SitesBLAST

D57 (= D38) mutation to A: Loss of transport activity.; mutation to E: Retains 50% of its transport activity.
R103 (= R91) mutation to A: Loss of transport activity.

Sites not aligning to the query:

54 D→A: Loss of transport activity.; D→E: Retains 50% of its transport activity.
309 W→V: Loss of transport activity.
312 D→A: Loss of transport activity.
313 R→A: Loss of transport activity.
317 mutation I->H,Y: Loss of transport activity.
386 R→A: Loss of transport activity.

A0A0H2VG78 Glucose transporter GlcP; Glucose/H(+) symporter from Staphylococcus epidermidis (strain ATCC 12228 / FDA PCI 1200) (see paper)
25% identity, 80% coverage: 86:460/469 of query aligns to 63:446/446 of A0A0H2VG78

query
sites
A0A0H2VG78

G

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x
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E

R102 (= R133) mutation to A: Loss of transport activity.
I105 (≠ Q136) mutation to S: Affects symport activity. May function as an uniporter.
E122 (= E153) mutation to A: Loss of transport activity.
Q137 (= Q168) mutation to A: Loss of transport activity.
Q250 (≠ T269) mutation to A: Loss of transport activity.
Q251 (≠ M270) mutation to A: Loss of transport activity.
N256 (vs. gap) mutation to A: Loss of transport activity.
W357 (vs. gap) mutation to A: Loss of transport activity.

Sites not aligning to the query:

22 D→N: Affects symport activity. May function as an uniporter.

8sc6A Human oct1 bound to thiamine in inward-open conformation (see paper)
23% identity, 77% coverage: 74:432/469 of query aligns to 140:447/447 of 8sc6A

query
sites
8sc6A

G

G

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A

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E

binding 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium: Q223 (= Q168), F226 (≠ A171), Y293 (= Y268), Q294 (≠ T269), E318 (≠ A293), I378 (≠ Y359), Q379 (≠ A360)

Q5EXK5 3-hydroxybenzoate transporter MhbT from Klebsiella oxytoca (see paper)
30% identity, 22% coverage: 86:186/469 of query aligns to 78:174/452 of Q5EXK5

query
sites
Q5EXK5

G

G

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D

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A

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-

F

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G

D82 (= D90) mutation to A: Loss of activity.

Sites not aligning to the query:

311 V→W: Loss of activity.
314 D→A: Loss of activity.

8sc3A Human oct1 bound to fenoterol in inward-open conformation (see paper)
23% identity, 77% coverage: 74:432/469 of query aligns to 140:445/445 of 8sc3A

query
sites
8sc3A

G

G

F

F

L

L

A

F

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L

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G

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-

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A

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M

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x
F

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V

-

A

A

V

V

L

L

G

G

I

L

V

L

S

A

A

A

V

G

S

V

L

T

F

L

A

L

L

L

P

P

E

E

binding Fenoterol: W199 (≠ Q144), M200 (≠ A145), Q223 (= Q168), F226 (≠ A171), W284 (≠ Q246), Y291 (= Y268), I376 (≠ Y359), C380 (≠ A363)

P77589 3-(3-hydroxy-phenyl)propionate transporter; 3HPP transporter; 3-(3-hydroxy-phenyl)propionate:H(+) symporter; 3HPP:H(+) symporter from Escherichia coli (strain K12) (see paper)
33% identity, 22% coverage: 71:174/469 of query aligns to 56:151/403 of P77589

query
sites
P77589

Y

F

A

S

V

A

G

G

F

I

L

L

A

G

R

L

P

L

L

P

G

G

G

A

I

L

V

V

F

G

G

G

H

M

F

L

G

A

D
|
D

R

R

V

Y

G

G

R

R

K

K

K

R

A

I

L

L

I

I

V

G

T

S

I

V

L

A

I

L

V

F

G

G

L

L

G

F

T

S

F

L

A

A

I

T

G

A

L

I

L

A

P

W

D

D

Y

F

Q

P

S

S

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

-

L

L

I

V

V

F

I

A

R

R

V

L

L

M

Q

T

G

G

F

V

G

G

V

L

G

G

G

A

E

A

Q

L

A

P

G

N

A

L

V

I

L

A

L

L

T

T

A

S

E

E

Y

A

A

A

P

G

P

P

A

R

R

F

R

R

G

G

F

T

F

A

A

V

S

S

L

L

V

M

Q

Y

L

C

G

G

A

V

P

P

A

I

G

G

D75 (= D90) mutation D->A,E: Lack of 3HPP transport activity.

Sites not aligning to the query:

27 E→A: Lack of 3HPP transport activity.; E→D: Slight decrease in 3HPP transport activity.
272 A→H: 30% increase in 3HPP transport activity.
276 K→D: Lack of 3HPP transport activity.

