SitesBLAST

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)
24% identity, 74% coverage: 106:447/465 of query aligns to 149:451/453 of 8sc2A

query
sites
8sc2A

G

G

H

Y

I

F

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

G

T

T

L

V

L

L

T

V

M

N

G

A

S

V

A

S

T

G

A

V

L

L

M

M

G

A

V

F

L

S

P

P

T

N

Y

Y

Q

M

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

N

W
|
W

S

M

G

A

S

G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

S

R

R

G

R

A

T

L

V

A

A

A

I

W

M

S

Y

P
x
Q

C

M

G

A

A
x
F

A

T

L

V

G

G

F

L

V

V

L

A

S

L

T

T

G

G

A

L

F

-

L

-

V

-

Q

-

N

-

L

-

S

-

S

A

T

Y

D

A

F

L

Q

P

S

H

W

W

G

R

W

W

-

L

R

Q

L

L

P

A

F

V

L

S

G

L

S

P

T

T

A

F

L

L

V

F

V

L

L

L

G

Y

L

Y

W

W

M

C

R

V

R

P

S

E

V

S

G

P

E

R

S

S

A

P

A

S

F

F

A

A

E

D

V

L

K

F

A

R

T

T

R

-

H

-

Q

-

S

-

R

-

M

-

P

-

V

-

I

-

E

-

V

-

L

-

K

-

Q

-

C

-

P

P

R

R

E

-

V

-

L

-

T

-

V

-

F

-

G

-

L

L

R

R

F

K

G

R

E

T

G

F

A

I

A

L

S

M

Y

Y

I

L

F
x
W

F

F

A

T

F

D

S
|
S

L

V

A

L

Y

Y

G

Q

Q

G

F

L

V

I

-

L

-

H

-

M

G

G

I

A

K

T

S

S

A

G

W

N

V

L

L

Y

S

L

G

D

L

F

T

L

I

Y

S

S

M

A

L

L

L

V

M

E

I

I

P

P

V

G

T

A

L

F

F

I

F

A

G

L

H

I

V

T

T

I

D

D

K

R

V

V

G

G

R

R

K

-

P

-

V

I

Y

Y

-

P

-

M

-

A

-

M

-

S

-

N

-

L

L

L

A

A

G

G

A

A

I

A

A

C

I

L

V

V

L

M

V

-

A

-

W

-

P

-

Y

-

F

-

V

I

L

F

L

I

G

S

S

P

G

D

E

L

Y

H

W

W

K

L

V

N

L

I

V

I

A

I

L

M

I

C

L

V

A

G

N

R

-

M

-

G

-

I

S

T

I

I

T

A

L
x
I

G

Q

M

M

L

I

E

C

G

L

A

V

Q

N

P

-

A

-

F

-

I

-

S

A

E

E

M

L

L

Y

P

P

V

T

H

F

L

V

R

R

F

N

S

L

G

G

L

V

G

M

I

V

G

C

R

S

E

S

V

L

S

C

S

D

V

I

L

-

G

G

G

I

L

I

S

T

P

P

M

F

I

I

A

V

T

F

A

R

L

L

L

R

A

E

H

V

Y

W

R

Q

S

-

A

A

L

L

P

P

V

L

A

I

L

L

Y

F

L

-

G

A

A

V

L

L

G

G

L

L

V

L

T

A

V

A

I

G

A

V

T

T

L

L

binding Diltiazem: W199 (= W164), Q223 (≠ P188), F226 (≠ A191), W293 (≠ F287), S297 (= S291), I385 (≠ L374)

