SitesBLAST

R257 (= R257) mutation to C: Sodium-independent binding affinity for proline.
C281 (= C281) 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 (= C344) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (= C349) 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 (= R376) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.

Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
24% identity, 87% coverage: 12:439/494 of query aligns to 33:494/656 of Q9ET37

query
sites
Q9ET37

V

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A

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D

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V

E457 (≠ A406) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
23% identity, 86% coverage: 12:437/494 of query aligns to 33:492/659 of Q9NY91

query
sites
Q9NY91

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x
E

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A

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P

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P

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K

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G

G

E457 (≠ A406) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
25% identity, 74% coverage: 72:435/494 of query aligns to 43:426/512 of 3dh4A

query
sites
3dh4A

G

G

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M

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E

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Y

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S

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K

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M

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L

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K

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G

G

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G

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G

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W

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G
x
N

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Y

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x
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H

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L

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A

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K

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C
x
K

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A

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S

T

S

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C

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M

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K

T

E

F

Y

L

I

R

S

K

P

S

D

A

S

S

G

Q

D

L

H

E

K

L

L

V

V

W

N

V

V

G

G

R

R

A

T

M

A

V

A

L

V

V

A

A

L

L

I

V

I

A

A

-

C

-

L

-

I

-

A

-

P

-

M

-

L

-

G

I

I

A

G

L

Q

A

A

A

F

N

Q

P

Y

E

I

N
x
Q

R

E

V

Y

L

T

G

G

L

L

V

V

S

S

Y

-

A

-

W

-

A

P

G

G

F

I

G

L

A

A

A

V

F

F

G

-

P

-

V

-

L

L

I

L

S

G

V

L

I

F

W

W

K

K

N

K

M

T

T

T

R

S

N

K

G

G

A

A

L

I

A

I

G

G

I

V

L

V

binding beta-D-galactopyranose: Y58 (= Y87), E59 (≠ N89), S62 (vs. gap), N225 (≠ G245), W229 (≠ F249), K259 (≠ C281), Q393 (≠ N395)
binding sodium ion: A326 (= A337), S329 (= S340)

Sites not aligning to the query:

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, 73% coverage: 33:391/494 of query aligns to 43:401/610 of Q8N695

query
sites
Q8N695

S

K

D

D

Y

F

I

L

L

M

G

G

R

R

S

R

L

M

G

T

S

A

V

V

V

P

T

V

A

A

L

L

S

S

A

L

G

T

A

A

S

S

D

F

M

M

S

S

G

A

W

V

L

T

L

V

M

L

G

G

L

T

P

P

G

S

A

E

I

V

Y

Y

M

R

S

F

G

G

L

A

S

I

E

F

S

S

W

I

I

F

A

A

I

F

G

-

L

-

I

-

V

-

G

-

A

T

Y

Y

L

F

N

F

W

V

L

V

F

V

V

I

A

S

G

A

R

E

L

V

R

F

V

L

Q

P

T

V

E

F

H

Y

N

K

G

L

D

G

A

I

L

T

T

S

L

T

P

Y

D

E

Y

Y

F

L

S

E

S

L

R

R

F

F

E

N

D

K

K

-

S

-

G

-

L

C

L

V

R

R

I

L

I

C

S

G

A

T

V

V

V

L

I

F

L

I

V

V

F

Q

F

T

T

I

I

L

Y

Y

C

T

A

G

S

I

G

V

I

I

V

Y

A

A

G

P

A

A

R

L

L

A

F

L

E

N

S

Q

T

V

F

T

G

G

M

F

S

D

Y

L

E

W

T

G

A

A

L

V

W

V

A

A

G

T

A

G

A

V

T

C

I

T

A

F

Y

Y

T

C

F

T

V

L

G

G

F

L

L

K

A

A

V

V

S

I

W

W

T

T

D

D

T

V

V

F

Q

Q

A
x
V

T

G

L

I

M

M

I

V

F

A

A

G

L

F

I

A

L

S

T

V

P

I

I

I

I

Q

V

A

L

V

A

M

T

Q

G

G

V

I

D

S

T

T

T

-

F

-

L

I

A

L

I

N

E

D

A

A

K

Y

D

D

P

G

S

G

S

R

F

L

D

N

M

F

-

W

-

N

-

F

-

N

-

P

-

N

-

P

L

L

K

Q

N

R

T

H

T

T

F

F

I

W

G

T

I

I

-

I

-

G

S

G

L

T

M
x
F

G

T

W

W

G

T

L

S

G

I

Y

Y

F

G

G

V

Q

N

P

Q

H

S

I

Q

L

V

A

Q

R

R

F

Y

M

I

A

S

A

C

D

K

S

S

V

R

K

F

S

Q

I

A

A

K

N

L

A

S

R

L

R

Y

I

I

S

N

M

L

T

V

-

G

-

L

W

W

M

A

I

I

L

L

C

-

L

-

G

-

T

T

V

C

A

S

V

V

G

-

F

F

F

C

G

G

I

L

A

A

Y

L

F

Y

S

S

A

R

H

Y

P

H

D

D

V

-

A

C

G

D

P

P

V

W

T

T

E

A

N

K

-

K

-

V

-

S

-

A

P

P

E

D

R

Q

V

L

-

M

-

P

F

Y

I

L

E

V

L

L

A

D

K

I

L

L

L

Q

F

D

N

Y

P

P

W

G

I

L

A

P

G

G

V

L

L

F

L

V

S

A

A

C

I

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

V

S

S

C

S

Q

S

L

I

L

N

V

A

C

L

S

A

A

V

L

T

T

V

E

E

D

D

F

L

Y

I

K

K

T

P

F

Y

L

F

R

R

K

-

S

S

A

L

S

S

Q

E

L

R

E

S

L

L

V

S

W

W

V

I

G

S

R

Q

A

G

M

M

V

S

L

V

V

Y

A

G

L

A

V

L

A

C

I

I

A

G

L

M

A

A

V193 (≠ A191) to I: in dbSNP:rs1709189
F251 (≠ M242) 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.

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
24% identity, 85% coverage: 12:431/494 of query aligns to 16:469/602 of 7wmvA