Q9Y7Q9 Probable metabolite transporter C2H8.02 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see paper)
29% identity, 33% coverage: 80:234/469 of query aligns to 98:259/583 of Q9Y7Q9

query
sites
Q9Y7Q9

L

M

G

G

G

Q

I

L

V

L

F

F

G

G

H

F

F

L

G

G

D

D

R

F

V

F

G

G

R

R

K

K

K

F

A

V

L

Y

I

G

V

K

T

E

I

M

L

M

I

V

V

V

G

I

L

I

G

A

T

T

F

I

A

L

I

I

G

I

L

C

L

L

P

P

D

D

Y

R

Q

I

S

P

I

T

G

P

I

T

W

A

A

K

P

M

I

M

A

W

L

L

I

F

V

A

I

F

R

R

V

V

L

M

Q

L

G

G

F

I

G

G

V

I

G

G

E

D

Q

Y

A

P

G

M

A

S

V

A

L

S

L

I

T

T

A

S

E

E

Y

Q

A

S

P

L

P

I

A

N

R

R

G

G

F

-

A

A

S

L

L

L

V

A

Q

W

L

I

G

F

A

S

P

N

A

Q

G

G

F

W

L

G

I

T

P

L

S

A

G

G

L

C

F

V

A

A

-

T

L

L

L

I

G

I

A

L

T

A

L

C

T

F

Q

E

A

K

Q

P

L

L

L

N

D

D

W

R

G

G

-

E

-

Y

-

T

-

K

-

L

-

N

-

G

-

V

W

W

R

R

I

I

P

Q

F

F

L

G

A

I

S

A

A

L

L

F

L

P

V

A

A

V

V

I

G

V

L

L

Y

I

I

P

R

R

L

L

R

R

T

M

E

Q

E

E

S

S

P

E

I

Q

F

F

A

K

T

N

I

S

Q

K

R

N

T

M

K

K

A

S

Sites not aligning to the query:

267 modified: Phosphoserine
269 modified: Phosphoserine
289 modified: Phosphoserine
290 modified: Phosphoserine
292 modified: Phosphoserine
330 modified: Phosphoserine

8et9A Cryo-em structure of the organic cation transporter 2 in complex with 1-methyl-4-phenylpyridinium (see paper)
22% identity, 84% coverage: 38:433/469 of query aligns to 122:500/517 of 8et9A