Sites not aligning to the query:

binding Diltiazem: 18

8et8A Cryo-em structure of the organic cation transporter 1 in complex with verapamil (see paper)
31% identity, 23% coverage: 92:200/465 of query aligns to 155:252/532 of 8et8A

query
sites
8et8A

T

N

V

V

G

G

F

F

I

F

A

-

R

-

P

-

I

L

G

G

G

S

V

L

L

G

C

V

G

G

H

Y

I

I

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

A

T

T

L

T

L

L

T

I

M

S

G

A

S

V

A

S

T

G

A

V

L

L

M

M

G

A

V

V

L

A

P

P

T

D

Y

Y

Q

T

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G
x
K

G

G

E

S

W
|
W

S

M

G

S

S

G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

Y

R

R

G

R

A

T

L

V

A

A

A

I

W

L

S

Y

P
x
Q

C

M

G

A

A

F

A

T

L

V

G

G

F

L

V

V

L

L

S

L

T

S

G

G

binding (2S)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile: K213 (≠ G161), W216 (= W164), Q240 (≠ P188)

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)
31% identity, 23% coverage: 92:200/465 of query aligns to 155:252/532 of 8et7A

query
sites
8et7A

T

N

V

V

G

G

F

F

I

F

A

-

R

-

P

-

I

L

G

G

G

S

V

L

L

G

C

V

G

G

H

Y

I

I

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

A

T

T

L

T

L

L

T

I

M

S

G

A

S

V

A

S

T

G

A

V

L

L

M

M

G

A

V

V

L

A

P

P

T

D

Y

Y

Q

T

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

S

W

W

S

M

G

S

S

G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

Y

R

R

G

R

A

T

L

V

A

A

A

I

W

L

S

Y

P

Q

C

M

G

A

A

F

A

T

L

V

G

G

F

L

V

V

L

L

S

L

T

S

G

G

Sites not aligning to the query:

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

O15245 Solute carrier family 22 member 1; Organic cation transporter 1; hOCT1 from Homo sapiens (Human) (see 10 papers)
23% identity, 77% coverage: 106:461/465 of query aligns to 167:530/554 of O15245

