SitesBLAST

C344 (≠ G412) mutation to S: Small decrease in proline uptake activity. Confers resistance to N-ethylmaleimide. Exhibits low Na(+)-dependent proline binding.
C349 (≠ I417) mutation to S: Does not affect proline uptake activity. Sensitive to N-ethylmaleimide. Na(+)-dependent proline binding activity is similar to wild-type carrier.
R376 (= R444) mutation R->E,Q: No change in activity.; mutation to K: Loss of activity.

Sites not aligning to the query:

257 R→C: Sodium-independent binding affinity for proline.
281 C→S: Does not affect proline uptake activity. Confers resistance to N-ethylmaleimide. Na(+)-dependent proline binding activity is similar to wild-type carrier.

P31639 Sodium/glucose cotransporter 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter; Solute carrier family 5 member 2 from Homo sapiens (Human) (see paper)
25% identity, 40% coverage: 7:243/589 of query aligns to 25:262/672 of P31639

query
sites
P31639

N

D

M

I

L

L

F

V

V

I

G

A

A

A

S

Y

F

F

L

L

Y

V

I

I

G

G

I

V

A

G

V

L

W

W

A

S

R

M

A

C

-

R

-

T

-

N

-

R

G

G

S

T

T

V

K

G

E

G

F

Y

Y

F

V

L

A

A

G

G

G

R

G

S

V

M

H

V

P

W

V

W

T

P

N

V

G

G

M

A

A

S

T

L

A

F

A

A

D

S

W

N

M

I

S

G

A

S

A

G

S

H

F

F

I

V

S

G

M

L

A

A

G

G

L

T

I

G

A

A

S

A

G

S

G

G

Y

L

A

A

T
x
V

S

A

V

G

Y
x
F

L

-

M

-

G

E

W

W

T

N

G

A

G

L

Y

F

V

V

-

V

-

L

L

L

A

G

M

W

L

L

L

F

A

A

P

P

Y

V

L

Y

R

L

K

T

F

A

G

G

K

V

F

I

T

T

V

M

P

P

D

Q

F

Y

I

L

G

R

D

K

R

R

F

F

Y

G

S

G

R

R

G

R

A

I

R

R

L

L

-

Y

T

L

A

S

V

V

V

L

C

S

L

L

I

F

L

L

I

Y

S

I

V

F

T

T

Y

K

V

I

I

S

G
x
V

Q

D

M

M

A

F

G

S

A

G

G

A

V

V

A

F

F

I

S

Q

R

Q

F

A

L

L

E

G

V

W

S

N

N

I

S

Y

A

A

G

S

I

V

W

I

I

A

A

L

A

G

I

I

V

T

F

M

A

I

Y

Y

A

T

V

V

F

T

G

G

M

L

K

A

G

A

I

L

T

M

Y

Y

T

T

Q

D

V

T

A

V

Q

Q

Y

T

I

F

V

V

L

I

I

L

I

G

A

G

Y

A

T

C

I

I

P

L

A

M

V

G

F

Y

I

A

A

F

M

H

Q

E

L

V

T

G

G

G

N

Y

P

S

I

-

P

-

M

-

F

-

G

G

M

L

F

F

G

D

T

K

H

Y

V

L

D

G

S

A

G

A

V

T

P

S

L

L

L

T

D

V

K

S

L

E

D

D

Q

P

V

A

V

V

T

G

D

N

L

I

G

S

F

S

A

F

A

C

Y

Y

T

R

A

P

D

R

V

P

D

D

N

S

V95 (≠ T73) mutation to A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
F98 (≠ Y76) mutation to A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin.
V157 (≠ G134) mutation to A: Decreases D-glucose transporter activity.

Sites not aligning to the query:

283 L→M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition.
453 F→A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin.

