SitesBLAST

Q9NRA2 Sialin; H(+)/nitrate cotransporter; H(+)/sialic acid cotransporter; AST; Membrane glycoprotein HP59; Solute carrier family 17 member 5; Vesicular excitatory amino acid transporter; VEAT from Homo sapiens (Human) (see 8 papers)
25% identity, 86% coverage: 36:406/430 of query aligns to 99:479/495 of Q9NRA2

query
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Q9NRA2

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K136 (= K73) to E: in SD; alters intracellular localization, only partially targeted to lysosomes and mainly detected in LAMP1-negative vesicles and in the Golgi apparatus; completely devoid of L-aspartate and L-glutamate transporter activity, but retains appreciable H(+)-coupled sialic acid transporter activity; dbSNP:rs80338795
H183 (≠ S118) to R: in ISSD; alters intracellular localization, only partially targeted to lysosomes and mainly detected in LAMP1-negative vesicles and in the Golgi apparatus; abolishes H(+)-coupled sialic acid transporter activity; has normal L-aspartate and L-glutamate transporter activity; dbSNP:rs119491109
LL 198:199 (≠ AI 133:134) mutation to AA: Localizes in vesicular structures mainly concentrated in the perinuclear region.
IL 266:267 (≠ LR 196:197) mutation to LA: Localizes in vesicular structures mainly concentrated in the perinuclear region.
SSLRN 268:272 (≠ AEGQG 198:202) natural variant: Missing (in ISSD; alters intracellular localization, only partially targeted to lysosomes and mainly detected in LAMP1-negative vesicles and in the Golgi apparatus; abolishes H(+)-coupled sialic acid transporter activity; has normal L-aspartate and L-glutamate transporter activity)
G328 (≠ S258) to E: in ISSD; some patients may manifest a milder phenotype consistent with Salla disease; markedly decreases H(+)-coupled sialic acid transporter activity; abolishes L-aspartate and L-glutamate transporter activity; dbSNP:rs386833996
P334 (= P264) to R: in ISSD; does not affect intracellular localization, targeted to lysosomes; abolishes H(+)-coupled sialic acid transporter activity; abolishes L-aspartate and L-glutamate transporter activity; dbSNP:rs119491110
G371 (≠ C300) to V: in ISSD; abolishes H(+)-coupled sialic acid transporter activity; abolishes L-aspartate and L-glutamate transporter activity; dbSNP:rs777862172

Sites not aligning to the query:

22:23 Dileucine internalization motif; LL→AA: Targeted to plasma membrane.; LL→GG: Targeted to plasma membrane; sialic acid uptake strongly activated at acidic pH.
39 R → C: in SD; frequent variant in Finland; alters intracellular localization, only partially targeted to lysosomes and mainly detected in LAMP1-negative vesicles and in the Golgi apparatus; completely devoid of L-aspartate and L-glutamate transport activity, but retains appreciable H(+)-coupled sialic acid and nitrate transporter activity; dbSNP:rs80338794

Q5Q0U0 Sialin; H(+)/nitrate cotransporter; H(+)/sialic acid cotransporter; AST; Solute carrier family 17 (Anion/sugar transporter), member 5; Vesicular excitatory amino acid transporter; VEAT from Rattus norvegicus (Rat) (see 2 papers)
26% identity, 85% coverage: 36:399/430 of query aligns to 99:472/495 of Q5Q0U0

query
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Q5Q0U0

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K136 (= K73) mutation to E: Markedly decreases H(+)-coupled sialic acid transporter activity.
R168 (= R103) mutation to C: Abolishes H(+)-coupled sialic acid transporter activity.
E171 (≠ F106) mutation to C: Decreases H(+)-coupled sialic acid transporter activity; when associated with C-175.
G172 (= G107) mutation to C: Decreases protein levels and alters subcellular localization.
E175 (= E110) mutation to C: Decreases H(+)-coupled sialic acid transporter activity; when associated with C-171.
G176 (= G111) mutation to C: Decreases protein levels and alters subcellular localization.
F179 (≠ S114) mutation to C: Decreases the affinity and transport rate for D-glucuronate. Does not affect H(+)-coupled sialic acid transporter activity.
P180 (≠ V115) mutation to C: Decreases protein levels and alters subcellular localization.
H183 (≠ S118) mutation to R: Abolishes H(+)-coupled sialic acid transporter activity.
W186 (≠ V121) mutation to C: Abolishes H(+)-coupled sialic acid transporter activity.
SSLKN 268:272 (≠ AEGQG 198:202) mutation Missing: Abolishes H(+)-coupled sialic acid transporter activity.
P334 (= P264) mutation to R: Abolishes H(+)-coupled sialic acid transporter activity.
G371 (≠ C300) mutation to V: Remains in the endoplasmic reticulum.

Sites not aligning to the query:

22:23 Dileucine internalization motif; LL→AA: Targeted to plasma membrane; sialic acid uptake strongly activated at acidic pH.
39 R→C: Markedly decreases H(+)-coupled sialic acid transporter activity.

