

G

R

R

binding cholesterol: G280 (≠ T268), Y287 (≠ S275)

Sites not aligning to the query:

binding cholesterol: 35, 551, 558

Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
25% identity, 76% coverage: 9:384/498 of query aligns to 32:439/656 of Q9ET37

query
sites
Q9ET37

L

I

A

V

I

I

Y

Y

F

F

I

V

A

V

M

V

L

M

A

A

I

V

G

G

L

V

F

W

A

A

Y

M

R

L

K

K

S

T

T

N

D

R

D

S

-

T

V

V

S

G

G

G

Y

F

I

F

L

L

G

A

G

G

R

R

Q

S

V

M

S

T

P

W

H

W

V

P

T

M

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D

N

M

I

S

G

G

S

W

G

M

H

L

F

M

V

G

G

L

L

P

A

G

G

-

T

-

G

-

A

-

S

A

G

M

I

F

A

L

V

V

T

G

A

F

F

E

E

T

S

L

H

Y

S

I

F

A

A

L

L

G

L

L

L

L

V

I

L

G

G

A

W

L

I

I

F

N

-

Y

-

L

-

V

-

A

-

P

-

K

-

L

-

R

-

V

V

Y

P

T

I

E

Y

V

I

A

K

D

A

N

G

A

V

L

M

T

T

I

M

P

P

E

E

F

Y

F

L

A

K

K

K

R

R

F

F

G

G

Q

G

A

K

D

R

N

L

S

Q

I

I

R

Y

I

L

I

-

A

-

A

S

I

I

I

L

V

F

I

L

F

F

F

I

T

C

-

V

-

I

L

L

Y

T

T

I

S

S

A

A

G

D

L

I

V

F

A

S

G

G

G

A

K

I

L

F

F

I

E

K

S

L

A

A

F

L

G

G

L

L

N

N

Y

L

D

Y

I

L

G

A

L

I

V

L

V

I

T

L

L

L

A

A

V

I

V

T

V

A

S

I

Y

F

T

T

L

I

L

T

G

G

F

L

L

A

A

S

V

V

S

I

L

Y

T

T

D

D

F

T

V

V

Q

Q

G

A

C

V

I

I

M

M

F

L

V

V

A

G

-

S

-

F

-

I

L

L

V

M

L

V

V

F

P

A

F

F

V

V

-

E

-

V

-

G

A

G

Y

Y

Q

E

E

S

F

F

T

T

S

-

A

-

D

E

R

K

M

F

M

M

N

N

F

-

A

-

Y

-

Q

-

S

A

I

I

P

P

H

S

F

V

T

V

D

E

A

G

M

-

Q

D

N

N

V

L

T

T

L

I

L

N

G

S

-

R

-

C

-

Y

-

T

-

P

-

Q

-

P

-

D

-

S

-

F

-

H

-

I

-

F

-

R

-

D

-

P

L

V

I

T

S

G

S

D

L

I

S

P

W

W

G

P

L

G

G

T

Y

A

F

F

G

G

Q

M

P

P

H

I

I

T

I

A

V

L

R

W

F

Y

M

W

A

C

I

I

R

N

S

Q

V

V

A

I

D

V

I

Q

K

R

T

C

A

L

R

C

R

G

I

K

G

N

I

L

S

S

W

H

M

V

T

K

V

A

T

A

I

C

I

I

G

L

A

C

L

G

A

Y

T

L

G

K

L

L

V

L

G

P

I

L

A

F

Y

F

A

M

N

V

K

M

F

P

G

G

M

M

-

I

-

S

-

R

K

I

L

L

S

Y

D

T

P

D

E

M

T

V

I

A

F

C

I

V

V

V

F

P

S

S

E

E

L

C

L

V

F

K

H

H

-

C

-

G

-

V

-

D

-

V

-

G

-

C

-

T

-

N

-

Y

-

A

-

Y

P

P

L

M

-

L

-

V

-

L

-

K

-

L

-

M

-

P

-

M

-

G

I

L

S

R

G

G

F

L

L

M

L

L

A

S

A

V

I

M

L

L

A

A

A

S

I

L

M

M

S

S

T

S

I

L

S

T

S

S

Q

V

L

F

L

N

V

S

S

A

S

S

S

T

S

L

L

F

T

T

E

I

D

D

I

L

Y

Y

R

T

T

K

L

I

S

R

K

K

Q

-

A

A

S

S

E

E

Q

R

E

E

M

L

V

L

K

I

M

A

G

G

R

R

Y

L

G

F

V

V

A

S

G

-

V

V

A

L

I

I

V

V

A

T

T

S

L

I

L

L

Sites not aligning to the query:

457 E→Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.

8hinA Structure of human sglt2-map17 complex with phlorizin (see paper)
23% identity, 74% coverage: 2:371/498 of query aligns to 9:403/588 of 8hinA

query
sites
8hinA

N

N

S

P

L

A

S

D

Y

I

V

L

S

V

L

I

A

A

I

A

Y

Y

F

F

I

L

A

L

M

V

L

I

A

G

I

V

G

G

L

L

F

W

A

S

Y

M

R

C

K

R

S

T

T

G

D

R

D

S

V

M

S

V

G

W

Y

W

I

P

L

V

G

G

G

A

R
x
S

Q

L

V

F

S
x
A

P
x
S

H

N

V

I

T

-

A

-

L

-

S

-

A

-

G
|
G

A

S

S

G

D

H

M

F

S

V

G

G

W

L

M

A

L

G

M

T

G

G

L

A

P

A

G

S

A

G

M

L

F

A

L

V

V

A

G

G

F

F

E

E

T

W

L

N

Y

A

I

L

A

F

L

V

G

V

L

L

I

L

G

G

A

W

L

L

I

F

N

-

Y

-

L

-

V

-

A

A

P

P

K

-

L

-

R

-

V

V

Y

Y

T

-

E

-

V

L

A

T

D

A

N

G

A

V

L

I

T

T

I

M

P

P

E

Q

F

Y

F

L

A

R

K

K

R

R

F

F

G

G

Q

-

A

-

D

G

N

R

S

R

I

I

R

R

I

L

I

Y

A

L

A

S

A

-

I

V

I

L

V

S

I

L

F

F

F

L

T

Y

L

I

Y

F

T

T

-

K

-

I

S

S

A

V

G

D

L

M

V

F

A

S

G

G

G

A

K

V

L

F

F

I

E

Q

S

Q

A

A

F

L

G

G

L

W

N

N

Y

I

D

Y

I

A

G

S

L

V

V

I

V

A

T

L

L

L

A

G

V

I

V

T

V

M

S

I

Y

Y

T

T

L

V

L

T

G

G

F

L

L

A

A

A

V

L

S

M

L

Y

T

T

D
|
D

F

T

V

V

Q

Q

G
x
T

C

F

I

V

M

I

F

L

V

G

A

G

L

A

V

C

L

I

V

L

P

M

F

G

V

Y

A

A

Y

F

Q

H

E

E

F

V

-

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

-

L

-

T

T

V

S

S

A

E

D

D

-

P

-

A

-

V

-

G

R

N

M

I

M

S

N

S

F

F

A

C

Y

Y

Q

R

S

P

I

R

P

P

H

D

F

S

T

Y

D

H

A

L

M

L

Q

R

N

H

V

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

L

L

G

G

L

L

I

T

S

I

S

V

L

S

S

G

W

W

G

-

L

-

G

-

Y

Y

F

W

G

C

Q

S

P

D

H

Q

I

V

I

I

V

V

-

Q

R
|
R

F

C

M

L

A

A

I

G

R

K

S

S

V

L

A

T

D

H

I

I

K

K

T

A

A

G

R

C

R

I

I

L

-

C

G

G

I

Y

S

L

W

K

M

L

T

T

V

P

T

M

I

F

I

L

G

M

A

V

L

M

A

P

T

G

G

M

L

I

V

S

G

R

I

I

A

L

Y

Y

A

P

N

D

K

E

F

V

G

A

M

C

K

V

L

V

S

-

D

-

P

P

E

E

T

V

I

C

F

R

I

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

F

C

S

S

E

N

L

I

L

A

F

Y

H

P

P

R

L

L

I

V

-

V

-

K

-

L

-

M

-

P

-

N

-

G

-

L

S

R

G

G

F

L

L

M

L

L

A

A

A

V

I

M

L

L

A

A

I

L

M

M

S

S

T
x
S

I

L

S

A

S

S

Q

I

L

F

L

N

V

S

S

S

S

T

S

L

L

F

T

T

E

M

D

D

I

I

Y

Y

R

T

T

R

L

L

S

-

K

R

K

P

Q

R

A

A

S

G

E

D

Q

R

E

E

M

L

V

L

K

L

M

V

G

G

R

R

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 (≠ R39), A49 (≠ S42), S50 (≠ P43), G53 (= G51), D177 (= D186), T181 (≠ G190), R276 (= R256), S369 (≠ T336)