query
sites
8et9A

D

D

F

G

F

W

V

V

Y

Y

G

D

T

T

A

P

A

G

V

S

L

S

V

I

F

V

G

T

Q

E

K

F

F

N

F

L

P

V

S

C

A

A

D

D

P

S

L

W

I

M

G

L

T

D

L

L

A

V

A

Q

F

-

A

A

T

A

Y

V

A

N

V

V

G

G

F

F

L

F

A

-

R

-

P

-

L

V

G

G

G

S

I

M

V

S

F

I

G

G

H

Y

F

I

G

A

D

D

R

R

V

F

G

G

R

R

K

K

K

L

A

C

L

L

I

L

V

V

T

T

I

I

L

L

I

I

V

N

G

A

L

I

G

S

T

G

F

V

A

L

I

M

G

A

L

V

L

A

P

P

D

N

Y

Y

Q

T

S

-

I

-

G

-

I

-

W

W

A

-

P

-

I

-

A

-

L

M

I

L

V

I

I

F

R

R

V

L

L

I

Q

Q

G

G

F

L

G

V

V

S

G

K

G

G

E

G

Q
x
W

A

L

G

I

A

G

V

Y

L

T

L

L

T

P

A

T

E

E

Y

F

A

V

P

G

P

L

A

E

R

Y

R

R

G

R

F

T

F

V

A

G

S

I

L

L

V

Y

Q
|
Q

L

M

G

A

A
x
F

P

S

A

V

G

G

F

L

L

L

-

V

-

L

-

A

-

G

-

V

-

A

-

Y

-

A

I

I

P

P

S

H

G

W

L

R

F

W

A

L

L

Q

L

L

G

A

A

V

T

T

L

L

T

P

Q

N

A

F

Q

F

L

F

L

L

D

L

W

Y

G

Y

W

W

R

C

I

I

P

P

F

-

L

-

A

-

S

-

A

-

L

-

V

-

A

-

V

-

G

-

L

-

Y

-

I

-

R

-

L

-

R

-

T

-

E

-

E

E

S

S

P

P

I

R

F

W

A

L

T

I

I

S

Q

Q

R

N

T

K

K

N

A

A

V

K

A

A

S

M

R

K

P

I

V

I

V

K

E

H

V

I

V

A

R

K

Q

K

F

N

G

G

P

K

T

K

I

L

V

P

K

K

G

S

V

E

G

K

A

L

K

N

-

P

-

S

-

F

-

L

-

D

L

L

I

V

E

R

A

T

C

P

A

Q

F

I

A

R

M

K

Y

H

T

T

M

L

I

I

V

L

L

M

-

Y

A

N

Y

W

G

F

K

T

A

S

H

S

G

V

I

L

A

Y

Q

Q

G

G

M

L

L

I

L

M

E

H

T

M

V

G

I

I

V

A

A

G

-

G

-

N

V

I

A

Y

L

L

E

D

-

F

-

Y

-

S

-

A

L

L

V

V

T

E

I

F

P

P

L

A

A

A

G

F

A

I

L

I

-

I

-

L

-

T

S

I

D

D

R

R

I

I

G

G

R

R

T

Y

T

P

F

W

-

A

I

A

A

N

G

M

A

V

L

A

L

G

H

A

V

A

A

C

L

L

V

I

V

T

P

A

F

F

F

L

M

F

A

W

I

L

D

K

S

T

G

T

N

V

R

A

A

C

A

L

I

G

Q

R

L

M

V

G

M

I

I

T

L

M

A

A

I
x
F

S

E

V

M

G

-

H

-

S

-

L

V

C

C

Y

F

A

V

P

N

Q

T

A

-

L

-

F

-

P

-

E

E

L

L

F

Y

P

P

A

T

R

F

V

I

R

R

C

N

S

L

G

G

I

V

A

L

L

V

-

C

-

S

I

L

W

C

Q

D

I

I

G

G

S

G

L

I

G

T

S

P

G

F

V

L

L

V

G

Y

L

R

L

L

A

A

V

S

K

I

L

W

I

L

Q

E

L

L

T

P

H

-

G

-

N

-

S

-

L

-

A

-

L

-

I

L

V

V

Y

V

V

F

A

A

V

V

L

L

G

G

I

L

V

I

S

A

A

G

V

G

S

L

L

V

F

L

A

L

L

L

P

P

E

E

T

T

binding 1-methyl-4-phenylpyridin-1-ium: W216 (≠ Q144), Q240 (= Q168), F243 (≠ A171), F430 (≠ I351)

O08966 Solute carrier family 22 member 1; Organic cation transporter 1; mOCT1 from Mus musculus (Mouse) (see paper)
28% identity, 26% coverage: 80:202/469 of query aligns to 162:284/556 of O08966

query
sites
O08966

L

L

G

G

G

S

I

L

V

V

F

V

G

G

H

Y

F

I

G

A

D

D

R

R

V

F

G

G

R

R

K

K

K

L

A

C

L

L

I

L

V

V

T

T

I

T

L

L

I

V

V

T

G

S

L

L

G

S

T

G

F

V

A

L

I

T

G

A

L

V

L

A

P

P

D

D

Y

Y

Q

T

S

S

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

-

L

M

I

L

V

L

I

F

R

R

V

L

L

L

Q

Q

G

G

F

M

G

V

V

S

G

K

G

G

E

S

Q

W

A

V

G

S

A

G

V

Y

L

T

L

L

T

I

A

T

E

E

Y

F

A

V

P

G

P

S

A

G

R

Y

R

R

G

R

F

T

A

A

S

I

L

L

V

Y

Q

Q

L

V

G

A

A

F

P

T

A

V

G

G

-

L

-

V

-

G

-

L

-

A

-

G

-

V

-

A

F

Y

L

A

I

I

P

P

S

D

G

W

L

R

F

W

A

L

L

Q

L

L

G

A

A

V

T

S

L

L

T

P

Q

T

A

F

Q

L

L

F

L

L

D

L

W

Y

G

Y

W

W

R

F

I

V

P

P

Sites not aligning to the query:

32 L→F: Increased trospium uptake. Increased trospium affinity. No change in fenoterol uptake.
36 Y→C: Decreased fenoterol uptake. Decreased fenoterol affinity. No change in trospium uptake. No change in terbutaline affinity.

8sc2A Human oct1 bound to diltiazem in inward-open conformation (see paper)
23% identity, 69% coverage: 74:398/469 of query aligns to 140:445/453 of 8sc2A

