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.

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, 72% coverage: 30:391/502 of query aligns to 42:403/643 of Q92911

query
sites
Q92911

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A102 (≠ W90) natural variant: A -> P
H226 (≠ K222) 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 (≠ N234) 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

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
22% identity, 74% coverage: 92:463/502 of query aligns to 110:508/659 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, 85% coverage: 35:463/502 of query aligns to 58:508/662 of P11170

query
sites
P11170

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R

E

N

P

G

G

A

A

L

F

A

W

G

G

M

L

I

V

I

L

G

G

A

F

L

L

T

-

V

-

I

-

V

-

W

-

K

-

Q

-

F

-

G

-

W

-

L

I

G

G

L

I

Y

S

E

R

I

M

I

I

P

T

G

E

F

F

I

A

F

Y

G

G

S

T

C255 (≠ S223) 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

Q9ET37 Solute carrier family 5 member 4A; SGLT3-a from Mus musculus (Mouse) (see paper)
23% identity, 85% coverage: 35:463/502 of query aligns to 58:508/656 of Q9ET37

query
sites
Q9ET37

Y

F

I

F

L

L

G

A

G

G

R

R

S

S

L

M

G

T

P

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

V

G

F

A

L

A

S

S

G

G

I

I

S

-

E

-

S

-

W

-

I

-

A

A

I

V

G

T

L

A

T

F

L

E

G

S

A

H

W

S

I

F

N

A

W

L

K

L

L

L

V

V

A

L

G

G

R

W

L

I

R

F

V

V

H

P

T

I

E

Y

Y

I

N

K

N

A

N

G

A

V

L

M

T

T

L

M

P

P

D

E

Y

Y

F

L

T

K

G

K

R

R

F

F

E

G

D

G

K

K

S

-

R

R

I

L

L

Q

R

I

I

Y

I

L

S

S

A

I

L

L

V

F

I

L

L

F

L

I

F

C

F

V

T

I

I

L

Y

T

C

I

A

S

S

A

G

D

I

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

S

N

Y

L

E

Y

T

L

A

A

L

I

W

L

A

I

G

L

A

L

A

A

A

I

T

T

I

A

L

I

Y

F

T

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

S

V

L

I

M

M

I

L

F

V

A

G

L

S

I

F

L

I

T

L

P

M

V

V

I

F

V

A

I

F

I

V

S

E

V

V

G

G

F

Y

-

E

-

S

-

F

-

T

-

E

-

K

-

F

-

M

-

N

-

A

-

I

-

P

-

S

-

V

-

E

G

G

D

D

S

N

L

L

E

T

V

I

I

N

K

S

Q

R

K

C

S

Y

I

T

E

P

N

Q

V

P

D

D

M

S

L

F

K

H

G

I

L

F

N

R

F

-

V

D

A

P

I

V

I

T

S

G

L

D

M

I

G

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

H

Q

I

V

L

I

A

V

R

Q

F

R

M

C

A

L

A

C

D

G

S

K

H

N

H

L

S

S

I

H

V

V

H

K

A

A

-

A

-

C

-

I

-

L

-

C

-

G

-

Y

-

L

-

K

-

L

-

P

-

L

-

F

-

M

-

V

-

M

-

P

-

G

-

M

-

I

R

S

R

R

I

I

S

L

M

Y

T

T

W

D

M

M

I

V

L

A

C

C

L

V

A

V

G

P

A

S

V

E

A

C

V

V

G

K

F

H

F

C

G

G

I

V

A

D

Y

-

F

-

N

-

D

-

H

-

P

-

A

-

L

-

A

V

G

G

A

C

V

T

N

N

Q

Y

N

A

A

Y

E

P

R

M

V

L

F

V

I

L

E

K

L

L

A

M

Q

P

I

M

L

-

F

-

N

-

P

-

W

G

I

L

A

R

G

G

I

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

V

L

F

L

N

V

S

C

A

S

S

S

T

A

L

I

F

T

T

E

I

D

D

L

L

Y

Y

K

T

A

K

F

-

L

I

R

R

K

K

H

K

A

A

S

S

Q

E

K

R

E

E

L

L

V

L

W

I

V

A

G

G

R

R

V

L

M

F

V

V

L

S

V

V

V

L

A

I

L

V

V

T

A

S

I

I

A

L

L

W

A

V

A

P

N

I

P

V

E

E

N

V

R

S

V

Q

L

G

G

G

L

Q

V

L

S

V

Y

H

A

Y

W

T

A
x
E

G

A

F

I

G

S

A

S

A

Y

F

L

G

G

P

P

-

P

-

I

