SitesBLAST

R257 (= R255) mutation to C: Sodium-independent binding affinity for proline.
C281 (≠ G279) 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 (≠ S355) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (≠ S360) 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 (= R387) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.

8zqpA High affinity choline transporter 1
27% identity, 94% coverage: 6:480/506 of query aligns to 5:464/470 of 8zqpA

query
sites
8zqpA

L

L

I

I

A

A

F

I

I

I

V

V

Y

F

L

Y

I

L

G

L

I

I

L

L

V

L

I

V

G

G

I

I

-

W

I

A

M

A

Y

W

R

R

M

T

T

K

N

N

N

S

L

G

S

S

D

A

-

E

-

R

-

S

-

E

-

A

Y

I

V

I

L

V

G

G

R

R

K

D

L

I

G

G

P

L

G

L

V

V

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D

W

M

V

S

G

G

G

W
x
G

L

Y

L

I

L

N

G

G

L

T

P

A

G

E

A

A

V

V

Y

Y

A

V

A

P

G

G

L

Y

A

G

E

L

A

A

W

W

M

A

-

Q

-

A

A

P

I

I

G

G

L
x
Y

S

S

I

L

G

S

A

L

Y

I

L

L

N

G

W

G

Q

L

F

F

V

F

A

A

K

K

R

P

L

M

R

R

I

-

Y

-

T

-

E

-

V

-

S

S

N

K

N

G

S

Y

I

V

T

T

V

M

P

L

D

D

F

P

L

F

E

Q

N

Q

R

I

F

Y

K

G

D

K

N

R

S

M

H

G

I

G

L

L

R

L

V

F

I

I

S

P

A

A

L

L

V

M

I

G

L

E

L

M

F

F

F

W

T

A

F

A

Y

A

T

I

S

F

S

S

G

A

M

L

V

-

A

-

G

G

A

A

K

T

L

I

F

-

E

S

A

V

S

I

F

I

G

D

L

V

D

D

Y

M

Q

H

A

I

A

S

L

V

W

I

I

I

G

S

T

A

I

L

V

I

V

A

V

T

S

L

Y

Y

T

T

L

L

L

V

G

G

F

L

L

Y

A

S

V

V

A

A

W

Y

T

T

D

D

F

V

V

V

Q

Q

G

L

S

F

L

C

M

I

F

F

L

V

A

G

L

L

-

W

I

I

V

S

V

V

P

P

I

F

V

A

-

L

-

S

-

H

-

P

A

A

I

V

N

A

E

D

M

I

G

G

G

-

W

-

N

F

T

T

A

A

V

V

Q

H

A

A

-

K

-

Y

-

Q

-

K

-

P

-

W

V

L

G

G

D

T

I