query
sites
8sc2A

G

G

F

F

L

L

A

F

R

G

P

S

L

L

G

G

G

-

I

-

V

-

F

V

G

G

H

Y

F

F

G

A

D

D

R

R

V

F

G

G

R

R

K

K

K

L

A

C

L

L

I

L

V

G

T

T

I

V

L

L

I

V

V

N

G

A

L

V

G

S

T

G

F

V

A

L

I

M

G

A

L

F

L

S

P

P

D

N

Y

Y

Q

M

S

S

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

-

L

M

I

L

V

L

I

F

R

R

V

L

L

L

Q

Q

G

G

F

L

G

V

V

S

G

K

G

G

E

N

Q
x
W

A

M

G

A

A

G

V

Y

L

T

L

L

T

I

A

T

E

E

Y

F

A

V

P

G

P

S

A

G

R

S

R

R

G

R

F

T

F

V

A

A

S

I

L

M

V

Y

Q
|
Q

L

M

G

A

A
x
F

P

T

A

V

G

G

F

L

L

V

I

A

P

L

S

T

G

G

L

L

-

A

F

Y

A

A

L

L

-

P

-

H

-

W

-

R

-

W

-

L

-

Q

L

L

G

A

A

V

T

S

L

L

T

P

Q

T

A

F

Q

L

L

F

L

L

D

L

W

Y

G

Y

W

W

R

C

I

V

P

P

F

-

L

-

A

-

S

-

A

-

L

-

V

-

A

-

V

-

G

-

L

-

Y

-

I

-

R

-

L

-

R

E

T

S

E

P

E

R

S

S

P

P

I

S

F

F

A

A

T

D

I

L

Q

F

R

R

T

T

K

P

A

R

V

L

A

R

S

K

R

R

P

T

V

F

V

I

E

L

V

M

V

Y

R

L

Q
x
W

F

F

G

T

P

D

T
x
S

I

V

V

-

K

-

G

-

V

-

G

-

A

-

K

-

L

-

I

-

E

-

A

-

C

-

A

-

F

-

A

-

M

L

Y

Y

T

Q

M

G

I

L

V

I

L

L

A

H

Y

M

G

G

K

A

A

T

H

S

G

G

I

N

A

L

Q

Y

G

L

M

D

L

F

L

L

E

Y

T

S

V

A

I

L

V

V

A

E

V

I

A

P

-

G

-

A

-

F

L

I

E

A

L

L

V

I

T

T

I

I

P

-

L

-

A

-

G

-

A

-

L

-

S

-

D

D

R

R

I

V

G

G

R

R

-

I

-

Y

-

P

-

M

-

A

R

M

T

S

T

N

F

L

I

L

A

A

G

G

A

A

L

-

H

-

V

-

A

A

L

C

V

L

V

V

P

M

F

I

F

F

M

I

A

S

I

P

D

D

S

-

G

-

N

-

R

L

A

H

A

W

I

L

Q

N

L

I

V

I

M

I

I

M

L

C

A

V

I

G

S

R

V

M

G

G

H

I

S

T

L

I

C

A

Y
x
I

A

Q

P

M

Q

I

A

C

A

L

L

V

F

N

P

A

E

E

L

L

F

Y

P

P

A

T

R

F

V

V

R

R

-

N

-

L

-

G

-

V

-

M

-

V

C

C

S

S

G

S

I

L

A

C

L

D

I

I

-

G

-

I

-

T

-

P

-

F

-

I

-

V

-

F

-

R

-

L

-

R

-

E

-

V

W

W

Q

Q

I

A

G

L

S

P

L

L

L

I

G

L

S

F

G

A

V

V

L

L

G

G

L

L

A

A

binding Diltiazem: W199 (≠ Q144), Q223 (= Q168), F226 (≠ A171), W293 (≠ Q246), S297 (≠ T250), I385 (≠ Y359)

Sites not aligning to the query:

binding Diltiazem: 18

Q63089 Solute carrier family 22 member 1; Organic cation transporter 1; rOCT1 from Rattus norvegicus (Rat) (see 4 papers)
27% identity, 36% coverage: 80:248/469 of query aligns to 162:311/556 of Q63089

