SitesBLAST

R257 (= R257) mutation to C: Sodium-independent binding affinity for proline.
C281 (≠ T281) 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 (≠ A344) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (≠ S349) 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.

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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E457 (≠ S402) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

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: 12:437/494 of query aligns to 33:492/662 of P11170

query
sites
P11170

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C255 (≠ A221) modified: Disulfide link with 608
Q457 (≠ S402) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
T460 (≠ W405) mutation to W: Decreased affinity for glucose and phlorizin.

Sites not aligning to the query:

608 modified: Disulfide link with 255

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)
24% identity, 74% coverage: 24:391/494 of query aligns to 36:403/643 of Q92911

query
sites
Q92911

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D

-

L

P

P

W

G

V

V

A

P

G

G

I

L

I

F

L

L

S

A

G

C

V

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

A

S

S

A

T

Q

S

L

I

L

N

V

A

S

M

S

A

A

V

L

T

T

V

Q

E

D

D

F

L

Y

I

K

K

A

P

M

R

L

L

R

R

K

S

N

L

A

A

S

P

Q

R

T

-

E

K

L

L

V

V

W

I

V

I

G

S

R

K

G

G

M

L

V

S

L

L

L

I

I

Y

A

G

L

S

I

A

A

C

I

L

G

T

I

V

A

A

S

A

A102 (vs. gap) natural variant: A -> P
H226 (≠ P224) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
D237 (= D228) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
Y242 (≠ L233) 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 (≠ S234) 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

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

V

I

I

Y

Y

I

F

A

V

M

V

I

M

L

A

I

V

G

G

F

V

I

W

A

A

Y

M

R

L

A

K

T

T

K

N

N

R

F

S

S

T

-

V

-

G

D

G

Y

F

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

T

S

W

F

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

L

H

L

F

M

V

G

G

L

L

P

A

G

G

A

T

-

G

-

A

-

S

-

G

I

I

F

A

V

V

A

T

G

A

L

F

S

E

E

S

S

H

W

S

I

F

A

A

I

L

G

L

L

L

I

V

V

L

G

G

A

-

W

-

L

-

N

-

W

W

L

I

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

A

H

-

T

-

E

-

H

-

N

-

H

-

N

G

A

V

L

M

T

T

L

M

P

P

D

E

Y

Y

F

L

S

K

H

K

R

R

F

F

E

G

D

G

E

K

S

-

R

R

M

L

L

Q

R

I

I

Y

F

L

S

S

A

I

L

L

V

F

I

L

L

F

V

I

F

C

F

V

T

I

I

L

Y

T

C

I

A

S

S

A

G

D

V

I

V

F

A

S

G

G

A

A

R

I

L

F

F

I

E

K

S

L

T

A

F

L

G

G

M

L

P

N

Y

L

E

Y

Y

L

A

A

L

I

W

L

V

I

G

L

A

L

A

A

A

I

T

T

I

A

L

I

Y

F

V

T

F

I

I

T

G

G

F

L

L

A

A

S

V

V

S

I

W

Y

T

T

D

D

T

T

V

V

Q

Q

A

A

T

V

L

I

M

M

I

L

F

V

A

G

L

S

L

F

V

I

T

L

P

M

V

V

F

F

V

A

I

F

L

V

A

E

L

V

G

G

D

G

-

Y

-

E

-

S

-

F

-

T

-

E

-

K

-

F

M

M

G

N

T

A

A

I

M

P

A

S

T

V

I

V

E

E

A

G

Q

D

N

N

-

L

-

T

-

I

-

N

-

S

-

R

-

C

-

Y

-

T

-

P

-

Q

P

P

A

D

N

S

F

F

D

H

M

I

F

F

R

R

G

D

L

-

S

-

F

-

V

-

A

P

I

V

V

T

S

G

L

D

L

I

A

P

W

W

G

P

L

G

G

T

Y

A

F

F

G

G

Q

M

P

P

-

I

-

T

-

A

-

L

-

W

-

Y

-

W

-

C

-

I

-

N

-

Q

H

V

I

I

L

V

V

Q

R

R

F

C

M

L

A

C

A

G

D

K

S

N

I

L

K

S

T

H

I

V

P

K

N

A

A

A

R

C

R

I

I

L

G

C

M

G

T

Y

W

L

M

K

I

L

L

L

T

P

L

L

A

F

G

F

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

T

D

D

H

M

-

V

-

A

-

C

-

V

P

P

E

S

Q

E

A

-

G

-

A

C

V

V

S

K

Q

H

N

C

G

G

E

V

R

D

V

V

-

G

-

C

-

T

-

N

-

Y

-

A

F

Y

M

P

E

M

L

L

V

V

K

L

I

K

L

L

F

M

N

P

P

M

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

S

G

V

V

M

L

L

A

A

A

S

V

L

M

M

S

S

T

S

L

L

S

T

A

S

Q

V

L

F

L

N

V

S

S

A

S

S

S

T

A

L

L

F

T

T

Q

I

D

D

F

L

Y

Y

K

T

A

K

M

-

L

I

R

R

K

K

N

K

A

A

S

S

Q

E

T

R

E

E

L

L

V

L

W

I

V

A

G

G

R

R

G

-

M

-

V

L

L

F

L

V

I

S

A

V

L

L

I

I

A

V

I

T

G

S

I

I

A

L

S

W

N

V

P

P

D

I

S

V

K

E

V

V

L

S

-

Q

-

G

G

Q

L

L

V

V

S

H

Y

Y

A

T

W
x
E

A

A

G

-

F

I

G

S

A

S

A

Y

F

L

G

G

P

P

-

P

-

I

-

A

V

V

V

F

L

L

I

V

S

A

L

V

L

F

W

C

K

K

R

R

M

A

T

N

R

E

N

Q

G

G

A

A

L

F

V

W

G

G

M

L

L

M

V

V

G

G

A

L

V

V

E457 (≠ W405) mutation to Q: Confers sodium-dependent sugar transport activity not found in the wild type protein.

7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
23% identity, 65% coverage: 108:430/494 of query aligns to 95:454/585 of 7slaA

query
sites
7slaA

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

G

E

Q

S

-

R

R

M

I

L

Q

R

V

I

Y

F

L

S

S

A

V

L

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

V

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

P

N

Y

L

E

Y

Y

L

A

S

L

I

W

I

V

L

G

L

A

L

A

A

A

I

T

T

I

A

L

L

Y

Y

V

T

F

I

I

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

L

L

V

I

T

L

P

M

V

G

F

F

V

A

I

F

L

H

A

E

L

V

G

G

D

G

M

Y

G

D

T

A

A

F

M

M

A

E

T

K

I

Y

E

M

A

K

Q

A

N

I

P

P

A

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

N

S

F

F

D

H

M

I

F

F

R

R

G

D

L

P

-

L

-

T

-

G

-

D

-

L

-

P

-

W

-

P

S

G

F

F

V

I

A

F

I

G

V

L

S

T

L

I

L

L

A

A

W

-

G

-

L

L

G

W

Y

Y

F

W

G

C

Q

T

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

D

K

S

N

I

M

K

S

T

H

I

V

P

K

N

G

A

G

R

C

R

I

I

L

G

A

M

G

T
x
Y

W

L

M

K

I

L

L

L

T

P

L

M

A

F

G

I

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

F

A

P

D

D

H

-

P

-

E

K

Q

V

A

A

G

C

A

V

V

V

S

P

Q

S

N

E

G

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

M

P

E

T

L

L

V

V

K

V

I

E

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

T

A

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

-

A

A

M

K

L

V

R

R

K

K

N

R

A

A

S

S

Q

E

T

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

G

L

M

F

V

V

L

L

L

F

I

L

A

V

L

V

I

V

A

S

I

I

G

A

-

W

-

I

-

P

-

I

I

V

A

Q

S

S

N

A

P

Q

D

S

S

G

K

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

L

I

L

F

W

W

K

K

R

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, 65% coverage: 108:430/494 of query aligns to 94:453/582 of 7sl8A