query
sites
O15245

G

G

H

Y

I

F

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

G

T

T

L

V

L

L

T

V

M

N

G

A

S

V

A
x
S

T

G

A

V

L

L

M

M

G

A

V

F

L

S

P

P

T

N

Y

Y

Q

M

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

N

W

W

S

M

G

A

S
x
G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

S

R

R

G

R

A

T

L

V

A

A

A

I

W

M

S
x
Y

P

Q

C

M

G

A

A

F

A

T

L

V

G

G

F

L

V

V

L

A

S

L

T

T

G

G

A

L

F

-

L

-

V

-

Q

-

N

-

L

-

S

-

S

A

T

Y

D

A

F

L

Q

P

S

H

W

W

G

R

W

W

-

L

R

Q

L

L

P

A

F

V

L

S

G

L

S

P

T

T

A

F

L

L

V

F

V

L

L

L

G

Y

L

Y

W

W

M

C

-

V

-
x
P

-

E

-

S

-

P

R
|
R

R

W

S

L

V

L

G

S

E

Q

S

K

A

R

A

N

F

T

A

E

E

A

V

I

K

K

A

I

T

M

R

D

H

H

-

I

-

A

-

Q

-

K

Q

N

S

G

R

K

M

L

P

P

-

P

-

A

-

D

-

L

-

K

-

M

-

L

-

S

-

L

-

E

-

D

V

V

I

T

E

E

V

K

L

L

K

S

Q

P

C

S

P

F

R

A

E

D

V

L

L

F

T

R

V

T

F
x
P

G
x
R

L

L

R

R

F

K

G

R

E

T

G

F

A

I

A

L

S

M

Y

Y

I

L

F

W

F

F

A

T

F

D

S

S

L

V

A

L

Y
|
Y

G

Q

Q

G

F

L

V

I

-

L

-

H

-

M

G

G

I

A

K

T

S

S

A

G

W

N

V

L

L
x
Y

S

L

G

D

L

F

T

L

I

Y

S

S

M

A

L

L

L

V

M

E

I

I

P

P

V

G

T

A

L

F

F

I

F

A

G

L

H

I

V

T

T

I

D

D

K

R

V

V

G
|
G

R

R

K

-

P

-

V

I

Y

Y

-

P

-

M

-

A

-
x
M

-

S

-

N

-

L

L

L

A

A

G

G

A

A

I

A

A

C

I

L

V

V

L
x
M

V

-

A

-

W

-

P

-

Y

-

F

-

V

I

L

F

L

I

G

S

S

P

G

D

E

L

Y

H

W

W

K

L

V

N

L

I

V

I

A

I

L

M

I

C

L

V

A

G

N

R

-
x
M

-

G

-

I

S

T

I

I

T

A

L

I

G

Q

M

M

L

I

E

C

G

L

A

V

Q

N

P

-

A

-

F

-

I

-

S

A

E

E

M

L

L

Y

P

P

V

T

H

F

L
x
V

R

R

F

N

S

L

G
|
G

L

V

G

M

I

V

G

C

R

S

E

S

V

L

S

C

S

D

V

I

L

-

G

G

G

I

L

I

S

T

P

P

M

F

I

I

A

V

T

F

A

R

L

L

L
x
R

A

E

H

V

Y

W

R

Q

S

-

A

A

L

L

P

P

V

L

A

I

L

L

Y

F

L

-

G

A

A

V

L

L

G

G

L

L

V

L

T

A

V

A

I

G

A

V

T

T

L

L

A

L

R

P

E

E

T

T

-

K

-

G

-

V

-

A

Y

L

P

P

K

E

A

T

M

M

R

K

I

D

A

A

A

E

R

N

S189 (≠ A128) to L: no changes in MPP(+) uptake; dbSNP:rs34104736
G220 (≠ S167) to V: affects transporter activity; reduction of MPP(+) uptake when associated with V-408; dbSNP:rs36103319
Y240 (≠ S187) mutation to F: Decreased TEA uptake.
P283 (vs. gap) to L: in dbSNP:rs4646277; mutation to A: Decreased TEA uptake.
R287 (= R236) to G: in dbSNP:rs4646278
P341 (≠ F274) 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 (≠ G275) to H: no changes in MPP(+) uptake when associated with V-408; dbSNP:rs34205214
Y361 (= Y294) mutation to F: Decreased TEA uptake.
Y376 (≠ L306) mutation to F: Decreased TEA uptake.
G401 (= G331) to S: affects transporter activity; reduction of MPP(+), serotonin and TEA uptake; no MPP(+) uptake when associated with L-160; dbSNP:rs34130495
M408 (vs. gap) 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 (≠ L345) 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 (vs. gap) to I: in dbSNP:rs35956182
V461 (≠ L393) to I: no changes in MPP(+) uptake when associated with V-408; dbSNP:rs34295611
G465 (= G397) 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 (≠ L421) 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
160 L → 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

O15244 Solute carrier family 22 member 2; Organic cation transporter 2; hOCT2 from Homo sapiens (Human) (see 8 papers)
34% identity, 18% coverage: 92:173/465 of query aligns to 157:227/555 of O15244

query
sites
O15244

T

N

V

V

G

G

F

F

I

F

A

-

R

-

P

-

I

I

G

G

G

S

V
x
M

L

S

C

I

G

G

H
x
Y

I

I

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

T

T

T

L

V

L

L

T

I

M

N

G

A

S

A

A

A

T

G

A

V

L

L

M

M

G

A

V

I

L

S

P

P

T

T

Y

Y

Q

-

I

-

G

-

I

-

A

-

P

-

V
x
T

M

W

L

M

V

L

L

I

L

F

R

R

I

L

M

I

Q

Q

G

G

L

L

A

V

A

S

G

K

G

A

E

G

W

W

S

L

G

I

S

G

I

Y

L

I

L

L

I

I

H

T

E

E

M165 (≠ V103) to I: lower Vmax for MPP(+) transport; no change in transport efficiency (Vmax/Km) and clearance of cyclo(his-pro) and salsolinol; dbSNP:rs8177507
Y169 (≠ H107) mutation to F: No change in TEA uptake.
T201 (≠ V147) to M: in dbSNP:rs145450955