7vsiA Structure of human sglt2-map17 complex bound with empagliflozin (see paper)
25% identity, 40% coverage: 7:243/589 of query aligns to 5:242/586 of 7vsiA

query
sites
7vsiA

N

D

M

I

L

L

F

V

V

I

G

A

A

A

S

Y

F

F

L

L

Y

V

I

I

G

G

I

V

A

G

V

L

W

W

A

S

R

M

A

C

-

R

-

T

-

N

-

R

G

G

S

T

T

V

K

G

E

G

F

Y

Y

F

V

L

A

A

G

G

G

R

G

S

V

M

H

V

P

W

V

W

T

P

N

V

G

G

M

A

A

S

T

L

A

F

A

A

D

S

W
x
N

M

I

S

G

A

S

A

G

S
x
H

F

F

I

V

S
x
G

M
x
L

A

A

G

G

L
x
T

I

G

A

A

S

A

G

S

G

G

Y

L

A

A

T
x
V

S

A

V

G

Y
x
F

L

-

M

-

G
x
E

W

W

T

N

G
x
A

G

L

Y

F

V

V

-

V

-

L

L

L

A

G

M

W

L

L

L

F

A

A

P

P

Y

V

L

Y

R

L

K

T

F

A

G

G

K

V

F

I

T

T

V

M

P

P

D

Q

F

Y

I

L

G

R

D

K

R

R

F

F

Y

G

S

G

R

R

G

R

A

I

R

R

L

L

-

Y

T

L

A

S

V

V

V

L

C

S

L

L

I

F

L

L

I

Y

S

I

V

F

T

T

Y

K

V

I

I

S

G
x
V

Q

D

M

M

A

F

G

S

A

G

G

A

V

V

A

F

F

I

S

Q

R

Q

F

A

L

L

E

G

V

W

S

N

N

I

S

Y

A

A

G

S

I

V

W

I

I

A

A

L

A

G

I

I

V

T

F

M

A

I

Y

Y

A

T

V

V

F

T

G

G

M

L

K

A

G

A

I

L

T

M

Y

Y

T

T

Q

D

V

T

A

V

Q

Q

Y

T

I

F

V

V

L

I

I

L

I

G

A

G

Y

A

T

C

I

I

P

L

A

M

V

G

F

Y

I

A

A

F

M

H

Q

E

L

V

T

G

G

G

N

Y

P

S

I

-

P

-

M

-

F

-

G

G

M

L

F

F

G

D

T

K

H

Y

V

L

D

G

S

A

G

A

V

T

P

S

L

L

L

T

D

V

K

S

L

E

D

D

Q

P

V

A

V

V

T

G

D

N

L

I

G

S

F

S

A

F

A

C

Y

Y

T

R

A

P

D

R

V

P

D

D

N

S

binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: N55 (≠ W53), H60 (≠ S58), G63 (≠ S61), L64 (≠ M62), T67 (≠ L65), V75 (≠ T73), F78 (≠ Y76), E79 (≠ G79), A82 (≠ G82), V137 (≠ G134)

Sites not aligning to the query:

binding (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol: 266, 267, 270, 271, 301, 433, 434, 437, 506

Q9NY91 Probable glucose sensor protein SLC5A4; Solute carrier family 5 member 4 from Homo sapiens (Human) (see paper)
23% identity, 39% coverage: 15:243/589 of query aligns to 36:262/659 of Q9NY91