Sites not aligning to the query:

binding : 574, 578, 581, 582, 585, 586

Q9GZV3 High affinity choline transporter 1; hCHT1; Hemicholinium-3-sensitive choline transporter; CHT; Solute carrier family 5 member 7 from Homo sapiens (Human) (see 5 papers)
23% identity, 76% coverage: 7:386/498 of query aligns to 9:397/580 of Q9GZV3

query
sites
Q9GZV3

V

I

S

A

L

I

A

I

I

V

Y

F

F

Y

I

L

A

L

M

I

L

L

A

L

I

V

G

G

L

I

F

W

A

A

Y

A

R

W

K

R

S

T

T

K

D

N

D

S

V

G

S

S

G

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

Q
x
D

V

I

S

G

P

L

H

L

V

V

T

G

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D

W

M

V

S

G

G
|
G

W

G

M

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

M

V

F

Y

L

V

V

P

G

G

F

Y

E

G

T

L

L

A

Y

W

I

A

-

Q

-

A

A

P

L
x
I

G

G

L

Y

L

S

I

L

G

S

A

L

L

I

I

L

N

G

Y

G

L

L

V

F

A

A

P

K

K
x
P

L

M

R

R

V

-

Y

-

T

-

E

-

V

-

A

S

D

K

N

G

A
x
Y

L

V

T

T

I

M

P

L

E

D

F

P

F

F

A

Q

K

Q

R

I

F

Y

G

G

Q

K

A

R

D

M

N

G

S

G

I

L

R

L

I

F

I

I

A

P

A

A

A

L

I

M

I

G

V

E

I

M

F

F

F

-

T

-

L

-

Y

W

T

A

S

A

A

A

G

I

L

F

V

S

A

A

G

L

G

G

K

A

L

T

F

I

E

S

S

V

A

I

F

I

G

D

L

V

N

D

Y

M

D

H

I

I

G

S

L

V

V

I

T

S

L

A

A

L

V

I

V

A

V

T

S

L

Y
|
Y

T

T

L

L

L

V

G

G

F

L

L

Y

A

S

V

V

S

A

L

Y

T

T

D

D

F

V

V

V

Q

Q

G

L

C

F

I

C

M

I

F

F

V

V

A

G

L

L

-

W

V

I

L

S

V

V

P

P

F

F

-

A

-

L

-

S

-

H

-

P

-

A

V

V

A

A

Y

D

Q

I

E

G

F

F

T

T

S

A

A

V

D

H

R

A

M

K

M

Y

N

Q

F

K

A

P

Y

W

Q

L

S

G

I

T

P

V

H

D

F

S

T

S

D

E

A

V

M

Y

Q

S

-

W

-

L

N

D

V

S

T

F

L

L

G

L

L

M

I

L

S

G

L

I

S

P

W

W

G

Q

L

-

G

A

Y

Y

F

F

G

Q

Q

-

P

-

H

-

I

-

V

-

R

R

F

V

M

L

A

S

I

S

R

S

S

S

V

A

A

T

D

Y

I

A

K

Q

T

V

A

L

R

S

R

F

I

L

G

A

I

A

S

F

W

G

M

C

T

L

V

V

T

M

I

A

I

I

G

P

A

A

L

I

A

L

T
x
I

G

G

L

A

V

I

G

G

I

A

A

S

Y

T

A

D

-

W

N

N

K

Q

F

T

G

A

M

Y

K

G

L

L

S

P

D

D

P

P

E

K

T

T

-

T

-

E

-

A

-

D

-

M

I

I

F

L

I

P

V

I

F

V

S

L

E

Q

L

Y

L

L

F

C

H

P

P

V

L

Y

I

I

S

S

G

F

F

F

L

G

L

L

A

G

A

A

I

V

L

S

A

A

I
x
V

M

M

S

S

T

S

I

A

S

D

S

S

Q

S

L

I

L

L

V

S

S

A

S

S

S

M

L

F

T

A

E
x
R

D

N

I

I

Y

Y

R

Q

T

L

L

S

S

F

K

R

K

Q

Q

N

A

A

S

S

E

D

Q

K

E

E

M

I

V

V

K

W

M

V

G

M

R

R

Y

I

G

T

V

V

A

F

G

V

V

F

A

G

I

A

V

S

A

A

T

T

L

A

L

M

A

A

L

L

D48 (≠ Q40) to G: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039768
G65 (= G57) to E: in CMS20; loss of choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039765
I89 (≠ L79) to V: 40% reduction in choline transmembrane transporter activity; found in 0.06 of Ashkenazi Jews; dbSNP:rs1013940; mutation to A: Decreased choline transmembrane transporter activity, only 20% of wild-type choline uptake activity.
P105 (≠ K95) to S: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039766
Y111 (≠ A106) to H: in CMS20; no effect on localization at plasma membrane
Y175 (= Y173) to C: in CMS20; uncertain significance; dbSNP:rs1331713195
I291 (≠ T287) to T: in CMS20; uncertain significance; dbSNP:rs375397889
V344 (≠ I333) to L: in CMS20; uncertain significance
R361 (≠ E350) to Q: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs147656110

Sites not aligning to the query:

418 F → V: in CMS20; uncertain significance
446 R → G: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane
451 E→Q: Decreased choline transmembrane transporter activity, only 5% of wild-type choline uptake activity.
527:532 Dileucine-like motif
530 I→A: No change in protein internalization. No change in choline transmembrane transporter activity.
531 L→A: Loss of protein internalization to vesicular structures in neurons. Increased choline transmembrane transporter activity.
531:532 LV→AA: Decreased protein internalization; when associated with V-538. Increased choline transmembrane transporter activity; when associated with V-538.
532 V→A: Decreased protein internalization. Increased choline transmembrane transporter activity.
538 K→V: Decreased protein internalization; when associated with 531-L-V-532. Increased choline transmembrane transporter activity; when associated with 531-L-V-532.

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)
21% identity, 68% coverage: 25:364/498 of query aligns to 41:382/643 of Q92911