Sites not aligning to the query:

54 P → S: in dbSNP:rs8177504
73 Y→F: No change in TEA uptake.
92 Y→F: No change in TEA uptake.
128 Y→F: No change in TEA uptake.
241 Y→F: Slight decrease in TEA uptake. No change in tyrosine phosphorylation. Strong decrease in TEA uptake; when associated with F-362. Strong decrease in TEA and metformin uptake and YES1-mediated tyrosine phosphorylation; when associated with F-362 and F-377.
257 Y→F: No change in TEA uptake.
270 S → A: decreased Ki value for TBA inhibition of MPP(+); no change in transport efficiency (Vmax/Km) and clearance of cyclo(his-pro) and salsolinol; dbSNP:rs316019
279 Y→F: No change in TEA uptake.
280 Y→F: No change in TEA uptake.
284 P→A: Decreased TEA and metformin uptake. Decreased tyrosine phosphorylation.
284:288 Proline-rich sequence
286 S→A: No change in TEA and metformin uptake. No change in tyrosine phosphorylation.
287 P→A: Decreased TEA and metformin uptake. Decreased tyrosine phosphorylation.
362 Y→F: Decreased TEA uptake and YES1-mediated tyrosine phosphorylation. Strong decrease in TEA uptake; when associated with F-241. Strong decrease in TEA uptake; when associated with F-377. Strong decrease in TEA and metformin uptake and YES1-mediated tyrosine phosphorylation; when associated with F-241 and F-377.
377 Y→F: Slight decrease in TEA uptake. No change in tyrosine phosphorylation. Strong decrease in TEA uptake; when associated with F-362. Strong decrease in TEA and metformin uptake and YES1-mediated tyrosine phosphorylation; when associated with F-241 and F-362.
400 R → C: lower Vmax and reduced Ki value for TBA inhibition of MPP(+); lower transport efficiency (Vmax/Km) and clearance of cyclo(his-pro); no change in transport efficiency (Vmax/Km) and clearance of salsolinol; dbSNP:rs8177516
432 K → Q: lower Km value for MPP(+) and reduced Ki value for TBA inhibition of MPP; no change in transport efficiency (Vmax/Km) and clearance of cyclo(his-pro) and salsolinol; dbSNP:rs8177517
458 Y→F: No change in TEA uptake.
544 Y→F: No change in TEA uptake.

Q63089 Solute carrier family 22 member 1; Organic cation transporter 1; rOCT1 from Rattus norvegicus (Rat) (see 4 papers)
23% identity, 76% coverage: 100:451/465 of query aligns to 162:517/556 of Q63089

