SitesBLAST

F136 (≠ L55) mutation to A: Decreases association with PtsG EIIB domain.
H247 (= H168) binding Zn(2+)
C257 (= C178) binding Zn(2+); mutation to A: Strongly reduced activity; when associated with A-259.; mutation to S: Strongly reduced activity; when associated with S-259.
C259 (= C180) binding Zn(2+); mutation to A: Strongly reduced activity; when associated with A-257.; mutation to S: Strongly reduced activity; when associated with S-257.
C264 (= C185) binding Zn(2+)
R306 (≠ Q227) mutation to G: Forms dimers but not tetramers; when associated with G-310.
L310 (= L231) mutation to G: Forms dimers but not tetramers; when associated with G-306.

Sites not aligning to the query:

52 R→H: Shows increased expression and forms larger colonies.
86 H→R: Can be bound and inactivated by MtfA.

2yi1A Crystal structure of n-acetylmannosamine kinase in complex with n- acetyl mannosamine 6-phosphate and adp. (see paper)
28% identity, 89% coverage: 5:284/316 of query aligns to 4:278/308 of 2yi1A

query
sites
2yi1A

A

S

T

A

I

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A

A

I

V

D

D

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G
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G

T
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T

R
x
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-

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A

binding adenosine-5'-diphosphate: G11 (= G12), T13 (= T14), N14 (≠ R15), R16 (≠ K17), T140 (= T142), G189 (≠ T192), L216 (≠ E219), V261 (= V265)
binding 2-acetamido-2-deoxy-6-O-phosphono-alpha-D-mannopyranose: G12 (= G13), G71 (≠ P73), G72 (= G74), R73 (≠ I75), S84 (≠ I86), T85 (≠ N87), L87 (≠ K89), N112 (= N114), D113 (= D115), G139 (= G141), T140 (= T142), G141 (= G143), I142 (= I144), E162 (≠ I164), H165 (= H168), E184 (= E187)
binding calcium ion: N112 (= N114), N115 (≠ R117), G144 (≠ T146), A161 (≠ G163)
binding zinc ion: H165 (= H168), C175 (= C178), C177 (= C180), C182 (= C185)

2yhyA Structure of n-acetylmannosamine kinase in complex with n- acetylmannosamine and adp (see paper)
28% identity, 89% coverage: 5:284/316 of query aligns to 4:278/308 of 2yhyA

query
sites
2yhyA

A

S

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A

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binding adenosine-5'-diphosphate: G11 (= G12), G12 (= G13), T13 (= T14), N14 (≠ R15), R16 (≠ K17), T140 (= T142), G189 (≠ T192), L216 (≠ E219), V261 (= V265)
binding calcium ion: N112 (= N114), N115 (≠ R117), G144 (≠ T146), A161 (≠ G163)
binding zinc ion: H165 (= H168), C175 (= C178), C177 (= C180), C182 (= C185)

Q9Y223 Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase; UDP-GlcNAc-2-epimerase/ManAc kinase; EC 3.2.1.183; EC 2.7.1.60 from Homo sapiens (Human) (see 18 papers)
29% identity, 85% coverage: 1:268/316 of query aligns to 404:673/722 of Q9Y223

query
sites
Q9Y223

M

L

E

E

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S

D413 (= D10) binding Mg(2+)
G416 (= G13) binding an N-acyl-D-mannosamine 6-phosphate
T417 (= T14) binding ADP
N418 (≠ R15) binding ADP
R420 (≠ K17) binding ADP
I472 (= I70) to T: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to 50% of the wild-type activity; decreased N-acylmannosamine kinase activity; corresponding to less than 10% of wild-type activity
G476 (= G74) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
R477 (≠ I75) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
T489 (≠ N87) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
N516 (= N114) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
D517 (= D115) active site; binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate; mutation D->A,N: Loss of N-acylmannosamine kinase activity. Decreased affinity for N-acyl-D-mannosamine. No effect on structure.
N519 (≠ R117) to S: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs1554658910; mutation to S: Decreased N-acylmannosamine kinase activity.
A524 (≠ G122) to V: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to less than 10% of wild-type activity; decreased N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs764698870
F528 (≠ H126) to C: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 70% of wild-type activity; decreased N-acylmannosamine kinase activity; dbSNP:rs986773986; mutation to C: Decreased N-acylmannosamine kinase activity.
G545 (= G143) binding an N-acyl-D-mannosamine 6-phosphate
E566 (≠ I164) binding an N-acyl-D-mannosamine
H569 (= H168) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate; binding Zn(2+)
V572 (≠ I171) to L: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 70-80% of wild-type activity; decreased N-acylmannosamine kinase activity; corresponding to less than 10% of wild-type activity; does not affect homohexamers formation; dbSNP:rs121908632
G576 (= G175) to E: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs121908625
C579 (= C178) binding Zn(2+)
C581 (= C180) binding Zn(2+)
C586 (= C185) binding Zn(2+)
I587 (≠ A186) to T: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs748949603; mutation to T: Decreased N-acylmannosamine kinase activity.
E588 (= E187) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
A630 (≠ C224) to T: in NM; decreased N-acylmannosamine kinase activity; does not affect homohexamers formation; dbSNP:rs1382191649
A631 (= A225) to T: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 80% of wild-type activity; decreased N-acylmannosamine kinase activity; retains 75% of wild-type activity; dbSNP:rs121908626; to V: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 70% of wild-type activity; decreased N-acylmannosamine kinase activity; does not affect homohexamers formation; dbSNP:rs62541771; mutation A->V,T: Decreased N-acylmannosamine kinase activity.