V

S

D

S

S

T

S

H

E

L

V

N

Y

M

S

V

W

E

L

G

D

V

S

S

F

I

L

A

L

I

M

I

L

S

G

L

I

A

P

W

W

G

Q

V

-

G

A

Y

Y

F

F

G

Q

Q

-

P

-

H

-

I

-

V

-

R

R

F

V

M

L

A

S

L

S

R

S

S

S

P

A

K

T

D

Y

V

A

P

Q

M

V

A

L

R

S

F

F

I

L

G

A

T

A

T

F

W

G

M

C

V

L

L

V

G

M

L

A

Y

I

G

P

A

A

I

I

F

L

T

I

G

G

F

A

V

I

G

G

L

A

A

S

F

T

I

D

S

W

T

N

Q

Q

E

T

V

A

S

Y

V

G

L

L

G

P

E

D

F

-

G

-

I

-

S

-

V

-

I

-

T

-

E

-

N

-

G

-

I

P

Q

K

M

T

L

T

E

E

D

E

P

A

E

D

K

M

I

I

F

L

I

P

A

I

F

V

S

L

Q

Q

L

Y

L

L

F

C

H

P

P

V

V

Y

I

I

A

S

G

F

I

F

L

G

L

L

A

G

A

A

I

V

L

S

S

A

A

A

I

V

M

M

S

S

T

S

I

A

D

D

S

S

Q

S

L

I

L

L

V

S

S

A

S

S

A

M

V

F

A

A

E

R

D

N

F

I

Y

Y

K

Q

A

L

I

S

F

F

K

R

K

Q

E

N

A

A

G

S

D

D

K

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

I

I

A

T

T

V

L

F

I

V

I

F

A

G

L

A

I

S

A

A

A

T

L

A

I

M

A

A

M

L

N

L

P

T

E

K

S

-

T

T

V

V

L

Y

E

G

L

L

V

W

S

Y

Y

L

A

S

W

S

A

D

G

L

F

V

G

Y

A

I

A

V

F

I

G

F

P

P

T

Q

I

L

L

L

L

C

A

V

L

L

F

F

W

V

K

K

G

G

F

T

T

N

R

T

N

Y

G

G

A

A

F

V

A

A

G

G

I

Y

L

V

A

S

G

G

A

L

V

F

T

L

V

R

I

I

V

T

W

-

G

-

F

-

L

-

S

-

G

-

G

G

I

P

F

F

D

K

L

T

Y

L

E

A

I

M

V

V

P

T

G

S

F

F

L

L

L

T

N

N

L

I

V

C

L

I

A

S

binding 4-methoxy-3-[(1-methylpiperidin-4-yl)oxy]-N-{[3-(propan-2-yl)-1,2-oxazol-5-yl]methyl}benzamide: G63 (≠ W57), Y88 (≠ L80)

8j74A Human high-affinity choline transporter cht1 in the hc-3-bound outward-facing open conformation, dimeric state (see paper)
27% identity, 88% coverage: 6:448/506 of query aligns to 6:440/515 of 8j74A