query
sites
Q63089

I

L

G

G

G

S

V

L

L

V

C

V

G

G

H

Y

I

I

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V
x
C

M

L

L

V

T

T

L

T

L

L

T

V

M

T

G

S

S

V

A

S

T

G

A

V

L

L

M

T

G

A

V

V

L

A

P

P

T

D

Y

Y

Q

T

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L
x
M

A
x
V

A
x
S

G
x
K

G
|
G

E
x
S

W
|
W

S
x
V

G
x
S

S
x
G

I
x
Y

L
x
T

L
|
L

I
|
I

H
x
T

E
|
E

N
x
F

A
x
V

P

G

Q

S

S

G

K

Y

R

R

G

R

A

T

L

T

A

A

A

I

W

L

S

Y

P

Q

C

M

G

A

A

F

A

T

L

V

G

G

F

L

V

V

L

G

S

L

T

A

G

G

A

V

F

A

L

Y

L

A

V

I

Q

P

N

D

L

-

S

-

T

-

D

-

F

-

Q

-

S

-

W

W

G

R

W

W

-

L

R

Q

L

L

P

A

F

V

L

S

G

L

S

P

T

T

A

F

L

L

V

F

V

L

L

L

G

Y

L

Y

W

W

M

F

R

-

S

-

V

V

G

P

E

E

S
|
S

A

P

A

R

F

W

-

L

A
x
S

E

Q

V

K

K

R

A
x
T

T

T

R

R

-

A

-

V

-

R

-

I

-

M

-

E

-

Q

-

I

-

A

-

Q

H

K

Q

N

S

G

R

K

M

V

P

P

V

P

I

A

E

D

V

L

L

K

K

M

Q

L

C
|
C

P

L

R

E

E

E

-

D

-

A

-
x
S

-

E

-

K

-

R

-

S

-

P

-

S

-

F

-

A

-

D

V

L

L

F

T

R

V

T

F

P

G

N

L

L

R

R

F

K

G

H

E

T

G

V

A

I

A

L

S

M

Y

Y

I

L

F

W

F

F

A

S

F
x
C

S

A

L

V

A

L

Y

Y

G

Q

-

G

-

L

-

I

Q

M

F

H

V

V

G

G

I

A

K

T

S

G

A

A

W

N

V

L

L

Y

S

L

G

D

L

F

T

F

I

Y

S

S

M

S

L

L

L

V

M

E

I

F

P

P

V

A

T

A

L

F

F

I

G

L

H

V

V

T

T

I

D

D

K

R

V

I

G

G

R

R

-

I

K

Y

P

P

V

I

-

A

-

S

-

N

Y

L

L

V

A

T

G

G

A

A

I

A

A
x
C

I

L

V

L

L

M

V

I

A

F

W

I

P

P

Y

H

F

E

V

L

L

-

G

-

S

-

G

-

E

H

Y

W

W

L

K

N

V

V

L

T

V

L

A

A

L
x
C

I

L

-

G

-

R

L

M

A

G

N

A

S

T

I

I

T

V

L

L

G

Q

M

M

L

V

E
x
C

G

L

A

V

Q

N

P

-

A

-

F

-

I

-

S

A

E

E

M

L

L

Y

P

P

V

T

H

F

L

I

R

R

F

N

S

L

G

G

L

M

G

M

I

V

G
x
C

R

S

E

A

V

L

S
x
C

S
x
D

V

-

L

L

G

G

G

I

L

F

S

T

P

P

M

F

I

M

A

V

T

F

A

R

L

L

L

M

A

E

H

V

Y

W

R

Q

S

-

A

A

L

L

P

P

V

L

A

I

L

L

Y

F

L

-

G

G

A

V

L

L

G

G

L

L

V

T

T

A

V

G

I

A

A

M

T

T

L

L

A

L

R

P

E

E

T

T

C179 (≠ V117) 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 (≠ L158) mutation to L: No change in TEA and MPP(+) uptake.
V213 (≠ A159) mutation to G: Decreased TEA uptake. No change in MPP(+) uptake.
S214 (≠ A160) mutation to G: Decreased TEA and MPP(+) uptake.
K215 (≠ G161) mutation to Q: Loss of TEA and MPP(+) uptake activity.; mutation to R: Loss of TEA and MPP(+) uptake activity.
G216 (= G162) mutation to A: Decreased TEA and MPP(+) uptake.
S217 (≠ E163) mutation to G: No change in TEA and MPP(+) uptake.
W218 (= W164) 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 (≠ S165) mutation to L: No change in TEA and MPP(+) uptake.
S220 (≠ G166) mutation to I: Decreased TEA and MPP(+) uptake.
G221 (≠ S167) mutation to A: Decreased TEA and MPP(+) uptake.
Y222 (≠ I168) 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 (≠ L169) mutation to I: Decreased TEA uptake. No change in MPP(+) uptake.
L224 (= L170) mutation to V: Decreased TEA and MPP(+) uptake.
I225 (= I171) mutation to G: No change in TEA and MPP(+) uptake.
T226 (≠ H172) mutation to A: Decreased TEA uptake. No change in MPP(+) uptake.
E227 (= E173) mutation to D: Loss of TEA and MPP(+) uptake activity.; mutation to Q: Loss of TEA and MPP(+) uptake activity.
F228 (≠ N174) mutation to I: No change in TEA and MPP(+) uptake.
V229 (≠ A175) mutation to A: Decreased TEA and MPP(+) uptake.; mutation to L: Loss of TEA and MPP(+) uptake activity.
S286 (= S242) 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 (≠ A246) 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 (≠ A250) 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.
C322 (= C266) mutation to 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.
S328 (vs. gap) 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-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.
C358 (≠ F290) mutation to 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.
C418 (≠ A342) mutation to 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.
C437 (≠ L366) mutation to 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.
C451 (≠ E378) mutation to 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.
C470 (≠ G401) mutation to 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.
C474 (≠ S405) mutation to 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.
D475 (≠ S406) mutation to E: Decreased MPP(+) uptake, no change in MPP(+) affinity. Decreased NMN uptake, increased NMN affinity. Decreased choline uptake, increased choline affinity.; mutation to N: Decreased MPP(+) uptake.; mutation to R: Decreased MPP(+) uptake.