-

A

V

V

V

F

L

L

F

V

S

A

V

V

M

F

W

C

S

K

R

R

M

A

T

N

R

E

N

Q

G

G

A

A

L

F

A

W

G

G

M

L

I

M

I

V

G

G

A

L

L

V

T

-

V

-

I

-

V

-

W

-

K

-

Q

-

F

-

G

-

W

-

L

M

G

G

L

L

Y

I

E

R

I

M

I

I

P

A

G

E

F

F

I

S

F

Y

G

G

S

T

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

Q9GZV3 High affinity choline transporter 1; Hemicholinium-3-sensitive choline transporter; CHT; Solute carrier family 5 member 7 from Homo sapiens (Human) (see 3 papers)
25% identity, 78% coverage: 1:390/502 of query aligns to 1:396/580 of Q9GZV3

query
sites
Q9GZV3

M

M

A

A

I

F

S

H

T

V

P

E

M

G

L

L

V

I

T

A

F

I

C

I

V

V

Y

F

I

Y

F

L

G

L

M

I

I

L

L

L

I

V

G

G

-

I

F

W

I

A

A

A

W

W

R

R

S

-

T

T

K

K

N

N

F

S

-

G

-

S

-

A

-

E

-

R

-

S

D

E

D

A

Y

I

I

I

L

V

G

G

R

R

S
x
D

L

I

G

G

P

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

V

V

F

Y

L

V

S

P

G

G

I

Y

S

G

E

L

S

A

W

W

-

A

-

Q

I

A

A

P

I
|
I

G

G

L

Y

T

S

L

L

G

S

A

L

W

I

I

L

N

G

W

G

K

L

L

F

V

F

A

A

G

K

R
x
P

L

M

R

R

V

-

H

-

T

-

E

-

Y

-

N

S

N

K

N

G

A
x
Y

L

V

T

T

L

M

P

L

D

D

Y

P

F

F

T

Q

G

Q

R

I

F

Y

E

G

D

K

K

R

S

M

R

G

I

G

L

L

R

L

I

F

I

I

S

P

A

A

L

L

V

M

I

G

L

E

L

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

L

L

Y
|
Y

T

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

S

-

L

F

M

C

I

I

F

F

A

V

L

G

I

L

L

W

T

I

P

S

V

V

I

P

V

F

I

A

I

L

S

S

V

H

G

P

G

A

F

V

G

A

D

D

-

I

-

G

-

F

-

T

S

A

L

V

E

H

V

A

I

K

K

Y

Q

Q

K

K

-

P

-

W

-

L

-

G

S

T

I

V

E

D

N

S

V

S

D

E

M

V

L

Y

K

S

G

W

L

L

N

D

F

S

V

F

A

L

I

L

S

M

L

L

M

G

G

G

-

I

-

P

W

W

G

Q

L

-

G

-

Y

-

F

-

G

-

Q

-

P

-

H

-

I

-

L

-

A

A

R

Y

F

F

M

Q

A

R

A

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D

L

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F

T

L

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A

M

A

I

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L

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C

C

L

L

A

V

G

M

A

A

V

I

A

P

V

A

G

I

F

L

F
x
I

G

G

-

A

-

I

-

G

-

A

-

S

-

T

-

D

-

W

-

N

-

Q

I

T

A

A

Y

Y

F

G

N

L

D

P

H

D

P

P

A

-

L

-

A

-

G

-

A

K

V

T

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T

Q

E

N

E

A

A

E

D

R

M

V

I

F

L

I

P

E

I

L

V

A

L

Q

Q

I

Y

L

L

F

C

N

P

P

V

W

Y

I

I

A

S

G

F

I

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

I

F

T

A

E
x
R

D

N

L

I

Y

Y

K

Q

A

L

F

S

L

F

R

R

K

Q

H

N

A

A

S

S

Q

D

K

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

V

I

M

T

V

V

L

F

V

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 uptake rate; found in 0.06 of Ashkenazi Jews; dbSNP:rs1013940; mutation to A: 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; unknown pathological significance; dbSNP:rs1331713195
I291 (≠ F291) to T: in CMS20; unknown pathological significance; dbSNP:rs375397889
V344 (= V338) to L: in CMS20; unknown pathological 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; unknown pathological significance
446 R → G: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane
451 E→Q: Only 5% of wild-type choline uptake activity.