query
sites
7sl8A

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

G

E

Q

S

-

R

R

M

I

L

Q

R

V

I

Y

F

L

S

S

A

V

L

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

V

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

P

N

Y

L

E

Y

Y

L

A

S

L

I

W

I

V

L

G

L

A

L

A

A

A

I

T

T

I

A

L

L

Y

Y

V

T

F

I

I

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

L

L

V

I

T

L

P

M

V

G

F

F

V

A

I

F

L

H

A

E

L

V

G

G

D

G

M

Y

G

D

T

A

A

F

M

M

A

E

T

K

I

Y

E

M

A

K

Q

A

N

I

P

P

A

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

N

S

F

F

D

H

M

I

F

F

R

R

G

D

L

P

-

L

-

T

-

G

-

D

-

L

-

P

-

W

-

P

S

G

F

F

V

I

A

F

I

G

V

L

S

T

L

I

L

L

A

A

W

-

G

-

L

L

G

W

Y

Y

F

W

G

C

Q

T

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

D

K

S

N

I

M

K

S

T

H

I

V

P

K

N
x
G

A

G

R

C

R

I

I

L

G

A

M

G

T
x
Y

W

L

M

K

I

L

L

L

T

P

L

M

A

F

G

I

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

F

A

P

D

D

H

-

P

-

E

K

Q

V

A

A

G

C

A

V

V

V

S

P

Q

S

N

E

G

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

M

P

E

T

L

L

V

V

K

V

I

E

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

T

A

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

-

A

A

M

K

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V

R

R

K

K

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R

A

A

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S

Q

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T

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

G

L

M

F

V

V

L

L

L

F

I

L

A

V

L

V

I

V

A

S

I

I

G

A

-

W

-

I

-

P

-

I

I

V

A

Q

S

S

N

A

P

Q

D

S

S

G

K

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

L

I

L

F

W

W

K

K

R

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

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
23% identity, 85% coverage: 12:430/494 of query aligns to 16:468/602 of 7wmvA

query
sites
7wmvA

V

V

I

I

Y

Y

I

F

A

V

M

V

I

M

L

A

I

V

G

G

F

L

I

W

A

A

Y

M

R

F

A

S

T

T

K

N

N

R

-

G

-

T

F

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

F

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

F

A

V

A

A

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

W

V

L

L

N

G

W

W

L

L

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

A

H

-

T

-

E

-

H

-

N

-

H

-

N

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

G

E

Q

S

R

R

I

M

Q

L

V

R

Y

I

L

F

S

S

L

A

L

L

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

-

V

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

P

N

Y

L

E

Y

Y

L

A

A

L

I

W

F

V

L

G

L

A

L

A

A

A

I

T

T

I

A

L

L

Y

Y

V

T

F

I

I

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

L

L

V

I

T

L

P

T

V

G

F

F

V

A

I

F

L

H

A

E

L

V

G

G

D

G

M

Y

G

D

T

A

A

F

M

M

A

E

T

K

I

Y

E

M

A

K

Q

A

N

I

P

P

A

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

N

S

F

F

D

H

M

I

F

F

R

R

G

D

L

-

S

-

F

-

V

-

A

P

I

L

V

T

S

G

L

D

L
|
L

A

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

V

L

R

W

F
x
Y

M
x
W

A

C

A

T

D

D

S

Q

I

V

K

I

T

V

I

-

P

-

N

-

A

Q

R

R

R

C

I

L

G

S

M

A

T

K

W

N

M

M

I

S

L

H

T

V

L

K

A

G

G

G

A

C

V

I

A

L

V

C

G

G

F

Y

L

L

G

K

-

L

-

M

-

P

-

M

-

F

-

I

-

M

-

V

-

M

-

P

-

G

-

M

I

I

A

S

Y

R

F

I

A

L

D

Y

H

T

P

E

E

K

Q

I

A

A

G

C

A

V

V

V

S

P

Q

S

N

E

G

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

M

P

E

T

L

L

V

V

K

V

I

E

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

S

G

V

V

M

L

L

A

A

A

S

V

L

M

M

S

S

T

S

L

L

S

T

A

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

-

A

A

M

K

L

V

R

R

K

K

N

R

A

A

S

S

Q

E

T

K

E

E

L

L

V

M

W

I

V

A

G

G

R

R

G

L

M

F

V

I

L

L

L

V

I

L

A

I

L

G

I

I

A

S

I

I

G

A

-

W

-

V

-

P

-

I

I

V

A

Q

S

S

N

A

P

Q

D

S

S

G

K

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

L

I

L

F

W

W

K

K

R

R

M

V

T

N

R

E

N

P

G

G

A

A

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 (= L242), 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

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)
23% identity, 85% coverage: 12:430/494 of query aligns to 33:485/664 of P13866