Sites not aligning to the query:

13 C → S: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to 20% of wild-type activity; no effect on N-acylmannosamine kinase activity; dbSNP:rs1209266607
19 binding UDP
23 binding UDP
113 binding UDP
132 H → Q: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to less than 10% of wild-type activity; impaired homohexamers formation
176 D → V: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to 20% of wild-type activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs139425890
177 R → C: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to less than 20% of wild-type activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs539332585
200 I → F: in NM; uncertain significance; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 90% of wild-type activity; decreased N-acylmannosamine kinase activity; retains 75% of wild-type activity; dbSNP:rs369328625
206 G → S: in NM; moderate phenotype with unusual involvement of quadriceps; dbSNP:rs766266918
220 binding UDP
253 binding UDP
259 binding CMP-N-acetyl-beta-neuraminate
263 R → L: in SIALURIA; strong reduction of feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908623
266 R → Q: in SIALURIA; abolishes feedback inhibition by CMP-Neu5Ac; dbSNP:rs121908622; R → W: in sialuria; dbSNP:rs121908621
271 binding CMP-N-acetyl-beta-neuraminate
280 binding CMP-N-acetyl-beta-neuraminate
281 binding CMP-N-acetyl-beta-neuraminate
282 binding UDP
301 binding UDP
302 binding UDP
303 C → V: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; retains 80% of wild-type activity; decreased N-acylmannosamine kinase activity; corresponding to 60% of wild-type activity; requires 2 nucleotide substitutions; dbSNP:rs121908633
307 binding UDP
321 binding UDP
331 V → A: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to 20% of wild-type activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation
378 D → Y: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; corresponding to 10-30% of wild-type activity; decreased N-acylmannosamine kinase activity; impaired homohexamers formation; dbSNP:rs199877522
708 G → S: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; severely decreased; dbSNP:rs1554657922
712 M→T: Decreased N-acylmannosamine kinase activity.

O35826 Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase; UDP-GlcNAc-2-epimerase/ManAc kinase; EC 3.2.1.183; EC 2.7.1.60 from Rattus norvegicus (Rat) (see paper)
28% identity, 85% coverage: 1:268/316 of query aligns to 404:673/722 of O35826