Q8BN82 Sialin; H(+)/nitrate cotransporter; H(+)/sialic acid cotransporter; AST; Solute carrier family 17 member 5; Vesicular excitatory amino acid transporter; VEAT from Mus musculus (Mouse) (see paper)
26% identity, 85% coverage: 36:399/430 of query aligns to 99:472/495 of Q8BN82

query
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Q8BN82

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V

I

F

G

G

A

A

V

I

H183 (≠ S118) mutation to R: Abolishes sialic acid transporter activity. Does not affect L-aspartate and L-glutamate transporter activity.

Sites not aligning to the query:

39 R→C: Completely abolishes L-aspartate and L-glutamate transporter activity. Retains appreciable H(+)-coupled sialic acid transporter activity.

Q03567 Uncharacterized transporter slc-17.2 from Caenorhabditis elegans (see paper)
27% identity, 56% coverage: 46:285/430 of query aligns to 84:337/493 of Q03567

query
sites
Q03567

G

G

M

M

I

V

F

L

S

S

F

F

V

Y

G

G

Y

Y

A

I

A

G

F

S

N

Q

F

I

I

I

G

G

W

H

A

L

A

A

D

S

R

R

Y

Y

G

G

A

G

K

K

T

R

T

V

L

V

-

F

-

V

-

T

L

I

L

L

A

G

M

S

V

A

L

L

W

L

S

T

L

L

F

L

S

N

G

P

L

V

T

A

V

A

L

R

T

T

V

S

G

E

F

Y

A

A

S

-

L

L

V

A

L

I

I

L

R

R

I

A

L

A

F

I

G

G

M

F

G

L

E

Q

G

G

P

A

L

T

S

F

V

P

T

A

T

M

S

H

K

T

M

M

V

W

N

S

N

V

W

W

Y

G

T

P

P

P

K

L

R

E

R

L

A

S

R

V

A

L

I

T

G

G

A

V

S

T

M

Y

S

A

G

G

T

A

P

Q

L

I

G

G

G

N

A

V

I

I

S

V

G

L

P

P

V

L

V

S

G

G

F

F

I

L

A

C

V

E

-

Y

-

G

-

F

T

D

Y

G

G

G

W

W

K

P

I

S

S

I

F

F

I

Y

I

I

M

G

L

V

I

F

G

G

L

V

V

L

W

W

A

T

A

A

V

V

W

W

F

W

K

Y

F

V

V

S

K

S

E

D

R

K

P

P

-

A

-

T

-

H

-

P

-

R

-

I

-

T

-

P

-

E

E

E

G

K

E

Q

G

Y

A

I

E

V

D

T

I

A

L

V

R

E

A

A

E

S

G

M

Q

G

G

K

E

D

L

T

A

G

A

K

Q

V

P

P

V

S

F

T

P

P

L

W

R

I

F

K

Y

I

L

L

K

T

Q

S

P

P

T

A

V

V

L

W

F

A

T

C

S

W

L

A

A

G

F

H

F

F

S

A

Y

G

N

D

Y

W

T

G

L

A

F

Y

F

T

F

M

L

L

T

V

W

S

F

L

P

P

S

S

Y

F

L

L

T

K

M

D

A

V

H

L

G

G

L

L

N

N

V

L

K

S

D

S

M

L

S

G

I

A

A

V

T

A

V

S

I

I

P

P

W

Y

V

I

L

A

G

Y

F

F

L

L

G

A

L

I

A

N

L

A

G

G

F

V

I

L

S

A

D

D

F

T

V

L

F

R

K

S

K

K

Sites not aligning to the query:

69 modified: carbohydrate, N-linked (GlcNAc...) asparagine

Q9Y2C5 Probable small intestine urate exporter; Solute carrier family 17 member 4 from Homo sapiens (Human) (see 2 papers)
23% identity, 84% coverage: 38:399/430 of query aligns to 103:475/497 of Q9Y2C5