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
21% identity, 73% coverage: 72:435/502 of query aligns to 43:426/512 of 3dh4A

query
sites
3dh4A

G

G

I

M

S

S

E

G

S

S

W

G

I

Y

A

S

I

I

G

G

L

L

T

A

L

I

G

A

A

S

W
x
Y

I

-

N
x
E

W

W

K

M

-
x
S

-

A

-

I

-

T

-

L

L

I

V

I

A

V

G

G

R

K

L

Y

R

F

V

L

H

P

T

I

E

F

Y

I

N

E

N

K

N

G

A

I

L

Y

T

T

L

I

P

P

D

E

Y

F

F

V

T

E

G

K

R

R

F

F

E

N

D

K

K

K

S

L

R

K

I

-

L

-

R

T

I

I

I

L

S

A

A

V

L

F

V

W

I

I

L

S

L

L

F

Y

F

I

T

F

I

V

Y

N

C

L

A

T

S

S

G

V

I

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

S

P

Y

L

E

M

T

Y

A

S

L

I

W

L

A

G

G

L

A

A

A

L

A

F

T

A

I

L

L

V

Y

Y

T

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

S

F

L

F

M

L

I

V

F

L

A

G

L

G

I

F

L

M

T

T

P

T

V

Y

I

M

V

A

I

V

I

S

S

F

V

I

G

G

F

T

G

D

-

G

-

W

-

F

-

A

-

G

-

V

-

S

-

K

-

M

-

V

-

D

-

A

-

P

D

G

S

H

L

F

E

E

V

M

I

I

K

L

Q

D

K

Q

S

S

I

N

E

P

N

Q

V

Y

D

M

M

N

L

L

K

P

G

G

L

I

N

A

F

V

V

L

A

I

-

G

-

L

-

W

I

V

I
x
A

S
x
N

L

L

M

Y

G
x
Y

W
|
W

G

G

L

F

G

N

Y

Q

F

Y

G

I

Q

I

P

Q

H

R

I

T

L

L

A

A

R

A

F

K

M

S

A

V

A

S

D

E

S

A

H

Q

H

K

S

G

I

I

V

V

H

F

A

A

R

A

R

F

I

L

S
x
K

M

L

T

I

W

V

M

P

I

F

L

L

C

V

L

V

A

L

G

P

A

G

V

I

A

A

V

-

G

-

F

-

G

-

I

-

A

A

Y

Y

-

V

F

I

N

T

D

S

H

D

P

P

A

Q

L

L

A

M

G

A

A

S

V

L

N

G

Q

D

-

I

-

A

-

T

-

N

-

L

-

P

-

S

-

A

N

N

A

A

E

D

R

K

V

A

F

Y

I

P

E

W

L

L

A

T

Q

Q

I

F

L

L

F

-

N

P

P

V

W

G

I

V

A

K

G

G

I

V

L

V

L

F

S

A

A

A

I

L

L

A

A

A

A
|
A

V

I

M

V

S
|
S

T

S

L

L

S

A

C

S

Q

M

L

L

L

N

V

S

C

T

S

A

S

T

A

I

I

F

T

T

E

M

D

D

L

I

Y

Y

K

K

A

E

F

Y

L

I

R

S

K

P

H

D

A

S

S

G

Q

D

K

H

E

K

L

L

V

V

W

N

V

V

G

G

R

R

V

T

M

A

V

A

L

V

V

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
x
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

