SitesBLAST

3tcyA Crystallographic structure of phenylalanine hydroxylase from chromobacterium violaceum (cpah) bound to phenylalanine in a site distal to the active site (see paper)
66% identity, 87% coverage: 27:283/297 of query aligns to 23:277/277 of 3tcyA

query
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3tcyA

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active site: H132 (= H136), H137 (= H141), E178 (= E184), S197 (= S203)
binding cobalt (ii) ion: H132 (= H136), H137 (= H141), E178 (= E184)
binding phenylalanine: A152 (= A156), Y153 (= Y157), K159 (= K163), L169 (= L175), T248 (= T254), P250 (= P256), D251 (= D257), F252 (= F258)

4etlA Crystallographic structure of phenylalanine hydroxylase from chromobacterium violaceum f258a mutation (see paper)
65% identity, 87% coverage: 27:283/297 of query aligns to 23:277/277 of 4etlA

query
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4etlA

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active site: H132 (= H136), H137 (= H141), E178 (= E184), S197 (= S203)
binding cobalt (ii) ion: H132 (= H136), H137 (= H141), E178 (= E184)

1ltzA Crystal structure of chromobacterium violaceum phenylalanine hydroxylase, structure has bound iron (iii) and oxidized cofactor 7, 8-dihydrobiopterin (see paper)
65% identity, 87% coverage: 27:283/297 of query aligns to 23:274/274 of 1ltzA

query
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1ltzA

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active site: H132 (= H136), H137 (= H141), E178 (= E184), S197 (= S203)
binding fe (iii) ion: H132 (= H136), H137 (= H141), E178 (= E184)
binding 7,8-dihydrobiopterin: I96 (≠ L100), D98 (= D102), F101 (= F105), Y173 (= Y179)

2v27B Structure of the cold active phenylalanine hydroxylase from colwellia psychrerythraea 34h (see paper)
39% identity, 75% coverage: 28:250/297 of query aligns to 11:230/272 of 2v27B

query
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2v27B

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active site: H119 (= H136), H124 (= H141), E164 (= E184), S183 (= S203)
binding fe (iii) ion: H119 (= H136), H124 (= H141), E164 (= E184)

5jk8A Phenylalanine hydroxylase from dictyostelium - bh2, norleucine complex
38% identity, 77% coverage: 28:255/297 of query aligns to 138:365/390 of 5jk8A

query
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5jk8A

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active site: H250 (= H136), H255 (= H141), E295 (= E184), S314 (= S203)
binding fe (iii) ion: H250 (= H136), H255 (= H141), E295 (= E184)
binding 7,8-dihydrobiopterin: L214 (= L100), A216 (≠ D102), F219 (= F105), S287 (≠ T176), Y290 (= Y179)
binding norleucine: Y242 (= Y128), T243 (≠ L129), H250 (= H136), S314 (= S203), S315 (= S204)
binding piperazine-n,n'-bis(2-ethanesulfonic acid): T203 (= T89), R226 (= R112), D266 (= D152), R365 (= R255)

Sites not aligning to the query:

binding piperazine-n,n'-bis(2-ethanesulfonic acid): 44, 382

5jk5A Phenylalanine hydroxylase from dictyostelium - bh2 complex
38% identity, 77% coverage: 28:255/297 of query aligns to 147:374/400 of 5jk5A

query
sites
5jk5A

E

E

Q

I

P

P

W

R

A

I

D

D

Y

Y

S

T

Q

E

T

E

D

E

H

I

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K

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W

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G

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V

Y

Y

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N

R

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R

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E

E

L

L

L

F

K

P

G

T

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N

A

A

C

C

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H

E

Q

-

H

-

A

-

Y

-

I

F

F

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P

D

L

G

L

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N

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T

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G

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L

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F

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x
L

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C

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N

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F

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V

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R

active site: H259 (= H136), H264 (= H141), E304 (= E184), S323 (= S203)
binding fe (iii) ion: H259 (= H136), H264 (= H141), E304 (= E184)
binding 7,8-dihydrobiopterin: G221 (= G98), L222 (= L99), L223 (= L100), F228 (= F105), L229 (≠ F106), S296 (≠ T176), Y299 (= Y179)
binding piperazine-n,n'-bis(2-ethanesulfonic acid): T212 (= T89), P271 (= P148), D275 (= D152), R374 (= R255)

6zvpD Atomic model of the em-based structure of the full-length tyrosine hydroxylase in complex with dopamine (residues 40-497) in which the regulatory domain (residues 40-165) has been included only with the backbone atoms (see paper)
35% identity, 90% coverage: 30:297/297 of query aligns to 181:449/458 of 6zvpD

query
sites
6zvpD

P

P

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A

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binding fe (iii) ion: H291 (= H136), H296 (= H141), E336 (= E184), A351 (= A199)
binding l-dopamine: P287 (= P132), H291 (= H136), H296 (= H141), Y331 (= Y179), E336 (= E184)