query
sites
7wmvA

V

V

I

I

Y

Y

I

F

A

V

M

V

V

M

L

A

I

V

G

G

L

L

M

W

A

A

Y

M

R

F

S

S

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

F

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

W

V

P

T

I

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

L
x
H

L

F

M

V

G

G

L
|
L

P

A

G

G

A

T

I

G

Y

A

M

A

S

S

G

G

L

-

S

-

E

-

S

-

W

-

I

I

A

A

I
|
I

G

G

-

G

-
x
F

-

E

-

W

-

N

-

A

L

L

I

V

V

L

G

V

A

V

Y

V

L

L

N

G

W

W

L

L

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

-

Q

-

T

-

E

-

H

-

N

-

G

A

D

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

Q

S

R

G

I

L

Q

L

V

R

Y

I

L

I

S

S

L

A

L

V

S

V

L

I

L

L

L

V

Y

F

I

F

F

T

T

I

K

Y

I

C

S

A

A

S

D

G

-

I

I

V

F

A

S

G

G

A

A

R

I

L

F

F

I

E

N

S

L

T

A

F

L

G

G

M

L

S

N

Y

L

E

Y

T

L

A

A

L

I

W

F

A

L

G

L

A

L

A

A

A

I

T

T

I

A

A

L

Y

Y

T

T

F

I

V

T

G

G

F

L

L

A

A

A

V

V

S

I

W

Y

T

T

D

D

T

T

V

L

Q

Q

A

T

T

V

L

I

M

M

I

L

F

V

A

G

L

S

I

L

L

I

T

L

P

T

I

G

I

F

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

D

-

A

-

F

-

M

-

E

-

K

-

Y

-

M

-

K

-

A

-

I

-

P

-

T

-

I

-

V

-

S

-

D

-

G

-

N

T

T

F

F

L

Q

A

E

I

-

E

K

A

C

K

Y

D

T

P

P

-

R

-

A

S

D

S

S

F

F

D

H

M

I

L

F

K

R

N

D

T

P

T

-

F

-

I

-

G

-

I

L

I

T

S

G

L

D

M
x
L

G

P

W

W

G

P

L

G

G

F

Y

I

F

F

G

G

Q
x
M

P

S

H

I

I
x
L

L
x
T

A

L

R

W

F
x
Y

M
x
W

A

C

A

T

D

D

S

Q

V

V

K

-

S

-

I

-

A

I

N

V

A

Q

R

R

R

C

I

L

S

S

M

A

T

K

W

N

M

M

I

S

L

H

C

V

L

K

G

G

T

C

V

I

A

L

V

C

G

G

F

Y

F

L

G

K

-

L

-

M

-

P

-

M

-

F

-

I

-

M

-

V

-

M

-

P

-

G

-

M

I

I

A

S

Y

R

F

I

S

L

A

Y

H

T

P

E

D

K

V

I

A

A

G

C

P

V

V

V

T

P

E

S

N

E

P

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

I

P

E

T

L

L

A

V

K

V

L

E

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

S

A

V

I

M

L

L

A

A

A

S

V

L

M

M

S

S

T

S

L

L

S

T

C

S

Q

I

L

F

L

N

V

S

C

A

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

A

T

K

F

-

L

V

R

R

K

K

S

R

A

A

S

S

Q

E

L

K

E

E

L

L

V

M

W

I

V

A

G

G

R

R

A

L

M

F

V

I

L

L

L

V

V

L

A

I

L

G

V

I

A

S

I

I

A

A

-

W

-

V

-

P

-

I

L

V

A

Q

A

S

N

A

P

Q

E

S

N

G

R

Q

V

L

L
x
F

G
x
D

L

Y

V

I

S
x
Q

Y

S

A

I

W

T

A

S

G

Y

F

L

G

G

A

P

F

I

G

A

P

A

V

V

V

F

L

L

I

L

S

A

V

I

I

F

W

W

K

K

N

R

M

V

T

N

R

E

N

P

G

G

A

A

L

F

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 (≠ D55), H66 (≠ L60), L70 (= L64), I81 (= I80), F84 (vs. gap), L257 (≠ M242), M266 (≠ Q251), L269 (≠ I254), T270 (≠ L255), Y273 (≠ F258), W274 (≠ M259), F436 (≠ L398), D437 (≠ G399), Q440 (≠ S402)

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

Q92911 Sodium/iodide cotransporter; Na(+)/I(-) cotransporter; Natrium iodide transporter; Sodium-iodide symporter; Na(+)/I(-) symporter; Solute carrier family 5 member 5 from Homo sapiens (Human) (see 3 papers)
23% identity, 74% coverage: 24:391/494 of query aligns to 36:403/643 of Q92911

query
sites
Q92911

M

L

A

A

Y

R

R

G

S

G

T

Q

N

R

N

S

L

A

S

E

D

D

Y

F

I

F

L

T

G

G

R

R

S

R

L

L

G

A

S

A

V

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

L

Q

L

V

M

L

G

G

L

V

P

P

G

S

A

E

I

A

Y

Y

M

R

S

Y

G

G

L

L

S

K

E

F

S

L

W

W

I

M

A

C

I

L

G

G

L

Q

I

L

V

L

G

N

A

S

Y

V

L

L

N

T

W
x
A

L

L

F

L

-

F

-

M

-

P

V

V

A

F

G

Y

R

R

L

L

R

G

V

L

Q

T

T

S

E

T

H

Y

N

-

G

-

D

-

A

-

L

-

T

-

L

-

P

-

D

E

Y

Y

F

L

S

E

S

M

R

R

F

F

E

-

D

-

K

-

S

S

G

R

L

A

L

V

R

R

I

L

I

C

S

G

A

T

V

L

V

Q

I

Y

L

I

V

V

F

A

F

T

T

M

I

L

Y

Y

C

T

A

G

S

I

G

V

I

I

V

Y

A

A

G

P

A

A

R

L

L

I

F

L

E

N

S

Q

T

V

F

T

G

G

M

L

S

D

Y

I

E

W

T

A

A

S

L

L

W

L

A

S

G

T

A

G

A

I

T

C

I

T

A

F

Y

Y

T

T

F

A

V

V

G

G

F

M

L

K

A

A

V

V

S

V

W

W

T

T

D

D

T

V

V

F

Q

Q

A

V

T

V

L

V

M

M

I

L

-

S

-

G

F

F

A

W

L

V

I

V

L

L

T

A

P

R

I

G

I

V

V

M

L

L

L

V

A

G

-

G

-

P

-

R

-

Q

-

V

-

L

T

T

G

L

G

A

V

Q

D

N

T
x
H

T

S

F

R

L

I

A

N

I

L

E

M

A

D

K

F

D

N

P

P

S
x
D

S

P

F

R

D

S

M

R

L
x
Y

K
x
T

N

F

T

W

T

T

F

F

I

V

G

-

I

V

I

G

S

G

L

T

M

L

G

V

W

W

G

L

L

S

G

M

Y

Y

F

G

G

V

Q

N

P

Q

H

A

I

Q

L

V

A

Q

R

R

F

Y

M

V

A

A

A

C

D

R

S

T

V

E

K

K

S

Q

I

A

A

K

N

L

A

A

R

L

I

I

S

N

M

Q

T

V

W

G

M

L

I

F

L

L

C

I

L

V

G

S

T

A

V

A

A

C

V

C

G

G

F

I

F

V

G

M

I

F

A

V

Y

F

F

Y

S

T

-

D

A

C

H

D

P

P

D

L

V

L

A

L

G

G

P

R

V

I

T

S

E

A

N

-

P

P

E

D

R

Q

V

Y

F

M

I

P

E

L

L

L

A

V

K

L

L

D

L

I

F

F

N

E

-

D

-

L

P

P

W

G

I

V

A

P

G

G

V

L

L

F

L

L

S

A

A

C

I

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

A

S

S

C

T

Q

S

L

I

L

N

V

A

C

M

S

A

A

V

L

T

T

V

E

E

D

D

F

L

Y

I

K

K

T

P

F

R

L

L

R

R

K

S

S

L

A

A

S

P

Q

R

L

-

E

K

L

L

V

V

W

I

V

I

G

S

R

K

A

G

M

L

V

S

L

L

L

I

V

Y

A

G

L

S

V

A

A

C

I

L

A

T

L

V

A

A

A102 (≠ W90) natural variant: A -> P
H226 (≠ T214) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
D237 (≠ S225) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
Y242 (≠ L230) 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 (≠ K231) 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

8zqoA Human high-affinity choline transporter cht1 bound to hc-3 under nacl condition, with sodium and chloride ions coordinated. (see paper)
25% identity, 78% coverage: 8:390/494 of query aligns to 6:394/515 of 8zqoA