query
sites
Q63089

L

L

G

G

G

S

I

L

V

V

F

V

G

G

H

Y

F

I

G

A

D

D

R

R

V

F

G

G

R

R

K

K

K

L

A
x
C

L

L

I

L

V

V

T

T

I

T

L

L

I

V

V

T

G

S

L

V

G

S

T

G

F

V

A

L

I

T

G

A

L

V

L

A

P

P

D

D

Y

Y

Q

T

S

S

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

-

L

M

I

L

V

L

I

F

R

R

V

L

L

L

Q

Q

G

G

F
x
M

G
x
V

V
x
S

G
x
K

G
|
G

E
x
S

Q
x
W

A
x
V

G
x
S

A
x
G

V
x
Y

L
x
T

L
|
L

T
x
I

A
x
T

E
|
E

Y
x
F

A
x
V

P

G

P

S

A

G

R

Y

R

R

G

R

F

T

A

A

S

I

L

L

V

Y

Q

Q

L

M

G

A

A

F

P

T

A

V

G

G

F

-

L

-

I

-

P

-

S

-

G

-

L

-

F

-

A

-

L

L

L

V

G

G

A

L

T

A

L

G

T

V

Q

A

A

Y

Q

A

L

I

L

P

D

D

W

W

G

R

W

W

R

L

I

Q

P

-

F

-

L

L

A

A

S

V

A

S

L

L

L

P

V

T

A

F

V

L

G

F

L

L

Y

L

I

Y

R

Y

L

W

R

F

T

V

E

P

E

E

S
|
S

P

P

I

R

F

W

A

L

T

L

I
x
S

Q

Q

R

K

T

R

K
x
T

A

T

V

R

A

A

S

V

R

R

P

I

V

M

V

E

E

Q

V

I

V

A

R

Q

Q

K

F

N

G

G

C179 (≠ A97) mutation to A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; S-322; A-358; A-418; S-437; A-470 and A-474.
M212 (≠ F138) mutation to L: No change in TEA and MPP(+) uptake.
V213 (≠ G139) mutation to G: Decreased TEA uptake. No change in MPP(+) uptake.
S214 (≠ V140) mutation to G: Decreased TEA and MPP(+) uptake.
K215 (≠ G141) mutation to Q: Loss of TEA and MPP(+) uptake activity.; mutation to R: Loss of TEA and MPP(+) uptake activity.
G216 (= G142) mutation to A: Decreased TEA and MPP(+) uptake.
S217 (≠ E143) mutation to G: No change in TEA and MPP(+) uptake.
W218 (≠ Q144) mutation to F: Decreased guanidine, histamine, serotonin and TEA uptake. No change in MPP(+) uptake. No change in TEA and MPP(+) affinity. Decreased TEA Vmax. No change in MPP(+) Vmax.; mutation to L: Decreased guanidine, histamine, serotonin, TEA and MPP(+) uptake. Decreased TEA affinity. No change in MPP(+) affinity. Decreased TEA and MPP(+) Vmax.; mutation to Y: Decreased guanidine, histamine, serotonin and TEA uptake. No change in MPP(+) uptake. Increased TEA and MPP(+) affinity. Decreased TEA and MPP(+) Vmax.
V219 (≠ A145) mutation to L: No change in TEA and MPP(+) uptake.
S220 (≠ G146) mutation to I: Decreased TEA and MPP(+) uptake.
G221 (≠ A147) mutation to A: Decreased TEA and MPP(+) uptake.
Y222 (≠ V148) mutation to F: No change in guanidine, histamine, serotonin, TEA and MPP(+) uptake. Increased TEA affinity. No change in MPP(+) affinity. Decreased TEA Vmax. No change in MPP(+) Vmax.; mutation to L: Decreased guanidine, serotonin, TEA and MPP(+) uptake. No change in histamine uptake. Increased TEA and MPP(+) affinity. Decreased TEA and MPP(+) Vmax.
T223 (≠ L149) mutation to I: Decreased TEA uptake. No change in MPP(+) uptake.
L224 (= L150) mutation to V: Decreased TEA and MPP(+) uptake.
I225 (≠ T151) mutation to G: No change in TEA and MPP(+) uptake.
T226 (≠ A152) mutation to A: Decreased TEA uptake. No change in MPP(+) uptake.
E227 (= E153) mutation to D: Loss of TEA and MPP(+) uptake activity.; mutation to Q: Loss of TEA and MPP(+) uptake activity.
F228 (≠ Y154) mutation to I: No change in TEA and MPP(+) uptake.
V229 (≠ A155) mutation to A: Decreased TEA and MPP(+) uptake.; mutation to L: Loss of TEA and MPP(+) uptake activity.
S286 (= S223) mutation to A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-292; A-296; A-328 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-292; A-296; A-328 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-292; A-296; A-328 and A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-292; A-296; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-292; A-296; A-328 and A-550.
S292 (≠ I229) mutation to A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-296; A-328 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-286; A-296; A-328 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-296; A-328 and A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-296; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-296; A-328 and A-550.
T296 (≠ K233) mutation to A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-328; A-550. Significant increase of the ASP uptake by PKA activation. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-328; A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-328; A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-292; A-328 and A-550.

Sites not aligning to the query:

26 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-155; A-179; S-322; A-358; A-418; S-437; A-470 and A-474.
155 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-179; S-322; A-358; A-418; S-437; A-470 and A-474.
322 C→S: Reduces the activation by MMTS. Abolishes the activation by MMTs; when associated with M-451. Choline affinity is increased fivefold by MMTS. Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; A-358; A-418; S-437; A-470 and A-474. Choline affinity is increased four- to fivefold; when associated with M-451.
328 S→A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-296 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-296 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-296; A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-296 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-292; A-296 and A-550.
358 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-418; S-437; A-470 and A-474.
418 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; S-437; A-470 and A-474.
437 C→S: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-470 and A-474.
451 C→M: Reduces the activation by MMTS. Abolishes the activation by MMTs; when associated with S-322. Abolishes the effect of MMTs on choline-induced currents. Choline affinity is not influenced by MMTS. Choline affinity is increased four- to fivefold; when associated with S-322.
470 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-437 and A-474.
474 C→A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-437 and A-470.
475 D→E: Decreased MPP(+) uptake, no change in MPP(+) affinity. Decreased NMN uptake, increased NMN affinity. Decreased choline uptake, increased choline affinity.; D→N: Decreased MPP(+) uptake.; D→R: Decreased MPP(+) uptake.
550 T→A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-296; A-328. Significant increase of the ASP uptake by PKA activation. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-296 and A-328. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-296; A-328. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-296 and A-328. suppresses phosphorylation by PKC; when associated with A-286; A-292; A-296 and A-328.

Q8MJI6 Solute carrier family 22 member 2; Organic cation transporter 2 from Oryctolagus cuniculus (Rabbit) (see paper)
24% identity, 77% coverage: 73:433/469 of query aligns to 157:516/554 of Q8MJI6