Sites not aligning to the query:

binding l-dopamine: 2

P07101 Tyrosine 3-monooxygenase; Tyrosine 3-hydroxylase; TH; EC 1.14.16.2 from Homo sapiens (Human) (see 32 papers)
35% identity, 90% coverage: 30:297/297 of query aligns to 251:519/528 of P07101

query
sites
P07101

P

P

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E

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E259 (≠ D38) to G: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T276 (≠ G55) to P: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs28934581
P301 (= P76) to A: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
F309 (≠ V84) to S: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T314 (= T89) to M: in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine 3-monooxygenase activity; dbSNP:rs121917764
R319 (≠ V94) to P: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
R328 (≠ E103) to W: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs1428589694
R337 (= R112) to H: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs28934580
C359 (≠ L134) to F: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs121917765
F375 (= F150) to L: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs763198914
A376 (= A151) to V: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
L387 (≠ F165) to M: in ARSEGS; no effect on tyrosine 3-monooxygenase activity
I394 (≠ L172) to T: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
T399 (≠ R177) to M: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs1057520384
Q412 (≠ T190) to K: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; reduced affinity for L-tyrosine; dbSNP:rs121917762
G414 (≠ E192) to R: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs370962049
G428 (= G206) to R: in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D); dbSNP:rs1264884607
R441 (≠ I220) to P: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs367874223
S467 (= S246) to G: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity
P492 (≠ E269) to L: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity; dbSNP:rs767635052
T494 (≠ H271) to M: in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity; dbSNP:rs45471299
D498 (= D275) to G: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs771351747
V499 (= V276) to M: in dbSNP:rs1800033
L510 (≠ R288) to Q: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity

Sites not aligning to the query:

19 modified: Phosphoserine; by CaMK2; S → C: found in a patient with ARSEGS; uncertain significance; dbSNP:rs766704202
62 modified: Phosphoserine; S→A: Affects subcellular localization. Accumulates mainly in the soma of the neuroblastoma cells.; S→E: Does not affect subcellular localization. Distributed throughout the soma and neurites.
71 modified: Phosphoserine; by CaMK2 and PKA; S→E: Suppresses feedback inhibition induced by dopamine. Suppresses feedback inhibition induced by dopamine; when associated with A-207.
112 V → M: in dbSNP:rs6356
207 C → Y: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; C→A: Suppresses the decrease in tyrosine 3-monooxygenase activity induced by NEM modification. Suppresses feedback inhibition induced by dopamine; when associated with E-71.
227 D → G: in ARSEGS; complete loss of tyrosine 3-monooxygenase activity
233 R → H: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs80338892
236 L → P: in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and tyrosine 3-monooxygenase activity; rare mutation; dbSNP:rs121917763
241 A → T: in ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; dbSNP:rs1260455415
246 H → Y: in ARSEGS; loss of about 40% of tyrosine 3-monooxygenase activity
247 G → S: in ARSEGS; loss of about 50% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa; dbSNP:rs762304556

2xsnA Crystal structure of human tyrosine hydroxylase catalytic domain
35% identity, 90% coverage: 30:297/297 of query aligns to 59:327/335 of 2xsnA

query
sites
2xsnA

P

P

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A

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H

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H

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G

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A

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L

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W

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E

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F

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S

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D

A

K

T

L

R

R

P

S

D

Y

F

A

T

S

P

R

I

I

Y

Q

A

R

-

P

-

F

D

S

L

V

K

K

T

F

R

D

E

P

A

Y

H

T

A

L

A

A

A

I

D

D

V

V

L

L

D

D

S

S

D

P

R

Q

V

A

F

-

T

V

R

R

G

R

T

S

R

L

E

E

G

G

F

V

A

Q

T

D

D

E

A

L

D

D

T

T

active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding zinc ion: H169 (= H136), H174 (= H141), E214 (= E184)

6zn2A Partial structure of tyrosine hydroxylase in complex with dopamine showing the catalytic domain and an alpha-helix from the regulatory domain involved in dopamine binding. (see paper)
35% identity, 90% coverage: 30:297/297 of query aligns to 58:326/335 of 6zn2A

