SitesBLAST

N16 (= N31) to I: in TYRSN1; loss of activity; dbSNP:rs121965073
A35 (= A51) to T: in TYRSN1; atypical mild phenotype
F62 (≠ C79) to C: in TYRSN1; loss of activity
A134 (= A149) to D: in TYRSN1; loss of activity; dbSNP:rs121965074
C193 (≠ S206) to R: in TYRSN1; loss of activity
D233 (= D246) to V: in TYRSN1; loss of activity; dbSNP:rs80338897
W234 (= W247) to G: in TYRSN1; loss of activity; dbSNP:rs1555441595
Q279 (≠ T294) to R: in TYRSN1; may affect splicing resulting in skipping of exon 8 alone or together with exon 9; lower activity as compared to wild type; dbSNP:rs121965078
R341 (= R363) to W: does not cause a clinically relevant phenotype; results in lower enzyme activity; dbSNP:rs11555096
P342 (≠ A364) to L: in TYRSN1; loss of activity; dbSNP:rs779040832
R381 (= R403) to G: in TYRSN1; loss of activity; dbSNP:rs121965077
F405 (= F428) to H: in TYRSN1; requires 2 nucleotide substitutions

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
2 modified: N-acetylserine

P35505 Fumarylacetoacetase; FAA; Beta-diketonase; Fumarylacetoacetate hydrolase; EC 3.7.1.2 from Mus musculus (Mouse) (see 3 papers)
42% identity, 95% coverage: 22:438/440 of query aligns to 7:415/419 of P35505