query
sites
Q9Y2C5

Y

Y

G

D

L

W

S

S

T

P

G

E

E

I

M

Q

G

G

M

I

I

I

F

L

S

S

F

L

F

N

V

Y

G

G

Y

S

A

F

A

L

F

A

N

P

F

I

I

P

G

S

G

G

W

Y

A

V

A

A

D

G

R

I

Y

F

G

G

A

A

K

K

T

Y

T

V

L

V

L

G

L

A

A

G

M

L

V

F

L

I

W

S

S

S

L

F

F

L

S

T

G

L

L

F

T

I

V

P

L

L

-

A

T

N

V

A

G

G

F

V

A

A

S

L

L

L

V

I

L

V

I

L

R

R

I

I

L

V

F

Q

G

G

M

I

G

A

E

Q

G

V

P

M

L

V

S

L

V

T

T

G

T

Q

S

Y

K

S

M

I

V

W

N

V

N

K

W

W

Y

A

T

P

P

P

K

L

R

E

R

R

A

S

R

Q

A

L

I

T

G

T

A

I

S

A

M

G

S

S

G

G

T

S

P

M

L

L

G

G

G

S

A

F

I

I

S

V

G

L

P

L

V

A

V

G

G

G

F

L

I

L

A

C

V

Q

T

T

Y

I

G

G

W

W

K

P

I

Y

S

V

F

F

I

Y

I

I

I

F

M

G

L

G

I

I

G

G

L

C

V

A

W

C

A

C

A

P

V

L

W

W

F

F

K

P

F

L

V

I

K

Y

E

D

R

D

P

P

E

V

G

N

E

H

-

P

-

F

-

I

-

S

-

A

-

G

G

E

A

K

E

R

D

Y

I

I

L

V

R

C

A

S

E

L

G

A

Q

Q

G

Q

E

D

L

C

A

S

A

P

Q

G

P

W

V

S

F

L

P

P

L

I

R

R

F

A

Y

M

L

I

K

K

Q

S

P

L

T

P

V

L

L

W

F

A

T

I

S

L

L

V

A

S

F

Y

F

F

S

C

Y

E

N

Y

Y

W

T

L

L

F

F

Y

F

T

F

I

L

M

T

A

W

Y

F

T

P

P

S

T

Y

Y

L

I

T

S

M

S

A

V

H

L

G

Q

L

A

N

N

V

L

K

R

D

D

M

S

S

G

I

I

A

L

T

S

V

A

I

L

P

P

W

F

V

V

L

V

G

G

F

C

L

I

G

C

L

I

A

I

L

L

G

G

F

L

I

L

S

A

D

D

F

F

V

L

F

L

-

S

K

R

K

K

T

I

G

L

R

R

M

L

M

I

F

T

S

I

R

R

K

K

V

L

V

F

L

T

V
x
A

T

-

C

-

L

-

A

-

C

-

A

-

V

-

C

-

I

-

A

-

C

-

A

-

G

-

M

-

V

I

T

G

T

V

L

L

Y

F

P

P

A

S

V

V

I

I

L

L

V

V

A

S

L

L

-

P

-

W

-

V

-

R

-

S

-

H

-

S

-

M

A

T

V

M

F

T

F

F

L

L

Y

V

L

L

T

S

G

S

A

A

I

I

Y

S

W

S

-

F

-

C

-

E

-

S

-

G

A

A

I

L

I

V

Q

N

D

F

T

L

V

D

P

I

A

A

A

P

R

R

V

Y

G

T

G

G

-

F

V

L

S

K

G

G

F

L

M

L

H

Q

F

V

L

F

A

A

N

H

T

I

S

A

G

G

I

A

V

I

G

S

P

P

T

T

L

A

T

A

G

G

F

F

L

F

V

I

Q

S

F

Q

T

D

G

S

S

E

F

F

-

G

-

W

T

R

S

N

A

V

F

F

L

L

A

S

G

A

L

A

L

V

T

N

V

I

I

S

G

G

A

L

V

V

A372 (≠ V298) to T: in dbSNP:rs11754288

Sites not aligning to the query:

66 modified: carbohydrate, N-linked (GlcNAc...) asparagine; N→A: Loss of glycosylation and significant reduction in the transport of thyroid hormones T3 and T4; when associated with A-75 and A-90.
75 modified: carbohydrate, N-linked (GlcNAc...) asparagine; N→A: Loss of glycosylation and significant reduction in the transport of thyroid hormones T3 and T4; when associated with A-66 and A-90.
90 modified: carbohydrate, N-linked (GlcNAc...) asparagine; N→A: Loss of glycosylation and significant reduction in the transport of thyroid hormones T3 and T4; when associated with A-75 and A-90.

Q9JI12 Vesicular glutamate transporter 2; VGluT2; Differentiation-associated BNPI; Differentiation-associated Na(+)-dependent inorganic phosphate cotransporter; Solute carrier family 17 member 6 from Rattus norvegicus (Rat) (see 2 papers)
24% identity, 62% coverage: 18:285/430 of query aligns to 95:376/582 of Q9JI12