query
sites
O35826

M

L

E

E

E
x
T

K
x
L

A
x
S

T
x
A

I
x
L

A
|
A

I
x
V

D
|
D

L
|
L

G
|
G

T
|
T

R
x
N

I
x
L

K
x
R

L
x
V

G
x
A

L
x
I

V
|
V

-
x
S

-
x
M

R
x
K

A
x
G

G
x
E

T
x
I

V
|
V

L
x
K

T
x
Y

S
x
T

Q
|
Q

M
x
F

E
x
N

S
x
P

Q
x
K

S
x
T

G
x
Y

Q
x
E

G
x
E

L
x
R

Q
x
I

A
x
S

R
x
L

L
x
I

P
x
L

Q
|
Q

L
x
M

-
x
C

-
x
V

E
|
E

T
x
A

A
|
A

I
x
A

N
x
E

A
|
A

M
x
V

L
x
K

A
x
L

Q
x
N

A
x
C

R
|
R

L
x
I

T
x
L

A

-

D

-

L

-

S

-

G
|
G

I
x
V

G
|
G

I
|
I

A
x
S

I
x
T

P
x
G

G
|
G

I
x
R

V
|
V

D
x
N

P
|
P

I
x
Q

N
x
E

K
x
G

R
x
V

V
|
V

L
|
L

T
x
H

I
x
S

N
x
T

G
x
K

K
x
L

Y
x
I

S
x
Q

D
x
E

A
x
W

P
x
N

N
x
S

L
x
V

D
|
D

L
|
L

P
x
R

A
x
T

W
x
P

A
x
L

H
x
S

E
x
D

T
|
T

W
x
L

G
x
H

L
|
L

P
|
P

L
x
V

Y
x
W

L
x
V

E
x
D

N
|
N

D
|
D

T
x
G

R
x
N

A
x
C

A
|
A

L
x
A

L
x
M

G
x
A

E
|
E

W
x
R

Q
x
K

H
x
F

G
|
G

S
x
Q

G
|
G

R
x
K

G
|
G

Y
x
Q

D
x
E

N
|
N

V
x
F

V
|
V

L
x
T

M
x
L

T
x
I

L
x
T

G
|
G

T
|
T

G
|
G

I
|
I

G
|
G

T
x
G

S
x
G

A
x
I

V
x
I

I
x
H

E
x
Q

G
x
H

R
x
E

L
|
L

L
x
I

R
x
H

G
|
G

R
x
S

H
x
S

F
|
F

Q
x
C

A
|
A

G
x
A

I
x
E

L
|
L

G

-

G
|
G

H
|
H

V
x
L

V
|
V

I
x
V

N
x
S

T
x
L

Q
x
D

G
|
G

N
x
P

Q
x
D

C
|
C

N
x
S

C
|
C

G
|
G

T
x
S

V
x
H

G
|
G

C
|
C

A
x
I

E
|
E

A
|
A

E
x
Y

A
|
A

S
|
S

T
x
G

W
x
M

S
x
A

L
|
L

N
x
Q

E
x
R

R
x
E

A
|
A

T
x
K

A
x
K

H
x
L

A
x
H

T
x
D

Y
x
E

P
x
D

Q
x
L

S
x
L

L
|
L

L
x
V

C
x
E

G
|
G

Y
x
M

D
x
S

T
x
V

V
x
P

D
x
K

Y
x
D

E
|
E

A
|
A

V
|
V

-
x
G

-
x
A

-
x
L

-
x
H

-
x
L

F
x
I

R
x
Q

C
x
A

A
|
A

Q
x
K

Q
x
L

G
|
G

D
x
N

A
x
V

L
x
K

A
|
A

T
x
Q

T
x
S

L
x
I

R
x
L

N
x
R

D
x
T

S
x
A

I
x
G

A
x
T

V
x
A

W
x
L

A
x
G

A
x
L

C
x
G

A
x
V

Y
x
V

N
|
N

L
x
I

V
x
L

Q
x
H

A
x
T

Y
x
M

D
x
N

P
|
P

E
x
S

V
x
L

L
x
V

I
|
I

L
|
L

G

-

G
x
S

G
|
G

V
|
V

M
x
L

A
|
A

S
|
S

D413 (= D10) mutation D->K,N: No effect on UDP-N-acetylglucosamine 2-epimerase activity. Does not affect feedback inhibition by CMP-Neu5Ac. Loss of N-acylmannosamine kinase activity. Does not interfere with oligomerization.
R420 (≠ K17) mutation to M: No effect on UDP-N-acetylglucosamine 2-epimerase activity. Does not affect feedback inhibition by CMP-Neu5Ac. Loss of N-acylmannosamine kinase activity. Does not interfere with oligomerization.

Sites not aligning to the query:

1 UDP-N-acetylglucosamine 2-epimerase
49 H→A: Loss UDP-N-acetylglucosamine 2-epimerase activity. No effect on N-acylmannosamine kinase activity. Does not interfere with enzyme oligomerization.
110 H→A: Loss UDP-N-acetylglucosamine 2-epimerase activity. No effect on N-acylmannosamine kinase activity. Partial reduction of the dimerization process.
132 H→A: Loss UDP-N-acetylglucosamine 2-epimerase activity. No effect on N-acylmannosamine kinase activity. Partial reduction of the dimerization process.
155 H→A: Loss UDP-N-acetylglucosamine 2-epimerase activity. No effect on N-acylmannosamine kinase activity. Strong reduction of the dimerization process.
157 H→A: Loss UDP-N-acetylglucosamine 2-epimerase activity. No effect on N-acylmannosamine kinase activity. Strong reduction of the dimerization process.
406:722 N-acetylmannosamine kinase