F

L

S

G

V

L

M

F

W

W

S

K

R

K

M

T

T

T

R

S

N

K

G

G

A

A

L

I

A

I

G

G

M

V

I

V

binding beta-D-galactopyranose: Y58 (≠ W87), E59 (≠ N89), S62 (vs. gap), A224 (≠ I239), N225 (≠ S240), Y228 (≠ G243), W229 (= W244), K259 (≠ S274), F389 (≠ A391), 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)
22% identity, 81% coverage: 33:437/502 of query aligns to 43:449/610 of Q8N695

query
sites
Q8N695

D

K

D

D

Y

F

I

L

L

M

G

G

R

R

S

R

L

M

G

T

P

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

V

V

F

Y

L

R

S

F

G

G

I

A

S

I

E

F

S

S

W

I

I

F

A

A

I

F

G

-

L

-

T

-

L

-

G

-

A

T

W

Y

I

F

N

F

W

V

K

V

L

V

V

I

A

S

G

A

R

E

L

V

R

F

V

L

H

P

T

V

E

F

Y

Y

N

K

N

L

N

G

A

I

L

T

T

S

L

T

P

Y

D

E

Y

Y

F

L

T

E

G

L

R

R

F

F

E

-

D

-

K

-

S

N

R

K

I

C

L

V

R

R

I

L

I

C

S

G

A

T

L

V

V

L

I

F

L

I

L

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

L

F

Y

Y

T

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

S

G

L

I

M

M

I

V

F

A

A

G

L

F

I

A

L

S

T

V

P

I

V

I

I

Q

V

A

I

V

S

M

V

Q

G

G

F

-

G

-

D

-

S

-

L

I

E

S

V

T

I

I

K

L

Q

N

K

D

S

A

I

Y

E

D

-

G

-

R

-

L

-

N

-

F

-

W

-

N

-

F

N

N

V

P

D

N

M

P

L

L

K

Q

G

R

L

H

N

T

F

F

V

W

A

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

H

R

H

F

S

Q

I

A

V

K

H

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

T

L

C

A

S

G

V

A

F

V

C

A

G

V

L

G

A

F

L

F

Y

G

S

I

-

A

R

Y

Y

F

H

N

D

D

C

H

D

P

P

A

W

L

T

A

A

G

K

A

K

V

V

N

S

Q

A

N

P

A

D

E

Q

R

L

V

M

F

P

I

Y

E

L

L

V

A

L

Q

D

I

I

L

L

F

Q

N

D

-

Y

P

P

W

G

I

L

A

P

G

G

I

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

I

T

T

V

E

E

D

D

L

L

Y

I

K

K

A

P

F

Y

L

F

R

R

K

S

H

-

A

L

S

S

Q

E

K

R

E

S

L

L

V

S

W

W

V

I

G

S

R

Q

V

G

M

M

V

S

L

V

V

V

V

Y

A

G

L

A

V

L

A

C

I

I

A

G

L

M

A

A

N

-

P

L

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

L

F

F

S

A

-

L

-

G

V

I

M

L

W

V

S

P

R

F

M

A

T

N

R

S

N

I

G

G

A

A

L

L

A

V

G

G

M

L

I

M

I

A

G

G

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.

7uuzA Structure of the sodium/iodide symporter (nis) in complex with perrhenate and sodium (see paper)
22% identity, 82% coverage: 39:448/502 of query aligns to 26:432/501 of 7uuzA