query
sites
Q9JI12

V

I

I

V

N

D

Y

M

L

V

D

N

R

N

S

S

A

T

L

I

S

H

V

R

A

G

P

K

F

V

I

I

Q

K

K

E

D

K

-

A

-

K

Y

F

G

N

L

W

S

D

T

P

G

E

E

T

M

V

G

G

M

M

I

I

F
x
H

S

G

S

S

F

F

V

W

G

G

Y

Y

A

I

F

T

N

Q

F

I

I

P

G

G

W

Y

A

I

A

A

D

S

R

R

Y

L

G

A

A

A

K

N

T

R

T

V

L

F

L

G

L

A

A

A

M

I

V

L

L

L

W

T

S

S

L

T

F

L

S

N

G

M

L

L

-

I

-

P

T

S

V

A

L

A

T

R

V

V

G

H

F

Y

A

G

S

C

L

V

V

I

L

F

I

V

R
|
R

I

I

L

L

F

Q

G

G

M

L

G

V

E
|
E

G

G

P

V

L

T

S

Y

V

P

T

A

T

C

S

H

K

G

M

I

V

W

N

S

N

K

W

W

Y

A

T

P

P

P

K

L

R

E

R

R

A

S

R

R

A

L

I

A

G

T

A

T

S

S

M

F

S

C

G

G

T

S

P

Y

L

A

G

G

G

A

A

V

I

I

S

A

G

M

P

P

V

L

V

A

G

G

F

I

I

L

A

V

V

Q

T

Y

Y

T

G

G

W

W

K

S

I

S

S

V

F

F

I

Y

I

V

I

Y

M

G

L

S

I

F

G

G

L

M

V

V

W

W

A

Y

A

M

V

F

W

W

F

L

K

L

F

V

V

S

K

Y

E

E

R

S

P

P

E

A

G

K

E

H

-

P

-

T

-

I

-

T

G

D

A

E

E

E

D

R

I

R

L

Y

R

I

A

E

E

E

G

S

Q

I

G

G

E

E

-

S

-

A

-

N

-

L

L

L

A

G

A

A

Q

M

P

E

V

K

F

F

-

K

-

T

P

P

L

W

R

R

F

K

Y

F

L

F

K

T

Q

S

P

M

T

P

V

V

L

Y

F

A

T

I

S

I

L

V

A

A

F

N

F

F

S

C

Y
x
R

N

S

Y

W

T

T

L

F

F

Y

F

L

L

L

T

I

W

S

F

Q

P

P

S

A

Y

Y

L

F

T

E

M

E

A

V

H

F

G

G

L

F

N

E

V

I

K

S

D

K

M

V

S

G

I

M

A

L

T

S

V

A

I

V

P

P

W

H

V

L

L

V

G

M

F

T

L

I

G

I

L

V

A

P

L

I

G

G

F

Q

I

I

S

A

D

D

F

F

V

L

F

R

K

S

K

K

H128 (≠ F49) mutation to A: Greatly lowers L-glutamate transport.
R184 (= R103) mutation R->A,E,K: Greatly lowers L-glutamate transport.
E191 (= E110) mutation to A: Greatly lowers L-glutamate transport.; mutation E->D,Q: Lowers L-glutamate transport.
R322 (≠ Y231) mutation to A: Loss of L-glutamate release. Abolishes the chloride ion conductance.

Sites not aligning to the query:

88 R→A: Impairs synaptic transmission. Abolishes the chloride ion conductance.

7t3nA R184q/e191q mutant of rat vesicular glutamate transporter 2 (vglut2)
24% identity, 62% coverage: 18:285/430 of query aligns to 37:318/452 of 7t3nA