query
sites
P13866

V

V

I

I

Y

Y

I

F

A

V

M

V

I

M

L

A

I

V

G

G

F

L

I

W

A

A

Y

M

R

F

A

S

T

T

K
x
N

N

R

-

G

-

T

F

V

S

G

D

G

Y

F

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S
x
W

F

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
x
H

L

F

M

V

G

G

L

L

P

A

G

G

A

T

I

G

F

A

V

A

A

S

G

G

L

-

S

-

E

-

S

-

W

-

I

I

A

A

I

I

G

G

-

G

-

F

-

E

-

W

-

N

-

A

L

L

I

V

V

L

G

V

A

V

W

V

L

L

N

G

W

W

L

L

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

A

H

-

T

-

E

-

H

-

N

-

H

-

N

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

H

K

R
|
R

F

F

E

G

D

G

E

Q

S

R

R

I

M

Q

L

V

R

Y

I

L

F

S

S

L

A

L

L

S

V

L

I

L

L

L

V

Y

F

I

F

F

T

T

I

K

Y

I

C
x
S

A

A

S

D

G

-

V

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

P

N

Y

L

E

Y

Y

L

A

A

L

I

W

F

V

L

G

L

A

L

A

A

A

I

T

T

I

A

L

L

Y
|
Y

V
x
T

F
x
I

I
x
T

G
|
G

F
x
L

L
x
A

A
|
A

V
|
V

S
x
I

W
x
Y

T
|
T

D
|
D

T
|
T

V
x
L

Q
|
Q

A
x
T

T
x
V

L
x
I

M
|
M

I
x
L

F
x
V

A
x
G

L
x
S

L
|
L

V
x
I

T
x
L

P
x
T

V
x
G

F
|
F

V
x
A

I
x
F

L
x
H

A
x
E

L
x
V

G
|
G

D
x
G

M
x
Y

G
x
D

T
x
A

A
x
F

M
|
M

A
x
E

T
x
K

I
x
Y

E
x
M

A
x
K

Q
x
A

N
x
I

P
|
P

A
x
T

-
x
I

-
x
V

-
x
S

-
x
D

-
x
G

-
x
N

-
x
T

-
x
F

-
x
Q

-
x
E

-
x
K

-
x
C

-
x
Y

-
x
T

-
x
P

-
x
R

-
x
A

-
x
D

N
x
S

F
|
F

D
x
H

M
x
I

F
|
F

R
|
R

G
x
D

L

-

S

-

F

-

V

-

A
x
P

I
x
L

V
x
T

S
x
G

L
x
D

L
|
L

A
x
P

W
|
W

G
x
P

L
x
G

G
x
F

Y
x
I

F
|
F

G
|
G

Q
x
M

P
x
S

H
x
I

I
x
L

L
x
T

V
x
L

R
x
W

F
x
Y

M
x
W

A
x
C

A
x
T

D
|
D

S
x
Q

I
x
V

K
x
I

T
x
V

I

-

P

-

N

-

A
x
Q

R
|
R

R
x
C

I
x
L

G
x
S

M
x
A

T
x
K

W
x
N

M
|
M

I
x
S

L
x
H

T
x
V

L
x
K

A
x
G

G
|
G

A
x
C

V
x
I

A
x
L

V
x
C

G
|
G

F
x
Y

L
|
L

G
x
K

-
x
L

-
x
M

-
x
P

-
x
M

-
x
F

-
x
I

-
x
M

-
x
V

-
x
M

-
x
P

-
x
G

-
x
M

I
|
I

A
x
S

Y
x
R

F
x
I

A
x
L

D
x
Y

H
x
T

P
x
E

E
x
K

Q
x
I

A
|
A

G
x
C

A
x
V

V
|
V

S
x
P

Q
x
S

N
x
E

G
x
C

E
|
E

R
x
K

-
x
Y

-
x
C

-
x
G

-
x
T

-
x
K

-
x
V

-
x
G

-
x
C

-
x
T

-
x
N

-
x
I

V
x
A

F
x
Y

M
x
P

E
x
T

L
|
L

V
|
V

K
x
V

I
x
E

L
|
L

F
x
M

N
x
P

P
x
N

W
x
G

V
x
L

A
x
R

G
|
G

I
x
L

I
x
M

L
|
L

S
|
S

G
x
V

V
x
M

L
|
L

A
|
A

A
x
S

V
x
L

M
|
M

S
|
S

T
x
S

L
|
L

S
x
T

A
x
S

Q
x
I

L
x
F

L
x
N

V
x
S

S
x
A

S
|
S

S
x
T

A
x
L

L
x
F

T
|
T

Q
x
M

D
|
D

F
x
I

Y
|
Y

K

-

A
|
A

M
x
K

L
x
V

R
|
R

K
|
K

N
x
R

A
|
A

S
|
S

Q
x
E

T
x
K

E
|
E

L
|
L

V
x
M

W
x
I

V
x
A

G
|
G

R
|
R

G
x
L

M
x
F

V
x
I

L
|
L

L
x
V

I
x
L

A
x
I

L
x
G

I
|
I

A
x
S

I
|
I

G
x
A

-
x
W

-
x
V

-
x
P

-
x
I

I
x
V

A
x
Q

S
|
S

N
x
A

P
x
Q

D
x
S

S
x
G

K
x
Q

V
x
L

L
x
F

G
x
D

L
x
Y

V
x
I

S
x
Q

Y
x
S

A
x
I

W
x
T

A
x
S

G
x
Y

F
x
L

G
|
G

A
x
P

F
x
I

G
x
A

P
x
A

V
|
V

V
x
F

L
|
L

I
x
L

S
x
A

L
x
I

L
x
F

W
|
W

K
|
K

R
|
R

M
x
V

T
x
N

R
x
E

N
x
P

G
|
G

A
|
A

N51 (≠ K30) to S: in GGM; slightly decreased activity; dbSNP:rs17683011
W67 (≠ S44) mutation to A: Strong reduction in D-glucose transporter activity.
S77 (= S54) mutation to A: Loss of activity.
H83 (≠ L60) 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 (= R117) to W: in GGM; loss of activity
S159 (≠ C141) to P: in GGM; loss of activity
A166 (= A149) to T: in GGM; about 90% reduction in activity
D204 (= D187) 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 (= W244) to L: in GGM; about 95% reduction in activity
T287 (≠ L255) 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 (≠ F258) 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 (≠ M259) mutation to A: Loss of D-glucose transporter activity.
C292 (≠ A260) to Y: in GGM; loss of activity; mutation to A: Has no effect on water permeability.
Q295 (≠ S263) to R: in GGM; loss of activity
R300 (= R271) to S: in GGM; loss of activity
A304 (≠ M275) to V: in GGM; impairs trafficking to the plasma membrane
K321 (≠ G292) mutation to Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
C345 (≠ G304) modified: Disulfide link with 351
C351 (≠ G310) modified: Disulfide link with 345
C355 (vs. gap) modified: Disulfide link with 361
C361 (vs. gap) modified: Disulfide link with 355
N363 (vs. gap) mutation to A: Loss of water permeation.
L369 (= L317) to S: in GGM; loss of activity
R379 (≠ A327) to Q: in GGM; loss of activity
A388 (= A336) to V: in GGM; loss of activity
S396 (≠ A344) mutation to A: Loss of activity.
F405 (≠ L353) to S: in GGM; loss of activity
A411 (= A360) to T: in GGM; slightly decreased activity; dbSNP:rs17683430
G426 (= G375) to R: in GGM; loss of activity
Q451 (≠ K396) mutation to A: Strong reduction in water permeation.
L452 (≠ V397) mutation to A: Loss of water permeation.
D454 (≠ G399) mutation to A: Has no effect on water permeation.
Q457 (≠ S402) mutation to A: Loss of D-glucose transporter activity.; mutation to C: Strong reduction in D-glucose transporter activity.
T460 (≠ W405) mutation to A: Loss of D-glucose transporter activity.
V470 (= V415) to N: in GGM; about 90% reduction in activity; requires 2 nucleotide substitutions

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)
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.

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
23% identity, 77% coverage: 72:452/494 of query aligns to 43:442/512 of 3dh4A