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.
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.

Q9Y7Q9 Probable metabolite transporter C2H8.02 from Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) (see paper)
33% identity, 20% coverage: 96:186/465 of query aligns to 94:184/583 of Q9Y7Q9

query
sites
Q9Y7Q9

I

I

A

G

R

N

P

I

I

M

G

G

G

Q

V

L

L

L

C

F

G

G

H

F

I

L

G

G

D

D

R

F

Y

F

G

G

R

R

K

K

V

F

V

V

M

Y

M

G

L

K

T

E

L

M

T

V

M

V

G

I

S

I

A

A

T

T

A

I

L

L

M

I

G

I

V

C

L

L

P

P

T

D

Y

R

Q

I

Q

P

I

T

G

P

I

T

A

A

A

K

P

M

V

M

M

W

L

L

V

F

L

A

L

F

R

R

I

V

M

M

Q

L

G

G

L

I

A

G

A

I

G

G

E

D

W

Y

S

P

G

M

S

S

I

A

L

S

L

I

I

T

H

S

E

E

N

Q

A

S

P

L

Q

I

S

N

K

R

R

R

G

G

A

A

L

L

A

L

A

A

W

W

Sites not aligning to the query:

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

Q8MJI6 Solute carrier family 22 member 2; Organic cation transporter 2 from Oryctolagus cuniculus (Rabbit) (see paper)
33% identity, 18% coverage: 92:173/465 of query aligns to 156:226/554 of Q8MJI6

query
sites
Q8MJI6

T

N

V

I

G

G

F

F

I

F

A

-

R

-

P

-

I

I

G

G

G

S

V

V

L

G

C

I

G

G

H

Y

I

L

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

V

T

T

L

I

L

L

T

I

M

N

G

A

S

A

A

A

T

G

A

V

L

L

M

M

G

A

V

V

L

S

P

P

T

N

Y

Y

Q

-

I

-

G

-

I

-

A

-

P

-

V

T

M

W

L

M

V

L

L

I

L

F

R

R

I

L

M

I

Q

Q

G

G

L

L

A

V

A

S

G

K

G

A

E

G

W

W

S

L

G

I

S

G

I

Y

L

I

L

L

I

I

H

T

E

E

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.