query
sites
6zn2A

P

P

W

R

A

V

D

E

Y

Y

S

T

Q

A

T

E

D

E

H

I

E

A

V

T

W

W

N

K

T

E

L

V

Y

Y

R

T

Q

L

R

K

E

G

L

L

L

Y

K

A

G

T

R

H

A

A

C

C

Q

G

E

E

F

H

L

L

D

E

G

A

-

F

-

A

-

L

I

L

E

E

R

R

F

F

-

S

G

G

M

Y

G

R

E

E

N

D

G

N

I

I

P

P

K

Q

F

L

A

E

D

D

L

V

N

S

K

R

V

F

L

L

G

K

E

E

T

R

T

T

G

G

W

F

E

Q

L

L

V

R

A

P

V

V

E

A

G

G

L

L

P

S

D
x
A

E

R

V

D

F

F

F

L

D

A

H

S

L

L

A

A

N

F

R

R

R

V

F

F

P

Q

V

C

S

T

W

Q

W

Y

I

I

R

R

R

H

P

A

D

S

Q

S

L

P

D

M

Y

H

L

S

S

P

E

E

P
|
P

D

D

L

C

F

C

H
|
H

D

E

L

L

F

L

G

G

H
|
H

V

V

P

P

L

M

L

L

L

A

N

D

P

R

V

T

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

D

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

S

P

D

E

E

A

E

L

I

M
x
E

N

K

L

L

T
x
S

R

T

L

L

Y
|
Y

W
|
W

Y

F

T

T

V

V

E
|
E

F

F

G

G

L

L

I

C

N

K

T

Q

S

N

E

G

G

E

M

V

R

K

I

A

Y

Y

G

G

A

A

G

G

I

L

V

L

S

S

K

Y

G

G

E

E

S

L

I

L

Y

H

C

C

L

L

D

-

S

S

A

E

P

P

N

E

R

I

I

R

G

A

F

F

G

D

L

P

E

E

R

A

V

A

M

A

N

V

T

Q

R

P

Y
|
Y

R

Q

I

D

D

Q

T

T

F

Y

Q

Q

Q

S

T

V

Y

Y

F

F

V

V

I

S

D

E

S

S

F

F

E

S

Q

D

L

A

F

K

D

D

A

K

T

L

R

R

P

S

D

Y

F

A

T

S

P

R

I

I

Y

Q

A

R

-

P

-

F

D

S

L

V

K

K

T

F

R

D

E

P

A

Y

H

T

A

L

A

A

A

I

D

D

V

V

L

L

D

D

S

S

D

P

R

Q

V

A

F

-

T

V

R

R

G

R

T

S

R

L

E

E

G

G

F

V

A

Q

T

D

D

E

A

L

D

D

T

T

binding fe (iii) ion: H168 (= H136), H173 (= H141), E213 (= E184)
binding l-dopamine: P164 (= P132), H173 (= H141), E213 (= E184)
binding : A134 (≠ D102), E202 (≠ M173), S205 (≠ T176), Y208 (= Y179), W209 (= W180), Y260 (= Y232)

P04176 Phenylalanine-4-hydroxylase; PAH; Phe-4-monooxygenase; EC 1.14.16.1 from Rattus norvegicus (Rat) (see 2 papers)
35% identity, 76% coverage: 30:255/297 of query aligns to 175:400/453 of P04176

query
sites
P04176

P

P

W

R

A

V

D

E

Y

Y

S

T

Q

E

T

E

D

E

H

K

E

Q

V

T

W

W

N

G

T

T

L

V

Y

F

R

R

R

T

Q

L

R

K

E

A

L

L

L

Y

K

K

G

T

R

H

A

A

C

C

Q

Y

E

E

-

H

-

N

-

H

F

I

L

F

D

P

G

L

I

L

E

E

R

K

F

Y

-

C

G

G

M

F

G

R

E

E

N

D

G

N

I

I

P

P

K

Q

F

L

A

E

D

D

L

V

N

S

K

Q

V

F

L

L

G

Q

E

T

T

C

T

T

G

G

W

F

E

R

L

L

V

R

A

P

V

V

E

A

G

G

L

L

P

S

D

S

E

R

V

D

F

F

F

L

D

G

H

G

L

L

A

A

N

F

R

R

R

V

F

F

P

H

V

C

S

T

W

Q

W

Y

I

I

R

R

R

H

P

G

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S

Q

K

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D

M

Y

Y

L

T

S

P

E

E

P

P

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D

L

I

F

C

H
|
H

D

E

L

L

F

L

G

G

H
|
H

V

V

P

P

L

L

L

F

L

S

N

D

P

R

V

S

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

E

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

P

P

D

E

E

A

Y

L

I

M

E

N

K

L

L

T

A

R

T

L

I

Y

Y

W

W

Y

F

T

T

V

V

E
|
E

F

F

G

G

L

L

I

C

N

K

T

E

S

G

E

D

G

S

M

I

R

K

I

A

Y

Y

G

G

A

A

G

G

I

L

V

L

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S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

D

A

K

P

P

N

K

R

L

I

L

G

P

F

L

G

E

L

L

E

E

R

K

V

T

M

A

N

C

T

Q

R

E

Y

Y

R

S

I

V

D

T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F

Y

V

V

I

A

D

E

S

S

F

F

E

S

Q

D

L

A

F

K

D

E

A

K

T

V

R

R

H285 (= H136) binding
H290 (= H141) binding
E330 (= E184) binding

Sites not aligning to the query:

16 modified: Phosphoserine; by PKA

5fgjA Structure of tetrameric rat phenylalanine hydroxylase, residues 1-453 (see paper)
35% identity, 76% coverage: 30:255/297 of query aligns to 153:378/428 of 5fgjA