query
sites
7t3nA

V

I

I

V

N

D

Y

M

L

V

D

N

R

N

S

S

A

T

L

I

S

H

V

R

A

G

P

K

F

V

I

I

Q

K

K

E

D

K

-

A

-

K

Y

F

G

N

L

W

S

D

T

P

G

E

E

T

M

V

G

G

M

M

I

I

F

H

S

G

S

S

F

F

V

W

G

G

Y
|
Y

A

I

F

T

N

Q

F

I

I

P

G

G

W

Y

A

I

A

A

D

S

R

R

Y

L

G

A

A

A

K

N

T

R

T

V

L

F

L

G

L

A

A

A

M

I

V

L

L

L

W

T

S

S

L

T

F

L

S

N

G

M

L

L

-

I

-

P

T

S

V

A

L

A

T

R

V

V

G

H

F

Y

A

G

S

C

L

V

V

I

L

F

I

V

R

Q

I

I

L

L

F

Q

G

G

M

L

G

V

E

Q

G

G

P

V

L

T

S
x
Y

V

P

T

A

T

C

S

H

K

G

M

I

V

W

N

S

N

K

W

W

Y

A

T

P

P

P

K

L

R
x
E

R

R

A

S

R

R

A

L

I

A

G

T

A

T

S

S

M

F

S

C

G
|
G

T

S

P
x
Y

L

A

G

G

G

A

A

V

I

I

S

A

G

M

P

P

V

L

V

A

G

G

F

I

I

L

A

V

V

Q

T

Y

Y

T

G

G

W

W

K

S

I

S

S

V

F

F

I

Y

I

V

I

Y

M

G

L

S

I

F

G

G

L

M

V

V

W

W

A

Y

A

M

V

F

W

W

F

L

K

L

F

V

V

S

K

Y

E

E

R

S

P

P

E

A

G

K

E

H

-

P

-

T

-

I

-

T

G

D

A

E

E

E

D

R

I

R

L

Y

R

I

A

E

E

E

G

S

Q

I

G

G

E

E

-

S

-

A

-

N

-

L

L

L

A

G

A

A

Q

M

P

E

V

K

F

F

-

K

-

T

P

P

L

W

R

R

F

K

Y

F

L

F

K

T

Q

S

P

M

T

P

V

V

L

Y

F

A

T

I

S

I

L

V

A

A

F

N

F

F

S

C

Y
x
R

N

S

Y

W

T

T

L
x
F

F
x
Y

F

L

L

L

T

I

W

S

F

Q

P

P

S

A

Y

Y

L

F

T

E

M

E

A

V

H

F

G

G

L

F

N

E

V

I

K

S

D

K

M

V

S

G

I

M

A

L

T

S

V

A

I

V

P

P

W

H

V

L

L

V

G

M

F

T

L

I

G

I

L

V

A

P

L

I

G

G

F

Q

I

I

S

A

D

D

F

F

V

L

F

R

K

S

K

K

binding (1s,3r)-1-aminocyclopentane-1,3-dicarboxylic acid: Y77 (= Y56), Y137 (≠ S114), Y165 (≠ P142), R264 (≠ Y231), F268 (≠ L235), Y269 (≠ F236)
binding (2R)-2-(methoxymethyl)-4-{[(25R)-spirost-5-en-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside: E152 (≠ R129), G163 (= G140)

Sites not aligning to the query:

binding (2R)-2-(methoxymethyl)-4-{[(25R)-spirost-5-en-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside: 12, 13

A2SWM2 Sphingosine-1-phosphate transporter SPNS2; Protein spinster homolog 2; Protein two of hearts from Danio rerio (Zebrafish) (Brachydanio rerio) (see paper)
24% identity, 85% coverage: 12:376/430 of query aligns to 60:435/504 of A2SWM2

query
sites
A2SWM2

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R153 (= R103) mutation to S: In ko157; displays cardia bifida (2 hearts).

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)
28% identity, 56% coverage: 8:246/430 of query aligns to 15:242/403 of P77589

query
sites
P77589

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E27 (≠ N20) mutation to A: Lack of 3HPP transport activity.; mutation to D: Slight decrease in 3HPP transport activity.
D75 (= D68) mutation D->A,E: Lack of 3HPP transport activity.

Sites not aligning to the query:

272 A→H: 30% increase in 3HPP transport activity.
276 K→D: Lack of 3HPP transport activity.

Q8IVW8 Sphingosine-1-phosphate transporter SPNS2; Protein spinster homolog 2 from Homo sapiens (Human) (see 2 papers)
24% identity, 87% coverage: 2:376/430 of query aligns to 97:482/549 of Q8IVW8

query
sites
Q8IVW8

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R200 (= R103) mutation to S: Loss of function; does not rescue the cardia bifida phenotype in the morpholino knockdown in zebrafish.
S319 (= S225) natural variant: Missing (in DFNB115; uncertain significance; dbSNP:rs749994718)

7yubR S1p-bound human spns2 (see paper)
24% identity, 87% coverage: 2:376/430 of query aligns to 5:370/429 of 7yubR

query
sites
7yubR

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binding (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate: Y24 (= Y21), F59 (≠ Y56), L229 (≠ F238), E321 (≠ V328), F325 (≠ Y332)

Q5EXK5 3-hydroxybenzoate transporter MhbT from Klebsiella oxytoca (see paper)
23% identity, 75% coverage: 9:329/430 of query aligns to 23:351/452 of Q5EXK5

query
sites
Q5EXK5

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D82 (= D68) mutation to A: Loss of activity.
V311 (≠ F277) mutation to W: Loss of activity.
D314 (= D280) mutation to A: Loss of activity.

7yudR Fty720p-bound human spns2 (see paper)
24% identity, 87% coverage: 5:376/430 of query aligns to 1:358/417 of 7yudR

query
sites
7yudR

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binding (2~{S})-2-azanyl-4-(4-octylphenyl)-2-[[oxidanyl-bis(oxidanylidene)-$l^{6}-phosphanyl]oxymethyl]butan-1-ol: Y17 (= Y21), Y21 (≠ S25), S143 (vs. gap), T214 (≠ L235), E309 (≠ V328)

Q9GQQ0 Protein spinster; Protein benchwarmer; Protein diphthong from Drosophila melanogaster (Fruit fly) (see paper)
21% identity, 81% coverage: 3:350/430 of query aligns to 110:459/605 of Q9GQQ0

query
sites
Q9GQQ0

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E217 (= E110) mutation to K: In bnch(N); leads to storage in yolk spheres during oogenesis and results in widespread accumulation of enlarged lysosomal and late endosomal inclusions.