query
sites
Q92911

R

Q

K

R

S

S

T

A

D

E

D

D

V

-

S

-

G

-

Y

F

I

F

L

T

G

G

R

R

Q

R

V

L

S

A

P

A

H

L

V

P

T

V

A

G

L

L

S

S

A

L

G

S

A

A

S

S

D

F

M

M

S

S

G

A

W

V

M

Q

L

V

M

L

G

G

L

V

P

P

G

S

A

E

M

A

F

Y

L

R

V

Y

G

G

F

L

E

K

T

F

L

L

Y

W

I

M

A

C

L

L

G

G

L

Q

L

L

I

L

G

N

A

S

L

V

I

L

N

T

Y
x
A

L

L

V

L

V

F

A

M

P

P

K

-

L

-

R

-

V

V

Y

F

T

Y

E

R

V

L

A

G

D

L

N

T

A

S

L

T

T

Y

I

-

P

-

E

E

F

Y

F

L

A

E

K

M

R

R

F

F

G

S

Q

R

A

A

D

-

N

-

S

-

I

V

R

R

I

L

I

C

A

G

A

T

A

L

I

Q

I

Y

V

I

I

V

F

A

F

T

T

M

L

L

Y

Y

T

T

S

G

A

I

G

V

L

I

V

Y

A

A

G

P

G

A

K

L

L

I

F

L

E

N

S

Q

A

V

F

T

G

G

L

L

N

D

Y

I

D

W

I

A

G

S

L

L

V

L

V

S

T

T

L

G

A

I

V

I

V

C

V

T

S

F

Y

Y

T

T

L

A

L

V

G

G

F

M

L

K

A

A

V

V

S

V

L

W

T

T

D

D

F

V

V

F

Q

Q

G

V

C

V

I

V

M

M

F

L

-

S

-

G

-

F

-

W

-

V

-

L

-

A

-

R

-

G

V

V

A

M

L

L

V

V

L

G

V

G

P

P

F

R

V

Q

A

V

Y

L

Q

T

E

L

F

A

T

Q

S

N

A
x
H

D

S

R

R

M

I

M

N

N

L

F

M

A

D

Y

F

Q

N

S

P

I
x
D

P

P

H

R

F

S

T

R

D
x
Y

A
x
T

M

F

Q

W

N

T

V

F

T

V

L

V

L

G

G

G

L

-

I

-

S

-

S

T

L

L

S

V

W

W

G

L

L

S

G

M

Y

Y

F

G

G

V

Q

N

P

Q

H

A

I

Q

I

V

V

Q

R

R

F

Y

M

V

A

A

I

C

R

R

S

T

V

E

A

K

D

Q

I

A

K

K

T

L

A

A

R

L

I

I

G

N

I

Q

S

V

W

G

M

L

T

F

V

L

T

I

I

V

I

S

G

S

A

A

L

A

A

C

T

C

G

G

L

I

V

V

G

M

I

F

A

V

Y

F

A

Y

N

T

K

D

F

C

G

D

M

P

-

L

-

G

K

R

L

I

S

S

D

A

P

P

E

D

T

Q

-

Y

-

M

-

P

-

L

I

V

F

L

I

D

V

I

F

F

S

E

E

D

L

L

L

-

F

-

H

-

P

P

L

G

I

V

S

P

G

G

F

L

L

F

L

L

A

A

A

C

I

A

L

Y

A

S

A

G

I

T

M

L

S

S

T

T

I

A

S

S

S

T

Q

S

L

I

L

N

V

A

S

M

S

A

S

V

L

T

T

V

E

E

D

D

I

L

Y

I

R

K

T

P

L

R

S

L

K

R

K

S

Q

L

A

A

S

P

E

R

Q

K

A102 (≠ Y89) natural variant: A -> P
H226 (≠ A211) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
D237 (≠ I222) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
Y242 (≠ D227) 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 (≠ A228) 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

Q9Y289 Sodium-dependent multivitamin transporter; Na(+)-dependent multivitamin transporter; hSMVT; Solute carrier family 5 member 6 from Homo sapiens (Human) (see 10 papers)
23% identity, 85% coverage: 18:440/498 of query aligns to 41:470/635 of Q9Y289