query
sites
P35505

A

A

P

E

T

D

C

S

D

D

F

F

P

P

I

I

Q

Q

N

N

L

L

P

P

F

Y

S

G

V

V

F

F

R

S

R

T

R

Q

H

-

S

S

D

N

E

P

A

K

F

P

R

R

G

I

A

G

V

V

A

A

I

I

G

G

D

D

Q

Q

V

I

I

L

D

D

I

L

A

S

A

V

W

-

A

-

S

I

R

K

A

H

G

L

L

F

N

T

G

G

I

P

A

A

-

L

G

S

E

K

G

H

A

Q

R

H

V

V

C

F

A

D

Q

E

P

T

V

T

L

L

N

N

E

N

F

F

F

M

S

G

M

L

G

G

P

Q

S

A

A

A

W

W

R

K

A

E

V

A

R

R

-

A

-

S

-

L

H

Q

A

N

L

L

F

L

A

S

A

A

L

S

H

Q

E

A

R

R

A

L

P

-

S

R

D

D

R

K

A

E

A

L

L

R

E

Q

A

R

C

A

L

F

I

T

P

S

Q

Q

S

A

E

S

V

A

E

T

Y

M

G

H

L

L

P

P

A

A

Q

T

I

I

G

G

D

D

Y

Y

T

T

D
|
D

F

F

Y

Y

T

S

S

S

I

R

H

Q

H

H

A

A

T

T

N

N

I

V

S

G

K

I

L

M

L

F

-

R

-

G

G

K

L

E

S

N

G

A

V

L

G

L

A

P

N

N

F

W

K

L

S

H

I

L

P

P

I

V

A

G

Y

Y

H

H

G

G

R

R

V

A

S

S

I

I

G

V

L

V

S

S

G

G

Q

T

R

P

F

I

R

R

P

P

A

M

G

G

Q

Q

I

M

M

R

L

P

P

D

G

N

E

S

D

K

A

P

P

P

I

V

F

Y

S

G

P

A

S

C

R

R

K

L

L

L

D

D

Y

M

E
|
E

L

L

E
|
E

L

M

G

A

I

F

Y

F

I

V

G

G

Q

P

G

G

N

N

A

R

A

F

G

G

E

E

P

P

I

I

A

P

L

I

D

S

Q

K

A

A

D

H

S

E

H

H

V

I

F

F

G

G

L

M

C

V

L

L

L

M

N

N

D
|
D

W

W

S

S

A

A

R

R

D

D

I

I

Q

Q

A

Q

W

W

E

E

M

Y

Q

V

P

P

L

L

G

G

P

P

F

F

L

L

A

G

K
|
K

N

S

F

F

A

G

T
|
T

T

T

I

I

S

S

P

P

W

W

I

V

V

V

T

P

M

M

E

D

A

A

L

L

A

M

P

P

F

F

R

V

L

V

P

P

L

N

P

P

R

K

P

-

H

-

T

Q

D

D

G

P

K

K

P

P

L

L

P

P

Y

Y

L

L

D

C

S

H

D

S

R

Q

N

P

S

Y

T

T

T

-

G

-

A

-

I

F

D

D

I

I

Q

N

L

L

E

S

V

V

C

S

I

L

E

K

T

G

S

E

R

-

H

-

Q

-

A

-

G

G

N

M

L

S

P

Q

A

A

Q

T

L

I

S

C

L

R

T

S

S

N

F

F

R

K

H

H

Q

M

Y

Y

W

W

S

T

I

M

A

L

Q

Q

M

Q

V

L

A

T

H

H

A

S

A

V

G

N

G

G

C

C

N

N

L

L

R

R

A

P

G

G

D

D

L

L

G

A

S

S

G

G

T

T

I

I

S

S

G

G

P

S

G

D

Q

P

S

E

E

S

A

F

G

G

A

S

L

M

M

L

E

E

L

L

A

S

R

W

N

K

A

G

S

T

E

K

P

A

V

I

T

D

L

V

N

E

T

Q

G

G

E

Q

K

T

R

R

S

T

Y

F

V

L

E

L

D

D

G

G

D

D

A

E

I

V

I

I

L

I

R

T

G

G

Y

H

C

C

E

Q

K

G

A

D

G

G

F

Y

A

-

R

R

I

V

G

G

F

F

G

G

E

Q

S

C

R

A

G

G

E

K

V

V

L

L

P

P

A

A

D126 (= D141) binding
E199 (= E212) binding
E201 (= E214) binding ; mutation to G: Decrease in activity.
D233 (= D246) binding ; binding
K253 (= K266) binding
T257 (= T270) binding

1hyoB Crystal structure of fumarylacetoacetate hydrolase complexed with 4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid (see paper)
42% identity, 95% coverage: 22:438/440 of query aligns to 9:417/419 of 1hyoB