query
sites
8zqoA

L

L

I

I

T

A

F

I

V

I

I

V

Y

F

I

Y

A

L

M

I

V

L

L

L

I

V

G

G

L

I

-

W

M

A

A

A

Y

W

R

R

S

T

T

K

N

N

N

S

L

G

S

S

D

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

S

D

L

I

G

G

S

L

V

L

V

V

T

G

A

G

L

F

S

T

A

M

G

T

A
|
A

S
x
T

D

W

M
x
V

S
x
G

G

G

W
x
G

L

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

I

V

Y

Y

M

V

S

P

G

G

L

Y

S

G

E

L

S

A

W

W

I

A

A

Q

-

A

-

P

I

I

G

G

L
x
Y

I

S

V

L

G

S

A

L

Y

I

L

L

N

G

W

G

L

L

F

F

V

F

A

A

G

K

R

P

L

M

R

R

V

S

Q

K

T

-

E

-

H

-

N

-

G

-

D

G

A

Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

R

I

F

Y

E

G

D

K

K

R

S

M

G

G

L

G

L

L

R

L

I

F

I

I

S

P

A

A

V

L

V

M

I

G

L

E

V

M

F

F

F
x
W

T

A

I

A

Y

A

C

I

A

F

S

S

G

A

I

L

V

-

A

-

G

G

A

A

R

T

L

I

F

-

E

S

S

V

T

I

F

I

G

D

M

V

S

D

Y

M

E

H

T

I

A

S

L

V

W

I

A

I

G

S

A

A

A

L

A

I

T

A

I

T

A

L

Y

Y

T

T

F

L

V

V

G

G

F

L

L

Y

A

S

V

V

S

A

W

Y

T

T

D
|
D

T

V

V

V

Q

Q

A

L

T

F

L

C

M

I

I

F

F

V

A

G

L

L

I

W

L

I

T

S

P

V

I

P

I

F

V

A

L

L

L

S

A

H

T

P

G

A

G

V

V

A

D

D

T

I

T

G

F

F

L

T

A

A

I

V

E

H

A

A

K

K

-

Y

-

Q

D

K

P

P

S

W

S

L

F

G

D

T

M

V

L

D

K

S

N

S

T

E

T

V

F

Y

I

S

G

W

I

L

I

D

S

S

L

F

M

L

G

L

W

L

G

M

L

L

G

G

Y

-

F

-

G

G

Q

I

P

P

H
x
W

I

-

L

Q

A

A

R

Y

F

F

M

Q

A

R

A

V

D

L

S

S

V

S

K

S

S

S

I

A

A

T

N

Y

A

A

R

Q

R

V

I

L

S

S

M

F

T

L

W

A

M

A

I

F

L

G

C

C

L

L

G

V

G

M

T

A

V

I

A

P

V

A

G

I

F

L

F

I

G

G

-

A

-

I

-

G

-

A

-

S

-

T

-

D

-

W

-

N

-

Q

I

T

A

A

Y

Y

F

G

S

L

A

P

H

D

P

P

D

K

V

-

A

-

G

-

P

-

V

T

T

T

E

E

N

E

P

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

K

Q

L

Y

L

L

F

C

N

P

P

V

W

Y

I

I

A

S

G

F

V

F

L

G

L

L

S

G

A

A

I

V

L

S

A

A

A
|
A

V

V

M

M

S
|
S

T
x
S

L

A

S
x
D

C
x
S

Q

S

L

I

L

L

V

S

C

A

S

S

A

M

L

F

T

A

E

R

D

N

F

I

Y

Y

K

Q

T

L

F

S

L

F

R

R

K

Q

S

N

A

A

S

S

Q

D

L

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

A

I

M

T

V

V

L

F

L

V

V

F

A

G

L

A

V

S

A

A

I

T

A

A

L

M

A

A

binding chloride ion: G64 (≠ W59), W139 (≠ F137)
binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): Y89 (≠ L82), W252 (≠ H253)
binding sodium ion: A58 (= A53), T59 (≠ S54), T59 (≠ S54), V61 (≠ M56), G62 (≠ S57), D186 (= D187), A341 (= A337), S344 (= S340), S344 (= S340), S345 (≠ T341), D347 (≠ S343), S348 (≠ C344)

Sites not aligning to the query:

binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): 404, 405

8j74A Human high-affinity choline transporter cht1 in the hc-3-bound outward-facing open conformation, dimeric state (see paper)
25% identity, 78% coverage: 8:390/494 of query aligns to 6:394/515 of 8j74A

query
sites
8j74A

L

L

I

I

T

A

F

I

V

I

I

V

Y

F

I

Y

A

L

M

I

V

L

L

L

I

V

G

G

L

I

-

W

M

A

A

A

Y

W

R

R

S

T

T

K

N

N

N

S

L

G

S

S

D

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

S

D

L

I

G

G

S

L

V

L

V

V

T

G

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D
x
W

M

V

S

G

G

G

W

G

L

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

I

V

Y

Y

M

V

S

P

G

G

L

Y

S

G

E

L

S

A

W

W

I

A

A

Q

-

A

-

P

I

I

G

G

L
x
Y

I

S

V

L

G

S

A

L

Y

I

L

L

N

G

W

G

L

L

F

F

V

F

A

A

G

K

R

P

L

M

R

R

V

S

Q

K

T

-

E

-

H

-

N

-

G

-

D

G

A

Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

R

I

F

Y

E

G

D

K

K

R

S

M

G

G

L

G

L

L

R

L

I

F

I

I

S

P

A

A

V

L

V

M

I

G

L

E

V

M

F

F

F
x
W

T

A

I

A

Y

A

C

I

A

F

S

S

G

A

I

L

V

-

A

-

G

G

A

A

R

T

L

I

F

-

E

S

S

V

T

I

F

I

G

D

M

V

S

D

Y

M

E

H

T

I

A

S

L

V

W

I

A

I

G

S

A

A

A

L

A

I

T

A

I

T

A

L

Y

Y

T

T

F

L

V

V

G

G

F

L

L

Y

A

S

V

V

S

A

W

Y

T

T

D

D

T

V

V

V

Q

Q

A

L

T

F

L

C

M

I

I

F

F

V

A

G

L

L

I

W

L

I

T

S

P

V

I

P

I
x
F

V

A

L

L

L
x
S

A
x
H

T

P

G

A

G

V

V

A

D

D

T
x
I

T
x
G

F
|
F

L

T

A

A

I

V

E
x
H

A

A

K

K

-

Y

-

Q

D

K

P

P

S

W

S

L

F

G

D

T

M

V

L

D

K

S

N

S

T

E

T

V

F

Y

I

S

G

W

I

L

I

D

S

S

L

F

M

L

G

L

W
x
L

G

M

L

L

G

G

Y

-

F

-

G

G

Q

I

P

P

H
x
W

I

-

L

Q

A

A

R

Y

F

F

M

Q

A

R

A

V

D

L

S

S

V

S

K

S

S

S

I

A

A

T

N

Y

A

A

R

Q

R

V

I

L

S

S

M

F

T

L

W

A

M

A

I

F

L

G

C

C

L

L

G

V

G

M

T

A

V

I

A

P

V

A

G

I

F

L

F

I

G

G

-

A

-

I

-

G

-

A

-

S

-

T

-

D

-

W

-

N

-

Q

I

T

A

A

Y

Y

F

G

S

L

A

P

H

D

P

P

D

K

V

-

A

-

G

-

P

-

V

T

T

T

E

E

N

E

P

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

K

Q

L

Y

L

L

F
x
C

N
x
P

P

V

W

Y

I

I

A

S

G

F

V

F

L

G

L

L

S

G

A

A

I

V

L

S

A

A

V

V

M

M

S

S

T

S

L

A

S

D

C

S

Q

S

L

I

L

L

V

S

C

A

S

S

A

M

L

F

T

A

E

R

D

N

F

I

Y

Y

K

Q

T

L

F

S

L

F

R

R

K

Q

S

N

A

A

S

S

Q

D

L

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

A

I

M

T

V

V

L

F

L

V

V

F

A

G

L

A

V

S

A

A

I

T

A

A

L

M

A

A

binding Lauryl Maltose Neopentyl Glycol: F203 (≠ I204), S206 (≠ L207), H207 (≠ A208), I213 (≠ T214), G214 (≠ T215), F215 (= F216), H219 (≠ E220), C326 (≠ F322), P327 (≠ N323)
binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): W60 (≠ D55), Y89 (≠ L82), W139 (≠ F137), L245 (≠ W244), W252 (≠ H253)