query
sites
Q9Y289

A

A

I

I

G

G

L

L

F

Y

-

H

A

A

Y

C

R

R

K

G

S

W

T

G

D

R

D

H

V

T

S

V

G

G

Y

E

I

L

L

L

-

M

G

A

G

D

R

R

Q

K

V

M

S

G

P
x
C

H

L

V

P

T

V

A

A

L

L

S

S

A

L

G

L

A

A

S
x
T

D

F

M

Q

S

S

G

A

W

V

M

A

L

I

M

L

G

G

L

V

P

P

G

S

A

E

M

I

F

Y

L
x
R

V
x
F

G
|
G

F
x
T

E
x
Q

T
x
Y

L
x
W

Y
x
F

I
x
L

A
x
G

L
x
C

G
x
C

L
x
Y

L
x
F

I
x
L

G
|
G

A
x
L

L
|
L

I
|
I

N
x
P

Y
x
A

L
x
H

V
x
I

V
x
F

A
x
I

P
|
P

K
x
V

L
x
F

-
x
Y

R
|
R

V
x
L

Y
x
H

T
x
L

E
x
T

V
x
S

A
|
A

D
x
Y

N

-

A

-

L

-

T

-

I

-

P

-

E
|
E

F
x
Y

F
x
L

A
x
E

K
x
L

R
|
R

F
|
F

G

-

Q

-

A

-

D
x
N

N
x
K

S
x
T

I
x
V

R
|
R

I
x
V

I
x
C

A
x
G

A
x
T

A
x
V

I
x
T

I
x
F

V
x
I

I
x
F

F
x
Q

F
x
M

T
x
V

L
x
I

Y
|
Y

T
x
M

S
x
G

A
x
V

G
x
V

L
|
L

V
x
Y

A
|
A

G
x
P

G
x
S

K
x
L

L
x
A

F
x
L

E
x
N

S
x
A

A
x
V

F
x
T

G
|
G

L
x
F

N
x
D

Y
x
L

D
x
W

I
x
L

G
x
S

L
x
V

V
x
L

V
x
A

T
x
L

L
x
G

A
x
I

V
|
V

V
x
C

V
x
T

S
x
V

Y
|
Y

T
|
T

L
x
A

L
|
L

G
|
G

F
x
L

L
x
K

A
|
A

V
|
V

S
x
I

L
x
W

T
|
T

D
|
D

F
x
V

V
x
F

Q
|
Q

G
x
T

C
x
L

I
x
V

M
|
M

F
|
F

V
x
L

A
x
G

L
x
Q

V
x
L

L
x
A

V
|
V

P
x
I

F
x
I

V
|
V

A
x
G

Y
x
S

Q
x
A

E
x
K

F
x
V

-
x
G

-
x
L

-
x
G

-
x
R

-
x
V

-
x
W

-
x
A

-
x
V

-
x
A

T
x
S

S
x
Q

A
x
H

D
x
G

R
|
R

M
x
I

M
x
S

N
x
G

F
|
F

A
x
E

Y
x
L

Q
x
D

S
x
P

I
x
D

P
|
P

H
x
F

F
x
V

T
x
R

D
x
H

A
x
T

M
x
F

Q
x
W

N
x
T

V
x
L

T
x
A

L
x
F

L
x
G

G
|
G

L
x
V

I
x
F

S
x
M

L
|
L

S
|
S

W
x
L

G

-

L

-

G

-

Y
|
Y

F
x
G

G
x
V

Q
x
N

P
x
Q

H
x
A

I
x
Q

I
x
V

V
x
Q

R
|
R

F
x
Y

M
x
L

A
x
S

I
x
S

R
|
R

S
x
T

V
x
E

A
x
K

D
x
A

I
x
A

K
x
V

T
x
L

A
x
S

R
x
C

R
x
Y

I
x
A

G
x
V

I
x
F

S
x
P

W
x
F

M
x
Q

T
x
Q

V
|
V

T
x
S

I
x
L

I
x
C

G
x
V

A
x
G

L
x
C

A
x
L

T
x
I

G
|
G

L
|
L

V
|
V

G
x
M

I
x
F

A
|
A

Y
|
Y

A
x
Y

N
x
Q

K
x
E

F
x
Y

G
x
P

M
|
M

K
x
S

L
x
I

S
x
Q

-
x
Q

-
x
A

-
x
Q

-
x
A

-
x
P

D
|
D

P
x
Q

E
x
F

T
x
V

I
x
L

F
x
Y

I
x
F

V
|
V

F
x
M

S
x
D

E
x
L

L
|
L

L
x
K

F
x
G

H
x
L

P
|
P

L
x
G

I
x
L

S
x
P

G
|
G

F
x
L

L
x
F

L
x
I

A
|
A

A
x
C

I
x
L

L
x
F

A
x
S

A
x
G

I
x
S

M
x
L

S
|
S

T
|
T

I
|
I

S
|
S

Q
x
A

L
x
F

L
x
N

V
x
S

S
x
L

S
x
A

S
x
T

S
x
V

L
x
T

T
x
M

E
|
E

D
|
D

I
x
L

Y
x
I

R
|
R

T
x
P

L
x
W

S

-

K
x
F

K
x
P

Q
x
E

A
x
F

S
|
S

E
|
E

Q
x
A

E
x
R

M
x
A

V
x
I

K
x
M

M
x
L

G
x
S

R
|
R

Y

-

G

-

V

-

A

-

G
|
G

V
x
L

A
|
A

I
x
F

V
x
G

A
x
Y

T
x
G

L
|
L

A
x
C

L
|
L

D
x
G

R
x
M

-
x
A

-
x
Y

-
x
I

S
|
S

N
x
S

S
x
Q

I
x
M

L
x
G

S
x
P

L
x
V

V
x
L

S
x
Q

N
x
A

A
|
A

W
x
I

A
x
S

G
x
I

F
|
F

G
|
G

A
x
M

A
x
V

F
x
G

G
|
G

P
|
P

L
|
L

V
x
L

-
x
G

L
|
L

F
|
F

S
x
C

L
|
L

-
x
G

-
x
M

Y
x
F

K
x
F

A
x
P

N
x
C

L
x
A

T
x
N

H
x
P

K
x
P

A
x
G

A
|
A

I
x
V

A
x
V

G
|
G

I
x
L

S
x
A

G
|
G

A

-

L
|
L

T
x
V

V
x
M

L
x
A

F
|
F

W
|
W

I
|
I

C68 (≠ P43) mutation to A: No effect on biotin transport.
T78 (≠ S53) mutation to A: Reduced membrane localization. Decrease in biotin transport.
C104 (≠ L79) mutation to A: No effect on biotin transport.
R123 (= R97) to L: in SMVTD; reduced membrane localization; impaired biotin transport
S128 (≠ V102) mutation to A: No effect on biotin transport.
N138 (≠ D121) mutation to A: Reduced protein levels. Decrease in biotin transport.
C144 (≠ I127) mutation to A: No effect on biotin transport.
Y162 (≠ V145) to C: in COMNB; no effect on membrane localization
C187 (≠ V170) mutation to A: No effect on biotin transport.
S242 (≠ M215) mutation to A: No effect on biotin transport.
S283 (≠ A259) mutation to A: No effect on protein levels or membrane localization.