query
sites
7uuzA

G

G

R

L

S

A

L

L

G

A

P

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

V

A

F

A

L

R

S

Y

G

G

I

L

S

K

E
x
F

S

L

W

W

I
x
M

A

C

I

A

G

G

L
x
Q

T

L

L

L

G

N

A

S

W

-

I

-

N

-

W

-

K

-

L

L

V

L

A

T

G

A

R

F

L

L

R

F

V

L

H

P

T

I

E

F

Y

Y

N

R

N

L

N

G

A

L

L

T

T

S

L

T

P

Y

D

Q

Y

Y

F

L

T

E

G

L

R

R

F

F

E

-

D

-

K

-

S

S

R

R

I

A

L

V

R

R

I

L

I

C

S

G

A

T

L

L

V

Q

I

Y

L

L

L

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

L

L

Y

Y

T

T

F

T

I

V

G

G

F

-

L

-

A

-

V

-

S

-

W

W

T

T

D

D

T

V

V

F

Q

Q

A

V

S

V

L

V

M

M

I

L

F

V

A

G

L

F

I

W

L

V

T

I

P

L

V

A

I

R

V

G

I

V

I

I

S

L

V

L

G

G

F

P

G

R

D

N

S

V

L

L

E

S

V

L

I

A

K

Q

Q

Q

K

H

S

S

I

R

E

I

N

N

V

L

-

M

-

D

-

F

-

D

-

P

D

D

M

P

L

R

K

S

G

R

L

Y

N

T

F

F

V

W

A

T

I

F

I

I

-

V

-

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

H

S

T

H

E

H

G

S

K

I

A

V

K

H

L

A

A

R

L

I

V

S

N

M

Q

T

L

W

G

M

L

I

F

L

L

C

I

L
x
V

A

A

G

S

A

A

V

A

A

C

V

C

G

G

F

I

F

V

G

M

I

F

A

V

Y

Y

F

Y

N

K

D

D

-

C

H

D

P

P

A

L

L

L

A

T

G

G

A

R

V

I

N

S

Q

A

N

P

A

D

E

Q

R

Y

V

M

F

P

I

L

E

L

L

V

A

L

Q

D

I

I

L

F

F

E

N

D

-

L

P

P

W

G

I

V

A

P

G

G

I

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

I

T

T

V

E

E

D

D

L

L

Y

I

K

K

A

P

F

R

L

M

R

P

K

G

H

L

A

A

S

P

Q

R

K

K

E

-

L

L

V

V

W

F

V

I

G

S

R

K

V

G

M

L

V

S

L

F

V

I

V

Y

A

G

L

S

V

A

A

C

I

L

A

T

L

V

A

A

N

L

P

S

E

S

N

L

R

L

V

G

L

G

G

G

L

V

V

L

S

Q

Y

G

A
x
S

W
x
F

A

T

G

V

F

M

G

G

A

V

A

I

F

S

G

G

P

P

V

L

-

G

-

A

-

F

L

T

F

L

S

G

V

M

M

L

W

L

S

P

R

A

M

C

T

N

R

T

N

P

G

G

A

V

L

L

A

S

G

G

M

L

I

A

G

G

A

-

L

L

T

A

V

V

I

S

V

L

W

W

K

V

Q

A

F

V

G

G

binding sodium ion: Q47 (≠ L60), Y119 (= Y140), S386 (≠ A404), F387 (≠ W405)
binding perrhenate: M43 (= M56), Q47 (≠ L60), F62 (≠ E75), M65 (≠ I78), Q69 (≠ L82), W225 (= W244), V263 (≠ L282), F387 (≠ W405)

7slaA Cryoem structure of sglt1 at 3.15 angstrom resolution (see paper)
32% identity, 21% coverage: 328:430/502 of query aligns to 349:454/585 of 7slaA

query
sites
7slaA

G

G

I

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

I

F

T

T

E

M

D

D

L

I

Y

Y

K

-

A

A

F

K

L

V

R

R

K

K

H

R

A

A

S

S

Q

E

K

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

V

L

M

F

V

V

L

L

V

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

F

L

S

A

V

I

M

F

W

W

S

K

R

R

M

V

T

N

R

E

N

Q

G

G

A

A

Sites not aligning to the query:

binding cholesterol hemisuccinate: 36, 277, 288, 554, 558, 561

7sl8A Cryoem structure of sglt1 at 3.4 a resolution (see paper)
32% identity, 21% coverage: 328:430/502 of query aligns to 348:453/582 of 7sl8A

query
sites
7sl8A

G

G

I

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

I

F

T

T

E

M

D

D

L

I

Y

Y

K

-

A

A

F

K

L

V

R

R

K

K

H

R

A

A

S

S

Q

E

K

K

E

E

L

L

V

M

W

I

V

V

G

G

R

R

V

L

M

F

V

V

L

L

V

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

F

L

S

A

V

I

M

F

W

W

S

K

R

R

M

V

T

N

R

E

N

Q

G

G

A

A

Sites not aligning to the query:

binding cholesterol: 35, 280, 287, 551, 554, 555, 558

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)
30% identity, 21% coverage: 326:431/502 of query aligns to 378:486/664 of P13866