query
sites
1hyoB

A

A

P

E

T

D

C

S

D

D

F

F

P

P

I

I

Q

Q

N

N

L

L

P

P

F

Y

S

G

V

V

F

F

R

S

R

T

R

Q

H

-

S

S

D

N

E

P

A

K

F

P

R

R

G

I

A

G

V

V

A

A

I

I

G

G

D

D

Q

Q

V

I

I

L

D

D

I

L

A

S

A

V

W

-

A

-

S

I

R

K

A

H

G

L

L

F

N

T

G

G

I

P

A

A

-

L

G

S

E

K

G

H

A

Q

R

H

V

V

C

F

A

D

Q

E

P

T

V

T

L

L

N

N

E

N

F

F

F

M

S

G

M

L

G

G

P

Q

S

A

A

A

W

W

R

K

A

E

V

A

R

R

-

A

-

S

-

L

H

Q

A

N

L

L

F

L

A

S

A

A

L

S

H

Q

E

A

R

R

A

L

P

-

S

R

D

D

R

K

A

E

A

L

L

R

E

Q

A

R

C

A

L

F

I

T

P

S

Q

Q

S

A

E

S

V

A

E

T

Y

M

G

H

L

L

P

P

A

A

Q

T

I

I

G

G

D

D

Y

Y

T

T

D
|
D

F
|
F

Y
|
Y

T

S

S

S

I

R

H

Q

H
|
H

A

A

T

T

N

N

I
x
V

S

G

K

I

L

M

L

F

-
x
R

-

G

G

K

L

E

S

N

G

A

V

L

G
x
L

A

P

N

N

F

W

K

L

S

H

I

L

P

P

I

V

A

G

Y
|
Y

H

H

G

G

R

R

V

A

S

S

I

I

G

V

L

V

S

S

G

G

Q

T

R

P

F

I

R

R

P

P

A

M

G

G

Q

Q

I

M

M

R

L

P

P

D

G

N

E

S

D

K

A

P

P

P

I

V

F

Y

S

G

P

A

S

C

R

R

K

L

L

L

D

D

Y

M

E
|
E

L

L

E
|
E

L

M

G

A

I

F

Y

F

I

V

G

G

Q

P

G

G

N

N

A

R

A

F

G

G

E

E

P

P

I

I

A

P

L

I

D

S

Q

K

A

A

D

H

S

E

H

H

V

I

F

F

G

G

L

M

C

V

L

L

L

M

N

N

D
|
D

W
|
W

S

S

A

A

R
|
R

D

D

I

I

Q
|
Q

A

Q

W

W

E

E

M

Y

Q

V

P

P

L

L

G

G

P

P

F

F

L

L

A

G

K
|
K

N

S

F

F

A
x
G

T
|
T

T

T

I

I

S

S

P

P

W

W

I

V

V

V

T

P

M

M

E

D

A

A

L

L

A

M

P

P

F

F

R

V

L

V

P

P

L

N

P

P

R

K

P

-

H

-

T

Q

D

D

G

P

K

K

P

P

L

L

P

P

Y

Y

L

L

D

C

S

H

D

S

R

Q

N

P

S

Y

T

T

T

-

G

-

A

-

I

F

D

D

I

I

Q

N

L

L

E

S

V

V

C

S

I

L

E

K

T

G

S

E

R

-

H

-

Q

-

A

-

G

G

N

M

L

S

P

Q

A

A

Q

T

L

I

S

C

L

R

T

S

S

N

F

F

R

K

H

H

Q

M

Y

Y

W

W

S

T

I

M

A

L

Q

Q

M

Q

V

L

A

T

H

H

A

S

A

V

G

N

G

G

C

C

N

N

L

L

R

R

A

P

G

G

D

D

L

L

G

A

S

S

G
|
G

T
|
T

I

I

S

S

G

G

P

S

G

D

Q

P

S

E

E

S

A

F

G

G

A

S

L

M

M

L

E
|
E

L

L

A

S

R

W

N

K

A

G

S

T

E

K

P

A

V

I

T

D

L

V

N

G

T

Q

G

G

E

Q

K

T

R

R

S

T

Y

F

V

L

E

L

D

D

G

G

D

D

A

E

I

V

I

I

L

I

R

T

G

G

Y

H

C

C

E

Q

K

G

A

D

G

G

F

Y

A

-

R

R

I

V

G

G

F

F

G

G

E

Q

S

C

R

A

G

G

E

K

V

V

L

L

P

P

A

A

active site: D128 (= D141), H135 (= H148), E201 (= E212), E203 (= E214), D235 (= D246), R239 (= R250), Q242 (= Q253), K255 (= K266), T259 (= T270), E366 (= E386)
binding acetate ion: Y130 (= Y143), V139 (≠ I152), R144 (vs. gap), L151 (≠ G162)
binding calcium ion: D128 (= D141), E201 (= E212), E203 (= E214), D235 (= D246)
binding 4-[hydroxy-[methyl-phosphinoyl]]-3-oxo-butanoic acid: D128 (= D141), F129 (= F142), Y130 (= Y143), H135 (= H148), Y161 (= Y172), E201 (= E212), E203 (= E214), R239 (= R250), Q242 (= Q253), K255 (= K266), G351 (= G371), T352 (= T372)
binding magnesium ion: D235 (= D246), W236 (= W247), K255 (= K266), G258 (≠ A269), T259 (= T270)

2hzyA Mouse fumarylacetoacetate hydrolase complexes with a transition-state mimic of the complete substrate (see paper)
42% identity, 95% coverage: 22:438/440 of query aligns to 7:415/416 of 2hzyA