T286 (≠ S262) mutation to A: Resistant to phorbol 12-myristate 13-acetate (PMA)-induced inhibition of biotin transport. No effect on protein levels or membrane localization.
C294 (≠ R270) mutation to A: Reduced membrane localization. Decrease in biotin transport (decreased Vmax, no change in Km).; mutation C->S,M: Decrease in biotin transport.
C309 (≠ L285) mutation to A: No effect on biotin transport.
C358 (≠ A328) mutation to A: No effect on biotin transport.
T366 (= T336) mutation to A: No effect on biotin transport.
R400 (= R371) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
C410 (≠ A385) mutation to A: No effect on biotin transport.
S429 (≠ A401) to G: in COMNB; no effect on membrane localization
C443 (≠ S414) mutation to A: No effect on biotin transport.
C450 (≠ N419) mutation to A: No effect on biotin transport.

Sites not aligning to the query:

94:635 natural variant: Missing (in SMVTD and COMNB; reduced membrane localization; impaired biotin transport; dbSNP:rs994218778)
481 S → F: in dbSNP:rs1395
489 N→A: Slight decrease in protein levels. Decrease in biotin transport.
498 N→A: No effect on biotin transport.
534 N→A: No effect on biotin transport.
567:635 mutation Missing: Loss of biotin transport. Loss of membrane localization.
570:635 mutation Missing: Loss of biotin transport. Loss of membrane localization.
575:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
577 C→A: No effect on biotin transport.
583 C→A: No effect on biotin transport.
584:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
600:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
612:635 mutation Missing: Partial loss (75%) of biotine transport. Apical membrane localization and intracellular structure localization in polarized cells.
616:635 mutation Missing: Loss of apical membrane localization in polarized cells. Basolateral localization in polarized cells.
620:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.
624:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.
627 T→A: No effect on biotin transport.
628 mutation C->A,S: Decrease in biotin transport.
632:635 mutation Missing: Partial loss (25%) of biotine transport. No change in apical membrane localization in polarized cells.

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)
24% identity, 83% coverage: 5:415/498 of query aligns to 14:430/610 of Q8N695

query
sites
Q8N695

S

D

Y

Y

V

V

S

V

L

F

A

A

I

G

Y

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F

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I

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A

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Y

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A

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A

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S

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A

A

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A

A

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T

L

Y

L

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I

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A

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Y

A

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E

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A

L

P

P

-

V

-

F

-

Y

K

K

L

L

R

G

V

I

Y

T

T

S

E

T

V

Y

A

-

D

-

N

-

A

-

L

-

T

-

I

-

P

-

E

E

F

Y

F

L

A

E

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L

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-

A

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Y

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A

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G

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A

A

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V

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T

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D

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Q

G
x
V

C

G

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I

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M

F

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V

A

-

G

-

F

A

A

L

S

V

V

L

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Q

F

A

V

V

A

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Y

M

Q

Q

E

G

F

G

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I

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S

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T

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-

R

-

M

I

M

L

N

N

F

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A

A

Y

Y

Q

D

-

G

-

R

-

L

S

N

I

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P

W

H

N

F

F

T

N

-

P

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N

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Q

N

R

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H

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T

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F

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I

I

-

I

-

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x
F

S

T

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W

G

T

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Y

F

G

G

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N

P

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V

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A

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I

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-

G

-

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W

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A

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-

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-

A

-

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-

A

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A

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-

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-

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-

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M

-

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A

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T

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S

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V

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E

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I

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-

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G

-

A

-

L

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C

A

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M

A

A

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A

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L

A

A

T

S

L

L

L

M

A

G

L

-

D

-

R

-

S

-

N

-

S

-

I

-

L

-

S

A

L

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L

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N

A

A

A

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L

A

S

G

V

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F

G

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A

M

A

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G

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L

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L

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F

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A

L

L

V193 (≠ G190) to I: in dbSNP:rs1709189
F251 (≠ L241) 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.