query
sites
8j74A

L

L

I

I

A

A

F

I

I

I

V

V

Y

F

L

Y

I

L

G

L

I

I

L

L

V

L

I

V

G

G

I

I

-

W

I

A

M

A

Y

W

R

R

M

T

T

K

N

N

N

S

L

G

S

S

D

A

-

E

-

R

-

S

-

E

-

A

Y

I

V

I

L

V

G

G

R

R

K

D

L

I

G

G

P

L

G

L

V

V

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D
x
W

M

V

S

G

G

G

W

G

L

Y

L

I

L

N

G

G

L

T

P

A

G

E

A

A

V

V

Y

Y

A

V

A

P

G

G

L

Y

A

G

E

L

A

A

W

W

M

A

-

Q

-

A

A

P

I

I

G

G

L
x
Y

S

S

I

L

G

S

A

L

Y

I

L

L

N

G

W

G

Q

L

F

F

V

F

A

A

K

K

R

P

L

M

R

R

I

-

Y

-

T

-

E

-

V

-

S

S

N

K

N

G

S

Y

I

V

T

T

V

M

P

L

D

D

F

P

L

F

E

Q

N

Q

R

I

F

Y

K

G

D

K

N

R

S

M

H

G

I

G

L

L

R

L

V

F

I

I

S

P

A

A

L

L

V

M

I

G

L

E

L

M

F

F

F
x
W

T

A

F

A

Y

A

T

I

S

F

S

S

G

A

M

L

V

-

A

-

G

G

A

A

K

T

L

I

F

-

E

S

A

V

S

I

F

I

G

D

L

V

D

D

Y

M

Q

H

A

I

A

S

L

V

W

I

I

I

G

S

T

A

I

L

V

I

V

A

V

T

S

L

Y

Y

T

T

L

L

L

V

G

G

F

L

L

Y

A

S

V

V

A

A

W

Y

T

T

D

D

F

V

V

V

Q

Q

G

L

S

F

L

C

M

I

F

F

L

V

A

G

L

L

-

W

I

I

V

S

V

V

P

P

I
x
F

V

A

-

L

-
x
S

-
x
H

-

P

A

A

I

V

N

A

E

D

M
x
I

G
|
G

G

-

W

-

N
x
F

T

T

A

A

V

V

Q
x
H

A

A

-

K

-

Y

-

Q

-

K

-

P

-

W

V

L

G

G

D

T

I

V

S

D

S

S

T

S

H

E

L

V

N

Y

M

S

V

W

E

L

G

D

V

S

S

F

I

L

A
x
L

I

M

I

L

S

G

L

I

A

P

W
|
W

G

Q

V

-

G

A

Y

Y

F

F

G

Q

Q

-

P

-

H

-

I

-

V

-

R

R

F

V

M

L

A

S

L

S

R

S

S

S

P

A

K

T

D

Y

V

A

P

Q

M

V

A

L

R

S

F

F

I

L

G

A

T

A

T

F

W

G

M

C

V

L

L

V

G

M

L

A

Y

I

G

P

A

A

I

I

F

L

T

I

G

G

F

A

V

I

G

G

L

A

A

S

F

T

I

D

S

W

T

N

Q

Q

E

T

V

A

S

Y

V

G

L

L

G

P

E

D

F

-

G

-

I

-

S

-

V

-

I

-

T

-

E

-

N

-

G

-

I

P

Q

K

M

T

L

T

E

E

D

E

P

A

E

D

K

M

I

I

F

L

I

P

A

I

F

V

S

L

Q

Q

L

Y

L

L

F
x
C

H
x
P

P

V

V

Y

I

I

A

S

G

F

I

F

L

G

L

L

A

G

A

A

I

V

L

S

S

A

A

A

I

V

M

M

S

S

T

S

I

A

D

D

S

S

Q

S

L

I

L

L

V

S

S

A

S

S

A

M

V

F

A

A

E

R

D

N

F

I

Y

Y

K

Q

A

L

I

S

F

F

K

R

K

Q

E

N

A

A

G

S

D

D

K

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

I

I

A

T

T

V

L

F

I

V

I

F

A

G

L

A

I

S

A

A

A

T

L

A

I

M

A

A

M

L

N

L

P

T

E

K

S

-

T

T

V

V

L

Y

E

G

L

L

V
x
W

S
x
Y

Y

L

A

S

W
x
S

A

D

G

L

F

V

G

Y

A

I

A

V

F

I

G

F

P

P

T

Q

I

L

L

L

L

C

A

V

L

L

F

F

W

V

K

K

G

G

F

T

T

N

R

T

N

Y

G

G

A

A

F

V

A

A

G

G

I

Y

L

V

A

S

G

G

binding Lauryl Maltose Neopentyl Glycol: F203 (≠ I201), S206 (vs. gap), H207 (vs. gap), I213 (≠ M207), G214 (= G208), F215 (≠ N211), H219 (≠ Q215), C326 (≠ F333), P327 (≠ H334)
binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): W60 (≠ D53), Y89 (≠ L80), W139 (≠ F135), L245 (≠ A235), W252 (= W242), W404 (≠ V412), Y405 (≠ S413), S408 (≠ W416)

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)
27% identity, 88% coverage: 6:448/506 of query aligns to 8:442/580 of Q9GZV3