query
sites
3dh4A

G

G

L

M

S

S

E

G

S

S

W

G

I

Y

A

S

I

I

G

G

L

L

I

A

V

I

G

A

A

S

W
x
Y

L

-

N
x
E

W

W

-

M

-
x
S

-

A

-

I

-

T

L

L

F

I

V

I

A

V

G

G

R

K

L

Y

R

F

V

L

H

P

T

I

E

F

H

I

N

E

H

K

N

G

A

I

L

Y

T

T

L

I

P

P

D

E

Y

F

F

V

S

E

H

K

R

R

F

F

E

N

D

K

E

K

S

L

R

K

M

-

L

-

R

T

I

I

F

L

S

A

A

V

L

F

V

W

I

I

L

S

V

L

F

Y

F

I

T

F

I

V

Y

N

C

L

A

T

S

S

G

V

V

L

V

Y

A

L

G

G

A

G

R

L

L

A

F

L

E

E

S

T

T

I

F

L

G

G

M

I

P

P

Y

L

E

M

Y

Y

A

S

L

I

W

L

V

G

G

L

A

A

A

L

A

F

T

A

I

L

L

V

Y

Y

V

S

F

I

I

-

G

-

F

-

L

-

A

-

V

V

S

V

W

W

T

T

D

D

T

V

V

I

Q

Q

A

V

T

F

L

F

M

L

I

V

F

L

A

G

L

G

L

F

V

M

T

T

P

T

V

Y

F

M

V

A

I

V

L

S

A

F

L

I

G

G

D

G

M

T

G

D

T

G

A

W

M

F

A

A

T

G

I

V

E

S

A

K

Q

M

-

V

-

D

-

A

N

A

P

P

A

G

N

H

F

F

D

E

M

M

-

I

-

L

-

D

-

Q

-

S

-

N

-

P

-

Q

F

Y

R

M

G

N

L

L

S

P

F

G

V

I

A

A

I

V

V

L

-

I

-

G

-

L

-

W

-

V

-

A

S
x
N

L

L

L

Y

A

Y

W
|
W

G

G

L

-

G

-

Y

-

F

F

G

N

Q

Q

P

-

H

Y

I

I

L

I

V

Q

R

R

F

T

M

L

A

A

D

-

S

-

I

-

K

K

T

S

I

V

P

S

N

E

A

A

R

Q

R

K

I

G

G

I

M

V

T

F

W

A

M

A

I

F

L

L

T
x
K

L

L

A

I

G

V

A

P

V

F

A

L

V

V

G

V

F

L

L

P

G

G

I

I

A

A

Y

A

F

Y

-

V

-

I

A

T

D

S

H

D

P

P

E

Q

Q

L

A

M

G

A

A

S

V

L

S

G

Q

D

-

I

-

A

-

T

-

N

-

L

-

P

-

S

-

A

N

N

G

A

E

D

R

K

V

A

F

Y

M

P

E

W

L

L

V

T

K

Q

I

F

L

L

F

-

N

P

P

V

W

G

V

V

A

K

G

G

I

V

L

F

S

A

G

A

V

L

L

A

A

A

A
|
A

V

I

M

V

S
|
S

T

S

L

L

S

A

A

S

Q

M

L

L

L

N

V

S

S

T

S

A

S

T

A

I

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

K

A

E

M

Y

L

I

R

S

K

P

N

D

A

S

S

G

Q

D

T

H

E

K

L

L

V

V

W

N

V

V

G

G

R

R

G

T

M

A

V

A

L

V

I

A

A

L

L

I

I

I

A

A

-

C

-

L

-

I

-

A

-

P

-

M

-

L

-

G

I

I

G

G

I

Q

A

A

S

F

N

Q

P

Y

D

I

S
x
Q

K

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

L

L

L

F

W

W

K

K

R

K

M

T

T

T

R

S

N

K

G

G

A

A

L

I

V

I

G

G

M

-

L

V

V

V

G

A

A

S

V

I

T

P

V

F

V

A

V

L

W

F

K

L

E

K

F

F

I

M

G

P

L

L

G

S

L

M

binding beta-D-galactopyranose: Y58 (≠ W87), E59 (≠ N89), S62 (vs. gap), N225 (≠ S240), W229 (= W244), K259 (≠ T281), Q393 (≠ S395)
binding sodium ion: A326 (= A337), S329 (= S340)

Sites not aligning to the query:

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, 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

I

L

L

L

I

V

G

G

F

I

I

W

A

A

Y

A

R

W

A

R

T

T

K

K

N

N

F

S

S

G

D

S

-

A

-

E

-

R

-

S

-

E

-

A

Y

I

I

I

L

V

G

G

R

R

S
x
D

L

I

G

G

S

L

F

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

F

Y

V

V

A

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

W

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

-

H

-

T

-

E

-

H

-

N

S

H

K

N

G

A
x
Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

S

Q

H

Q

R

I

F

Y

E

G

D

K

E

R

S

M

R

G

M

G

L

L

R

L

I

F

F

I

S

P

A

A

L

L

V

M

I

G

L

E

V

M

F

F

F

W

T

A

-

A

I

I

Y

F

C

S

A

A

S

L

G

G

V

A

V

T

A

I

G

S

A

V

R

I

L

I

F

-

E

-

S

-

T

-

F

-

G

D

M

V

P

D

Y

M

E

H

Y

I

A

S

L

V

W

I

V

I

G

S

A

A

A

L

A

I

T

A

I

T

L

L

Y
|
Y

V

T

F

L

I

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

L

W

V

I

T

S

P

V

V

P

F

F

V

A

I

L

-

S

-

H

L

P

A

A

L

V

G

A

D

D

M

I

G

G

T

F

A

T

M

A

A

V

T

H

I

A

E

K

A

Y

Q

Q

N

K

P

P

A

W

N

L

F

G

D

T

M

V

F

D

R

S

G

S

L

E

S

V

F

Y

V

S

A

W

I

L

V

D

S

S

L

F

L

L

A

L

W

L

G

M

L

L

G

G

Y

G

F

I

G

P

Q

W

P

Q

H

A

I

Y

L

F

V

Q

R

R

F

V

M

L

A

S

D

S

S

S

I

A

K

T

T

Y

I

A

P

Q

N

V

A

L

R

S

R

F

I

L

G

A

M

A

T

F

W

G

M

C

I

L

L

V

T

M

L

A

A

I

G

P

A

A

V

I

A

L

V
x
I

G

G

F

A

L

I

G

G

-

A

-

S

-

T

-

D

-

W

-

N

-

Q

I

T

A

A

Y

Y

F

G

A

L

D

P

H

D

P

P

E

K

Q

-

A

-

G

-

A

-

V

T

S

T

Q

E

N

E

G

A

E

D

R

M

V

I

F

L

M

P

E

I

L

V

V

L

K

Q

I

Y

L

L

F

C

N

P

P

V

W

Y

V

I

A

S

G

F

I

F

I

G

L

L

S

G

G

A

V

V

L

S

A

A

V
|
V

M

M

S

S

T

S

L

A

S

D

A

S

Q

S

L

I

L

L

V

S

S

A

S

S

A

M

L

F

T

A

Q
x
R

D

N

F

I

Y

Y

K

Q

A

L

M

S

L

F

R

R

K

Q

N

N

A

A

S

S

Q

D

T

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

G

I

M

T

V

V

L

F

L

V

I

F

A

G

L

A

I

S

A

A

I

T

G

A

I

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 (≠ V288) to T: in CMS20; uncertain significance; dbSNP:rs375397889
V344 (= V338) to L: in CMS20; uncertain significance
R361 (≠ Q355) 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.

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)
22% identity, 86% coverage: 33:457/494 of query aligns to 43:467/610 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