query
sites
2hzyA

A

A

P

E

T

D

C

S

D

D

F

F

P

P

I

I

Q

Q

N

N

L

L

P

P

F

Y

S

G

V

V

F

F

R

S

R

T

R

Q

H

-

S

S

D

N

E

P

A

K

F

P

R

R

G

I

A

G

V

V

A

A

I

I

G

G

D

D

Q

Q

V

I

I

L

D

D

I

L

A

S

A

V

W

-

A

-

S

I

R

K

A

H

G

L

L

F

N

T

G

G

I

P

A

A

-

L

G

S

E

K

G

H

A

Q

R

H

V

V

C

F

A

D

Q

E

P

T

V

T

L

L

N

N

E

N

F

F

F

M

S

G

M

L

G

G

P

Q

S

A

A

A

W

W

R

K

A

E

V

A

R

R

-

A

-

S

-

L

H

Q

A

N

L

L

F

L

A

S

A

A

L

S

H

Q

E

A

R

R

A

L

P

-

S

R

D

D

R

K

A

E

A

L

L

R

E

Q

A

R

C

A

L

F

I

T

P

S

Q

Q

S

A

E

S

V

A

E

T

Y

M

G

H

L

L

P

P

A

A

Q

T

I

I

G
|
G

D
|
D

Y

Y

T

T

D
|
D

F

F

Y

Y

T

S

S

S

I

R

H

Q

H
|
H

A

A

T

T

N

N

I

V

S

G

K

I

L

M

L

F

-

R

-

G

G

K

L

E

S

N

G

A

V

L

G

L

A

P

N

N

F

W

K

L

S

H

I

L

P

P

I

V

A

G

Y

Y

H

H

G

G

R

R

V

A

S

S

I

I

G

V

L

V

S

S

G

G

Q

T

R

P

F

I

R

R

P

P

A

M

G

G

Q

Q

I

M

M

R

L

P

P

D

G

N

E

S

D

K

A

P

P

P

I

V

F

Y

S

G

P

A

S

C

R

R

K

L

L

L

D

D

Y

M

E
|
E

L

L

E
|
E

L

M

G

A

I

F

Y

F

I

V

G

G

Q

P

G

G

N

N

A

R

A

F

G

G

E

E

P

P

I

I

A

P

L

I

D

S

Q

K

A

A

D

H

S

E

H

H

V

I

F

F

G

G

L

M

C

V

L

L

L

M

N

N

D
|
D

W

W

S

S

A

A

R
|
R

D

D

I

I

Q
|
Q

A

Q

W

W

E

E

M

Y

Q

V

P

P

L

L

G

G

P

P

F

F

L

L

A

G

K
|
K

N

S

F

F

A

G

T
|
T

T

T

I

I

S

S

P

P

W

W

I

V

V

V

T

P

M

M

E

D

A

A

L

L

A

M

P

P

F

F

R

V

L

V

P

P

L

N

P

P

R

K

P

-

H

-

T

Q

D

D

G

P

K

K

P

P

L

L

P

P

Y

Y

L

L

D

C

S

H

D

S

R

Q

N

P

S

Y

T

T

T

-

G

-

A

-

I

F

D

D

I

I

Q

N

L

L

E

S

V

V

C

S

I

L

E

K

T

G

S

E

R

-

H

-

Q

-

A

-

G

G

N

M

L

S

P

Q

A

A

Q

T

L

I

S

C

L

R

T

S

S

N

F

F

R

K

H

H

Q

M

Y

Y

W

W

S

T

I

M

A

L

Q

Q

M

Q

V

L

A

T

H

H

A

S

A

V

G

N

G

G

C

C

N

N

L

L

R

R

A

P

G

G

D

D

L

L

G

A

S

S

G

G

T

T

I

I

S

S

G

G

P

S

G

D

Q

P

S

E

E

S

A

F

G

G

A

S

L

M

M

L

E
|
E

L

L

A

S

R

W

N

K

A

G

S

T

E

K

P

A

V

I

T

D

L

V

N

G

T

Q

G

G

E

Q

K

T

R

R

S

T

Y

F

V

L

E

L

D

D

G

G

D

D

A

E

I

V

I

I

L

I

R

T

G

G

Y

H

C

C

E

Q

K

G

A

D

G

G

F

Y

A

-

R

R

I

V

G

G

F

F

G

G

E

Q

S

C

R

A

G

G

E

K

V

V

L

L

P

P

A

A

active site: D126 (= D141), H133 (= H148), E199 (= E212), E201 (= E214), D233 (= D246), R237 (= R250), Q240 (= Q253), K253 (= K266), T257 (= T270), E364 (= E386)
binding calcium ion: G122 (= G137), D123 (= D138)
binding manganese (ii) ion: D126 (= D141), E199 (= E212), E201 (= E214), D233 (= D246)

1qcoA Crystal structure of fumarylacetoacetate hydrolase complexed with fumarate and acetoacetate (see paper)
42% identity, 95% coverage: 22:438/440 of query aligns to 7:415/416 of 1qcoA