8sc6A Human oct1 bound to thiamine in inward-open conformation (see paper)
24% identity, 74% coverage: 106:450/465 of query aligns to 149:447/447 of 8sc6A

query
sites
8sc6A

G

G

H

Y

I

F

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

G

T

T

L

V

L

L

T

V

M

N

G

A

S

V

A

S

T

G

A

V

L

L

M

M

G

A

V

F

L

S

P

P

T

N

Y

Y

Q

M

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

N

W

W

S

M

G

A

S

G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

S

R

R

G

R

A

T

L

V

A

A

A

I

W

M

S

Y

P
x
Q

C

M

G

A

A
x
F

A

T

L

V

G

G

F

L

V

V

L

A

S

L

T

T

G

G

A

L

F

-

L

-

V

-

Q

-

N

-

L

-

S

-

S

A

T

Y

D

A

F

L

Q

P

S

H

W

W

G

R

W

W

-

L

R

Q

L

L

P

A

F

V

L

S

G

L

S

P

T

T

A

F

L

L

V

F

V

L

L

L

G

Y

L

Y

W

W

M

-

R

-

S

-

V

-

G

-

E

-

S

S

A

P

A

S

F

F

A

A

E

D

V

L

K

F

A

R

T

T

R

-

H

-

Q

-

S

-

R

-

M

-

P

-

V

-

I

-

E

-

V

-

L

-

K

-

Q

-

C

-

P

P

R

R

E

-

V

-

L

-

T

-

V

-

F

-

G

-

L

L

R

R

F

K

G

R

E

T

G

F

A

I

A

L

S

M

Y

Y

I

L

F

W

F

F

A

T

F

D

S

S

L

V

A

L

Y
|
Y

G
x
Q

Q

G

F

L

V

I

-

L

-

H

-

M

G

G

I

A

K

T

S

S

A

G

W

N

V

L

L

Y

S

L

G

D

L

F

T

L

I

Y

S

S

M

A

L

L

L

V

M
x
E

I

I

P

P

V

G

T

A

L

F

F

I

F

A

G

L

H

I

V

T

T

I

D

D

K

R

V

V

G

G

R

R

K

-

P

-

V

I

Y

Y

-

P

-

M

-

A

-

M

-

S

-

N

-

L

L

L

A

A

G

G

A

A

I

A

A

C

I

L

V

V

L

M

V

-

A

-

W

-

P

-

Y

-

F

-

V

I

L

F

L

I

G

S

S

P

G

D

E

L

Y

H

W

W

K

L

V

N

L

I

V

I

A

I

L

M

I

C

L

V

A

G

N

R

-

M

-

G

-

I

S

T

I

I

T

A

L
x
I

G
x
Q

M

M

L

I

E

C

G

L

A

V

Q

N

P

-

A

-

F

-

I

-

S

A

E

E

M

L

L

Y

P

P

V

T

H

F

L

V

R

R

F

N

S

L

G

G

L

V

G

M

I

V

G

C

R

S

E

S

V

L

S

C

S

D

V

I

L

-

G

G

G

I

L

I

S

T

P

P

M

F

I

I

A

V

T

F

A

R

L

L

L

R

A

E

H

V

Y

W

R

Q

S

-

A

A

L

L

P

P

V

L

A

I

L

L

Y

F

L

-

G

A

A

V

L

L

G

G

L

L

V

L

T

A

V

A

I

G

A

V

T

T

L

L

A

L

R

P

E

E

binding 3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium: Q223 (≠ P188), F226 (≠ A191), Y293 (= Y294), Q294 (≠ G295), E318 (≠ M316), I378 (≠ L374), Q379 (≠ G375)

Q9R0W2 Solute carrier family 22 member 2; Organic cation transporter 2; rOCT2 from Rattus norvegicus (Rat) (see paper)
32% identity, 18% coverage: 92:173/465 of query aligns to 157:227/555 of Q9R0W2

query
sites
Q9R0W2

T

N

V

V

G

G

F

F

I

F

A

-

R

-

P

-

I

I

G

G

G

A

V

M

L

M

C

I

G

G

H

Y

I

L

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

F

V

C

M

L

L

V

T

T

L

I

L

L

T

I

M

N

G

A

S

I

A

S

T

G

A

A

L

L

M

M

G

A

V

I

L

S

P

P

T

N

Y

Y

Q

-

I

-

G

-

I

-

A

-

P

-

V

A

M

W

L

M

V

L

L

V

L

F

R

R

I

F

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

A

E

G

W

W

S

L

G

I

S

G

I

Y

L

I

L

L

I

I

H

T

E

E

Sites not aligning to the query:

451 Involved in recognition of organic cations and participates in structural changes that occur during translocation of organic cations; C→M: Transport activity strongly reduced.