F

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

F

Y

V

R

A

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

W

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

H

P

T

V

E

F

H

Y

N

K

H

L

N

G

A

I

L

T

T

S

L

T

P

Y

D

E

Y

Y

F

L

S

E

H

L

R

R

F

F

E

-

D

-

E

-

S

N

R

K

M

C

L

V

R

R

I

L

F

C

S

G

A

T

L

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

V

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

-

P

-

Y

-

E

-

Y

F

A

D

L

L

W

W

V

G

G

A

A

V

A

A

T

T

-

G

-

V

-

C

I

T

L

F

Y

Y

V

C

F

T

I

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

L

A

V

S

T

V

P

I

V

I

F

Q

V

A

I

V

L

V

A

M

L

Q

G

G

D

G

M

I

G

S

T

T

A

I

M

L

A

N

T

D

I

A

E

Y

A

D

Q

G

N

G

P

R

A

L

N

N

F

F

-

W

-

N

-

F

-

N

-

P

D

N

M

P

F

L

R

Q

G

R

L

H

S

T

F

F

V

W

A

T

I

I

V

I

-

I

-

G

S

G

L

T

L
x
F

A

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

V

Q

R

R

F

Y

M

I

A

S

A

C

D

K

S

S

I

R

K

F

T

Q

I

A

P

K

N

L

A

S

R

L

R

Y

I

I

G

N

M

L

T

V

-

G

-

L

W

W

M

A

I

I

L

L

T

T

L

C

A

S

G

-

A

-

V

-

A

-

V

-

G

V

F

F

L

C

G

G

I

L

A

A

Y

L

F

Y

A

S

D

R

H

Y

-

H

-

D

-

C

-

D

P

P

E

W

Q

T

A

A

G

K

A

K

V

V

S

S

Q

A

N

P

G

D

E

Q

R

L

V

M

F

P

M

Y

E

L

L

V

V

L

K

D

I

I

L

L

F

Q

N

D

-

Y

P

P

W

G

V

L

A

P

G

G

I

L

I

F

L

V

S

A

G

C

V

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

V

S

S

A

S

Q

S

L

I

L

N

V

A

S

L

S

A

A

V

L

T

T

V

Q

E

D

D

F

L

Y

I

K

K

A

P

M

Y

L

F

R

R

K

-

N

S

A

L

S

S

Q

E

T

R

E

S

L

L

V

S

W

W

V

I

G

S

R

Q

G

G

M

M

V

S

L

V

I

Y

A

G

L

A

I

L

A

C

I

I

G

G

I

M

A

A

S

A

N

-

P

-

D

L

S

A

K

S

V

L

L

M

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

L

I

L

L

W

V

K

P

R

F

M

A

T

N

R

S

N

I

G

G

A

A

L

L

V

V

G

G

M

L

L

M

V

A

G

G

A

-

V

F

T

A

V

I

V

S

V

L

W

W

K

V

E

G

F

-

I

I

G

G

L

A

G

Q

L

I

Y

Y

E

P

I

P

I

L

P

P

V193 (≠ A191) to I: in dbSNP:rs1709189
F251 (≠ L242) 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)
22% identity, 69% coverage: 90:430/494 of query aligns to 82:447/566 of 7yniA

query
sites
7yniA

W

W

L

L

F

F

V

V

A

P

G

I

R

Y

L

I

R

K

V

A

H

-

T

-

E

-

H

-

N

-

H

-

N

G

A

V

L

V

T

T

L

M

P

P

D

E

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

G

E

Q

S

R

R

I

M

Q

L

V

R

Y

I

L

F

S

S

L

A

L

L

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

-

V

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

P

N

Y

L

E

Y

Y

L

A

A

L

I

W

F

V

L

G

L

A

L

A

A

A

I

T

T

I

A

L

L

Y

Y

V

T

F

I

I

-

G

-

F

-

L

-

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

L

L

V

I

T

L

P

T

V

G

F

F

V

A

I

F

L

H

A

E

L

V

G

G

D

G

M

Y

G

D

T

A

A

F

M

M

A

E

T

K

I

Y

E

M

A

K

Q

A

N

I

P

P

A

T

-

I

-

V

-

S

-

D

-

G

-

N

-

T

-

F

-

Q

-

E

-

K

-

C

-

Y

-

T

-

P

-

R

-

A

-

D

N

S

F

F

D

H

M

I

F

F

R

R

G

D

L

-

S

-

F

-

V

-

A

P

I

L

V

T

S

G

L

D

L

L

A

P

W

W

G

P

L

G

G

F

Y

I

F

F

G

G

Q

M

P

S

H

I

I
x
L

L

T

V

L

R

W

F
x
Y

M

W

A

C

A

T

D

D

S

Q

I

V

K

I

T

V

I

-

P

-

N

-

A

Q

R

R

R

C

I

L

G

S

M

A

T

K

W

N

M

M

I

S

L

H

T

V

L

K

A

G

G

G

A

C

V

I

A

L

V

C

G

G

F

Y

L

L

G

K

-

L

-

M

-

P

-

M

-

F

-

I

-

M

-

V

-

M

-

P

-

G

-

M

I

I

A

S

Y

R

F

I

A

L

D

Y

H

T

P

E

E

K

Q

I

A

A

G

C

A

V

V

V

S

P

Q

S

N

E

G

C

E

E

R

K

-

Y

-

C

-

G

-

T

-

K

-

V

-

G

-

C

-

T

-

N

-

I

V

A

F

Y

M

P

E

T

L

L

V

V

K

V

I

E

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

S

G

V

V

M

L

L

A

A

A

S

V

L

M

M

S

S

T

S

L

L

S

T

A

S

Q

I

L

F

L

N

V

S

S

A

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

-

A

A

M

K

L

V

R

R

K

K

N

R

A

A

S

S

Q

E

T

K

E

E

L

L

V

M

W

I

V

A

G

G

R

R

G

L

M

F

V

I

L

L

L

V

I

L

A

I

L

G

I

I

A

S

I

I

G

A

-

W

-

V

-

P

-

I

I

V

A

Q

S

S

N

A

P

Q

D

S

S

G

K

Q

V

L

L
x
F

G

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

L

I

L

F

W

W

K

K

R

R

M

V

T

N

R

E

N

P

G

G

A

A

binding (2R,3R,4R,5S,6R)-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol: L248 (≠ I254), Y252 (≠ F258), F415 (≠ L398), Q419 (≠ S402)

Sites not aligning to the query:

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

Q9Y289 Sodium-dependent multivitamin transporter; Na(+)-dependent multivitamin transporter; hSMVT; Solute carrier family 5 member 6 from Homo sapiens (Human) (see 10 papers)
21% identity, 84% coverage: 26:439/494 of query aligns to 45:465/635 of Q9Y289