query
sites
5fgjA

P

P

W

R

A

V

D

E

Y

Y

S

T

Q

E

T

E

D

E

H

K

E

Q

V

T

W

W

N

G

T

T

L

V

Y

F

R

R

R

T

Q

L

R

K

E

A

L

L

L

Y

K

K

G

T

R

H

A

A

C

C

Q

Y

E

E

-

H

-

N

-

H

F

I

L

F

D

P

G

L

I

L

E

E

R

K

F

Y

-

C

G

G

M

F

G

R

E

E

N

D

G

N

I

I

P

P

K

Q

F

L

A

E

D

D

L

V

N

S

K

Q

V

F

L

L

G

Q

E

T

T

C

T

T

G

G

W

F

E

R

L

L

V

R

A

P

V

V

E

A

G

G

L

L

P

S

D

S

E

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V

D

F

F

F

L

D

G

H

G

L

L

A

A

N

F

R

R

R

V

F

F

P

H

V

C

S

T

W

Q

W

Y

I

I

R

R

R

H

P

G

D

S

Q

K

L

P

D

M

Y

Y

L

T

S

P

E

E

P

P

D

D

L

I

F

C

H
|
H

D

E

L

L

F

L

G

G

H
|
H

V

V

P

P

L

L

L

F

L

S

N

D

P

R

V

S

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

E

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

P

P

D

E

E

A

Y

L

I

M

E

N

K

L

L

T

A

R

T

L

I

Y

Y

W

W

Y

F

T

T

V

V

E
|
E

F

F

G

G

L

L

I

C

N

K

T

E

S

G

E

D

G

S

M

I

R

K

I

A

Y

Y

G

G

A

A

G

G

I

L

V

L

S
|
S

S

S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

D

A

K

P

P

N

K

R

L

I

L

G

P

F

L

G

E

L

L

E

E

R

K

V

T

M

A

N

C

T

Q

R

E

Y

Y

R

S

I

V

D

T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F

Y

V

V

I

A

D

E

S

S

F

F

E

S

Q

D

L

A

F

K

D

E

A

K

T

V

R

R

active site: H263 (= H136), H268 (= H141), E308 (= E184), S327 (= S203)
binding fe (iii) ion: H263 (= H136), H268 (= H141), E308 (= E184)

P16331 Phenylalanine-4-hydroxylase; PAH; Phe-4-monooxygenase; EC 1.14.16.1 from Mus musculus (Mouse) (see paper)
35% identity, 76% coverage: 30:255/297 of query aligns to 175:400/453 of P16331

query
sites
P16331

P

P

W

R

A

V

D

E

Y

Y

S

T

Q

E

T

E

D

E

H

R

E

K

V

T

W

W

N

G

T

T

L

V

Y

F

R

R

R

T

Q

L

R

K

E

A

L

L

L

Y

K

K

G

T

R

H

A

A

C

C

Q

Y

E

E

-

H

-

N

-

H

F

I

L

F

D

P

G

L

I

L

E

E

R

K

F

Y

-

C

G

G

M

F

G

R

E

E

N

D

G

N

I

I

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P

K

Q

F

L

A

E

D

D

L

V

N

S

K

Q

V

F

L

L

G

Q

E

T

T

C

T

T

G

G

W

F

E

R

L

L

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R

A

P

V

V

E

A

G

G

L

L

P

S

D

S

E

R

V

D

F

F

F

L

D

G

H

G

L

L

A

A

N

F

R

R

R

V

F
|
F

P

H

V

C

S

T

W

Q

W

Y

I

I

R

R

R

H

P

G

D

S

Q

K

L

P

D

M

Y

Y

L

T

S

P

E

E

P

P

D

D

L

I

F

C

H

H

D

E

L

L

F

L

G

G

H

H

V

V

P

P

L

L

L

F

L

S

N

D

P

R

V

S

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

E

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

P

P

D

E

E

A

Y

L

I

M

E

N

K

L

L

T

A

R

T

L

I

Y

Y

W

W

Y

F

T

T

V

V

E

E

F

F

G

G

L

L

I

C

N

K

T

E

S

G

E

D

G

S

M

I

R

K

I

A

Y

Y

G

G

A

A

G

G

I

L

V

L

S

S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

D

A

K

P

P

N

K

R

L

I

L

G

P

F

L

G

E

L

L

E

E

R

K

V

T

M

A

N

C

T

Q

R

E

Y

Y

R

T

I

V

D

T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F

Y

V

V

I

A

D

E

S

S

F

F

E

N

Q

D

L

A

F

K

D

E

A

K

T

V

R

R

F263 (= F114) mutation to S: Mutant mice have features of phenylketonuria.

Sites not aligning to the query:

1 modified: Initiator methionine, Removed
2 modified: N-acetylalanine
106 V→A: Mutant mice have mild features of phenylketonuria.

P00439 Phenylalanine-4-hydroxylase; PAH; Phe-4-monooxygenase; EC 1.14.16.1 from Homo sapiens (Human) (see 43 papers)
34% identity, 76% coverage: 30:255/297 of query aligns to 175:400/452 of P00439