query
sites
1qcoA

A

A

P

E

T

D

C

S

D

D

F

F

P

P

I

I

Q

Q

N

N

L

L

P

P

F

Y

S

G

V

V

F

F

R

S

R

T

R

Q

H

-

S

S

D

N

E

P

A

K

F

P

R

R

G

I

A

G

V

V

A

A

I

I

G

G

D

D

Q

Q

V

I

I

L

D

D

I

L

A

S

A

V

W

-

A

-

S

I

R

K

A

H

G

L

L

F

N

T

G

G

I

P

A

A

-

L

G

S

E

K

G

H

A

Q

R

H

V

V

C

F

A

D

Q

E

P

T

V

T

L

L

N

N

E

N

F

F

F

M

S

G

M

L

G

G

P

Q

S

A

A

A

W

W

R

K

A

E

V

A

R

R

-

A

-

S

-

L

H

Q

A

N

L

L

F

L

A

S

A

A

L

S

H

Q

E

A

R

R

A

L

P

-

S

R

D

D

R

K

A

E

A

L

L

R

E

Q

A

R

C

A

L

F

I

T

P

S

Q

Q

S

A

E

S

V

A

E

T

Y

M

G

H

L

L

P

P

A

A

Q

T

I

I

G

G

D

D

Y

Y

T

T

D
|
D

F
|
F

Y
|
Y

T

S

S

S

I

R

H

Q

H
|
H

A

A

T

T

N

N

I
x
V

S

G

K

I

L

M

L
x
F

-
x
R

-

G

G

K

L

E

S

N

G

A

V

L

G

L

A

P

N

N

F

W

K

L

S

H

I

L

P

P

I

V

A

G

Y
|
Y

H

H

G

G

R

R

V

A

S

S

I

I

G

V

L

V

S

S

G

G

Q

T

R

P

F

I

R

R

P

P

A

M

G

G

Q

Q

I

M

M

R

L

P

P

D

G

N

E

S

D

K

A

P

P

P

I

V

F

Y

S

G

P

A

S

C

R

R

K

L

L

L

D

D

Y

M

E
|
E

L

L

E
|
E

L

M

G

A

I

F

Y

F

I

V

G

G

Q

P

G

G

N

N

A

R

A

F

G

G

E

E

P

P

I

I

A

P

L

I

D

S

Q

K

A

A

D

H

S

E

H

H

V

I

F

F

G

G

L

M

C

V

L

L

L

M

N

N

D
|
D

W

W

S

S

A

A

R

R

D

D

I

I

Q
|
Q

A

Q

W

W

E

E

M
x
Y

Q

V

P

P

L

L

G

G

P

P

F

F

L

L

A

G

K
|
K

N

S

F

F

A

G

T

T

I

I

S

S

P

P

W

W

I

V

V

V

T

P

M

M

E

D

A

A

L

L

A

M

P

P

F

F

R

V

L

V

P

P

L

N

P

P

R

K

P

-

H

-

T

Q

D

D

G

P

K

K

P

P

L

L

P

P

Y

Y

L

L

D

C

S

H

D

S

R

Q

N

P

S

Y

T

T

T

-

G

-

A

-

I

F

D

D

I

I

Q

N

L

L

E

S

V

V

C

S

I

L

E

K

T

G

S

E

R

-

H

-

Q

-

A

-

G

G

N

M

L

S

P

Q

A

A

Q

T

L

I

S

C

L

R

T

S

S

N

F

F

R

K

H

H

Q

M

Y

Y

W

W

S

T

I

M

A

L

Q

Q

M

Q

V

L

A

T

H

H

A

S

A

V

G

N

G

G

C

C

N

N

L

L

R

R

A

P

G

G

D

D

L

L

G

A

S

S

G
|
G

T
|
T

I

I

S

S

G

G

P

S

G

D

Q

P

S

E

E

S

A

F

G

G

A

S

L

M

M

L

E

E

L

L

A

S

R

W

N

K

A

G

S

T

E

K

P

A

V

I

T

D

L

V

N

G

T

Q

G

G

E

Q

K

T

R

R

S

T

Y

F

V

L

E

L

D

D

G

G

D

D

A

E

I

V

I

I

L

I

R

T

G

G

Y

H

C

C

E

Q

K

G

A

D

G

G

F

Y

A

-

R

R

I

V

G

G

F

F

G

G

E

Q

S

C

R

A

G

G

E

K

V

V

L

L

P

P

A

A

active site: K253 (= K266)
binding acetoacetic acid: D126 (= D141), F127 (= F142), Y128 (= Y143), H133 (= H148), Y159 (= Y172), E199 (= E212), E201 (= E214), K253 (= K266), G349 (= G371), T350 (= T372)
binding calcium ion: D126 (= D141), E199 (= E212), E201 (= E214), D233 (= D246)
binding fumaric acid: Y128 (= Y143), V137 (≠ I152), F141 (≠ L156), R142 (vs. gap), Q240 (= Q253), Y244 (≠ M257)

Query Sequence

>BPHYT_RS11790 BPHYT_RS11790 fumarylacetoacetase
MQHILNQTHDPAARSWVESANAPTCDFPIQNLPFSVFRRRHSDEAFRGAVAIGDQVIDIA
AWASRAGLNGIAGEGARVCAQPVLNEFFSMGPSAWRAVRHALFAALHERAPSDDRAALEA
CLIPQSEVEYGLPAQIGDYTDFYTSIHHATNISKLLGLSGVGANFKSIPIAYHGRVSSIG
LSGQRFRRPAGQIMLPGEDAPIFSPSRKLDYELELGIYIGQGNAAGEPIALDQADSHVFG
LCLLNDWSARDIQAWEMQPLGPFLAKNFATTISPWIVTMEALAPFRLPLPRPHTDGKPLP
YLDSDRNSTTGAIDIQLEVCIETSRHQAGNLPAAQLSLTSFRHQYWSIAQMVAHHAAGGC
NLRAGDLLGSGTISGPGQSEAGALMELARNASEPVTLNTGEKRSYVEDGDAIILRGYCEK
AGFARIGFGESRGEVLPAKR

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