8jhqA Cryo-em structure of human s1p transporter spns2 bound with s1p (see paper)
23% identity, 87% coverage: 2:376/430 of query aligns to 3:387/446 of 8jhqA

query
sites
8jhqA

F

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G

G

M

L

I

L

F

Q

S

S

S

V

F

F

F

I

V

C

G

S

Y

F

A

M

A

V

F

A

N

A

F

P

I

I

G

F

G

G

W

Y

A

L

A

G

D

D

R

R

Y

F

G

N

A

R

K

K

T

V

T

I

L

L

L

S

L

C

A

G

M

I

V

F

L

F

W

W

S

S

-

A

-

V

L

T

F

F

S

S

G

S

L

S

T

F

V

I

L

P

T

Q

V

Q

G

Y

F

F

A

W

S

L

L

L

V

V

L

L

I

S

R

R

I

G

L

L

F

V

G

G

M

I

G

G

E

E

G

A

P

S

L

Y

S

S

V

T

T

I

T

A

S

P

K

T

M

I

V

I

N

G

N

D

W

L

Y

F

T

-

P

K

K

N

R

T

R

R

A

T

R

L

A

M

I

L

G

S

A

V

S

F

M

Y

S

F

G

A

T

I

P

P

L

L

G

G

-

S

-

G

-

L

G

G

A

Y

I

I

S

T

G

G

P

S

V

S

V

V

G

K

F

Q

I

A

A

A

V

G

T

D

Y

W

G

H

W

W

K

A

I

L

S

R

F

-

I

-

I

V

I

S

M

P

L

V

I

L

G

G

L

M

V

I

W

T

A

G

A

T

V

L

W

I

F

L

K

I

F

L

V

V

K

P

E

A

R

T

P

K

E

R

G

G

E

H

G

A

A

D

E

Q

-

L

-

G

D

D

I

Q

L

L

R

K

A

A

E

R

G

-

Q

-

G

-

E

-

L

-

A

-

A

T

Q

S

P

W

V

L

F

R

P

D

L

M

R

K

F

A

Y

L

L

I

K

R

Q

N

P

R

T

S

V

Y

L

V

F

F

T

S

S

S

L

L

A

A

F
x
T

F

S

S

A

Y

V

N

S

Y

F

T

A

L

T

F

G

F

A

F
x
L

L

G

T

M

W

W

F

I

P

P

S

L

Y

Y

L

L

T

H

M

R

A

A

H

Q

G

V

L

V

N

Q

-

K

-

T

-

A

-

E

-

T

-

C

-

N

-

S

-

P

-

C

-

G

V

A

K

K

D

D

M

S

S

L

I

I

A

F

T

G

V

A

I

I

P

T

W

C

V

F

L

T

G

G

F

F

L

L

G

G

L

V

A

V

L

T

G

G

G

A

F

G

I

A

S

T

D

R

F

W

V

C

F

R

K

L

K

K

T

T

G

Q

R

R

M

-

F

-

S

A

R

D

K

P

V

L

V

V

L

C

V

A

T

V

C

G

L

M

L

L

A

G

C

S

A

A

-

I

-

F

V

I

C

C

I

L

A

I

C

F

A

V

G

A

M

A

V

K

T

S

L

I

Y

V

P

G

A

A

V

Y

I

I

L

C

V

I

A

F

L

V

A

G

V
x
E

F

T

F

L

L

L

Y
x
F

L

S

T

N

G

W

A

A

I

I

Y

T

W

A

A

D

I

I

I

L

Q

M

D

Y

T

V

V

V

P

I

A

P

A

T

R

R

V

R

G

A

G

T

V

A

S

V

G

A

F

L

M
x
Q

H

S

F

F

L

T

A

S

N

H

T

L

S

L

G

G

I

D

V

A

G

G

-

S

P

P

T

Y

L

L

T

I

G

G

F

F

L

I

binding (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate: T227 (≠ F228), L237 (≠ F238), E338 (≠ V328), F342 (≠ Y332), Q368 (≠ M358)

8g92A Structure of inhibitor 16d-bound spns2 (see paper)
24% identity, 87% coverage: 4:376/430 of query aligns to 1:358/415 of 8g92A