query
sites
P00439

P

P

W
x
R

A
x
V

D
x
E

Y

Y

S

M

Q

E

T

E

D

E

H

K

E

K

V

T

W

W

N

G

T

T

L
x
V

Y

F

R

K

R

T

Q

L

R

K

E

S

L

L

L

Y

K

K

G

T

R
x
H

A

A

C

C

Q
x
Y

E

E

F

Y

-
x
N

-

H

-

I

L

F

D
x
P

G

L

I
x
L

E

E

R

K

F

Y

-

C

G
|
G

M

F

G

H

E
|
E

N
x
D

G

N

I
|
I

P
|
P

K

Q

F

L

A

E

D

D

L
x
V

N

S

K

Q

V
x
F

L

L

G

Q

E

T

T

C

T
|
T

G

G

W

F

E
x
R

L

L

V
x
R

A
x
P

V
|
V

E

A

G
|
G

L

L

L
|
L

P

S

D

S

E
x
R

V

D

F

F

F
x
L

D

G

H

G

L

L

A
|
A

N

F

R
|
R

R

V

F

F

P

H

V

C

S

T

W

Q

W

Y

I
|
I

R
|
R

R

H

P

G

D
x
S

Q

K

L
x
P

D
x
M

Y
|
Y

L

T

S

P

E
|
E

P
|
P

D
|
D

L
x
I

F

C

H

H

D

E

L

L

F

L

G

G

H

H

V

V

P

P

L

L

L

F

L

S

N

D

P
x
R

V

S

F
|
F

A
|
A

D

Q

Y

F

M
x
S

Q

Q

A

E

Y
x
I

G

-

R

-

G

-

G

G

M

L

K
x
A

A
x
S

F
x
L

G

G

I

A

G
x
P

P

D

E

E

A

Y

L
x
I

M

E

N

K

L

L

T
x
A

R

T

L

I

Y

Y

W

W

Y

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V

V

E

E

F
|
F

G

G

L

L

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N

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E
x
D

G

S

M

I

R

K

I
x
A

Y

Y

G

G

A
|
A

G

G

I

L

V
x
L

S
|
S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

E

A

K

P

P

N

K

R
x
L

I

L

G

P

F

L

G

E

L

L

E

E

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V

T

M

A

N

I

T

Q

R

N

Y
|
Y

R

T

I

V

D
x
T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F
x
Y

V
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V

I

A

D
x
E

S

S

F

F

E

N

Q

D

L
x
A

F

K

D

E

A

K

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V

R

R

R176 (≠ W31) to L: in non-PKU HPA and PKU; dbSNP:rs74486803
V177 (≠ A32) to L: in PKU; haplotype 6; dbSNP:rs199475602
E178 (≠ D33) to G: in non-PKU HPA; dbSNP:rs77958223
V190 (≠ L45) to A: in PKU; haplotype 3; dbSNP:rs62514919
H201 (≠ R56) to Y: in non-PKU HPA; haplotype 1; dbSNP:rs62517205
Y204 (≠ Q59) to C: in PKU; mild; haplotypes 3,4; dbSNP:rs62514927
N207 (vs. gap) to S: in PKU; severe; haplotype 4; dbSNP:rs62508721
P211 (≠ D63) to T: in PKU; haplotype 4; dbSNP:rs62514931
L213 (≠ I65) to P: in PKU; severe; dbSNP:rs62516109
G218 (= G69) to V: in PKU; haplotypes 1,2; dbSNP:rs62514933
E221 (= E72) to G: in PKU; haplotype 4; dbSNP:rs62514934
D222 (≠ N73) to V: in PKU; haplotypes 3,4; dbSNP:rs62507319
I224 (= I75) to M: in PKU; haplotype 4; dbSNP:rs199475576
P225 (= P76) to T: in PKU; haplotype 1; dbSNP:rs199475589
V230 (≠ L81) to I: in non-PKU HPA and PKU; haplotype 4; dbSNP:rs62516152
F233 (≠ V84) to L: in PKU; haplotypes 2,3; dbSNP:rs62517208
T238 (= T89) to P: in PKU; haplotype 4; dbSNP:rs199475577
R241 (≠ E92) to C: in non-PKU HPA and PKU; haplotype 34; dbSNP:rs76687508; to H: in PKU; haplotypes 1,5; dbSNP:rs62508730
R243 (≠ V94) to Q: in non-PKU HPA and PKU; haplotypes 4,7,9; dbSNP:rs62508588
P244 (≠ A95) to L: in PKU; haplotype 12; dbSNP:rs118203923
V245 (= V96) to A: in PKU, HPA and non-PKU HPA; haplotypes 3,7; dbSNP:rs796052017; to E: in PKU; haplotype 11; dbSNP:rs76212747
G247 (= G98) to V: in PKU; haplotype 4; dbSNP:rs199475579