query
sites
Q9NY91

F

F

L

L

L

V

Y

V

I

M

G

A

I

V

A

G

V

L

W

W

A

A

-

M

-

L

-

K

-

T

R

N

A

R

G

G

S

T

T

I

K

G

E

G

F

F

Y

F

V

L

A

A

G

G

G

R

G

D

V

M

H

A

P

W

V

W

T

P

N

M

G

G

M

A

A

S

T

L

A

F

A

A

D

S

W

N

M

I

S

G

A

S

A

N

S

H

F

Y

I

V

S

G

M

L

A

A

G

G

L

T

I

G

A

A

S

A

G

S

G

G

Y

V

A

A

T

T

S

V

V

T

Y

F

L

-

M

-

G

E

W

W

T

T

G

S

Y

V

V

M

L

L

A

I

M

L

-

G

-

W

L

I

L

F

A

V

P

P

Y

I

L

Y

R

I

K

K

F

S

G

G

K

V

F

M

T

T

V

M

P

P

D

E

F

Y

I

L

G

K

D

K

R

R

F

F

Y

G

S

G

R

E

G

R

A

L

R

Q

L

V

T

Y

A

L

V

S

V

I

C

L

L

S

I

L

L

F

I

I

S

C

V

V

T

V

Y

L

V

L

I

I

G

S

Q

A

M

D

A

I

G

F

A

A

G

G

V

A

A

I

F

F

S

I

R

K

F

L

-

A

L

L

E

G

V

L

S

D

N

L

S

Y

A

L

G

A

I

I

W

F

I

I

A

L

A

A

I

M

V

T

F

A

A

V

Y

Y

A

T

V

T

F

T

G

G

M

L

K

A

G

S

I

V

T

I

Y

Y

T

T

Q

D

V

T

A

L

Q

Q

Y

T

I

I

V

I

L

M

I

L

I

I

A

G

Y

S

T

-

I

-

P

-

A

-

V

-

F

F

I

I

A

L

M

M

Q

G

L

F

T

A

G

F

N

N

P

E

I

V

P

G

M

G

F

Y

G

E

M

S

F

F

G

T

T

E

H

K

V

Y

D

V

S

N

G

A

V

T

P

P

L

S

L

V

D

V

K

E

L

G

D

D

Q

N

V

L

V

T

T

-

D

-

L

I

G

S

F

A

A

S

A

C

Y

Y

T

T

A

P

D

R

V

A

D

D

N

S

Sites not aligning to the query:

457 E→Q: Confers sugar transport activity not found in the wild-type protein. Increased sensitivity to inhibitor phlorizin.

P11170 Sodium/glucose cotransporter 1; Na(+)/glucose cotransporter 1; High affinity sodium-glucose cotransporter; Solute carrier family 5 member 1 from Oryctolagus cuniculus (Rabbit) (see 2 papers)
27% identity, 27% coverage: 351:507/589 of query aligns to 338:494/662 of P11170

query
sites
P11170

M

L

Y

Y

N

T

D

D

A

K

N

V

A

A

K

C

F

V

T

V

P

P

T

S

A

E

T

C

E

E

R

R

G

-

W

Y

N

C

G

G

N

T

E

R

L

V

T

G

V

C

N

T

N

N

D

-

I

-

I

I

V

A

L

F

A

P

N

T

P

L

E

V

I

V

A

E

N

L

L

M

P

P

G

N

W

G

V

L

I

R

G

G

L

L

I

M

A

L

A

S

G

V

A

M

I

M

A

A

A

S

A

L

L

M

S

S

T

S

A

L

A

T

G

S

L

I

L

F

L

N

A

S

I

A

S

S

S

T

A

L

I

F

S

T

H

M

D

D

L

-

I

I

K

Y

T

T

L

K

I

I

N

R

P

K

K

K

I

A

S

S

E

E

K

K

N

E

E

L

M

M

L

I

A

A

A

G

R

R

L

L

S

F

M

M

T

L

A

F

A

L

I

I

L

G

L

I

A

S

-

I

T

A

W

W

L

V

G

P

L

I

N

V

P

Q

P

S

G

A

F

Q

A

S

A

G

Q

Q

V

L

-

F

-

D

-

Y

-

I

-
x
Q

-

S

V

I

A
x
T

L

S

A

Y

F

L

G

G

L

P

A

P

A

I

A

A

S

A

L

V

F

F

P

-

A

-

L

-

M

L

G

A

I

I

F

F

S

W

K

K

R

R

V

V

N

N

S

E

K

P

G

G

A

A

V

F

A

W

G

G

M

L

L

V

V

L

G

G

V

F

I

L

Q457 (vs. gap) mutation to W: Drasticly decreased affinity for glucose and phlorizin.
T460 (≠ A470) mutation to W: Decreased affinity for glucose and phlorizin.

Sites not aligning to the query:

255 modified: Disulfide link with 608
608 modified: Disulfide link with 255

Q92911 Sodium/iodide cotransporter; Na(+)/I(-) cotransporter; Natrium iodide transporter; Sodium-iodide symporter; Na(+)/I(-) symporter; Solute carrier family 5 member 5 from Homo sapiens (Human) (see 3 papers)
24% identity, 35% coverage: 15:223/589 of query aligns to 24:233/643 of Q92911