Sites not aligning to the query:

binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): 404, 405, 408

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)
25% identity, 78% coverage: 8:390/494 of query aligns to 8:396/580 of Q9GZV3

query
sites
Q9GZV3

L

L

I

I

T

A

F

I

V

I

I

V

Y

F

I

Y

A

L

M

I

V

L

L

L

I

V

G

G

L

I

-

W

M

A

A

A

Y

W

R

R

S

T

T

K

N

N

N

S

L

G

S

S

D

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

S
x
D

L

I

G

G

S

L

V

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

L

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

I

V

Y

Y

M

V

S

P

G

G

L

Y

S

G

E

L

S

A

W

W

I

A

A

Q

-

A

-

P

I
|
I

G

G

L

Y

I

S

V

L

G

S

A

L

Y

I

L

L

N

G

W

G

L

L

F

F

V

F

A

A

G

K

R
x
P

L

M

R

R

V

S

Q

K

T

-

E

-

H

-

N

-

G

-

D

G

A
x
Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

R

I

F

Y

E

G

D

K

K

R

S

M

G

G

L

G

L

L

R

L

I

F

I

I

S

P

A

A

V

L

V

M

I

G

L

E

V

M

F

F

F

W

T

A

I

A

Y

A

C

I

A

F

S

S

G

A

I

L

V

G

A

A

G

T

A

I

R

S

L

V

F

I

E

-

S

-

T

-

F

I

G

D

M

V

S

D

Y

M

E

H

T

I

A

S

L

V

W

I

A

I

G

S

A

A

A

L

A

I

T

A

I

T

A

L

Y
|
Y

T

T

F

L

V

V

G

G

F

L

L

Y

A

S

V

V

S

A

W

Y

T

T

D

D

T

V

V

V

Q

Q

A

L

T

F

L

C

M

I

I

F

F

V

A

G

L

L

I

W

L

I

T

S

P

V

I

P

I

F

V

A

L

L

L

S

A

H

T

P

G

A

G

V

V

A

D

D

T

I

T

G

F

F

L

T

A

A

I

V

E

H

A

A

K

K

-

Y

-

Q

D

K

P

P

S

W

S

L

F

G

D

T

M

V

L

D

K

S

N

S

T

E

T

V

F

Y

I

S

G

W

I

L

I

D

S

S

L

F

M

L

G

L

W

L

G

M

L

L

G

G

Y

-

F

-

G

G

Q

I

P

P

H

W

I

-

L

Q

A

A

R

Y

F

F

M

Q

A

R

A

V

D

L

S

S

V

S

K

S

S

S

I

A

A

T

N

Y

A

A

R

Q

R

V

I

L

S

S

M

F

T

L

W

A

M

A

I

F

L

G

C

C

L

L

G

-

T

V

V

M

A

A

V

I

G

P

F

A

F

I

G

L

I
|
I

A

G

Y

A

F

I

S

G

A

A

H

S

P

T

D

D

-

W

-

N

-

Q

-

T

-

A

-

Y

-

G

V

L

A

P

G

D

P

P

-

K

V

T

T

T

E

E

N

E

P

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

K

Q

L

Y

L

L

F

C

N

P

P

V

W

Y

I

I

A

S

G

F

V

F

L

G

L

L

S

G

A

A

I

V

L

S

A

A

V
|
V

M

M

S

S

T

S

L

A

S

D

C

S

Q

S

L

I

L

L

V

S

C

A

S

S

A

M

L

F

T

A

E
x
R

D

N

F

I

Y

Y

K

Q

T

L

F

S

L

F

R

R

K

Q

S

N

A

A

S

S

Q

D

L

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

A

I

M

T

V

V

L

F

L

V

V

F

A

G

L

A

V

S

A

A

I

T

A

A

L

M

A

A

D48 (≠ S41) to G: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039768
G65 (= G58) to E: in CMS20; loss of choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039765
I89 (= I80) 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 (≠ R96) to S: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039766
Y111 (≠ A107) to H: in CMS20; no effect on localization at plasma membrane
Y175 (= Y174) to C: in CMS20; uncertain significance; dbSNP:rs1331713195
I291 (= I293) to T: in CMS20; uncertain significance; dbSNP:rs375397889
V344 (= V338) to L: in CMS20; uncertain significance
R361 (≠ E355) 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.

8zqpA High affinity choline transporter 1 (see paper)
26% identity, 78% coverage: 8:390/494 of query aligns to 5:393/470 of 8zqpA

query
sites
8zqpA

L

L

I

I

T

A

F

I

V

I

I

V

Y

F

I

Y

A

L

M

I

V

L

L

L

I

V

G

G

L

I

-

W

M

A

A

A

Y

W

R

R

S

T

T

K

N

N

N

S

L

G

S

S

D

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

S

D

L

I

G

G

S

L

V

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
x
G

L

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

I

V

Y

Y

M

V

S

P

G

G

L

Y

S

G

E

L

S

A

W

W

I

A

A

Q

-

A

-

P

I

I

G

G

L
x
Y

I

S

V

L

G

S

A

L

Y

I

L

L

N

G

W

G

L

L

F

F

V

F

A

A

G

K

R

P

L

M

R

R

V

S

Q

K

T

-

E

-

H

-

N

-

G

-

D

G

A

Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

R

I

F

Y

E

G

D

K

K

R

S

M

G

G

L

G

L

L

R

L

I

F

I

I

S

P

A

A

V

L

V

M

I

G

L

E

V

M

F

F

F

W

T

A

I

A

Y

A

C

I

A

F

S

S

G

A

I

L

V

-

A

-

G

G

A

A

R

T

L

I

F

-

E

S

S

V

T

I

F

I

G

D

M

V

S

D

Y

M

E

H

T

I

A

S

L

V

W

I

A

I

G

S

A

A

A

L

A

I

T

A

I

T

A

L

Y

Y

T

T

F

L

V

V

G

G

F

L

L

Y

A

S

V

V

S

A

W

Y

T

T

D
|
D

T

V

V

V

Q

Q

A

L

T

F

L

C

M

I

I

F

F

V

A

G

L

L

I

W

L

I

T

S

P

V

I

P

I

F

V

A

L

L

L

S

A

H

T

P

G

A

G

V

V

A

D

D

T

I

T

G

F

F

L

T

A

A

I

V

E

H

A

A

K

K

-

Y

-

Q

D

K

P

P

S

W

S

L

F

G

D

T

M

V

L

D

K

S

N

S

T

E

T

V

F

Y

I

S

G

W

I

L

I

D

S

S

L

F

M

L

G

L

W

L

G

M

L

L

G

G

Y

-

F

-

G

G

Q

I

P

P

H

W

I

-

L

Q

A

A

R

Y

F

F

M

Q

A

R

A

V

D

L

S

S

V

S

K

S

S

S

I

A

A

T

N

Y

A

A

R

Q

R

V

I

L

S

S

M

F

T

L

W

A

M

A

I

F

L

G

C

C

L

L

G

-

T

V

V

M

A

A

V

I

G

P

F

A

F

I

G

L

I

I

A

G

Y

A

F

I

S

G

A

A

H

S

P

T

D

D

-

W

-

N

-

Q

-

T

-

A

-

Y

-

G

V

L

A

P

G

D

P

P

-

K

V

T

T

T

E

E

N

E

P

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

K

Q

L

Y

L

L

F

C

N

P

P

V

W

Y

I

I

A

S

G

F

V

F

L

G

L

L

S

G

A

A

I

V

L

S

A

A

V

V

M

M

S
|
S

T

S

L

A

S
x
D

C
x
S

Q

S

L

I

L

L

V

S

C

A

S

S

A

M

L

F

T

A

E

R

D

N

F

I

Y

Y

K

Q

T

L

F

S

L

F

R

R

K

Q

S

N

A

A

S

S

Q

D

L

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

A

I

M

T

V

V

L

F

L

V

V

F

A

G

L

A

V

S

A

A

I

T

A

A

L

M

A

A

binding 4-methoxy-3-[(1-methylpiperidin-4-yl)oxy]-N-{[3-(propan-2-yl)-1,2-oxazol-5-yl]methyl}benzamide: G63 (≠ W59), Y88 (≠ L82)
binding sodium ion: D185 (= D187), S343 (= S340), D346 (≠ S343), S347 (≠ C344)