L249 (= L100) to F: in PKU; haplotype 1; dbSNP:rs74503222
R252 (≠ E103) to G: in PKU; haplotype 7; dbSNP:rs5030847; to Q: in PKU; haplotype 1; dbSNP:rs62644503; to W: in PKU; haplotypes 1,6,7,8,42, 69; complete loss of activity; dbSNP:rs5030847
L255 (≠ F106) to S: in PKU; haplotype 36; dbSNP:rs62642930; to V: in PKU; haplotypes 18,21; dbSNP:rs62642931
A259 (= A110) to T: in PKU; haplotype 3; dbSNP:rs62642932; to V: in PKU; haplotypes 7,42; dbSNP:rs118203921
R261 (= R112) to Q: in HPA and PKU; mild; haplotypes 1,2,4,22, 24,28; dbSNP:rs5030849
I269 (= I120) to L: in non-PKU HPA; dbSNP:rs62508692
R270 (= R121) to S: in PKU; haplotype 1; dbSNP:rs62514951
S273 (≠ D124) to F: in PKU; haplotype 7; dbSNP:rs62514953
P275 (≠ L126) to L: in PKU; reduced activity; increased affinity for the substrate; mildly reduced substrate activation; decreased cofactor affinity; dbSNP:rs62508715
M276 (≠ D127) to V: in PKU; haplotype 4; dbSNP:rs62516149
Y277 (= Y128) to D: in PKU; haplotype 2; dbSNP:rs78655458
E280 (= E131) to K: in PKU; haplotypes 1,2,4,16,38; partial residual activity; dbSNP:rs62508698
P281 (= P132) to L: in PKU; haplotypes 1,4; dbSNP:rs5030851
D282 (= D133) to N: in PKU; haplotype 1; dbSNP:rs199475582
I283 (≠ L134) to F: in PKU; haplotype 21; dbSNP:rs62517168; to N: in PKU; severe; dbSNP:rs62508693; mutation to C: Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation.
R297 (≠ P148) to C: in PKU; haplotype 4; dbSNP:rs62642945
F299 (= F150) to C: in PKU; haplotype 8; dbSNP:rs62642933
A300 (= A151) to S: in PKU and HPA; haplotype 1; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs5030853
S303 (≠ M154) to P: in PKU; haplotype 5; dbSNP:rs199475608
I306 (≠ Y157) to V: in non-PKU HPA and PKU; haplotype 4; dbSNP:rs62642934
A309 (≠ K163) to D: in PKU; haplotype 7; dbSNP:rs62642935
S310 (≠ A164) to F: in PKU; haplotype 7; dbSNP:rs62642913; to Y: in HPA; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs62642913
L311 (≠ F165) to P: in PKU; haplotypes 1,7,10; dbSNP:rs62642936
P314 (≠ G168) to S: in HPA; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs199475650
I318 (≠ L172) to T: in PKU; partial loss of activity; dbSNP:rs62642918
A322 (≠ T176) to G: in PKU; haplotype 12; dbSNP:rs62514958; to T: in PKU; haplotype 1; dbSNP:rs62514957
F331 (= F185) to L: in PKU; haplotype 1; dbSNP:rs62517179
D338 (≠ E192) to Y: in PKU; haplotype 4; dbSNP:rs62516150
A342 (≠ I196) to T: in PKU; haplotype 5; dbSNP:rs62507282
A345 (= A199) to T: in PKU; haplotype 7; dbSNP:rs62516062
L348 (≠ V202) to V: in PKU; mild haplotype 9; dbSNP:rs62516092
S349 (= S203) to L: in PKU; severe; dbSNP:rs62507279; to P: in PKU; haplotypes 1,4; dbSNP:rs62508646
S350 (= S204) to T: in PKU; haplotype 2; dbSNP:rs62517183
L364 (≠ R219) natural variant: Missing (in PKU; haplotype 5; dbSNP:rs62516096)
Y377 (= Y232) to C: in PKU; haplotype 4; dbSNP:rs62642942
T380 (≠ D235) to M: in non-PKU HPA and PKU; haplotype 4; dbSNP:rs62642937
Y387 (≠ F242) to H: in PKU; haplotype 1; dbSNP:rs62517194
V388 (= V243) to M: in PKU; haplotypes 1,4; dbSNP:rs62516101
E390 (≠ D245) to G: in PKU and non-PKU HPA; haplotype 4; dbSNP:rs5030856
A395 (≠ L250) to P: in PKU; haplotype 1; dbSNP:rs62516103

Sites not aligning to the query:

16 modified: Phosphoserine; by PKA; S → P: in PKU; uncertain significance; dbSNP:rs62642946
39 F → L: in HPA and PKU; haplotype 1; dbSNP:rs62642926; natural variant: Missing (in PKU; haplotypes 9,21)
41 L → P: in PKU; mild; dbSNP:rs62642916
42 K → I: in PKU; haplotype 21; dbSNP:rs62635346
46 G → S: in PKU; haplotype 5; significantly reduces phenylalanine binding; dbSNP:rs74603784
47 A → V: in non-PKU HPA; haplotype 4; significantly reduces phenylalanine binding; dbSNP:rs118203925
48 L → S: in PKU; mild; haplotypes 3,4; dbSNP:rs5030841
55 F → L: in HPA and PKU; does not affect oligomerization; results in loss of substrate activation; dbSNP:rs199475598
56 E → D: in PKU; haplotype 10; dbSNP:rs199475567
63:64 natural variant: TH -> PN (in PKU; haplotype 1; abolishes phenylalanine binding)
65 I → S: in PKU; results in disturbed oligomerization; results in loss of substrate activation; dbSNP:rs75193786; I → T: in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding; dbSNP:rs75193786; I → V: in HPA and PKU; dbSNP:rs199475643
67 S → P: in PKU; haplotype 4; dbSNP:rs5030842
68 R → S: in PKU; haplotype 1; dbSNP:rs76394784
76 E → G: in non-PKU HPA; dbSNP:rs62507347
84 D → Y: in PKU; haplotype 4; dbSNP:rs62514902
87 S → R: in non-PKU HPA; haplotype 1; dbSNP:rs62516151
94 natural variant: Missing (in PKU; mild; haplotype 2)
98 L → S: in non-PKU HPA; dbSNP:rs62517167
104 A → D: in PKU; mild; haplotype 1; dbSNP:rs62642929
124 T → I: in PKU; haplotype 28; dbSNP:rs199475571
143 D → G: in PKU; haplotype 11; dbSNP:rs199475572
148 G → S: in PKU; haplotypes 1,2,7; dbSNP:rs80297647
151 D → H: in PKU; haplotypes 1,8; dbSNP:rs199475597
157 R → N: in PKU; severe; 5% activity; requires 2 nucleotide substitutions; dbSNP:rs1565853495
158 R → Q: in PKU; haplotypes 1,2,4,7,16, 28; dbSNP:rs5030843
161 F → S: in PKU; haplotype 4; dbSNP:rs79635844
164 I → T: in PKU; haplotype 1; dbSNP:rs199475595
170 H → Q: in PKU; does not affect oligomerization; dbSNP:rs199475652
171 G → A: in PKU; haplotype 1; dbSNP:rs199475596
173 P → T: in PKU; haplotype 4; dbSNP:rs199475574
174 I → T: in PKU; haplotype 1; dbSNP:rs138809906
403 A → V: in non-PKU HPA and PKU; haplotype 43; dbSNP:rs5030857
408 R → Q: in PKU; haplotypes 4,12; dbSNP:rs5030859; R → W: in HPA and PKU; haplotypes 1,2,4,5,13,34,41,44; most common mutation; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs5030858
410 F → S: in PKU; mild; dbSNP:rs62644475
413 R → P: in non-PKU HPA and PKU; haplotype 4; dbSNP:rs79931499; R → S: in PKU; haplotype 1; dbSNP:rs62644467
414 Y → C: in HPA and PKU; haplotype 4; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs5030860
415 D → N: in PKU, HPA and non-PKU HPA; haplotype 1; dbSNP:rs62644499
417 Y → H: in PKU; reduction in activity is probably due to a global conformational change in the protein that reduces allostery; dbSNP:rs62644471
418 T → P: in PKU; haplotype 4; dbSNP:rs62644501

4anpA Crystal structure of human phenylalanine hydroxylase in complex with a pharmacological chaperone (see paper)
34% identity, 76% coverage: 30:255/297 of query aligns to 59:284/309 of 4anpA

query
sites
4anpA

P

P

W

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-

N

-

H

-

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F

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x
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S

S

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Y

Y

C

C

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L

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-

S

S

A

E

A

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P

N

K

R

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F

L

G

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L

L

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N

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Y

R

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R

active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding 5,6-dimethyl-3-(4-methyl-2-pyridinyl)-2-thioxo-2,3-dihydrothieno[2,3- d]pyrimidin-4(1h)-one: F138 (= F105), P163 (≠ S130), P165 (= P132), H169 (= H136), W210 (= W180), E214 (= E184)
binding fe (iii) ion: H169 (= H136), H174 (= H141), E214 (= E184)

1tg2A Crystal structure of phenylalanine hydroxylase a313t mutant with 7,8- dihydrobiopterin bound (see paper)
34% identity, 76% coverage: 30:255/297 of query aligns to 59:284/308 of 1tg2A

query
sites
1tg2A

P

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L

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x
S

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F

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S

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S

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R

active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding fe (iii) ion: H169 (= H136), H174 (= H141), E214 (= E184)
binding 2-amino-6-(1,2-dihydroxy-propyl)-7,8-dihydro-6h-pteridin-4-one: L133 (= L100), S135 (≠ D102), F138 (= F105), Y209 (= Y179)

6pahA Human phenylalanine hydroxylase catalytic domain dimer with bound l- dopa (3,4-dihydroxyphenylalanine) inhibitor (see paper)
34% identity, 76% coverage: 30:255/297 of query aligns to 59:284/308 of 6pahA

query
sites
6pahA

P

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A

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S

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Y

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S

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active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding 3,4-dihydroxyphenylalanine: H169 (= H136), H174 (= H141), Y209 (= Y179), E214 (= E184)
binding fe (iii) ion: H169 (= H136), H174 (= H141), E214 (= E184)