query
sites
P13866

I
x
L

A
x
R

G
|
G

I
x
L

L
x
M

L
|
L

S
|
S

A
x
V

I
x
M

L
|
L

A
|
A

A
x
S

V
x
L

M
|
M

S
|
S

T
x
S

L
|
L

S
x
T

C
x
S

Q
x
I

L
x
F

L
x
N

V
x
S

C
x
A

S
|
S

S
x
T

A
x
L

I
x
F

T
|
T

E
x
M

D
|
D

L
x
I

Y
|
Y

K

-

A
|
A

F
x
K

L
x
V

R
|
R

K
|
K

H
x
R

A
|
A

S
|
S

Q
x
E

K
|
K

E
|
E

L
|
L

V
x
M

W
x
I

V
x
A

G
|
G

R
|
R

V
x
L

M
x
F

V
x
I

L
|
L

V
|
V

V
x
L

A
x
I

L
x
G

V
x
I

A
x
S

I
|
I

A
|
A

-
x
W

-
x
V

-
x
P

-
x
I

L
x
V

A
x
Q

A
x
S

N
x
A

P
x
Q

E
x
S

N
x
G

R
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

F
x
L

S
x
A

V
x
I

M
x
F

W
|
W

S
x
K

R
|
R

M
x
V

T
x
N

R
x
E

N
x
P

G
|
G

A
|
A

L
x
F

R379 (≠ A327) to Q: in GGM; loss of activity
A388 (= A336) to V: in GGM; loss of activity
S396 (≠ C344) mutation to A: Loss of activity.
F405 (≠ I353) 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 (≠ R396) 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; requires 2 nucleotide substitutions; about 90% reduction in activity

Sites not aligning to the query:

51 N → S: in GGM; slightly decreased activity; dbSNP:rs17683011
67 W→A: Strong reduction in D-glucose transporter activity.
77 S→A: Loss of activity.
83 H→L: Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and C-290.; H→Q: Loss of D-glucose transporter activity.
135 R → W: in GGM; loss of activity
159 S → P: in GGM; loss of activity
166 A → T: in GGM; about 90% reduction in activity
191:664 natural variant: Missing (in GGM; loss of activity)
204 D→A: Loss of activity.
248 modified: carbohydrate, N-linked (GlcNAc...) asparagine; N→Q: Loss of N-glycosylation.
255 modified: Disulfide link with 511
276 W → L: in GGM; about 95% reduction in activity
287 T→A: Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with L-83 and C-290.; T→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.
290 Y→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.
291 W→A: Loss of D-glucose transporter activity.
292 C → Y: in GGM; loss of activity; C→A: Has no effect on water permeability.
295 Q → R: in GGM; loss of activity
300 R → S: in GGM; loss of activity
304 A → V: in GGM; impairs trafficking to the plasma membrane
321 K→Q: Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
345 modified: Disulfide link with 351
351 modified: Disulfide link with 345
355 modified: Disulfide link with 361
361 modified: Disulfide link with 355
363 N→A: Loss of water permeation.
369 L → S: 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.

7wmvA Structure of human sglt1-map17 complex bound with lx2761 (see paper)
31% identity, 21% coverage: 328:430/502 of query aligns to 363:468/602 of 7wmvA

query
sites
7wmvA

G

G

I

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

I

F

T

T

E

M

D

D

L

I

Y

Y

K

-

A

A

F

K

L

V

R

R

K

K

H

R

A

A

S

S

Q

E

K

K

E

E

L

L

V

M

W

I

V

A

G

G

R

R

V

L

M

F

V

I

L

L

V

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

F

L

S

A

V

I

M

F

W

W

S

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: 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: 61, 66, 70, 81, 84, 85, 88, 256, 257, 266, 269, 270, 273, 274, 304, 508

7yniA Structure of human sglt1-map17 complex bound with substrate 4d4fdg in the occluded conformation
31% identity, 21% coverage: 328:430/502 of query aligns to 342:447/566 of 7yniA

query
sites
7yniA

G

G

I

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

I

F

T

T

E

M

D

D

L

I

Y

Y

K

-

A

A

F

K

L

V

R

R

K

K

H

R

A

A

S

S

Q

E

K

K

E

E

L

L

V

M

W

I

V

A

G

G

R

R

V

L

M

F

V

I

L

L

V

V

V

L

A

I

L

G

V

I

A

S

I

I

A

A

-

W

-

V