SitesBLAST

P21439 Phosphatidylcholine translocator ABCB4; ATP-binding cassette sub-family B member 4; Multidrug resistance protein 3; P-glycoprotein 3; EC 7.6.2.1 from Homo sapiens (Human) (see 22 papers)
30% identity, 46% coverage: 5:231/497 of query aligns to 394:621/1286 of P21439

query
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P21439

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Y403 (≠ F14) to H: in PFIC3; does not alter cytoplasmic and cell membrane location; inhibits efflux activity for PC and cholesterol; dbSNP:rs121918443
R406 (vs. gap) binding ATP; to Q: found in patients with cholangitis; uncertain significance; dbSNP:rs763807769
GCGKST 432:437 (≠ GAGKST 40:45) binding ATP
K435 (= K43) mutation to M: Inhibits efflux activity for PC and cholesterol, but does not alter glycosylation and surface expression in the presence of taurocholate.
E450 (≠ A58) to G: in dbSNP:rs1189003716
D459 (≠ E67) to H: in PFIC3; retained in the reticulum endoplasmic; greatly reduced expression
Q477 (= Q86) binding ATP
P479 (≠ N89) to L: in PFIC3; greatly reduced expression; alters efflux activity for PC; dbSNP:rs748657435
L481 (= L91) to R: in PFIC3; does not alter cytoplasmic and cell membrane location; inhibits efflux activity for PC and cholesterol
A511 (≠ S121) to T: in PFIC3 and GBD1; dbSNP:rs1257887155
E528 (vs. gap) to D: in GBD1; uncertain significance; moderate decrease of phosphatidylcholine transporter activity; does not alter plasma membrane location; dbSNP:rs8187797
G535 (≠ I143) to D: in PFIC3; reduced phosphatidylcholine transporter activity; does not alter plasma membrane location; dbSNP:rs1810849139
G536 (≠ A144) binding ATP; to R: in GBD1; loss of phosphatidylcholine transporter activity; does not alter plasma membrane location
I541 (≠ V149) to F: in PFIC3 and GBD1; dbSNP:rs66904256
A546 (= A154) to D: in ICP3; disruption of protein trafficking with subsequent lack of functional protein at the cell surface; dbSNP:rs121918441
E558 (= E166) mutation to Q: Loss of floppase activity. Strongly reduce the ATPase activity.
H589 (= H198) to T: in GBD1; requires 2 nucleotide substitutions
R590 (= R199) to Q: found in patients with gallbladder and cholestasis; uncertain significance; dbSNP:rs45575636

Sites not aligning to the query:

34 modified: Phosphothreonine; T → M: in GBD1; reduces efflux activity for PC in a phosphorylation-dependent manner; dbSNP:rs142794414; T→D: Does not inhibit efflux activity for PC.
44 T→A: Reduces efflux activity for PC. Does not alter apical membrane location.
47 R → G: in GBD1; partly retained intracellularly; reduces efflux activity for PC in a phosphorylation-dependent manner; R → Q: found in patients with cholangitis; uncertain significance; dbSNP:rs372685632
49 S→A: Reduces efflux activity for PC. Does not alter apical membrane location.
68 G → R: in PFIC3; retained in the reticulum endoplasmic; greatly reduced expression; dbSNP:rs1343667900
73 L → V: in PFIC3 and GBD1; dbSNP:rs8187788
87 natural variant: D -> E
95 P → S: in dbSNP:rs377268767
175 T → A: found in patients with gallbladder and cholestasis; uncertain significance; dbSNP:rs58238559
201 T → M: in PFIC3; greatly reduced expression; alters efflux activity for PC; dbSNP:rs753318087
238 L → V: in dbSNP:rs45596335
263 I → V: in dbSNP:rs45547936
286 A → V: in PFIC3 and GBD1; does not alter plasma membrane location; inhibits efflux activity for PC; dbSNP:rs765478923
320 S → F: in ICP3, GBD1 and PFIC3; uncertain significance; does not alter plasma membrane location; does not inhibit efflux activity for PC; dbSNP:rs72552778
367 I → V: in dbSNP:rs1168923653
651 T → N: in dbSNP:rs45476795
652 R → G: in dbSNP:rs2230028
726 P → L: in GBD1; loss of phosphatidylcholine transporter activity; does not alter plasma membrane location; dbSNP:rs141677867
742 natural variant: G -> S
764 I → L: in a heterozygous patient with risperidone-induced cholestasis
775 T → M: found in patients with cholangitis; uncertain significance; dbSNP:rs148052192
788 R → Q: in GBD1; benign; dbSNP:rs8187801
934 A → T: found in patients with gallbladder and cholestasis; uncertain significance; dbSNP:rs61730509
953 A→D: Accumulates predominantly in intracellular compartments with only a small fraction at the plasma membrane and inhibits partially the efflux activity for PC.
964 V → T: found in patients with cholangitis; uncertain significance; requires 2 nucleotide substitutions
978 S → P: in PFIC3; alters efflux activity for PC; dbSNP:rs1051861187
985 V→M: Significantly reduces phosphatidylcholine floppase activity; when associated with Q-989 and V-990.
989 H→Q: Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and V-990.
990 A→V: Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and Q-989.
1046 binding ATP
1071:1077 binding ATP
1075 K→M: Inhibits efflux activity for PC and cholesterol, but does not alter glycosylation and surface expression in the presence of taurocholate.
1082 L → Q: in a heterozygous patient with amoxicillin/clavulanic acid-induced cholestasis; dbSNP:rs1214110864
1124 binding ATP
1125 E → K: in PFIC3; alters efflux activity for PC
1168 P → S: in GBD1; reduced phosphatidylcholine transporter activity; does not alter plasma membrane location; dbSNP:rs121918442
1183 S → L: in GBD1; severely reduced phosphatidylcholine transporter activity; does not alter plasma membrane location
1184:1186 binding ATP
1185 G → S: in GBD1; loss of phosphatidylcholine transporter activity; does not alter plasma membrane location

8k1oB Mycobacterial efflux pump, amppnp bound state
28% identity, 44% coverage: 5:224/497 of query aligns to 6:215/215 of 8k1oB

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binding phosphoaminophosphonic acid-adenylate ester: N40 (= N39), G43 (= G42), K44 (= K43), S45 (= S44), T46 (= T45), T131 (≠ K140), S133 (= S142)

1ji0A Crystal structure analysis of the abc transporter from thermotoga maritima
25% identity, 46% coverage: 4:234/497 of query aligns to 6:233/240 of 1ji0A

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binding adenosine-5'-triphosphate: Y16 (≠ F14), G42 (= G40), G44 (= G42), K45 (= K43), T46 (≠ S44), T47 (= T45), E88 (≠ Q86), E165 (= E166)

7niwA Nanodisc reconstituted human abcb4 in complex with 4b1-fab (posaconazole-bound, inward-open conformation) (see paper)
30% identity, 46% coverage: 5:231/497 of query aligns to 343:570/1140 of 7niwA

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Sites not aligning to the query:

binding cholesterol: 70, 152, 160, 266, 641, 645, 648, 839
binding 1,2-dilinoleoyl-sn-glycero-3-phosphocholine: 173, 183, 250, 254, 257, 261, 286, 294, 298, 617, 882
binding posaconazole: 250, 291, 294, 658, 661, 726, 841, 871, 874, 878, 882

6s7pA Nucleotide bound abcb4 (see paper)
30% identity, 46% coverage: 5:231/497 of query aligns to 333:560/1128 of 6s7pA