query
sites
Q9GZV3

L

L

I

I

A

A

F

I

I

I

V

V

Y

F

L

Y

I

L

G

L

I

I

L

L

V

L

I

V

G

G

I

I

-

W

I

A

M

A

Y

W

R

R

M

T

T

K

N

N

N

S

L

G

S

S

D

A

Y

E

-

E

-

R

-

S

-

E

-

A

-

I

V

I

L

V

G

G

R

R

K
x
D

L

I

G

G

P

L

G

L

V

V

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

L

N

G

G

L

T

P

A

G

E

A

A

V

V

Y

Y

A

V

A

P

G

G

L

Y

A

G

E

L

A

A

W

W

M

A

-

Q

-

A

A

P

I
|
I

G

G

L

Y

S

S

I

L

G

S

A

L

Y

I

L

L

N

G

W

G

Q

L

F

F

V

F

A

A

K

K

R
x
P

L

M

R

R

I

-

Y

-

T

-

E

-

V

-

S

S

N

K

N

G

S
x
Y

I

V

T

T

V

M

P

L

D

D

F

P

L

F

E

Q

N

Q

R

I

F

Y

K

G

D

K

N

R

S

M

H

G

I

G

L

L

R

L

V

F

I

I

S

P

A

A

L

L

V

M

I

G

L

E

L

M

F

F

F

W

T

A

F

A

Y

A

T

I

S

F

S

S

G

A

M

L

V

G

A

A

G

T

A

I

K

S

L

V

F

I

E

-

A

-

S

-

F

I

G

D

L

V

D

D

Y

M

Q

H

A

I

A

S

L

V

W

I

I

I

G

S

T

A

I

L

V

I

V

A

V

T

S

L

Y
|
Y

T

T

L

L

L

V

G

G

F

L

L

Y

A

S

V

V

A

A

W

Y

T

T

D

D

F

V

V

V

Q

Q

G

L

S

F

L

C

M

I

F

F

L

V

A

G

L

L

-

W

I

I

V

S

V

V

P

P

I

F

V

A

-

L

-

S

-

H

-

P

A

A

I

V

N

A

E

D

M

I

G

G

G

-

W

-

N

F

T

T

A

A

V

V

Q

H

A

A

-

K

-

Y

-

Q

-

K

-

P

-

W

V

L

G

G

D

T

I

V

S

D

S

S

T

S

H

E

L

V

N

Y

M

S

V

W

E

L

G

D

V

S

S

F

I

L

A

L

I

M

I

L

S

G

L

I

A

P

W

W

G

Q

V

-

G

A

Y

Y

F

F

G

Q

Q

-

P

-

H

-

I

-

V

-

R

R

F

V

M

L

A

S

L

S

R

S

S

S

P

A

K

T

D

Y

V

A

P

Q

M

V

A

L

R

S

F

F

I

L

G

A

T

A

T

F

W

G

M

C

V

L

L

V

G

M

L

A

Y

I

G

P

A

A

I

I

F

L

T
x
I

G

G

F

A

V

I

G

G

L

A

A

S

F

T

I

D

S

W

T

N

Q

Q

E

T

V

A

S

Y

V

G

L

L

G

P

E

D

F

-

G

-

I

-

S

-

V

-

I

-

T

-

E

-

N

-

G

-

I

P

Q

K

M

T

L

T

E

E

D

E

P

A

E

D

K

M

I

I

F

L

I

P

A

I

F

V

S

L

Q

Q

L

Y

L

L

F

C

H

P

P

V

V

Y

I

I

A

S

G

F

I

F

L

G

L

L

A

G

A

A

I

V

L

S

S

A

A

A

I
x
V

M

M

S

S

T

S

I

A

D

D

S

S

Q

S

L

I

L

L

V

S

S

A

S

S

A

M

V

F

A

A

E
x
R

D

N

F

I

Y

Y

K

Q

A

L

I

S

F

F

K

R

K

Q

E

N

A

A

G

S

D

D

K

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

I

I

A

T

T

V

L

F

I

V

I

F

A

G

L

A

I

S

A

A

A

T

L

A

I

M

A

A

M

L

N

L

P

T

E

K

S

-

T

T

V

V

L

Y

E

G

L

L

V

W

S

Y

Y

L

A

S

W

S

A

D

G

L

F

V

G

Y

A

I

A

V

F

I

G
x
F

P

P

T

Q

I

L

L

L

L

C

A

V

L

L

F

F

W

V

K

K

G

G

F

T

T

N

R

T

N

Y

G

G

A

A

F

V

A

A

G

G

I

Y

L

V

A

S

G

G

D48 (≠ K39) to G: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039768
G65 (= G56) to E: in CMS20; loss of choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039765
I89 (= I78) 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 (≠ R94) to S: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs886039766
Y111 (≠ S105) to H: in CMS20; no effect on localization at plasma membrane
Y175 (= Y172) to C: in CMS20; uncertain significance; dbSNP:rs1331713195
I291 (≠ T286) to T: in CMS20; uncertain significance; dbSNP:rs375397889
V344 (≠ I349) to L: in CMS20; uncertain significance
R361 (≠ E366) to Q: in CMS20; decreased choline transmembrane transporter activity; no effect on localization at plasma membrane; dbSNP:rs147656110
F418 (≠ G424) to V: in CMS20; uncertain significance

Sites not aligning to the query:

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.

9bimA Cryo-em structure of human cht1 in the hc-3 bound outward-facing state
27% identity, 88% coverage: 6:448/506 of query aligns to 7:439/516 of 9bimA