9bimA Cryo-em structure of human cht1 in the hc-3 bound outward-facing state (see paper)
25% identity, 78% coverage: 8:390/494 of query aligns to 7:393/516 of 9bimA

query
sites
9bimA

L

L

I

I

T

A

F

I

V

I

I

V

Y

F

I

Y

A

L

M

I

V

L

L

L

I

V

G

G

L

I

-

W

M

A

A

A

Y

W

R

R

S

T

T

K

N

G

N

S

L

A

S

E

D

E

Y

R

-

S

-

E

-

A

-

I

I

I

L

V

G

G

R

R

S

D

L

I

G

G

S

L

V

L

V

V

T

G

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D
x
W

M

V

S

G

G

G

W

G

L

Y

L

I

M

N

G

G

L

T

P

A

G

E

A

A

I

V

Y

Y

M

V

S

P

G

G

L
x
Y

S

G

E

L

S

A

W

W

I

A

A

Q

-

A

-

P

I

I

G

G

L
x
Y

I

S

V

L

G

S

A

L

Y

I

L

L

N

G

W

G

L

L

F

F

V

F

A

A

G

K

R

P

L

M

R

R

V

S

Q

K

T

-

E

-

H

-

N

-

G

-

D

G

A

Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

R

I

F

Y

E

G

D

K

K

R

S

M

G

G

L

G

L

L

R

L

I

F

I

I

S

P

A

A

V

L

V

M

I

G

L

E

V

M

F

F

F
x
W

T

A

I

A

Y

A

C

I

A

F

S

S

G

A

I

L

V

-

A

-

G

G

A

A

R

T

L

I

F

-

E

S

S

V

T

I

F

I

G

D

M

V

S

D

Y

M

E

H

T

I

A

S

L

V

W

I

A

I

G

S

A

A

A

L

A

I

T

A

I

T

A

L

Y

Y

T

T

F

L

V

V

G

G

F

L

L

Y

A

S

V

V

S

A

W

Y

T

T

D

D

T

V

V

V

Q

Q

A

L

T

F

L

C

M

I

I

F

F

V

A

G

L

L

I

W

L

I

T

S

P

V

I

P

I

F

V

A

L

L

L

S

A

H

T

P

G

A

G

V

V

A

D

D

T

I

T

G

F

F

L

T

A

A

I

V

E

H

A

A

K

K

-

Y

-

Q

D

K

P

P

S

W

S

L

F

G

D

T

M

V

L

D

K

S

N

S

T

E

T

V

F

Y

I

S

G

W

I

L

I

D

S

S

L

F

M

L

G

L

W

L

G

M

L

L

G

G

Y

-

F

-

G

G

Q

I

P

P

H
x
W

I

-

L

Q

A

A

R

Y

F

F

M

Q

A

R

A

V

D

L

S

S

V

S

K

S

S

S

I

A

A

T

N

Y

A

A

R

Q

R

V

I

L

S

S

M

F

T

L

W

A

M

A

I

F

L

G

C

C

L

L

G

V

G

M

T

A

V

I

A

P

V

A

G

I

F

L

F

I

G

G

-

A

-

I

-

G

-

A

-

S

-

T

-

D

-

W

-

N

-

Q

I

T

A

A

Y

Y

F

G

S

L

A

P

H

D

P

P

D

K

V

-

A

-

G

-

P

-

V

T

T

T

E

E

N

E

P

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

K

Q

L

Y

L

L

F

C

N

P

P

V

W

Y

I

I

A

S

G

F

V

F

L

G

L

L

S

G

A

A

I

V

L

S

A

A

V

V

M

M

S

S

T

S

L

A

S

D

C

S

Q

S

L

I

L

L

V

S

C

A

S

S

A

M

L

F

T

A

E

R

D

N

F

I

Y

Y

K

Q

T

L

F

S

L

F

R

R

K

Q

S

N

A

A

S

S

Q

D

L

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

A

I

M

T

V

V

L

F

L

V

V

F

A

G

L

A

V

S

A

A

I

T

A

A

L

M

A

A

binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): W59 (≠ D55), Y77 (≠ L73), Y88 (≠ L82), W138 (≠ F137), W251 (≠ H253)

Sites not aligning to the query:

binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): 404, 407

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)
31% identity, 38% coverage: 12:201/494 of query aligns to 33:219/662 of P11170

query
sites
P11170

V

V

I

I

Y

Y

I

F

A

L

A

V

M

V

V

M

L

A

I

V

G

G

L

L

M

W

A

A

Y

M

R

F

S

S

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

F

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

W

V

P

T

I

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D

N

M

I

S

G

G

S

W

G

L

H

L

F

M

V

G

G

L

L

P

A

G

G

A

T

I

G

Y

A

M

A

S

S

G

G

L

I

S

A

E

T

-

G

-

F

S

E

W

W

I

N

A

A

I

L

G

I

L

M

I

V

V

V

G

-

A

-

Y

V

L

L

N

G

W

W

L

V

F

F

V

V

A

P

G

I

R

Y

L

I

R

R

V

-

Q

-

T

-

E

-

H

-

N

-

G

A

D

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

Q

S

K

R

R

F

F

E

G

D

G

K

K

S

R

G

I

L

Q

L

I

R

Y

I

L

I

S

S

I

A

L

V

S

V

L

I

L

L

L

V

Y

F

I

F

F

T

T

I

K

Y

I

C

S

A

A

S

D

G

-

I

I

V

F

A

S

G

G

A

A

R

I

L

F

F

I

E

Q

S

L

T

T

F

L

G

G

M

L

S

D

Y

I

E

Y

T

V

A

A

L

I

W

I

A

I

G

L

A

L

A

V

A

I

T

T

I

G

A

L

Y

Y

T

T

F

I

V

T

G

G

F

L

L

A

A

A

V

V

S

I

W

Y

T

T

D

D

T

T

V

L

Q

Q

-

T

A

A

T

I

L

M

M

M

I

V

F

G

A

S

L

V

I

I

L

L

T

T

Sites not aligning to the query:

255 modified: Disulfide link with 608
457 Q→W: Drasticly decreased affinity for glucose and phlorizin.
460 T→W: Decreased affinity for glucose and phlorizin.
608 modified: Disulfide link with 255

7sl9A Cryoem structure of smct1 (see paper)
24% identity, 80% coverage: 41:437/494 of query aligns to 30:428/497 of 7sl9A