query
sites
Q9Y289

Y

Y

R

H

A

A

T

C

K

R

N

G

F

W

S

G

D

R

Y

H

I

T

L

V

G

G

-

E

-

L

-

M

-

A

G

D

R

R

S

K

L

M

G

G

S
x
C

F

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

L

A

L

I

M

L

G

G

L

V

P

P

G

S

A

E

I

I

F

Y

V
x
R

A
x
F

G
|
G

L

-

S
x
T

E
x
Q

S
x
Y

W
|
W

I
x
F

A
x
L

-
x
G

-
x
C

-
x
Y

-
x
F

I
x
L

G
|
G

L
|
L

I
x
L

V
x
I

G
x
P

A
|
A

W
x
H

L
x
I

N

-

W

-

L

-

F
|
F

V
x
I

A
x
P

G
x
V

R
x
F

L
x
Y

R
|
R

V
x
L

H
|
H

T
x
L

E
x
T

H
x
S

N
x
A

H
x
Y

N

-

A

-

L

-

T

-

L

-

P

-

D
x
E

Y
|
Y

F
x
L

S
x
E

H
x
L

R
|
R

F
|
F

E

-

D

-

E

-

S
x
N

R
x
K

M
x
T

L
x
V

R
|
R

I
x
V

F
x
C

S
x
G

A
x
T

L
x
V

V
x
T

I
x
F

L
x
I

V
x
F

F
x
Q

F
x
M

T
x
V

I
|
I

Y
|
Y

C
x
M

A
x
G

S
x
V

G
x
V

V
x
L

V
x
Y

A
|
A

G
x
P

A
x
S

R
x
L

L
x
A

F
x
L

E
x
N

S
x
A

T
x
V

F
x
T

G
|
G

M

-

P

-

Y

-

E

-

Y
x
F

A
x
D

L
|
L

W
|
W

V
x
L

G
x
S

A
x
V

A
x
L

A
|
A

-
x
L

-
x
G

-
x
I

-
x
V

T
x
C

I
x
T

L
x
V

Y
|
Y

V
x
T

F
x
A

I
x
L

G
|
G

F
x
L

L
x
K

A
|
A

V
|
V

S
x
I

W
|
W

T
|
T

D
|
D

T
x
V

V
x
F

Q
|
Q

A
x
T

T
x
L

L
x
V

M
|
M

I
x
F

F
x
L

A
x
G

L
x
Q

L
|
L

V
x
A

T
x
V

P
x
I

V
x
I

F
x
V

V
x
G

I
x
S

L
x
A

A
x
K

L
x
V

G
|
G

D
x
G

M
x
L

G
|
G

T
x
R

A
x
V

M
x
W

A
|
A

T
x
V

I
x
A

E
x
S

A
x
Q

Q
x
H

-
x
G

-
x
R

-
x
I

-
x
S

-
x
G

-
x
F

-
x
E

-
x
L

N
x
D

P
|
P

A
x
D

N
x
P

F
|
F

-
x
V

-
x
R

D
x
H

M
x
T

F
|
F

R
x
W

G
x
T

L
|
L

S
x
A

F
|
F

V
x
G

A
x
G

I
x
V

V
x
F

S
x
M

L
x
M

L
|
L

A
x
S

-
x
L

W
x
Y

G
|
G

L
x
V

G

-

Y

-

F

-

G
x
N

Q
|
Q

P
x
A

H
x
Q

I
x
V

L

-

V
x
Q

R
|
R

F
x
Y

M
x
L

A
x
S

D
x
R

S
x
T

I
x
E

K
|
K

T
x
A

I
x
A

P
x
V

N
x
L

A
x
S

R
x
C

R
x
Y

I
x
A

G
x
V

M
x
F

T
x
P

W
x
F

M
x
Q

I
x
Q

L
x
V

T
x
S

L
|
L

A
x
C

G
x
V

A
x
G

V
x
C

A
x
L

V
x
I

G
|
G

F
x
L

L
x
V

G
x
M

I
x
F

A
|
A

Y
|
Y

F
x
Y

A
x
Q

D
x
E

H
x
Y

P
|
P

-
x
M

-
x
S

-
x
I

E
x
Q

Q
|
Q

A
|
A

G
x
Q

A
|
A

V
x
A

S
x
P

Q
x
D

N
x
Q

G
x
F

E
x
V

R
x
L

V
x
Y

F
|
F

-
x
V

M
|
M

E
x
D

L
|
L

V
x
L

K
|
K

I
x
G

L
|
L

F

-

N

-

P
|
P

W
x
G

V
x
L

A
x
P

G
|
G

I
x
L

I
x
F

L
x
I

S
x
A

G
x
C

V
x
L

L
x
F

A
x
S

A
x
G

V
x
S

M
x
L

S
|
S

T
|
T

L
x
I

S
|
S

A
x
S

Q
x
A

L
x
F

L
x
N

V
x
S

S
x
L

S
x
A

S
x
T

A
x
V

L
x
T

T
x
M

Q
x
E

D
|
D

F
x
L

Y
x
I

K
x
R

A
x
P

M
x
W

L
x
F

R

-

K
x
P

N
x
E

A
x
F

S
|
S

Q
x
E

T
x
A

E
x
R

L
x
A

V
x
I

W
x
M

V
x
L

G
x
S

R
|
R

G
|
G

M
x
L

V
x
A

L
x
F

L
x
G

I
x
Y

A
x
G

L
|
L

I
x
L

A
x
C

I
x
L

G
|
G

I
x
M

A
|
A

S
x
Y

N
x
I

P

-

D
x
S

S
|
S

K
x
Q

V
x
M

L
x
G

G
x
P

L
x
V

V
x
L

S
x
Q

Y
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

V
x
L

-
x
G

-
x
L

-
x
F

L
x
C

I
x
L

S
x
G

L
x
M

L
x
F

W
x
F

K
x
P

R
x
C

M
x
A

T
x
N

R
x
P

N
x
P

G
|
G

A
|
A

L
x
V

V
|
V

G
|
G

M
x
L

L
|
L

V
x
A

G
|
G

A
x
L

V
|
V

C68 (≠ S44) mutation to A: No effect on biotin transport.
T78 (≠ S54) mutation to A: Reduced membrane localization. Decrease in biotin transport.
C104 (vs. gap) mutation to A: No effect on biotin transport.
R123 (= R98) to L: in SMVTD; reduced membrane localization; impaired biotin transport
S128 (≠ H103) mutation to A: No effect on biotin transport.
N138 (≠ S122) mutation to A: Reduced protein levels. Decrease in biotin transport.
C144 (≠ F128) mutation to A: No effect on biotin transport.
Y162 (≠ V146) to C: in COMNB; no effect on membrane localization
C187 (≠ T171) mutation to A: No effect on biotin transport.
S242 (vs. gap) mutation to A: No effect on biotin transport.
S283 (≠ A260) mutation to A: No effect on protein levels or membrane localization.
T286 (≠ S263) 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 (≠ R271) 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 (≠ V286) mutation to A: No effect on biotin transport.
C358 (≠ G333) mutation to A: No effect on biotin transport.
T366 (= T341) mutation to A: No effect on biotin transport.
R400 (= R376) to T: in SMVTD; impaired biotin transport; dbSNP:rs370950187
C410 (≠ A386) mutation to A: No effect on biotin transport.
S429 (≠ A406) to G: in COMNB; no effect on membrane localization
C443 (≠ L417) mutation to A: No effect on biotin transport.
C450 (≠ R424) 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.

8hg7A Structure of human sglt2-map17 complex with sotagliflozin (see paper)
26% identity, 69% coverage: 35:376/494 of query aligns to 35:407/590 of 8hg7A

query
sites
8hg7A

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

F

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

F

A

V

A

A

S

G

G

L

L

S

A

E

V

S

A

-

G

-

F

-
x
E

W

W

I

N

A

A

I

-

G

-

L

L

I

F

V

V

G

V

A

L

W

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

H

-

T

-

E

-

H

-

N

T

H

A

N

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

-

E

-

S

G

R

R

M

R

L

I

R

R

I

L

F

Y

-

L

S

S

A

V

L

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

V

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

P

N

Y

I

E

Y

Y

A

A

S

L

V

W

I

V

A

G

L

A

L

A

G

A

I

T

T

I

M

L

I

Y

Y

V

T

F

V

I

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

L

C

V

I

T

L

P

M

V

G

F

Y

V

A

I

F

L

H

A

E

L

V

G

G

D

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

M

L

G

G

T

A

A

A

M

T

A

S

T

L

I

T

E

V

A

S

Q

E

N

D

P

P

A

A

-

V

-

G

N

N

F

I

D

S

M

S

F

F

-

C

-

Y

-

R

-

P

R

R

G

P

L

D

S

S

F

Y

-

H

-

L

-

R

V

H

A

P

I

V

V

T

S

G

L

D

L

L

A

P

W

W

G

P

-

A

-

L

L

L

G

G

-

L

-

T

-

I

-
x
V

-
x
S

-

G

-

W

Y
|
Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

I

L

K

T

T

H

I

I

P

-

N

K

A

A

R

G

R

C

I

I

G

L

M

C

T

G

W

Y

M

L

I
x
K

L

L

T

T

-

P

L

M

A

F

G

L

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

P

D

D

H

-

P

-

E

E

Q

V

A

A

G

C

A

V

V

V

S

P

Q

E

N

V

G

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

M

P

E

R

L

L

V

V

K

V

I

K

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

A

S

Q

I

L

F

L

N

V

S

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

T

A

-

M

R

L

L

R

R

K

P

N

R

A

A

S

G

Q

D

T

R

E

E

L

L

V

L

W

L

V

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 (≠ D55), G59 (≠ W59), H60 (≠ L60), G63 (= G63), L64 (= L64), E79 (vs. gap), V266 (vs. gap), S267 (vs. gap), Y270 (= Y248), W271 (≠ F249), K301 (≠ I279)
binding sodium ion: A53 (= A53), S54 (= S54), I56 (≠ M56), G57 (≠ S57), A369 (= A337), S372 (= S340), S373 (≠ T341)

Sites not aligning to the query:

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
26% identity, 69% coverage: 35:376/494 of query aligns to 35:407/586 of 7vsiA

query
sites
7vsiA

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

F

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

L
x
H

L

F

M

V

G
|
G

L
|
L

P

A

G

G

A

T

I

G

F

A

V

A

A

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

W

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

H

-

T

-

E

-

H

-

N

T

H

A

N

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

-

E

-

S

G

R

R

M

R

L

I

R

R

I

L

F

Y

-

L

S

S

A

V

L

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

V

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

P

N

Y

I

E

Y

Y

A

A

S

L

V

W

I

V

A

G

L

A

L

A

G

A

I

T

T

I

M

L

I

Y

Y

V

T

F

V

I

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

L

C

V

I

T

L

P

M

V

G

F

Y

V

A

I

F

L

H

A

E

L

V

G

G

D

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

M

L

G

G

T

A

A

A

M

T

A

S

T

L

I

T

E

V

A

S

Q

E

N

D

P

P

A

A

-

V

-

G

N

N

F

I

D

S

M

S

F

F

-

C

-

Y

-

R

-

P

R

R

G

P

L

D

S

S

F

Y

-

H

-

L

-

R

V

H

A

P

I

V

V

T

S

G

L

D

L

L

A

P

W

W

G

P

-

A

-

L

L

L

G

G

-

L

-

T

-

I

-
x
V

-
x
S

-

G

-

W

Y
|
Y

F

W

G

C

Q

S

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

I

L

K

T

T

H

I

I

P

-

N

K

A

A

R

G

R

C

I

I

G

L

M

C

T

G

W

Y

M

L

I

K

L

L

T

T

-

P

L

M

A

F

G

L

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

P

D

D

H

-

P

-

E

E

Q

V

A

A

G

C

A

V

V

V

S

P

Q

E

N

V

G

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

M

P

E

R

L

L

V

V

K

V

I

K

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

A

A

S

Q

I

L

F

L

N

V

S

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

T

A

-

M

R

L

L

R

R

K

P

N

R

A

A

S

G

Q

D

T

R

E

E

L

L

V

L

W

L

V

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 (≠ D55), H60 (≠ L60), G63 (= G63), L64 (= L64), V75 (≠ E75), F78 (vs. gap), E79 (vs. gap), V266 (vs. gap), S267 (vs. gap), Y270 (= Y248)

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

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)
26% identity, 69% coverage: 35:376/494 of query aligns to 55:427/672 of P31639

query
sites
P31639

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

F

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

L

H

L

F

M

V

G

G

L

L

P

A

G

G

A

T

I

G

F

A

V

A

A

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

W

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

H

-

T

-

E

-

H

-

N

T

H

A

N

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

-

E

-

S

G

R

R

M

R

L

I

R

R

I

L

F

Y

-

L

S

S

A

V

L

L

V

S

I

L

L

F

V

L

F

Y

F

I

T

F

I

T

Y

K

C

I

A

S

S
x
V

G

D

V

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

P

N

Y

I

E

Y

Y

A

A

S

L

V

W

I

V

A

G

L

A

L

A

G

A

I

T

T

I

M

L

I

Y

Y

V

T

F

V

I

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

L

C

V

I

T

L

P

M

V

G

F

Y

V

A

I

F

L

H

A

E

L

V

G

G

D

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

M

L

G

G

T

A

A

A

M

T

A

S

T

L

I

T

E

V

A

S

Q

E

N

D

P

P

A

A

-

V

-

G

N

N

F

I

D

S

M

S

F

F

-

C

-

Y

-

R

-

P

R

R

G

P

L

D

S

S

F

Y

-

H

-

L

-

R

V

H

A

P

I

V

V

T

S

G

L

D

L

L

A

P

W

W

G

P

-

A

-

L

L

L

G

G

-
x
L

-

T

-

I

-

V

-

S

-

G

-

W

Y

Y

F

W

G

C

Q

S

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

I

L

K

T

T

H

I

I

P

-

N

K

A

A

R

G

R

C

I

I

G

L

M

C

T

G

W

Y

M

L

I

K

L

L

T

T

-

P

L

M

A

F

G

L

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

P

D

D

H

-

P

-

E

E

Q

V

A

A

G

C

A

V

V

V

S

P

Q

E

N

V

G

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

M

P

E

R

L

L

V

V

K

V

I

K

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

V

L

M

M

S

S

T

S

L

L

S

A

A

S

Q

I

L

F

L

N

V

S

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

-

A

T

M

R

L

L

R

R

K

P

N

R

A

A

S

G

Q

D

T

R

E

E

L

L

V

L

W

L

V

V

G

G

R

R

V95 (≠ E75) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (vs. gap) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
V157 (≠ S143) mutation to A: Decreases D-glucose transporter activity.
L283 (vs. gap) 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.

7uuzA Structure of the sodium/iodide symporter (nis) in complex with perrhenate and sodium (see paper)
22% identity, 69% coverage: 39:378/494 of query aligns to 26:360/501 of 7uuzA

query
sites
7uuzA

G

G

R

L

S

A

L

L

G

A

S

A

F

V

V

P

T

V

A

G

L

L

S

S

A

L

G

A

A

A

S

S

D

F

M

M

S

S

G

A

W

V

L
x
Q

L

V

M

L

G

G

L

V

P

P

G

A

A

E

I

A

F

A

V

R

A

Y

G

G

L

L

S

K

E

F

S

L

W

W

I
x
M

A

C

I

A

G

G

L
x
Q

I

L

V

L

G

N

A

S

W

L

L

L

N

T

-

A

W

F

L

L

F

F

V

L

A

P

G

I

R

F

L

Y

R

R

V

L

H

G

T

L

E

T

H

S

N

T

H

Y

N

Q

A

-

L

-

T

-

L

-

P

-

D

-

Y

Y

F

L

S

E

H

L

R

R

F

F

E

-

D

-

E

-

S

S

R

R

M

A

L

V

R

R

I

L

F

C

S

G

A

T

L

L

V

Q

I

Y

L

L

V

V

F

A

F

T

T

M

I

L

Y
|
Y

C

T

A

G

S

I

G

V

V

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

P

D

Y

I

E

W

Y

A

A

S

L

L

W

L

V

S

G

T

A

G

A

I

T

C

I

T

L

L

Y

Y

V

T

F

T

I

V

G

G

F

-

L

-

A

-

V

-

S

-

W

W

T

T

D

D

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F

Q

Q

A

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L

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M

M

I

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I

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V

G

I

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I

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L

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L

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M

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G

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T

N

A

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M

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T

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I

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A

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H

-

S

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-

I

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N

P

L

A

M

N

D

F

F

D

D

-

P

-

D

-

P

-

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-

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M

R

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Y

R

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G

F

L

W

S

T

F

F

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I

A

-

I

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G

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A

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W
|
W

G

-

L

L

G

S

Y

M

F

Y

G

G

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V

P

N

H

Q

I

A

L

Q

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V

-

Q

R

R

F

Y

M

V

A

A

A

C

D

H

S

T

I

E

K

G

T

K

I

A

P

K

N

L

A

A

R

L

I

V

G

N

M

Q

T

L

W

G

M

L

I

F

L

L

T

I

L
x
V

A

A

G

S

A

A

V

A

A

C

V

C

G

G

F

I

L

V

G

M

I

F

A

V

Y

Y

F

Y

A

K

D

D

-

C

H

D

P

P

E

L

Q

L

A

T

G

G

A

R

V

I

S

S

Q

A

N

P

G

D

E

Q

R

Y

V

M

F

P

M

L

E

L

L

V

V

L

K

D

I

I

L

F

F

E

N

D

-

L

P

P

W

G

V

V

A

P

G

G

I

L

I

F

L

L

S

A

G

C

V

A

L

Y

A

S

A

G

V

T

M

L

S

S

T

T

L

A

S

S

A

T

Q

S

L

I

L

N

V

A

S

M

S

A

A

V

L

T

T

V

Q

E

D

D

F

L

Y

I

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K

A

P

M

R

L

M

R

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K

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N

L

A

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-

E

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L

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L

binding sodium ion: Q47 (≠ L60), Y119 (= Y140)
binding perrhenate: Q47 (≠ L60), M65 (≠ I78), Q69 (≠ L82), W225 (= W244), V263 (≠ L282)