query
sites
9bimA

L

L

I

I

A

A

F

I

I

I

V

V

Y

F

L

Y

I

L

G

L

I

I

L

L

V

L

I

V

G

G

I

I

-

W

I

A

M

A

Y

W

R

R

M

T

T

K

N

G

N

S

L

A

S

E

D

E

Y

R

-

S

-

E

-

A

-

I

V

I

L

V

G

G

R

R

K

D

L

I

G

G

P

L

G

L

V

V

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D
x
W

M

V

S

G

G

G

W

G

L

Y

L

I

L

N

G

G

L

T

P

A

G

E

A

A

V

V

Y

Y

A

V

A

P

G

G

L
x
Y

A

G

E

L

A

A

W

W

M

A

-

Q

-

A

A

P

I

I

G

G

L
x
Y

S

S

I

L

G

S

A

L

Y

I

L

L

N

G

W

G

Q

L

F

F

V

F

A

A

K

K

R

P

L

M

R

R

I

-

Y

-

T

-

E

-

V

-

S

S

N

K

N

G

S

Y

I

V

T

T

V

M

P

L

D

D

F

P

L

F

E

Q

N

Q

R

I

F

Y

K

G

D

K

N

R

S

M

H

G

I

G

L

L

R

L

V

F

I

I

S

P

A

A

L

L

V

M

I

G

L

E

L

M

F

F

F
x
W

T

A

F

A

Y

A

T

I

S

F

S

S

G

A

M

L

V

-

A

-

G

G

A

A

K

T

L

I

F

-

E

S

A

V

S

I

F

I

G

D

L

V

D

D

Y

M

Q

H

A

I

A

S

L

V

W

I

I

I

G

S

T

A

I

L

V

I

V

A

V

T

S

L

Y

Y

T

T

L

L

L

V

G

G

F

L

L

Y

A

S

V

V

A

A

W

Y

T

T

D

D

F

V

V

V

Q

Q

G

L

S

F

L

C

M

I

F

F

L

V

A

G

L

L

-

W

I

I

V

S

V

V

P

P

I

F

V

A

-

L

-

S

-

H

-

P

A

A

I

V

N

A

E

D

M

I

G

G

G

-

W

-

N

F

T

T

A

A

V

V

Q

H

A

A

-

K

-

Y

-

Q

-

K

-

P

-

W

V

L

G

G

D

T

I

V

S

D

S

S

T

S

H

E

L

V

N

Y

M

S

V

W

E

L

G

D

V

S

S

F

I

L

A

L

I

M

I

L

S

G

L

I

A

P

W
|
W

G

Q

V

-

G

A

Y

Y

F

F

G

Q

Q

-

P

-

H

-

I

-

V

-

R

R

F

V

M

L

A

S

L

S

R

S

S

S

P

A

K

T

D

Y

V

A

P

Q

M

V

A

L

R

S

F

F

I

L

G

A

T

A

T

F

W

G

M

C

V

L

L

V

G

M

L

A

Y

I

G

P

A

A

I

I

F

L

T

I

G

G

F

A

V

I

G

G

L

A

A

S

F

T

I

D

S

W

T

N

Q

Q

E

T

V

A

S

Y

V

G

L

L

G

P

E

D

F

-

G

-

I

-

S

-

V

-

I

-

T

-

E

-

N

-

G

-

I

P

Q

K

M

T

L

T

E

E

D

E

P

A

E

D

K

M

I

I

F

L

I

P

A

I

F

V

S

L

Q

Q

L

Y

L

L

F

C

H

P

P

V

V

Y

I

I

A

S

G

F

I

F

L

G

L

L

A

G

A

A

I

V

L

S

S

A

A

A

I

V

M

M

S

S

T

S

I

A

D

D

S

S

Q

S

L

I

L

L

V

S

S

A

S

S

A

M

V

F

A

A

E

R

D

N

F

I

Y

Y

K

Q

A

L

I

S

F

F

K

R

K

Q

E

N

A

A

G

S

D

D

K

K

E

E

L

I

V

V

W

W

V

V

G

M

R

R

I

I

A

T

T

V

L

F

I

V

I

F

A

G

L

A

I

S

A

A

A

T

L

A

I

M

A

A

M

L

N

L

P

T

E

K

S

-

T

T

V

V

L

Y

E

G

L

L

V

W

S
x
Y

Y

L

A

S

W
x
S

A

D

G

L

F

V

G

Y

A

I

A

V

F

I

G

F

P

P

T

Q

I

L

L

L

L

C

A

V

L

L

F

F

W

V

K

K

G

G

F

T

T

N

R

T

N

Y

G

G

A

A

F

V

A

A

G

G

I

Y

L

V

A

S

G

G

binding (2S,2'S)-2,2'-biphenyl-4,4'-diylbis(2-hydroxy-4,4-dimethylmorpholin-4-ium): W59 (≠ D53), Y77 (≠ L71), Y88 (≠ L80), W138 (≠ F135), W251 (= W242), Y404 (≠ S413), S407 (≠ W416)