query
sites
7sl9A

S

A

L

M

G

T

S

A

V

V

V

P

T

V

A

A

L

L

S

S

A

L

G

T

A

A

S

S

D

F

M

M

S

S

G

A

W

V

L

T

L

V

M

L

G

G

L

T

P

P

G

S

A

E

I

V

Y

Y

M

R

S

F

G

G

L

A

S

I

E

F

S

S

W

I

I

F

A

A

I

F

G

-

L

-

I

-

V

-

G

-

A

T

Y

Y

L

F

N

F

W

V

L

V

F

V

V

I

A

S

G

A

R

E

L

V

R

F

V

L

Q

P

T

V

E

F

H

Y

N

K

G

L

D

G

A

I

L

T

T

S

L

T

P

Y

D

E

Y

Y

F

L

S

E

S

L

R

R

F

F

E

N

D

K

K

-

S

-

G

-

L

C

L

V

R

R

I

L

I

C

S

G

A

T

V

V

V

L

I

F

L

I

V

V

F

Q

F

T

T

I

I

L

Y
|
Y

C

T

A

G

S

I

G

V

I

I

V

Y

A

A

G

P

A

A

R

L

L

A

F

L

E

N

S

Q

T

V

F

T

G

G

M

F

S

D

Y

L

E

W

T

G

A

A

L

V

W

V

A

A

G

T

A

G

A

V

T

C

I

T

A

F

Y

Y

T

C

F

T

V

L

G

G

F

L

L

K

A

A

V

V

S

I

W

W

T

T

D

D

T

V

V

F

Q

Q

A

V

T

G

L

I

M

M

I

V

-

A

-

G

F

F

A

A

L

S

I

V

L

I

T

I

P

Q

I

A

I

V

V

V

L

M

L

-

A

-

T

Q

G

G

V

I

D

S

T

T

T

-

F

-

L

I

A

L

I

N

E

D

A

A

K

Y

D

D

P

G

S

G

S

R

F

L

D

N

M

F

-

W

-

N

-

F

-

N

-

P

-

N

-

P

L

L

K

Q

N

R

T

H

T

T

F

F

I

W

G

T

I

I

-

I

-

G

S

G

L

T

M

F

G

T

W

W

G

T

L

S

G
x
I

Y

Y

F

G

G

V

Q

N

P

Q

H

S

I
x
Q

L

V

A

Q

R

R

F

Y

M

I

A

S

A

C

D

K

S

S

V

R

K

F

S

Q

I

A

A

K

N

L

A

S

R

L

R

Y

I

I

S

N

M

L

T

V

-

G

-

L

W

W

M

A

I

I

L

L

C

-

L

-

G

-

T

T

V

C

A

S

V

V

G

-

F

F

F

C

G

G

I

L

A

A

Y

L

F

Y

S

S

A

R

H

Y

P

H

D

D

V

-

A

C

G

D

P

P

V

W

T

T

E

A

N

K

-

K

-

V

-

S

-

A

P

P

E

D

R

Q

V

L

-

M

-

P

F

Y

I

L

E

V

L

L

A

D

K

I

L

L

L

Q

F

D

N

Y

P

P

W

G

I

L

A

P

G

G

V

L

L

F

L

V

S

A

A

C

I

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

V

S

S

C

S

Q

S

L

I

L

N

V

A

C

L

S

A

A

V

L

T

T

V

E

E

D

D

F

L

Y

I

K

K

T

P

F

Y

L

F

R

R

K

-

S

S

A

L

S

S

Q

E

L

R

E

S

L

L

V

S

W

W

V

I

G

S

R

Q

A

G

M

M

V

S

L

V

V

Y

A

G

L

A

V

L

A

C

I

I

A

G

L

M

A

A

N

L

P

-

E

A

N

S

R

L

V

M

L

G

G

A

L

L

V

L

S

Q

Y

A

A

A

W

L

A

S

G

V

F

F

G

G

A

M

A

V

F

G

G

G

P

P

V

L

V

M

-

G

-

L

-

F

L

A

I

L

S

G

V

I

I

L

W

V

K

P

N

F

M

A

T

N

R

S

N

I

G

G

A

A

L

L

A

V

G

G

I

L

L

M

V

A

G

G

binding butanoic acid: Y121 (= Y140), I235 (≠ G247), Q242 (≠ I254)

7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
23% identity, 74% coverage: 66:430/494 of query aligns to 49:454/585 of 7slaA

query
sites
7slaA

G

G

A

S

I

G

Y

H

M

F

S

I

G

G

L

L

S

A

E

G

S

T

W

G

I

A

A

A

I

S

G

G

L

L

I

A

V

V

G

G

A

G

Y

F

-

E

-

W

-

N

-

A

-

L

-

V

-

L

-

V

L

L

N

G

W

W

L

V

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

-

Q

-

T

-

E

-

H

-

N

-

G

A

D

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

Q

S

R

G

-

L

I

L

Q

R

V

I

Y

I

L

S

S

A

V

V

L

V

S

I

L

L

F

V

L

F

Y

F

I

T

F

I

T

Y

K

C

I

A

S

S

V

G

D

I

I

V

F

A

S

G

G

A

A

R

I

L

F

F

I

E

N

S

L

T

A

F

L

G

G

M

W

S

N

Y

L

E

Y

T

L

A

S

L

I

W

I

A

L

G

L

A

L

A

A

A

I

T

T

I

A

A

L

Y

Y

T

T

F

I

V

T

G

G

F

L

L

A

A

A

V

V

S

I

W

Y

T

T

D

D

T

T

V

L

Q

Q

A

T

T

L

L

I

M

M

I

L

F

I

A

G

L

A

I

L

L

I

T

L

P

M

I

G

I

F

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

D

-

A

-

F

-

M

-

E

-

K

-

Y

-

M

-

K

-

A

-

I

-

P

-

T

-

I

-

V

-

S

-

D

-

G

-

N

T

T

F

F

L

Q

A

E

I

K

E

C

A

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

-

F

K

R

D

D

P

P

S

L

S

T

F

G

D

D

M

L

L

P

K

W

N

P

T

G

T

F

F

I

I

F

G

G

I

L

I

T

S

I

L

L

M

A

G

L

W

W

G

-

L

-

G

-

Y

Y

F

W

G

C

Q

T

P

D

H

Q

-

V

I

I

L

V

A

Q

R

R

F

C

M

L

A

A

D

K

S

N

V

M

K

S

S

H

I

V

A

K

N

G

A

G

R

C

R

I

I

L

S

A

M

G

T
x
Y

W

L

M

K

I

L

L

L

C

P

L

M

G

F

G

I

T

M

V

V

A

M

V

P

G

G

F

M

F

I

G

S

I

R

A

I

Y

L

F

F

S

-

A

-

H

-

P

P

D

D

-

K

V

V

A

A

G

C

P

V

V

V

T

P

E

S

N

E

P

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

I

P

E

T

L

L

A

V

K

V

L

E

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

A

A

V

I

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

T

C

S

Q

I

L

F

L

N

V

S

C

A

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

A

T

K

F

-

L

V

R

R

K

K

S

R

A

A

S

S

Q

E

L

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

A

L

M

F

V

V

L

L

L

F

V

L

A

V

L

V

V

V

A

S

I

I

A

A

-

W

-

I

-

P

-

I

L

V

A

Q

A

S

N

A

P

Q

E

S

N

G

R

Q

V

L

L

F

G

D

L

Y

V

I

S

Q

Y

S

A

V

W

S

A

S

G

Y

F

L

G

A

A

P

F

V

G

A

P

A

V

V

V

F

L

L

I

L

S

A

V

I

I

F

W

W

K

K

N

R

M

V

T

N

R

E

N

Q

G

G

A

A

binding cholesterol hemisuccinate: Y288 (≠ T276)

Sites not aligning to the query:

binding cholesterol hemisuccinate: 36, 554

7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
23% identity, 74% coverage: 66:430/494 of query aligns to 48:453/582 of 7sl8A