5pahA Human phenylalanine hydroxylase catalytic domain dimer with bound dopamine inhibitor (see paper)
34% identity, 76% coverage: 30:255/297 of query aligns to 59:284/308 of 5pahA

query
sites
5pahA

P

P

W

R

A

V

D

E

Y

Y

S

M

Q

E

T

E

D

E

H

K

E

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W

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G

T

T

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F

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T

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L

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K

E

S

L

L

L

Y

K

K

G

T

R

H

A

A

C

C

Q

Y

E

E

F

Y

-

N

-

H

-

I

L

F

D

P

G

L

I

L

E

E

R

K

F

Y

-

C

G

G

M

F

G

H

E

E

N

D

G

N

I

I

P

P

K

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F

L

A

E

D

D

L

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N

S

K

Q

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F

L

L

G

Q

E

T

T

C

T

T

G

G

W

F

E

R

L

L

V

R

A

P

V

V

E

A

G

G

L

L

P

S

D

S

E

R

V

D

F

F

F

L

D

G

H

G

L

L

A

A

N

F

R

R

R

V

F

F

P

H

V

C

S

T

W

Q

W

Y

I

I

R

R

R

H

P

G

D

S

Q

K

L

P

D

M

Y

Y

L

T

S

P

E

E

P

P

D

D

L

I

F

C

H
|
H

D

E

L

L

F

L

G

G

H
|
H

V

V

P

P

L

L

L

F

L

S

N

D

P

R

V

S

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

E

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

P

P

D

E

E

A

Y

L

I

M

E

N

K

L

L

T

A

R

T

L

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Y
|
Y

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W

Y

F

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E

F

F

G

G

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L

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E

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G

S

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I

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A

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Y

G

G

A

A

G

G

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L

S
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S

S

S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

E

A

K

P

P

N

K

R

L

I

L

G

P

F

L

G

E

L

L

E

E

R

K

V

T

M

A

N

I

T

Q

R

N

Y

Y

R

T

I

V

D

T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F

Y

V

V

I

A

D

E

S

S

F

F

E

N

Q

D

L

A

F

K

D

E

A

K

T

V

R

R

active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding fe (iii) ion: H169 (= H136), H174 (= H141), E214 (= E184)
binding l-dopamine: H169 (= H136), H174 (= H141), Y209 (= Y179), E214 (= E184)

4pahA Human phenylalanine hydroxylase catalytic domain dimer with bound nor- adrenaline inhibitor (see paper)
34% identity, 76% coverage: 30:255/297 of query aligns to 59:284/308 of 4pahA

query
sites
4pahA

P

P

W

R

A

V

D

E

Y

Y

S

M

Q

E

T

E

D

E

H

K

E

K

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W

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G

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T

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Y

F

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K

E

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L

L

L

Y

K

K

G

T

R

H

A

A

C

C

Q

Y

E

E

F

Y

-

N

-

H

-

I

L

F

D

P

G

L

I

L

E

E

R

K

F

Y

-

C

G

G

M

F

G

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E

N

D

G

N

I

I

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K

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F

L

A

E

D

D

L

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C

T

T

G

G

W

F

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L

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E

A

G

G

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L

P

S

D

S

E

R

V

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F
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F

F

L

D

G

H

G

L

L

A

A

N

F

R

R

R

V

F

F

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H

V

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T

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Q

W

Y

I

I

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R

R

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H
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H

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E

L

L

F

L

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H
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H

V

V

P

P

L

L

L

F

L

S

N

D

P

R

V

S

F

F

A

A

D

Q

Y

F

M

S

Q

Q

A

E

Y

I

G

-

R

-

G

-

G

G

M

L

K

A

A

S

F

L

G

G

I

A

G

P

P

D

E

E

A

Y

L

I

M

E

N

K

L

L

T

A

R

T

L

I

Y
|
Y

W

W

Y

F

T

T

V

V

E
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E

F

F

G

G

L

L

I

C

N

K

T

Q

S

G

E

D

G

S

M

I

R

K

I

A

Y

Y

G

G

A

A

G

G

I

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V

L

S
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S

S

S

K

F

G

G

E

E

S

L

I

Q

Y

Y

C

C

L

L

D

-

S

S

A

E

A

K

P

P

N

K

R

L

I

L

G

P

F

L

G

E

L

L

E

E

R

K

V

T

M

A

N

I

T

Q

R

N

Y

Y

R

T

I

V

D

T

T

E

F

F

Q

Q

Q

P

T

L

Y

Y

F

Y

V

V

I

A

D

E

S

S

F

F

E

N

Q

D

L

A

F

K

D

E

A

K

T

V

R

R

active site: H169 (= H136), H174 (= H141), E214 (= E184), S233 (= S203)
binding fe (iii) ion: H169 (= H136), H174 (= H141), E214 (= E184)
binding l-norepinephrine: F138 (= F105), H169 (= H136), H174 (= H141), Y209 (= Y179), E214 (= E184)

Query Sequence

>N515DRAFT_3052 FitnessBrowser__Dyella79:N515DRAFT_3052
MDHSTPRKVEHQQTDRGYVPVYATGVVEQPWADYSQTDHEVWNTLYRRQRELLKGRACQE
FLDGIERFGMGENGIPKFADLNKVLGETTGWELVAVEGLLPDEVFFDHLANRRFPVSWWI
RRPDQLDYLSEPDLFHDLFGHVPLLLNPVFADYMQAYGRGGMKAFGIGPEALMNLTRLYW
YTVEFGLINTSEGMRIYGAGIVSSKGESIYCLDSAAPNRIGFGLERVMNTRYRIDTFQQT
YFVIDSFEQLFDATRPDFTPIYADLKTREAHAAADVLDSDRVFTRGTREGFATDADT

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