3dh4A Crystal structure of sodium/sugar symporter with bound galactose from vibrio parahaemolyticus (see paper)
25% identity, 78% coverage: 51:447/506 of query aligns to 33:427/512 of 3dh4A

query
sites
3dh4A

A

A

S

A

D

N

M
x
I

S

S

G

A

W

E

L
x
Q

L

F

L

I

G

G

L

M

P

S

G

G

A

S

V

G

Y

Y

A

S

A

I

G

G

L

L

A

A

E

I

A

A

-

S

-
x
Y

-
x
E

W

W

M

M

-
x
S

A

A

I

I

G

T

L

L

S

I

I

I

-

V

G

G

A

K

Y

Y

L

F

N

L

W

P

Q

I

F

F

V

I

A

E

K

K

R

G

L

I

R

Y

I

-

Y

-

T

-

E

-

V

-

S

-

N

-

S

-

I

-

T

T

V

I

P

P

D

E

F

F

L

V

E

E

N

K

R

R

F

F

K

-

D

-

N

N

S

K

H

K

I

L

L

K

R

T

V

I

I

L

S

A

A

V

L

F

V

W

I

I

L

S

L

L

F

Y

F

I

T

F

F

V

Y

N

T

L

S

T

S

S

G

V

M

L

V

Y

A

L

G

G

A

G

K

L

L

A

F

L

E

E

A

T

S

I

F

L

G

G

L

I

D

P

Y

L

Q

M

A

Y

A

S

L

I

W

L

I

G

G

L

T

A

I

L

V

F

V

A

V

L

S

V

Y

Y

T

S

L

I

L

-

G

-

F

-

L

-

A

-

V

V

A

V

W

W

T

T

D

D

F

V

V

I

Q

Q

G

V

S

F

L

F

M

L

F

V

L

L

A

G

L

G

I

F

V

M

V

T

P

T

I

Y

V

M

A

A

I

V

N

S

E

F

M

I

G

G

-

T

-

D

-

G

W

W

N

F

T

A

A

G

V

V

Q

S

A

K

V

M

G

V

D

D

I

A

S

A

S

P

T

G

H

H

L

F

N

E

M

M

V

I

-

L

-

D

-

Q

-

S

-

N

-

P

-

Q

-

Y

-

M

-

N

-

L

E

P

G

G

V

I

S

A

I

V

I

L

A

I

-

G

-

L

-

W

I

V

I

A

S
x
N

S

L

L

Y

A

Y

W
|
W

G

G

V

-

G

-

Y

-

F

F

G

N

Q

Q

P

-

H

Y

I

I

V

Q

R

R

F

T

M

L

A

A

L

A

R

K

S

S

P

V

K

S

D

E

V

A

P

Q

M

K

A

G

R

I

F

V

I

F

G

A

T

A

T

F

W

L

M
x
K

V

L

L

I

G

V

L

P

Y

F

G

L

A

V

I

V

F

L

T

P

G

G

F

I

V

A

G

-

L

-

A

A

F

Y

I

V

S

I

T

T

Q

S

E

D

V

P

S

Q

V

L

L

M

G

A

E

S

F

L

G

G

I

-

S

-

V

D

I

I

T

A

E

A

N

T

G

N

I

L

Q

P

M

S

L

A

E

A

D

N

P

A

E

D

K

K

I

A

F

Y

I

P

A

W

F

L

S

T

Q

Q

L

-

F

F

H

L

P

P

V

V

-

G

I

V

A

K

G

G

I

V

L

V

L

F

A

A

I

L

L

A

S

A

A
|
A

I

I

M

V

S
|
S

T

S

I

L

D

A

S

S

Q

M

L

L

L

N

V

S

S

T

S

A

S

T

A

I

V

F

A

T

E

M

D

D

F

I

Y

Y

K

K

A

E

I

Y

F

I

K

S

K

P

E

D

A

S

G

G

D

D

K

H

E

K

L

L

V

V

W

N

V

V

G

G

R

R

I

T

A

A

T

A

L

V

I

V

I

A

A

L

L

I

I

I

A

A

A

C

L

L

I

I

A

A

M

P

-

M

-

L

-

G

-

I

-

G

N

Q

P

A

E

F

S

Q

T

Y

V

I

L
x
Q

E

E

L

Y

V

T

S

G

Y

L

A

V

W

S

A

P

G

G

F

I

G

L

A

A

A

V

F

F

G

-

P

-

T

-

I

-

L

L

A

G

L

L

F

F

W

W

K

K

G

K

F

T

T

T

R

S

N

K

G

G

A

A

F

I

A

I

G

G

I

V

L

V

A

A

binding beta-D-galactopyranose: Q40 (≠ L58), Y58 (vs. gap), E59 (vs. gap), S62 (vs. gap), N225 (≠ S238), W229 (= W242), K259 (≠ M276), Q393 (≠ L409)
binding sodium ion: I36 (≠ M54), A326 (= A348), S329 (= S351)