query
sites
Q8MJI6

V

I

G

G

F

F

L

F

A

-

R

-

P

-

L

I

G

G

G

S

I

V

V

G

F

I

G

G

H

Y

F

L

G

A

D

D

R

R

V

F

G

G

R

R

K

K

K

L

A

C

L

L

I

L

V

V

T

T

I

I

L

L

I

I

V

N

G

A

L

A

G

A

T

G

F

V

A

L

I

M

G

A

L

V

L

S

P

P

D

N

Y

Y

Q

T

S

-

I

-

G

-

I

-

W

W

A

-

P

-

I

-

A

-

L

M

I

L

V

I

I

F

R

R

V

L

L

I

Q

Q

G

G

F

L

-

V

G

S

V

K

G

A

G

G

E

W

Q

L

A

I

G

G

A

Y

V

I

L

L

L

I

T

T

A

-

E

E

Y

F

A

V

P

G

P

L

A

N

R

Y

R

R

G

R

F

T

F

V

A

G

S

I

L

L

V

Y

Q

Q

L

V

G

A

A

F

P

T

A

V

G

G

F

L

L

L

I

V

P

L

S

A

G

G

L

V

-

A

F

Y

A

A

L

L

-

P

-

R

-

W

-

R

-

W

-

L

-

Q

L

L

G

T

A

V

T

T

L

L

T

P

Q

Y

A

F

Q

C

L

F

L

L

D

L

W

Y

G

Y

W

W

R

C

I

I

P

P

F

-

L

-

A

-

S

-

A

-

L

-

V

-

A

-

V

-

G

-

L

-

Y

-

I

-

R

-

L

-

R

-

T

-

E

-

E

E

S

S

P

P

I

R

F

W

A

L

T

I

I

S

Q

Q

R

N

T

K

K

N

A

A

V

K

A

A

S

M

R

R

P

I

V

M

V

E

E

H

V

I

V

A

R

K

Q

K

F

N

G

G

P

K

T

S

I

L

-

P

-

V

-

S

-

L

-

Q

-

S

-

L

-

R

-

A

V

A

K

E

G

D

V

V

G

G

A

E

K

K

L

L

-

N

-

P

-

S

-

F

-

L

-

D

-

L

-

V

-

R

-

T

-

P

-

Q

-

I

-

R

I

K

E

H

A

T

C

C

-

I

-

L

A

M

F

Y

A

N

M

W

Y

F

T

T

M

S

I

S

V

V

L

L

A

Y

Y

Q

G

G

-

L

-

I

K

M

A

H

H

L

G

G

I

L

A

A

Q

G

G

G

M

D

L

I

L

Y

E

L

T

D

V

F

I

F

V

Y

A

S

V

A

A

L

L

V

E

E

L

F

V

P

T

A

I

A

P

F

L

L

A

I

G

I

A

A

L

T

S

I

D

D

R

R

I

V

G

G

R

R

-

Y

-

P

-

W

-

A

-

V

T

S

T

N

F

M

I

V

A

A

G

G

A

A

L

A

L

C

H

L

V

A

A

S

L

V

V

F

V

V

P

P

F

D

M

L

A

-

I

-

D

-

S

Q

G

G

N

L

R

R

A

I

A

T

I

V

Q

A

L

C

V

L

M

G

I

R

L

M

A

G

I

I

S

T

V

M

G

A

H

Y

S

E

L

M

C

V

Y

C

A

L

P

V

Q

N

A

A

A

-

L

-

F

-

P

-

E

E

L

L

F

Y

P

P

A

T

R

F

V

I

R

R

C

N

S

L

G

G

I

V

A

L

L

V

I

C

W

S

Q

S

I

L

G

C

S

D

L

-

L

V

G

G

S

G

G

I

V

V

L

T

G

P

L

F

L

L

A

V

V

Y

K

R

L

L

I

T

Q

A

L

I

T

W

H

L

G

-

N

-

S

Q

L

L

A

P

L

L

I

V

V

V

Y

F

V

-

A

A

V

V

L

V

G

G

I

L

V

V

S

A

A

G

V

G

S

L

L

V

F

L

A

M

L

L

P

P

E

E

T

T

Sites not aligning to the query:

71 N→Q: Higher affinity for TEA. Loss of plasma membrane localization; when associated with Q-76. Loss of plasma membrane localization; when associated with Q-112. Loss of plasma membrane localization; when associated with Q-76 and Q-112.
96 N→Q: Higher affinity for TEA and lower Vmax.
112 N→Q: Higher affinity for TEA, lower Vmax and loss of plasma membrane localization.

8bvsA Cryo-em structure of rat slc22a6 bound to tenofovir (see paper)
27% identity, 29% coverage: 49:186/469 of query aligns to 92:221/502 of 8bvsA

query
sites
8bvsA

V

V

F

Y

G

D

Q

N

K

S

F

T

F

F

P

P

S

S

A

T

D

I

-

V

-

T

-

E

-

W

P

N

L

L

I

V

G

C

T

S

L

H

A

R

A

A

F

F

-

R

-

Q

-

L

-

A

-

Q

A

S

T

L

Y

Y

A

M

V

V

G

G

F

V

L

L

A

-

R

-

P

-

L

L

G

G

G

A

I

M

V

V

F

F

G

G

H

Y

F

L

G

A

D

D

R

R

V

L

G

G

R

R

K

R

K

K

A

V

L

L

I

I

V

L

T

N

I

Y

L

L

I

Q

V

T

G

A

L

V

G

S

T

G

F

T

A

C

I

A

G

A

L

Y

L

A

P

P

D

N

Y

Y

Q

T

S

-

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

V

L

Y

I

C

V

V

I

F

R

R

V

L

L

L

Q

S

G

G

F

M

G

S

V

L

G

A

G

S

E

I

Q

A

A

I

G

N

A

C

V

M

L

T

L

L

T

N

A

V

E

E

Y

W

A

M

P

P

P

I

A

H

R

T

R

R

G

A

F

Y

F

V

A

G

S

T

L

L

V

I

Q

-

L

-

G

-

A

-

P

-

A

-

G

G

F

Y

L

V

I
x
Y

P

S

S

L

G

G

L

Q

F

F

A

L

L

L

L

A

G

G

binding [2-(6-amino-9h-purin-9-yl)-1-methylethoxy]methylphosphonic acid: Y212 (≠ I177)