8et9A Cryo-em structure of the organic cation transporter 2 in complex with 1-methyl-4-phenylpyridinium (see paper)
33% identity, 16% coverage: 92:164/465 of query aligns to 155:216/517 of 8et9A

query
sites
8et9A

T

N

V

V

G

G

F

F

I

F

A

-

R

-

P

-

I

V

G

G

G

S

V

M

L

S

C

I

G

G

H

Y

I

I

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

V

T

T

L

I

L

L

T

I

M

N

G

A

S

I

A

S

T

G

A

V

L

L

M

M

G

A

V

V

L

A

P

P

T

N

Y

Y

Q

-

I

-

G

-

I

-

A

-

P

-

V

T

M

W

L

M

V

L

L

I

L

F

R

R

I

L

M

I

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

G

W
|
W

binding 1-methyl-4-phenylpyridin-1-ium: W216 (= W164)

Sites not aligning to the query:

binding 1-methyl-4-phenylpyridin-1-ium: 240, 243, 430

8sc3A Human oct1 bound to fenoterol in inward-open conformation (see paper)
29% identity, 20% coverage: 106:200/465 of query aligns to 149:235/445 of 8sc3A

query
sites
8sc3A

G

G

H

Y

I

F

G

A

D

D

R

R

Y

F

G

G

R

R

K

K

V

L

V

C

M

L

L

G

T

T

L

V

L

L

T

V

M

N

G

A

S

V

A

S

T

G

A

V

L

L

M

M

G

A

V

F

L

S

P

P

T

N

Y

Y

Q

M

Q

S

I

-

G

-

I

-

A

-

P

-

V

-

M

-

L

M

V

L

L

L

L

F

R

R

I

L

M

L

Q

Q

G

G

L

L

A

V

A

S

G

K

G

G

E

N

W
|
W

S
x
M

G

A

S

G

I

Y

L

T

L

L

I

I

H

T

E

E

N

F

A

V

P

G

Q

S

S

G

K

S

R

R

G

R

A

T

L

V

A

A

A

I

W

M

S

Y

P
x
Q

C

M

G

A

A
x
F

A

T

L

V

G

G

F

L

V

V

L

A

S

L

T

T

G

G

binding Fenoterol: W199 (= W164), M200 (≠ S165), Q223 (≠ P188), F226 (≠ A191)

Sites not aligning to the query:

binding Fenoterol: 284, 291, 376, 380

Query Sequence

>H281DRAFT_01646 FitnessBrowser__Burk376:H281DRAFT_01646
MDAGILTSCFPIIMNPDAVNPHLSAPSSTTRPVPRTRSAARRAVTTAVLGQILEWYDFFL
YGTAAALVFGKLFFPVGSDPLTGTIAAFGGFTVGFIARPIGGVLCGHIGDRYGRKVVMML
TLLTMGSATALMGVLPTYQQIGIAAPVMLVLLRIMQGLAAGGEWSGSILLIHENAPQSKR
GALAAWSPCGAALGFVLSTGAFLLVQNLSSTDFQSWGWRLPFLGSTALVVLGLWMRRSVG
ESAAFAEVKATRHQSRMPVIEVLKQCPREVLTVFGLRFGEGAASYIFFAFSLAYGQFVGI
KSAWVLSGLTISMLLMIPVTLFFGHVTDKVGRKPVYLAGAIAIVLVAWPYFVLLGSGEYW
KVLVALILANSITLGMLEGAQPAFISEMLPVHLRFSGLGIGREVSSVLGGGLSPMIATAL
LAHYRSALPVALYLGALGLVTVIATLLARETYPKAMRIAAREQAE

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