Sites not aligning to the query:

8hdhA Structure of human sglt2-map17 complex with canagliflozin (see paper)
26% identity, 69% coverage: 35:376/494 of query aligns to 35:407/586 of 8hdhA

query
sites
8hdhA

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

F

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

F

A

V

A

A

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

W

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

H

-

T

-

E

-

H

-

N

T

H

A

N

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

-

E

-

S

G

R

R

M

R

L

I

R

R

I

L

F

Y

-

L

S

S

A

V

L

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

V

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

P

N

Y

I

E

Y

Y

A

A

S

L

V

W

I

V

A

G

L

A

L

A

G

A

I

T

T

I

M

L

I

Y

Y

V

T

F

V

I

T

G

G

F

L

L

A

A

A

V

L

S

M

W

Y

T

T

D

D

T

T

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V

Q

Q

A

T

T

F

L

V

M

I

I

L

F

G

A

G

L

A

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C

V

I

T

L

P

M

V

G

F

Y

V

A

I

F

L

H

A

E

L

V

G

G

D

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

M

L

G

G

T

A

A

A

M

T

A

S

T

L

I

T

E

V

A

S

Q

E

N

D

P

P

A

A

-

V

-

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N

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I

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M

S

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F

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C

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Y

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-

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Y

-

H

-

L

-

R

V

H

A

P

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T

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G

L

D

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A

P

W

W

G

P

-

A

-

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L

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G

-

L

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-

I

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x
S

-

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x
W

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-

Q

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A

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K

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I

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-

N

K

A

A

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C

I

I

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C

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G

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Y

M

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I

K

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L

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T

-

P

L

M

A

F

G

L

A

M

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A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

P

D

D

H

-

P

-

E

E

Q

V

A

A

G

C

A

V

V

V

S

P

Q

E

N

V

G

C

E

R

R

R

V

V

-

C

-

G

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T

-

E

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V

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G

-

C

-

S

-

N

-

I

-

A

F

Y

M

P

E

R

L

L

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K

V

I

K

L

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F

M

N

P

P

N

W

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V

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A

R

G

G

I

L

I

M

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L

S

A

G

V

V

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

A

S

Q

I

L

F

L

N

V

S

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

T

A

-

M

R

L

L

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K

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N

R

A

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binding (2~{S},3~{R},4~{R},5~{S},6~{R})-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl]-4-methyl-phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ D55), G59 (≠ W59), H60 (≠ L60), G63 (= G63), L64 (= L64), F78 (vs. gap), E79 (vs. gap), S267 (vs. gap), 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)
26% identity, 69% coverage: 35:376/494 of query aligns to 35:407/586 of 8hb0A

query
sites
8hb0A

Y

Y

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

V

S

W

F

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

F

A

V

A

A

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

W

L

L

L

N

G

W

W

L

L

F

F

V

A

A

P

G

V

R

Y

L

L

R

-

V

-

H

-

T

-

E

-

H

-

N

T

H

A

N

G

A

V

L

I

T

T

L

M

P

P

D

Q

Y

Y

F

L

S

R

H

K

R

R

F

F

E

G

D

-

E

-

S

G

R

R

M

R

L

I

R

R

I

L

F

Y

-

L

S

S

A

V

L

L

V

S

I

L

L

F

V

L

F

Y

F

I

T

F

I

T

Y

K

C

I

A

S

S
x
V

G

D

V

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

P

N

Y

I

E

Y

Y

A

A

S

L

V

W

I

V

A

G

L

A

L

A

G

A

I

T

T

I

M

L

I

Y

Y

V

T

F

V

I

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

L

C

V

I

T

L

P

M

V

G

F

Y

V

A

I

F

L

H

A

E

L

V

G

G

D

G

-

Y

-

S

-

G

-

L

-

F

-

D

-

K

-

Y

M

L

G

G

T

A

A

A

M

T

A

S

T

L

I

T

E

V

A

S

Q

E

N

D

P

P

A

A

-

V

-

G

N

N

F

I

D

S

M

S

F

F

-

C

-

Y

-

R

-

P

R

R

G

P

L

D

S

S

F

Y

-

H

-

L

-

R

V

H

A

P

I

V

V

T

S

G

L

D

L

L

A

P

W

W

G

P

-

A

-

L

L

L

G

G

-

L

-

T

-

I

-
x
V

-
x
S

-

G

-

W

Y

Y

F
x
W

G

C

Q

S

P

D

H

Q

I

V

L

I

V

V

-

Q

R

R

F

C

M

L

A

A

A

G

D

K

S

S

I

L

K

T

T

H

I

I

P

-

N

K

A

A

R

G

R

C

I

I

G

L

M

C

T

G

W

Y

M

L

I

K

L

L

T

T

-

P

L

M

A

F

G

L

A

M

V

V

A

M

V

P

G

G

F

M

L

I

G

S

I

R

A

I

Y

L

F

Y

A

P

D

D

H

-

P

-

E

E

Q

V

A

A

G

C

A

V

V

V

S

P

Q

E

N

V

G

C

E

R

R

R

V

V

-

C

-

G

-

T

-

E

-

V

-

G

-

C

-

S

-

N

-

I

-

A

F

Y

M

P

E

R

L

L

V

V

K

V

I

K

L

L

F

M

N

P

P

N

W

G

V

L

A

R

G

G

I

L

I

M

L

L

S

A

G

V

V

M

L

L

A

A

A
|
A

V

L

M

M

S
|
S

T
x
S

L

L

S

A

A

S

Q

I

L

F

L

N

V

S

S

S

S

T

A

L

L

F

T

T

Q

M

D

D

F

I

Y

Y

K

T

A

-

M

R

L

L

R

R

K

P

N

R

A

A

S

G

Q

D

T

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 (vs. gap), S267 (vs. gap), W271 (≠ F249)
binding sodium ion: A53 (= A53), I56 (≠ M56), G57 (≠ S57), A369 (= A337), S372 (= S340), S373 (≠ T341)

Sites not aligning to the query:

Query Sequence

>GFF3017 FitnessBrowser__psRCH2:GFF3017
MNVSTPTLITFVIYIAAMILIGFIAYRATKNFSDYILGGRSLGSFVTALSAGASDMSGWL
LMGLPGAIFVAGLSESWIAIGLIVGAWLNWLFVAGRLRVHTEHNHNALTLPDYFSHRFED
ESRMLRIFSALVILVFFTIYCASGVVAGARLFESTFGMPYEYALWVGAAATILYVFIGGF
LAVSWTDTVQATLMIFALLVTPVFVILALGDMGTAMATIEAQNPANFDMFRGLSFVAIVS
LLAWGLGYFGQPHILVRFMAADSIKTIPNARRIGMTWMILTLAGAVAVGFLGIAYFADHP
EQAGAVSQNGERVFMELVKILFNPWVAGIILSGVLAAVMSTLSAQLLVSSSALTQDFYKA
MLRKNASQTELVWVGRGMVLLIALIAIGIASNPDSKVLGLVSYAWAGFGAAFGPVVLISL
LWKRMTRNGALVGMLVGAVTVVVWKEFIGLGLYEIIPGFILASIAIFVVSKLGAEPAPSI
VKRFEEADADYHAG

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