query
sites
Q92911

F

L

L

L

L

V

Y

S

I

T

G

G

I

I

A

G

V

L

W

W

-

V

-

G

-

L

A

A

R

R

A

G

G

G

-

Q

-

R

S

S

T

A

K

E

E

D

F

F

Y

F

V

T

A

G

G

G

G

R

V

L

H

A

P

A

V

L

T

P

N

V

G

G

M

L

A

S

T

L

A

S

A

A

D

S

W

F

M

M

S

S

A

A

A

V

S

Q

F

V

I

L

S

G

M

V

A

P

G

S

L

E

I

A

A

Y

S

R

G

Y

G

G

Y

L

A

K

T

F

S

L

V

W

Y

M

L

C

M

L

G

G

W

Q

T

L

G

L

G

N

Y

S

V

V

L

L

L

T

A
|
A

M

L

L

L

L

F

A

M

P

P

Y

V

L

F

R

Y

K

R

F

L

G

G

K

L

F

T

T

S

V

T

P

Y

D

E

F

Y

I

L

G

E

D

M

R

R

F

F

Y

-

S

S

R

R

G

A

A

V

R

R

L

L

T

C

A

G

V

-

C

-

L

-

I

-

L

-

I

-

S

T

V

L

T

Q

Y

Y

V

I

I

V

G

A

Q

T

M

M

A

L

G

Y

A

T

G

G

-

I

V

V

A

I

F

Y

S

A

R

P

F

A

L

L

E

I

V

L

S

N

N

Q

S

V

A

T

G

G

I

L

W

D

I

I

A

W

A

A

A

S

-

L

-

S

-

T

-

G

-

I

I

I

V

C

F

T

A

F

Y

Y

A

T

V

A

F

V

G

G

M

M

K

K

G

A

I

V

T

V

Y

W

T

T

Q

D

V

V

A

F

Q

Q

Y

V

I

V

V

V

L

M

I

L

I

S

A

G

Y

F

T

W

I

V

P

-

A

V

V

L

F

A

I

R

A

G

M

V

Q

M

L

L

T

V

G

G

N

G

P

P

I

R

P

Q

M

V

F

L

G

T

M

L

F

A

G

Q

T

N

H
|
H

V

-

D

-

S

S

G

R

V

I

P

N

L

L

L

M

D

D

A102 (= A88) natural variant: A -> P
H226 (= H214) mutation H->A,D,E,K: Significant loss of iodide transport activity but no effect on its localization to the cell membrane.

Sites not aligning to the query:

237 D→A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
242 Required for homodimerization; Y→A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471. Loss of iodide transport activity; when associated with F-535.
243 Required for homodimerization; T→A: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471.
471 Required for homodimerization; Q→A: No effect on localization to the cell membrane, iodide transport activity and homodimerization. Significant loss of homodimerization; when associated with A-242 or A243.
525 A→F: Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Loss of iodide transport activity; when associated with A-242.
536 T → Q: requires 2 nucleotide substitutions
556 S → Q: requires 2 nucleotide substitutions

Query Sequence

>GFF346 FitnessBrowser__psRCH2:GFF346
MSQYWINMLFVGASFLLYIGIAVWARAGSTKEFYVAGGGVHPVTNGMATAADWMSAASFI
SMAGLIASGGYATSVYLMGWTGGYVLLAMLLAPYLRKFGKFTVPDFIGDRFYSRGARLTA
VVCLILISVTYVIGQMAGAGVAFSRFLEVSNSAGIWIAAAIVFAYAVFGGMKGITYTQVA
QYIVLIIAYTIPAVFIAMQLTGNPIPMFGMFGTHVDSGVPLLDKLDQVVTDLGFAAYTAD
VDNKLNMFLFTLSLMIGTAGLPHVIIRFFTVPKVADARWSAGWTLVFIALLYLTAPAVAS
MARLNLVNTIYPEGPQAEAIRYEDRPEWVQTWERTGLIKWEDKNADGRVQMYNDANAKFT
PTATERGWNGNELTVNNDIIVLANPEIANLPGWVIGLIAAGAIAAALSTAAGLLLAISSA
ISHDLIKTLINPKISEKNEMLAARLSMTAAILLATWLGLNPPGFAAQVVALAFGLAAASL
FPALMMGIFSKRVNSKGAVAGMLVGVISTAVYIFLYLGWFFIPGTASIPNTPDQWWMGIS
PQAFGAVGAMLNFAVAYAVSMATEAPPQEIQDLVESVRTPKGAGVALDH

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