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
21% identity, 88% coverage: 4:448/506 of query aligns to 27:492/659 of Q9NY91

query
sites
Q9NY91

A

A

T

D

L

I

I

S

A

V

F

I

I

V

V

I

Y

Y

L

F

I

L

G

V

I

V

L

M

V

A

I

V

G

G

I

L

I

W

M

A

Y

M

R

L

M

K

T

T

N

N

N

R

-

G

-

T

L

I

S

G

D

G

Y

F

V

F

L

L

G

A

G

G

R

R

K

D

L

M

G

A

P

W

G

W

V

P

A

M

A

G

L

A

S

S

A

L

G

F

A

A

S

S

D

N

M

I

S

G

G

S

W

N

L

H

L

Y

L

V

G

G

L

L

P

A

G

G

A

T

V

G

Y

A

A

A

A

S

G

G

L

V

A

A

E

T

A

V

W

T

M

F

A

E

I

W

G

T

L

S

S

S

I

V

G

M

A

L

Y

L

-

I

L

L

N

G

W

W

Q

I

F

F

V

V

A

P

K

-

R

-

L

-

R

-

I

I

Y

Y

T

-

E

-

V

I

S

K

N

S

N

G

S

V

I

M

T

T

V

M

P

P

D

E

F

Y

L

L

E

K

N

K

R

R

F

F

K

-

D

G

N

G

S

E

H

R

I

L

L

Q

R

V

V

Y

I

L

S

S

A

I

L

L

V

S

I

L

L

F

L

I

F

C

F

V

T

V

F

L

Y

L

T

I

S

S

S

A

G

D

M

I

V

F

A

A

G

G

A

A

K

I

L

F

F

I

E

K

A

L

S

A

F

L

G

G

L

L

D

D

Y

L

Q

Y

A

L

A

A

L

I

W

F

I

I

G

L

T

L

I

A

V

M

V

T

V

A

S

V

Y

Y

T

T

L

T

G

G

F

L

L

A

A

S

V

V

A

I

W

Y

T

T

D

D

F

T

V

L

Q

Q

G

T

S

I

L

I

M

M

F

L

L

I

A

G

L

S

I

F

V

I

V

L

P

M

I

G

V

F

A

A

I

F

N

N

E

E

M

V

G

G

W

Y

N

E

T

S

A

F

V

T

Q

E

A

K

V

Y

G

V

D

N

I

A

S

T

S

P

T

S

H

-

L

-

N

-

M

V

V

V

E

E

G

G

V

D

S

N

I

L

I

T

-

I

-

S

-

A

-

S

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C

-

Y

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T

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P

-

R

-

A

-

D

-

S

-

F

-

H

-

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-

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-

R

-

D

A

A

I

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I

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S

G

S

D

L

I

A

P

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W

G

P

V

G

G

I

Y

I

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F

G

G

Q

M

P

P

-

I

-

T

-

A

-

L

-

W

-

Y

-

W

-

C

-

T

-

N

-

Q

H

V

I

I

I

V

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Q

R

R

F

C

M

L

A

C

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V

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M

A

A

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F

M

T

P

G

G

F

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M

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P

E

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F

E

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V

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I

C

-

G

T

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E

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N

V

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T

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N

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Y

E

A

D

Y

P

P

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T

K

M

I

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F

L

I

E

A

L

F

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S

P

Q

Q

L

G

L

L

F

-

H

-

P

-

V

-

I

-

A

R

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L

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A

V

I

M

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L

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A

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I

L

D

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Q

I

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A

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A

L

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F

A

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E

I

D

D

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Y

Y

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A

K

I

M

F

-

K

R

K

K

E

Q

A

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S

D

E

K

K

E

E

L

L

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L

W

I

V

A

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G

R

R

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I

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F

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L

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L

A

T

L

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A

S

-

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-

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-

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A

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L

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A

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M

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N

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P

Q

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N

S

G

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Q

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L

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H

L

Y

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x
E

Y

S

A

I

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S

A

S

G

Y

F

L

G

G

A

P

F

I

G

A

P

A

T

V

I

F

L

V

L

L

A

A

L

I

F

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C

K

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G

E457 (≠ S413) mutation to Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

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)
26% identity, 71% coverage: 32:392/506 of query aligns to 46:393/643 of Q92911