query
sites
7sl8A

G

G

A

S

I

G

Y

H

M

F

S

I

G

G

L

L

S

A

E

G

S

T

W

G

I

A

A

A

I

S

G

G

L

L

I

A

V

V

G

G

A

G

Y

F

-

E

-

W

-

N

-

A

-

L

-

V

-

L

-

V

L

L

N

G

W

W

L

V

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

-

Q

-

T

-

E

-

H

-

N

-

G

A

D

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

Q

S

R

G

-

L

I

L

Q

R

V

I

Y

I

L

S

S

A

V

V

L

V

S

I

L

L

F

V

L

F

Y

F

I

T

F

I

T

Y

K

C

I

A

S

S

V

G

D

I

I

V

F

A

S

G

G

A

A

R

I

L

F

F

I

E

N

S

L

T

A

F

L

G

G

M

W

S

N

Y

L

E

Y

T

L

A

S

L

I

W

I

A

L

G

L

A

L

A

A

A

I

T

T

I

A

A

L

Y

Y

T

T

F

I

V

T

G

G

F

L

L

A

A

A

V

V

S

I

W

Y

T

T

D

D

T

T

V

L

Q

Q

A

T

T

L

L

I

M

M

I

L

F

I

A

G

L

A

I

L

L

I

T

L

P

M

I

G

I

F

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

D

-

A

-

F

-

M

-

E

-

K

-

Y

-

M

-

K

-

A

-

I

-

P

-

T

-

I

-

V

-

S

-

D

-

G

-

N

T

T

F

F

L

Q

A

E

I

K

E

C

A

Y

-

T

-

P

-

R

-

A

-

D

-

S

-

F

-

H

-

I

-

F

K

R

D

D

P

P

S

L

S

T

F

G

D

D

M

L

L

P

K

W

N

P

T

G

T

F

F

I

I

F

G

G

I

L

I

T

S

I

L

L

M

A

G

L

W

W

G

-

L

-

G

-

Y

Y

F

W

G

C

Q

T

P

D

H

Q

-

V

I

I

L

V

A

Q

R

R

F

C

M

L

A

A

D

K

S

N

V

M

K

S

S

H

I

V

A

K

N
x
G

A

G

R

C

R

I

I

L

S

A

M

G

T
x
Y

W

L

M

K

I

L

L

L

C

P

L

M

G

F

G

I

T

M

V

V

A

M

V

P

G

G

F

M

F

I

G

S

I

R

A

I

Y

L

F

F

S

-

A

-

H

-

P

P

D

D

-

K

V

V

A

A

G

C

P

V

V

V

T

P

E

S

N

E

P

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

I

P

E

T

L

L

A

V

K

V

L

E

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

A

A

V

I

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

T

C

S

Q

I

L

F

L

N

V

S

C

A

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

A

T

K

F

-

L

V

R

R

K

K

S

R

A

A

S

S

Q

E

L

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

A

L

M

F

V

V

L

L

L

F

V

L

A

V

L

V

V

V

A

S

I

I

A

A

-

W

-

I

-

P

-

I

L

V

A

Q

A

S

N

A

P

Q

E

S

N

G

R

Q

V

L

L

F

G

D

L

Y

V

I

S

Q

Y

S

A

V

W

S

A

S

G

Y

F

L

G

A

A

P

F

V

G

A

P

A

V

V

V

F

L

L

I

L

S

A

V

I

I

F

W

W

K

K

N

R

M

V

T

N

R

E

N

Q

G

G

A

A

binding cholesterol: G280 (≠ N269), Y287 (≠ T276)

Sites not aligning to the query:

binding cholesterol: 35, 551, 558

8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
25% identity, 76% coverage: 4:376/494 of query aligns to 1:407/586 of 8hdhA

query
sites
8hdhA

S

D

N

N

P

P

T

A

-

D

L

I

I

L

T

V

F

I

V

A

I

A

Y

Y

I

F

A

L

M

V

V

I

L

G

I

V

G

G

L

L

M

W

A

S

Y

M

R

C

S

R

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

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

L
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

A

T

I

G

Y

A

M

A

S

S

G

G

L

L

S

A

E

V

S

A

-

G

-
x
F

-
x
E

W

W

I

N

A

A

I

-

G

-

L

L

I

F

V

V

G

V

A

L

Y

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

Q

-

T

-

E

-

H

-

N

T

G

A

D

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

R

S

R

G

I

L

R

L

L

R

Y

I

L

I

S

S

V

A

L

V

S

V

L

I

F

L

L

V

Y

F

I

F

F

T

T

I

-

Y

K

C

I

A

S

S

V

G

D

I

M

V

F

A

S

G

G

A

A

R

V

L

F

F

I

E

Q

S

Q

T

A

F

L

G

G

M

W

S

N

Y

I

E

Y

T

A

A

S

L

V

W

I

A

A

G

L

A

L

A

G

A

I

T

T

I

M

A

I

Y

Y

T

T

F

V

V

T

G

G

F

L

L

A

A

A

V

L

S

M

W

Y

T

T

D

D

T

T

V

V

Q

Q

A

T

T

F

L

V

M

I

I

L

F

G

A

G

L

A

I

C

L

I

T

L

P

M

I

G

I

Y

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

S

T

G

T

L

F

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

L

L

A

T

I

V

E

S

A

E

K

D

D

P

-

A

-

V

-

G

-

N

-

I

-

S

-

F

-

C

-

Y

-

R

-

P

-

R

P

P

S

D

S

S

F

Y

D

H

M

L

L

L

K

R

N

H

T

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

F

L

I

L

G

G

I

L

I

T

S

I

L

V

M
x
S

G

G

W

W

G

-

L

-

G

-

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

-

V

I

I

L

V

A

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

V

L

K

T

S

H

I

I

A

K

N

A

A

G

R

-

I

-

S

-

M

-

T

-

W

-

M

C

I

I

L

L

C

C

L

G

G

Y

G

L

T

K

V

L

A

T

V

P

G

M

F

F

F

L

-

M

-

V

-

M

-

P

G

G

I

M

A

I

Y

S

F

R

S

I

A

L

H

Y

P

P

D

D

-

E

V

V

A

A

G

C

P

V

V

V

T

P

E

E

N

V

P

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

I

P

E

R

L

L

A

V

K

V

L

K

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

A

A

V

I

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

C

S

Q

I

L

F

L

N

V

S

C

S

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

-

T

T

F

R

L

L

R

R

K

P

S

R

A

A

S

G

Q

D

L

R

E

E

L

L

V

L

W

L

V

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 (≠ D55), G59 (≠ W59), H60 (≠ L60), G63 (= G63), L64 (= L64), F78 (vs. gap), E79 (vs. gap), S267 (≠ M242), W271 (≠ F249)
binding sodium ion: A53 (= A53), S54 (= S54), I56 (≠ M56), G57 (≠ S57), A369 (= A337), S372 (= S340), S373 (≠ T341)

Sites not aligning to the query:

8hb0A Structure of human sglt2-map17 complex with ta1887 (see paper)
25% identity, 76% coverage: 4:376/494 of query aligns to 1:407/586 of 8hb0A

query
sites
8hb0A

S

D

N

N

P

P

T

A

-

D

L

I

I

L

T

V

F

I

V

A

I

A

Y

Y

I

F

A

L

M

V

V

I

L

G

I

V

G

G

L

L

M

W

A

S

Y

M

R

C

S

R

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

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

L
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

A
x
T

I

G

Y

A

M

A

S

S

G

G

L

L

S

A

E
x
V

S

A

-

G

-
x
F

-
x
E

W

W

I

N

A

A

I

-

G

-

L

L

I

F

V

V

G

V

A

L

Y

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

Q

-

T

-

E

-

H

-

N

T

G

A

D

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

R

S

R

G

I

L

R

L

L

R

Y

I

L

I

S

S

V

A

L

V

S

V

L

I

F

L

L

V

Y

F

I

F

F

T

T

I

-

Y

K

C

I

A

S

S
x
V

G

D

I

M

V

F

A

S

G

G

A

A

R

V

L

F

F

I

E

Q

S

Q

T

A

F

L

G

G

M

W

S

N

Y

I

E

Y

T

A

A

S

L

V

W

I

A

A

G

L

A

L

A

G

A

I

T

T

I

M

A

I

Y

Y

T

T

F

V

V

T

G

G

F

L

L

A

A

A

V

L

S

M

W

Y

T

T

D

D

T

T

V

V

Q

Q

A

T

T

F

L

V

M

I

I

L

F

G

A

G

L

A

I

C

L

I

T

L

P

M

I

G

I

Y

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

S

T

G

T

L

F

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

L

L

A

T

I

V

E

S

A

E

K

D

D

P

-

A

-

V

-

G

-

N

-

I

-

S

-

F

-

C

-

Y

-

R

-

P

-

R

P

P

S

D

S

S

F

Y

D

H

M

L

L

L

K

R

N

H

T

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

F

L

I

L

G

G

I

L

I

T

S

I

L
x
V

M
x
S

G

G

W

W

G

-

L

-

G

-

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

-

V

I

I

L

V

A

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

V

L

K

T

S

H

I

I

A

K

N

A

A

G

R

-

I

-

S

-

M

-

T

-

W

-

M

C

I

I

L

L

C

C

L

G

G

Y

G

L

T

K

V

L

A

T

V

P

G

M

F

F

F

L

-

M

-

V

-

M

-

P

G

G

I

M

A

I

Y

S

F

R

S

I

A

L

H

Y

P

P

D

D

-

E

V

V

A

A

G

C

P

V

V

V

T

P

E

E

N

V

P

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

I

P

E

R

L

L

A

V

K

V

L

K

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

A

A

V

I

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

C

S

Q

I

L

F

L

N

V

S

C

S

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

-

T

T

F

R

L

L

R

R

K

P

S

R

A

A

S

G

Q

D

L

R

E

E

L

L

V

L

W

L

V

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 (≠ D55), H60 (≠ L60), G63 (= G63), L64 (= L64), T67 (≠ A67), V75 (≠ E75), F78 (vs. gap), E79 (vs. gap), V137 (≠ S143), V266 (≠ L241), S267 (≠ M242), W271 (≠ F249)
binding sodium ion: A53 (= A53), I56 (≠ M56), G57 (≠ S57), A369 (= A337), S372 (= S340), S373 (≠ T341)