query
sites
8g92A

Q

E

G

K

R

R

S

K

L

A

I

A

M

I

L

L

F

S

L

L

A

G

G

N

V

V

I

L

N

N

Y

Y

L

L

D

D

R

R

S
x
Y

A

T

L

V

S

A

V

G

A

V

A

L

P

L

F

D

I

I

Q

Q

K

Q

D

H

Y

F

G

G

L

V

S

K

T

D

G

R

E

G

M

A

G

G

M

L

I

L

F

Q

S

S

S

V

F

F

F

I

V

C

G

S

Y

F

A

M

A

V

F

A

N

A

F

P

I

I

G

F

G

G

W

Y

A

L

A

G

D

D

R

R

Y

F

G

N

A

R

K

K

T

V

T

I

L

L

L

S

L

C

A

G

M

I

V

F

L

F

W

W

S

S

-

A

-

V

L

T

F

F

S

S

G

S

L

S

T

F

V

I

L

P

T

Q

V

Q

G

Y

F

F

A

W

S

L

L

L

V

V

L

L

I

S

R

R

I

G

L

L

F

V

G

G

M

I

G

G

E

E

G

A

P

S

L

Y

S

S

V

T

T

I

T

A

S

P

K

T

M

I

V

I

N

G

N

D

W

L

Y

F

T

T

P

K

K

N

R

T

R

R

A

T

R

L

A

M

I

L

G

S

A

V

S

F

M
x
Y

S

F

G

A

T
x
I

P

P

L

L

G

G

-
x
S

-

G

-

L

G

G

A

Y

I

I

S

T

G

G

P

S

V

S

V

V

G

K

F

Q

I

A

A

A

V

G

T

D

Y

W

G

H

W

W

K

A

I

L

S

R

F

-

I

-

I

V

I

S

M

P

L

V

I

L

G

G

L

M

V

I

W

T

A

G

A

T

V

L

W

I

F

L

K

I

F

L

V

V

K

-

E

-

R

-

P

-

E

-

G

-

E

P

G

A

A

T

E

K

D

S

I

W

L

L

R

R

A

-

E

-

G

-

Q

-

G

-

E

-

L

-

A

-

Q

-

P

-

V

-

F

-

P

D

L

M

R

K

F

A

Y

L

L

I

K

R

Q

N

P

R

T

S

V

Y

L

V

F

F

T

S

S

S

L

L

A

A

F

T

F

S

S

A

Y

V

N

S

Y

F

T

A

L

T

F

G

F

A

F

L

L
x
G

T

M

W

W

F

I

P

P

S

L

Y

Y

L

L

T

H

M

R

A

A

H

Q

G

V

L

V

N

Q

-

K

V

A

K

K

D

D

M

S

S

L

I

I

A

F

T

G

V

A

I

I

P

T

W

C

V

F

L

T

G

G

F

F

L

L

G

G

L

V

A

V

L

T

G

G

G

A

F

G

I

A

S

T

D

R

F

W

V

C

F

R

K

L

K

K

T

T

G

Q

R

R

M

-

F

-

S

A

R

D

K

P

V

L

V

V

L

C

V

A

T

V

C

G

L

M

L

L

A

G

C

S

A

A

-

I

-

F

V

I

C

C

I

L

A

I

C

F

A

V

G

A

M

A

V

K

T

S

L

I

Y

V

P

G

A

A

V

Y

I

I

L

C

V

I

A

F

L

V

A

G

V

E

F

T

F

L

L

L

Y
x
F

L

S

T

N

G
x
W

A

A

I

I

Y

T

W

A

A

D

I

I

I

L

Q

M

D

Y

T

V

V

V

P

I

A

P

A

T

R

R

V

R

G

A

G

T

V

A

S

V

G

A

F

L

M

Q

H

S

F

F

L

T

A

S

N

H

T

L

S

L

G

G

I

D

V

A

G

G

-

S

P

P

T

Y

L

L

T

I

G

G

F

F

L

I

binding 3-[3-(4-decylphenyl)-1,2,4-oxadiazol-5-yl]propan-1-amine: Y22 (≠ S25), Y137 (≠ M138), I140 (≠ T141), S144 (vs. gap), G220 (≠ L239), F313 (≠ Y332), W316 (≠ G335)

Q6ZSM3 Monocarboxylate transporter 12; MCT 12; Creatine transporter 2; CRT2; Solute carrier family 16 member 12 from Homo sapiens (Human) (see 3 papers)
25% identity, 70% coverage: 120:420/430 of query aligns to 163:478/516 of Q6ZSM3