2yhwA High-resolution crystal structures of n-acetylmannosamine kinase: insights about substrate specificity, activity and inhibitor modelling. (see paper)
28% identity, 89% coverage: 5:284/316 of query aligns to 4:279/309 of 2yhwA

query
sites
2yhwA

A

S

T

A

I

L

A

A

I

V

D

D

L

L

G

G

T

T

R

N

I

L

K

R

L

V

G

A

L

I

V

V

-

S

-

M

R

K

A

G

G

E

T

I

V

V

L

K

T

Y

S

T

Q

Q

M

F

E

N

S

P

Q

K

S

T

G

Y

Q

E

G

E

L

R

Q

I

A

N

R

L

L

I

P

L

Q

Q

L

M

-

C

-

V

E

E

T

A

A

A

I

A

N

E

A

A

M

V

L

K

A

L

Q

N

A

C

R

R

L

I

T

L

A

-

D

-

L

-

S

-

G

G

I

V

G

G

I

I

A

S

I

T

P

G

G

G

I

R

V

V

D

N

P

P

I

R

N

E

K

G

R

I

V

V

L

L

T

H

I

S

N

T

G

K

K

L

Y

I

S

Q

D

E

A

W

P

N

N

S

L

V

D

D

L

L

P

R

A

T

W

P

A

L

H

S

E

D

T

T

W

L

G

H

L

L

P

P

L

V

Y

W

L

V

E

D

N
|
N

D

D

T

G

R
x
N

A

C

A

A

L

A

L

L

G

A

E

E

W

R

Q

K

H

F

G

G

S

Q

G

G

R

K

G

G

Y

L

D

E

N

N

V

F

V

V

L

T

M

L

T

I

L

T

G

G

T

T

G

G

I

I

G

G

T
x
G

S

G

A

I

V

I

I

H

E

Q

G

H

R

E

L

L

L

I

R

H

G

G

R

S

H

S

F

F

Q

C

A

A

G
x
A

I

E

L

L

G

-

G

G

H
|
H

V

L

V

V

I

V

N

S

T

L

Q

N

G

G

N

P

Q

D

C
|
C

N

S

C
|
C

G

G

T

S

V

H

G

G

C
|
C

A

I

E

E

A

A

E

Y

A

A

S

S

T

G

W

M

S

A

L

L

N

Q

E

R

R

E

A

A

T

K

A

K

H

L

A

H

T

D

Y

E

P

D

Q

L

S

L

L

L

L

V

C

E

G

G

Y

M

D

S

T

V

-

A

V

V

D

G

Y

A

E

L

A

H

V

L

F

I

R

Q

C

A

A

A

Q

K

Q

L

G

G

D

N

A

A

L

K

A

A

T

Q

T

S

L

I

R

L

N

R

D

T

S

A

I

G

A

T

V

A

W

L

A

G

A

L

C

G

A

V

Y

V

N

N

L

I

V

L

Q

H

A

T

Y

M

D

N

P

P

E

S

V

L

L

V

I

I

L

L

G

-

G

S

G

G

V

V

M

L

A

A

S

S

R

H

D

-

A

-

I

Y

I

I

P

H

P

I

I

V

Q

K

E

D

R

V

L

I

N

R

Q

Q

N

Q

A

A

binding calcium ion: N112 (= N114), N115 (≠ R117), G144 (≠ T146), A161 (≠ G163)
binding zinc ion: H165 (= H168), C175 (= C178), C177 (= C180), C182 (= C185)

6jdoA Crystal structure of n-acetyl mannosmaine kinase with amp-pnp from pasteurella multocida
25% identity, 96% coverage: 7:308/316 of query aligns to 4:283/293 of 6jdoA

query
sites
6jdoA

I

L

A

A

I

L

D

D

L

I

G

G

T

T

R

K

I

I

K

A

L

S

G

A

L

I

V

V

R

T

A

D

G

G

T

K

V

I

L

E

L

Q

T

R

S

Q

Q

Q

M

I

E

A

S

T

Q

P

S

Q

G

A

Q

D

G

A

L

A

Q

N

A

A

R

M

L

H

P

D

Q

T

L

L

E

A

T

N

A

I

I

L

N

A

A

L

M

Y

L

A

A

G

Q

Q

A

F

R

D

L

Y

T

V

A

A

A

-

D

-

L

V

S

A

G

S

I

T

G

G

I

I

A

I

I

N

P

H

G

G

I

V

V

L

D

T

P

A

I

L

N
&nb