7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation (see paper)
23% identity, 53% coverage: 107:371/498 of query aligns to 94:389/566 of 7yniA

query
sites
7yniA

L

V

T

T

I

M

P

P

E

E

F

Y

F

L

A

R

K

K

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R

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G

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I

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I

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A

L

A

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I

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L

I

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F

I

F

F

T

T

L

-

Y

K

T

I

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S

A

A

G

D

L

I

V

F

A

S

G

G

G

A

K

I

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F

F

I

E

N

S

L

A

A

F

L

G

G

L

L

N

N

Y

L

D

Y

I

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G

A

L

I

V

F

V

L

T

L

L

L

A

A

V

I

V

T

V

A

S

L

Y

Y

T

T

L

I

L

-

G

-

F

-

L

-

A

-

V

V

S

I

L

Y

T

T

D

D

F

T

V

L

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Q

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T

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I

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M

F

L

V

V

A

G

L

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V

L

L

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V

L

P

T

F

G

V

F

A

A

Y

F

Q

H

E

E

F

V

T

G

S

G

A

Y

D

D

R

A

M

F

M

M

N

E

F

K

A

Y

Y

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K

S

A

I

I

P

P

H

T

-

I

-

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-

S

-

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-

G

-

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-

T

-

F

-

Q

-

E

-

K

-

C

-

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-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

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F

F

T

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D

D

A

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M

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Q

T

-

G

N

D

V

L

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P

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L

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G

G

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I

S

F

S

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x
L

G

T

L

L

G

W

Y
|
Y

F

W

G

C

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T

P

D

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Q

I

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I

I

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V

-

Q

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R

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L

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A

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M

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I

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A

M

T

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G

G

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V

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I

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L

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Y

A

T

N

E

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K

F

I

G

A

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K

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L

V

-

P

S

S

D

E

P

C

E

E

T

K

I

Y

F

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

I

I

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A

F

Y

S

P

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T

L

L

L

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V

H

E

P

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I

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N

G

G

-

L

-

R

-

G

F

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L

L

A

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A

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L

L

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A

A

S

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M

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L

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V

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S

A

S

S

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S

L

L

F

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D

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Y

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A

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K

L

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S

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K

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K

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R

A

A

S

S

E

E

Q

K

E

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L

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M

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M

A

G

G

R

R

binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: L248 (≠ W243), Y252 (= Y247)

Sites not aligning to the query:

binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: 51, 70, 415, 419
binding : 548, 552, 555, 556, 559, 560, 563, 564

Query Sequence

>7026926 FitnessBrowser__ANA3:7026926
MNSLSYVSLAIYFIAMLAIGLFAYRKSTDDVSGYILGGRQVSPHVTALSAGASDMSGWML
MGLPGAMFLVGFETLYIALGLLIGALINYLVVAPKLRVYTEVADNALTIPEFFAKRFGQA
DNSIRIIAAAIIVIFFTLYTSAGLVAGGKLFESAFGLNYDIGLVVTLAVVVSYTLLGGFL
AVSLTDFVQGCIMFVALVLVPFVAYQEFTSADRMMNFAYQSIPHFTDAMQNVTLLGLISS
LSWGLGYFGQPHIIVRFMAIRSVADIKTARRIGISWMTVTIIGALATGLVGIAYANKFGM
KLSDPETIFIVFSELLFHPLISGFLLAAILAAIMSTISSQLLVSSSSLTEDIYRTLSKKQ
ASEQEMVKMGRYGVAGVAIVATLLALDRSNSILSLVSNAWAGFGAAFGPLVLFSLYKANL
THKAAIAGIISGALTVLFWIYAPVLSDGKALSSLVYEMIPGFVVSSTVIYLVSKFDNDPC
AKTTKQFHQAGRVLAEES

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