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N

N

A

V

R

N

E

Y

S

L

M

R

D

E

A

I

G

-

I

I

G

G

I

V

H

S

Q
|
Q

E

E

L

-

N

P

L

V

L

L

P

F

D

S

L

T

S

T

V

I

A

A

E

E

N

N

I

I

Y

C

L

Y

G

G

R

R

E

G

P

N

T

V

K

T

L

M

G

D

K

E

I

I

Q

K

W

K

D

A

V

V

V

K

Q

E

R

A

E

N

S

A

K

Y

K

E

Y

F

L

I

A

M

Q

K

L

L

K

P

Q

Q

D

K

I

F

D

D

P

-

T

-

T

T

P

L

L

V

G

G

-

E

-

R

-

G

-

A

K
x
Q

L

L

S
|
S

I

G

A
x
G

Q
|
Q

Q

K

Q

Q

M

R

V

I

E

A

I

I

A

A

K

R

A

A

L

L

S

V

L

R

N

N

A

P

E

K

V

I

I

L

M

L

D

D

E

Q

P

A

T

T

D

S

A

A

L

L

T

D

D

T

I

E

E

S

T

E

A

A

I

E

L

V

F

Q

E

A

V

A

V

L

D

D

E

K

L

A

R

R

A

-

Q

E

G

G

K

R

G

T

L

T

V

I

F

V

I

I

S

A

H

H

R

R

L

L

G

S

E

T

I

V

F

-

Q

R

M

N

C

A

D

D

D

V

I

I

A

A

I

G

L

F

R

E

D

D

G

G

Q

V

M

I

V

V

H

E

Q

Q

G

G

A

S

V

H

A

S

D

E

I

L

S

M

E

K

D

K

D

E

binding adenosine-5'-triphosphate: Y342 (≠ F14), S344 (vs. gap), R345 (vs. gap), G371 (= G40), G373 (= G42), K374 (= K43), S375 (= S44), Q416 (= Q86), Q471 (≠ K140), S473 (= S142), G475 (≠ A144), Q476 (= Q145)

Sites not aligning to the query:

binding adenosine-5'-triphosphate: 920, 922, 923, 948, 949, 951, 952, 953, 954, 994, 1033, 1053, 1054, 1056
binding cholesterol: 25, 32, 35, 65, 824, 834, 834, 838
binding magnesium ion: 953, 994

4f4cA The crystal structure of the multi-drug transporter (see paper)
31% identity, 41% coverage: 17:222/497 of query aligns to 1036:1241/1250 of 4f4cA

query
sites
4f4cA

I

I

N

E

V

I

L

L

K

K

S

G

V

L

D

S

L

F

T

S

I

V

R

E

A

P

G

G

R

Q

V

T

V

L

A

A

L

L

A

V

G

G

E

P

N

S

G

G

A

C

G

G

K

K

S

S

T

T

L

V

M

V

K

A

I

L

S

E

G

R

I

F

Y

Y

Q

D

R

T

D

L

A

G

G

G

T

E

V

I

F

F

Y

I

K

D

G

G

H

S

E

E

V

I

E

K

F

T

T

L

N

N

A

P

R

-

E

E

S

H

M

T

D

R

A

S

G

Q

I

I

G

A

I

I

I

V

H

S

Q

Q

E

E

L

P

N

T

L

L

L

F

P

-

D

D

L

C

S

S

V

I

A

A

E

E

N

N

I

I

Y

I

L

Y

G

G

R

L

E

D

P

P

T

S

K

S

L

V

G

T

K

M

I

A

Q

Q

W

V

D

E

V

E

V

A

Q

A

R

R

E

L

S

A

K

N

-

I

-

H

K

N

Y

F

L

I

A

A

Q

E

L

L

K

P

Q

E

D

G

I

F

D

E

P

-

T

-

T

T

P

R

L

V

G

G

-

D

-

R

-

G

-

T

K

Q

L

L

S

S

I

G

A

G

Q

Q

Q

K

Q

Q

M

R

V

I

E

A

I

I

A

A

K

R

A

A

L

L

S

V

L

R

N

N

A

P

E

K

V

I

I

L

M

L

D

D

E

E

P

A

T

T

D

S

A

A

L

L

T

D

D

T

I

E

E

S

T

E

A

K

I

V

L

V

F

Q

E

E

V

A

V

L

D

D

E

R

L

A

R

R

A

-