Sites not aligning to the query:

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 2 papers)
25% identity, 76% coverage: 3:376/494 of query aligns to 20:427/672 of P31639

query
sites
P31639

V

I

S

D

N

N

P

P

T

A

-

D

L

I

I

L

T

V

F

I

V

A

I

A

Y

Y

I

F

A

L

M

V

V

I

L

G

I

V

G

G

L

L

M

W

A

S

Y

M

R

C

S

R

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

W

V

P

T

V

A

G

L

A

S

S

A

L

G

F

A
|
A

S
|
S

D

N

M
x
I

S

G

G

S

W

G

L

H

L

F

M

V

G

G

L

L

P

A

G

G

A

T

I

G

Y

A

M

A

S

S

G

G

L

L

S

A

E
x
V

S

A

-

G

-
x
F

-

E

W

W

I

N

A

A

I

-

G

-

L

L

I

F

V

V

G

V

A

L

Y

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

Q

-

T

-

E

-

H

-

N

T

G

A

D

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

S

K

R

R

F

F

E

G

D

G

K

R

S

R

G

I

L

R

L

L

R

Y

I

L

I

S

S

V

A

L

V

S

V

L

I

F

L

L

V

Y

F

I

F

F

T

T

I

-

Y

K

C

I

A

S

S
x
V

G

D

I

M

V

F

A

S

G

G

A

A

R

V

L

F

F

I

E

Q

S

Q

T

A

F

L

G

G

M

W

S

N

Y

I

E

Y

T

A

A

S

L

V

W

I

A

A

G

L

A

L

A

G

A

I

T

T

I

M

A

I

Y

Y

T

T

F

V

V

T

G

G

F

L

L

A

A

A

V

L

S

M

W

Y

T

T

D
|
D

T

T

V

V

Q

Q

A

T

T

F

L

V

M

I

I

L

F

G

A

G

L

A

I

C

L

I

T

L

P

M

I

G

I

Y

V

A

L

F

L

H

A

E

T

V

G

G

V

Y

D

S

T

G

T

L

F

F

-

D

-

K

-

Y

-

L

-

G

-

A

-

T

-

S

L

L

A

T

I

V

E

S

A

E

K

D

D

P

-

A

-

V

-

G

-

N

-

I

-

S

-

F

-

C

-

Y

-

R

-

P

-

R

P

P

S

D

S

S

F

Y

D

H

M

L

L

L

K

R

N

H

T

P

T

V

-

T

-

G

-

D

-

L

-

P

-

W

-

P

-

A

-

L

F

L

I

L

G

G

I
x
L

I

T

S

I

L

V

M

S

G

G

W

W

G

-

L

-

G

-

Y

Y

F

W

G

C

Q

S

P

D

H

Q

-

V

I

I

L

V

A

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

V

L

K

T

S

H

I

I

A

K

N

A

A

G

R

-

I

-

S

-

M

-

T

-

W

-

M

C

I

I

L

L

C

C

L

G

G

Y

G

L

T

K

V

L

A

T

V

P

G

M

F

F

F

L

-

M

-

V

-

M

-

P

G

G

I

M

A

I

Y

S

F

R

S

I

A

L

H

Y

P

P

D

D

-

E

V

V

A

A

G

C

P

V

V

V

T

P

E

E

N

V

P

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

I

P

E

R

L

L

A

V

K

V

L

K

L

L

F

M

N

P

P

N

W

G

I

L

A

R

G

G

V

L

L

M

L

L

S

A

A

V

I

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

C

S

Q

I

L

F

L

N

V

S

C

S

S

S

S

T

A

L

L

F

T

T

E

M

D

D

F

I

Y

Y

K

-

T

T

F

R

L

L

R

R

K

P

S

R

A

A

S

G

Q

D

L

R

E

E

L

L

V

L

W

L

V

V

G

G

R

R

A73 (= A53) binding Na(+)
S74 (= S54) mutation to A: Impairs phlorizin binding and its inhibition on glucose uptake.
I76 (≠ M56) binding Na(+)
V95 (≠ E75) mutation to I: Strong reduction in D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
F98 (vs. gap) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes empagliflozin binding and its inhibition on glucose uptake. Impairs phlorizin binding and its inhibition on glucose uptake.
V157 (≠ S143) mutation to A: Decreases D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
D201 (= D187) mutation to A: Impairs phlorizin binding and its inhibition on glucose uptake.
L283 (≠ I238) mutation to M: Strong reduction in D-glucose transporter activity. Impairs inhibition by empagliflozin on glucose uptake.
A389 (= A337) binding Na(+)
S392 (= S340) binding Na(+)
S393 (≠ T341) binding Na(+)

Sites not aligning to the query:

453 F→A: Slightly decreases D-glucose transporter activity. Impairs empagliflozin binding and its inhibition on glucose uptake. Impairs phlorizin binding and its inhibition on glucose uptake.

8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
25% identity, 76% coverage: 4:376/494 of query aligns to 1:407/590 of 8hg7A

query
sites
8hg7A

S

D

N

N

P

P

T

A

-

D

L

I

I

L

T

V

F

I

V

A

I

A

Y

Y

I

F

A

L

M

V

V

I

L

G

I

V

G

G

L

L

M

W

A

S

Y

M

R

C

S

R

T

T

N

N

N

R

-

G

-

T

L

V

S

G

D

G

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

V

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

L
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

A

T

I

G

Y

A

M

A

S

S

G

G

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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 (≠ D55), G59 (≠ W59), H60 (≠ L60), G63 (= G63), L64 (= L64), E79 (vs. gap), V266 (≠ L241), S267 (≠ M242), Y270 (= Y248), W271 (≠ F249), K301 (≠ T285)
binding sodium ion: A53 (= A53), S54 (= S54), I56 (≠ M56), G57 (≠ S57), A369 (= A337), S372 (= S340), S373 (≠ T341)

Sites not aligning to the query:

Query Sequence

>AO356_09010 FitnessBrowser__pseudo5_N2C3_1:AO356_09010
MSVSNPTLITFVIYIAAMVLIGLMAYRSTNNLSDYILGGRSLGSVVTALSAGASDMSGWL
LMGLPGAIYMSGLSESWIAIGLIVGAYLNWLFVAGRLRVQTEHNGDALTLPDYFSSRFED
KSGLLRIISAVVILVFFTIYCASGIVAGARLFESTFGMSYETALWAGAAATIAYTFVGGF
LAVSWTDTVQATLMIFALILTPIIVLLATGGVDTTFLAIEAKDPSSFDMLKNTTFIGIIS
LMGWGLGYFGQPHILARFMAADSVKSIANARRISMTWMILCLGGTVAVGFFGIAYFSAHP
DVAGPVTENPERVFIELAKLLFNPWIAGVLLSAILAAVMSTLSCQLLVCSSALTEDFYKT
FLRKSASQLELVWVGRAMVLLVALVAIALAANPENRVLGLVSYAWAGFGAAFGPVVLISV
IWKNMTRNGALAGILVGAITVIVWKHFALLGLYEIIPGFIFASLAIYLVSKMGSPTAGML
QRFDAAEKDFRLNQ

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