Sites not aligning to the query:

binding [2-(6-amino-9h-purin-9-yl)-1-methylethoxy]methylphosphonic acid: 330

8bvtA Cryo-em structure of rat slc22a6 bound to probenecid (see paper)
28% identity, 25% coverage: 71:186/469 of query aligns to 132:230/508 of 8bvtA

query
sites
8bvtA

Y

Y

A

M

V

V

G

G

F

V

L

L

A

-

R

-

P

-

L

L

G

G

G

A

I

M

V

V

F

F

G

G

H

Y

F

L

G

A

D

D

R

R

V

L

G

G

R

R

K

R

K

K

A

V

L

L

I

I

V

L

T

N

I

Y

L

L

I

Q

V

T

G

A

L

V

G

S

T

G

F

T

A

C

I

A

G

A

L

Y

L

A

P

P

D

N

Y

Y

Q

T

S

-

I

-

G

-

I

-

W

-

A

-

P

-

I

-

A

V

L

Y

I

C

V

V

I

F

R

R

V

L

L

L

Q

S

G

G

F

M

G

S

V

L

G

A

G

S

E

I

Q

A

A

I

G

N

A

C

V
x
M

L

T

L

L

T

N

A

V

E

E

Y

W

A

M

P

P

P

I

A

H

R

T

R

R

G

A

F

Y

F

V

A

G

S

T

L

L

V
x
I

Q

-

L

-

G

-

A

-

P

-

A

-

G

G

F

Y

L

V

I
x
Y

P

S

S

L

G

G

L

Q

F

F

A

L

L

L

L

A

G

G

binding 4-(dipropylsulfamoyl)benzoic acid: M198 (≠ V148), I217 (≠ V167), Y221 (≠ I177)

Sites not aligning to the query:

binding 4-(dipropylsulfamoyl)benzoic acid: 31, 35, 339

8bw7A Cryo-em structure of rat slc22a6 bound to alpha-ketoglutaric acid (see paper)
27% identity, 29% coverage: 49:186/469 of query aligns to 92:221/497 of 8bw7A

query
sites
8bw7A

V

V

F

Y

G

D

Q

N

K

S

F

T

F

F

P

P

S

S

A

T

D

I

-

V

-

T

-

E

-

W

P

N

L

L

I

V

G

C

T

S

L

H

A

R

A

A

F

F

-

R

-

Q

-

L

-

A

-

Q

A

S

T

L

Y

Y

A

M

V

V

G

G

F

V

L

L

A

-

R

-

P

-

L

L

G

G

G

A

I

M

V

V

F

F

G

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binding 2-oxoglutaric acid: G209 (= G174), Y212 (≠ I177)

Sites not aligning to the query:

binding 2-oxoglutaric acid: 354

O15245 Solute carrier family 22 member 1; Organic cation transporter 1; hOCT1 from Homo sapiens (Human) (see 10 papers)
22% identity, 77% coverage: 74:433/469 of query aligns to 158:516/554 of O15245

query
sites
O15245

G

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L160 (= L76) to F: no changes in both MPP(+) and TEA uptake; abolishes MPP(+) uptake when associated with S-401; largely localized to the plasma membrane; dbSNP:rs683369
S189 (≠ G108) to L: no changes in MPP(+) uptake; dbSNP:rs34104736
G220 (≠ A147) to V: affects transporter activity; reduction of MPP(+) uptake when associated with V-408; dbSNP:rs36103319
Y240 (≠ V167) mutation to F: Decreased TEA uptake.
P283 (= P202) to L: in dbSNP:rs4646277; mutation to A: Decreased TEA uptake.
R287 (vs. gap) to G: in dbSNP:rs4646278
P341 (≠ K233) to L: affects transporter activity; reduction of TEA uptake; reduction o MPP(+) uptake when associated with V-408; largely localized to the plasma membrane; dbSNP:rs2282143
R342 (≠ A234) to H: no changes in MPP(+) uptake when associated with V-408; dbSNP:rs34205214
Y361 (= Y268) mutation to F: Decreased TEA uptake.
Y376 (≠ Q283) mutation to F: Decreased TEA uptake.
G401 (= G312) to S: affects transporter activity; reduction of MPP(+), serotonin and TEA uptake; no MPP(+) uptake when associated with L-160; dbSNP:rs34130495
M408 (≠ R314) to V: does not affect transporter activity; no changes in MPP(+) uptake when associated with F-14; no changes in MPP(+) uptake when associated with F-85; no changes in MPP(+) uptake when associated with L-189; no changes in MPP(+) uptake when associated with H-342; no changes in MPP(+) uptake when associated with M-420 del; no changes in MPP(+) uptake when associated with I-440; no changes in MPP(+) uptake when associated with I-461; no changes in MPP(+) uptake when associated with M-488; reduction of MPP uptake when associated with C-61; no MPP(+) uptake when associated with V-220; reduction of MPP(+) uptake when associated with L-341; no MPP(+) uptake when associated with S-401; no MPP(+) uptake when associated with R-465; dbSNP:rs628031
M420 (≠ P330) natural variant: Missing (reduction of serum O-isobutanoyl-(R)-carnitine levels; no change in MPP(+) uptake; no changes in MPP(+) uptake when associated with V-408; dbSNP:rs72552763)
M440 (≠ V353) to I: in dbSNP:rs35956182
V461 (= V374) to I: no changes in MPP(+) uptake when associated with V-408; dbSNP:rs34295611
G465 (= G378) to R: reduction of the localization to the basolateral membrane; no MPP(+) uptake when associated with V-408; dbSNP:rs34059508; mutation to A: No changes in MPP(+) uptake.
R488 (≠ I402) to M: no changes in MPP(+) uptake when associated with V-408; dbSNP:rs35270274