query
sites
Q92911

D

D

Y

F

V

F

L

T

G

G

R

R

K

R

L

L

G

A

P

A

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A

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A

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A

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M

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V

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G

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A

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A

Y

Y

A

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A

Y

G

G

L

L

A

K

E

F

A

L

W

W

M

M

A

C

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L

G

G

L

Q

S

L

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L

G

N

A

S

Y

V

L

L

N

T

-
x
A

-

L

W

F

Q

M

F

P

V

V

A

F

K

Y

R

R

L

L

R

G

I

L

Y

T

T

S

E

T

V

Y

S

-

N

-

S

-

I

-

T

-

V

-

P

-

D

E

F

Y

L

L

E

E

N

M

R

R

F

F

K

-

D

-

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-

S

S

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A

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Y

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A

A

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A

A

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A

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G

G

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L

D

D

Y

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A

A

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A

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A

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D

D

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F

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Q

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-

Q

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A

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Q

A

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x
H

G

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H

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L

F

N

N

M

P

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x
D

E

P

G

R

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S

S

R

-
x
Y

-
x
T

-

F

-

W

I

T

I

F

A

V

I

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I

G

S

G

S

T

L

L

A

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W

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F

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G

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L

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S

A

A

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C

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L

F

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C

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D

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S

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G

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L

-

E

-

D

-

P

P

E

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F

L

I

D

A

I

F

F

S

E

Q

D

L

L

L

-

F

-

H

-

P

P

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G

I

V

A

P

G

G

I

L

L

F

L

L

A

A

A

C

I

A

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Y

S

S

A

G

I

T

M

L

S

S

T

T

I

A

D

S

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Q

S

L

I

L

N

V

A

S

M

S

A

A

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A

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E

E

D

D

F

L

Y

I

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K

A

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-

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P

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I

A102 (vs. gap) natural variant: A -> P
H226 (≠ V217) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
D237 (≠ V228) mutation to A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
Y242 (vs. gap) 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 (vs. gap) 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

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, 88% coverage: 4:448/506 of query aligns to 27:492/662 of P11170

query
sites
P11170

A

A

T

D

L

I

I

S

A

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F

I

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Y

L

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M

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T

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D

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G

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A

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G

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L

F

L

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G

G

L

L

P

A

G

G

A

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G

Y

A

A

A

A

S

G

G

L

I

A

A

E

T

A

G

-

G

-

F

-

E

W

W

M

N

A

A

I

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G

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S

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I

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-

A

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F

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F

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Y

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G

A

A

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x
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-

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-

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F

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D

Y

Y

A

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-

A
x
Q

G

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F

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G
x
T

A

S

A

Y

F

L

G

G

P

P

T

P

I

I

-

A

-

V

-

F

L

L

A

A

L

I

F

F

W

W

K

K

G

R

F

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N

R

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G

G

A

A

F

F

A

W

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G

C255 (≠ T223) modified: Disulfide link with 608
Q457 (≠ A417) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
T460 (≠ G420) mutation to W: Decreased affinity for glucose and phlorizin.

Sites not aligning to the query:

608 modified: Disulfide link with 255

8j77A Human high-affinity choline transporter cht1 in the choline-bound inward-facing occluded conformation (see paper)
26% identity, 88% coverage: 6:448/506 of query aligns to 6:418/493 of 8j77A

query
sites
8j77A

L

L

I

I

A

A

F

I

I

I

V

V

Y

F

L

Y

I

L

G

L

I

I

L

L

V

L

I

V

G

G

I

I

I

-

M

-

Y

-

R

-

M

-

T

-

N

-

L

-

S

-

D

-

Y

W

V

A

L

A

G

W

G

R

R

R

K

D

L

I

G

G

P

L

G

L

V

V

A

G

L

F

S

T

A

M

G

T

A

A

S

T

D
x
W

M

V

S

G

G

G

W

G

L

Y

L

I

L

N

G

G

L

T

P

A

G

E

A

A

V

V

Y

Y

A

V

A

P

G

G

L

Y

A

G

E

L

A

A

W

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binding choline ion: W42 (≠ D53), Y71 (≠ L80), W230 (= W242)

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)
25% identity, 93% coverage: 31:500/506 of query aligns to 43:487/610 of Q8N695

query
sites
Q8N695

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