query
sites
Q6ZSM3

M

M

V

V

N

G

N

K

W

Y

Y

F

T

S

P

-

K

R

R

R

R

K

A

A

R

L

A

A

I

Y

G

G

A

I

S

A

M

M

S

S

G

G

T

S

P

G

L

I

G

G

G

T

A

F

I

I

S

L

G

A

P

P

V

V

G

Q

F

L

I

L

A

I

V

E

T

Q

Y

F

G

S

W

W

K

R

I

G

S

A

F

L

I

L

I

I

I

L

-

G

-

F

-

V

-

L

-

N

-

L

M

C

L

V

I

C

G

G

L

A

V

L

W

M

A

R

A

P

V

I

W

T

F

L

K

K

F

E

V

D

K

H

E

T

R

T

P

P

E

E

G

Q

E

N

G

H

-

V

-

C

-

R

-

T

-
x
Q

A
x
K

E
|
E

D
|
D

I
|
I

L
x
K

R
|
R

A
x
V

E
x
S

G
x
P

Q
x
Y

G
x
S

E
x
S

L
|
L

A
x
T

A
x
K

Q
x
E

-
x
W

P
x
A

V
x
Q

F
x
T

P
x
C

L
|
L

R
x
C

F
x
C

Y
x
C

L
|
L

K
x
Q

Q
|
Q

P
x
E

-
x
Y

-
x
S

-
x
F

-
x
L

-
x
M

-
x
S

-
x
D

-
x
F

T
x
V

V
|
V

L
|
L

F
x
A

T
x
V

S
|
S

L
x
V

A
x
L

F
|
F

F
x
M

S
x
A

Y
|
Y

N
x
G

Y
x
C

T
x
S

-
x
P

L
|
L

F
|
F

F
x
V

F
x
Y

L
|
L

T
x
V

W
x
P

F
x
Y

P
x
A

S
x
L

Y
x
S

L
x
V

T
x
G

M
x
V

A
x
S

H
|
H

G
x
Q

L
x
Q

N
x
A

V
x
A

K
x
F

D
x
L

M
|
M

S
|
S

I
|
I

A
x
L

T
x
G

V
|
V

I
|
I

P

-

W

-

V

-

L

-

G
x
D

F
x
I

L
x
I

G
|
G

L
x
N

A
x
I

L
x
T

G
x
F

G
|
G

F
x
W

I
x
L

S
x
T

D
|
D

F
x
R

V
x
R

F
x
C

K
x
L

K
|
K

T
x
N

G
x
Y

R
x
Q

M
x
Y

M
x
V

F
x
C

S
x
Y

R
x
L

K
x
F

V
x
A

V
|
V

L
x
G

V
x
M

T
x
D

C

-

L

-

A

-

C

-

A
x
G

V
x
L

C
|
C

I
x
Y

A
x
L

C
|
C

A
x
L

G
x
P

M
|
M

V
x
L

T
x
Q

T
x
S

L
|
L

Y

-

P

-

A

-

V
x
P

I
x
L

L
|
L

V
|
V

A
x
P

L
x
F

A
x
S

V
x
C

F
x
T

F
|
F

L
x
G

Y
|
Y

L
x
F

T
x
D

G
|
G

A
|
A

-
x
Y

-
x
V

-
x
T

I
x
L

Y
x
I

W
x
P

A
x
V

I
x
V

I
x
T

Q
x
T

D
x
E

T
x
I

V
|
V

P
x
G

A
x
T

R
x
S

V
x
L

G
x
S

V
x
A

S
x
L

G
|
G

F
x
V

M
x
V

H
x
Y

F
|
F

L
|
L

A
x
H

N
x
A

T
x
V

S
x
P

G
x
Y

I
x
L

V
|
V

G
x
S

P
|
P

T
x
P

L
x
I

T
x
A

G
|
G

F
x
R

L
|
L

V
|
V

Q
x
D

F
x
T

T
|
T

G
|
G

S
|
S

F
x
Y

T
|
T

S
x
A

A
|
A

F
|
F

L
|
L

A
x
C

G
|
G

L
x
F

L
x
S

T
x
M

V
x
I

I
x
F

G
x
S

A
x
S

V
|
V

C
x
L

V
x
L

-
x
G

-
x
F

A
|
A

R
|
R

Y
x
L

V
x
I

K
|
K

P
x
R

L
x
M

S
x
R

V
x
K

A
x
T

D
x
Q

T
x
L

G
x
Q

N
x
F

A
x
I

A
|
A

A
x
K

Q
x
E

S
|
S

D329 (≠ G268) mutation to A: Decreases creatine efflux activity. Loss of localization to the plasma membrane.
D360 (≠ T299) mutation to A: Does not affect creatine efflux activity. Does not affect plasma membrane localization.
D387 (≠ T334) mutation to A: Does not affect creatine efflux activity.
G437 (= G381) to S: found in a patient with age-related cataract; uncertain significance; decreases creatine transport; dbSNP:rs759863805

Sites not aligning to the query:

67 R→A: Abolishes creatine efflux activity. Does not affect plasma membrane localization.
95 D→A: Decreases in the creatine efflux activity. Does not affect plasma membrane localization.
245:516 natural variant: Missing (in CTRCT47; loss of localization to the plasma membrane; retained in the endoplasmic reticulum where it undergoes degradation by the proteasome; has no dominant effect on wild-type protein expression and localization)

Query Sequence

>AO356_28540 FitnessBrowser__pseudo5_N2C3_1:AO356_28540
MFGQGRSLIIIMLFLAGVINYLDRSALSVAAPFIQKDYGLSTGEMGMIFSSFFVGYAAFN
FIGGWAADRYGAKTTLLLAMVLWSLFSGLTVLTVGFASLVLIRILFGMGEGPLSVTTSKM
VNNWYTPKRRARAIGASMSGTPLGGAISGPVVGFIAVTYGWKISFIIIMLIGLVWAAVWF
KFVKERPEGEGAEDILRAEGQGELAAQPVFPLRFYLKQPTVLFTSLAFFSYNYTLFFFLT
WFPSYLTMAHGLNVKDMSIATVIPWVLGFLGLALGGFISDFVFKKTGRMMFSRKVVLVTC
LLACAVCIACAGMVTTLYPAVILVALAVFFLYLTGAIYWAIIQDTVPAARVGGVSGFMHF
LANTSGIVGPTLTGFLVQFTGSFTSAFLLAGLLTVIGAVCVARYVKPLSVADTGNAAAQS
PQPVSALGRS

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