Sites not aligning to the query:

14 S → F: exclusively found in the African American population; increased MPP(+) uptake when associated with V-408; dbSNP:rs34447885
24 I→L: No change in fenoterol uptake. No change in trospium uptake. No change in terbutaline uptake.
28 L→I: No change in fenoterol uptake. No change in trospium uptake. No change in terbutaline uptake.
31 A→S: No change in fenoterol uptake. No change in trospium uptake. No change in terbutaline uptake.
32 F→L: No change in fenoterol uptake. Decreased trospium uptake. Decreased trospium affinity.
36 C→Y: Increased fenoterol uptake. Increased fenoterol affinity. No change in trospium uptake. No change in terbutaline uptake. No change in terbutaline affinity.
41 F → L: in dbSNP:rs2297373
61 R → C: affects transporter activity; reduction of MPP(+) uptake; reduction of serum O-isobutanoyl-(R)-carnitine levels; reduction of MPP(+) uptake when associated with V-408; dbSNP:rs12208357
85 L → F: no changes in MPP(+) uptake; when associated with V-408; dbSNP:rs35546288
88 C → R: affects transporter activity; reduction of MPP(+), serotonin and TEA uptake; dbSNP:rs55918055

8et8A Cryo-em structure of the organic cation transporter 1 in complex with verapamil (see paper)
30% identity, 23% coverage: 73:181/469 of query aligns to 156:253/532 of 8et8A

query
sites
8et8A

V

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binding (2S)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile: K213 (≠ G141), W216 (≠ Q144), Q240 (= Q168)

Sites not aligning to the query:

binding (2S)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile: 31, 35, 353, 360, 378, 381, 385, 449, 469

8et7A Cryo-em structure of the organic cation transporter 1 in complex with diphenhydramine (see paper)
30% identity, 23% coverage: 73:181/469 of query aligns to 156:253/532 of 8et7A

query
sites
8et7A

V

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G

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Sites not aligning to the query:

binding n-[2-(benzhydryloxy)ethyl]-n,n-dimethylamine: 35, 385, 445

Q4U2R8 Solute carrier family 22 member 6; Organic anion transporter 1; hOAT1; PAH transporter; hPAHT; Renal organic anion transporter 1; hROAT1 from Homo sapiens (Human) (see 6 papers)
29% identity, 26% coverage: 67:186/469 of query aligns to 137:239/563 of Q4U2R8

query
sites
Q4U2R8

A

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G

Y230 (≠ I177) mutation to A: Loss of membrane protein expression and little uptake of cidofovir.

Sites not aligning to the query:

7 L → P: in dbSNP:rs1415632329
30 L→A: Complete loss of PAH transport activity.
36 T→A: Complete loss of PAH transport activity.
39 modified: carbohydrate, N-linked (GlcNAc...) asparagine; N→Q: Complete loss of PAH transport activity.
50 R → H: lower Vmax; increase in substrate affinity and increase in the affinity for the nucleoside phosphonate analogs cidofovir, adefovir and tenofovir; dbSNP:rs11568626
56 modified: carbohydrate, N-linked (GlcNAc...) asparagine
92 modified: carbohydrate, N-linked (GlcNAc...) asparagine
97 modified: carbohydrate, N-linked (GlcNAc...) asparagine
104 P → L: in dbSNP:rs11568627
113 modified: carbohydrate, N-linked (GlcNAc...) asparagine
431 K→A: Decrease in the level of membrane protein expression and 70 % loss of PAH uptake.
438 F→A: Decrease in the level of membrane protein expression, 70 % loss of PAH uptake, increased affinity for cidofovir, lower Vmax for PAH, and lower Km and Vmax for cidofovir.

Query Sequence

>BPHYT_RS23435 FitnessBrowser__BFirm:BPHYT_RS23435
METRVNPARPQATAPASTAMLRRVAFASTIGTAAEYYDFFVYGTAAVLVFGQKFFPSADP
LIGTLAAFATYAVGFLARPLGGIVFGHFGDRVGRKKALIVTILIVGLGTFAIGLLPDYQS
IGIWAPIALIVIRVLQGFGVGGEQAGAVLLTAEYAPPARRGFFASLVQLGAPAGFLIPSG
LFALLGATLTQAQLLDWGWRIPFLASALLVAVGLYIRLRTEESPIFATIQRTKAVASRPV
VEVVRQFGPTIVKGVGAKLIEACAFAMYTMIVLAYGKAHGIAQGMLLETVIVAVALELVT
IPLAGALSDRIGRRTTFIAGALLHVALVVPFFMAIDSGNRAAIQLVMILAISVGHSLCYA
PQAALFPELFPARVRCSGIALIWQIGSLLGSGVLGLLAVKLIQLTHGNSLALIVYVAVLG
IVSAVSLFALPETAPLRRGGDLHDWGGGEPVEARTAARASSSSSSLAQP

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