SitesBLAST

2yhwA High-resolution crystal structures of n-acetylmannosamine kinase: insights about substrate specificity, activity and inhibitor modelling. (see paper)
28% identity, 86% coverage: 3:278/320 of query aligns to 4:278/309 of 2yhwA

query
sites
2yhwA

S

S

Y

A

A

L

G

A

V

V

D

D

L

L

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G

T

T

N

N

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T

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E

-

V

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Y

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K
x
N

D

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A
x
N

A

C

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A

E

E

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A

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-

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Y

T

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A
x
G

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I

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H

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C

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x
C

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I

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A

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Y

C

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binding calcium ion: N112 (≠ K111), N115 (≠ A114), G144 (≠ A142), A161 (≠ G159)
binding zinc ion: H165 (= H163), C175 (= C174), C177 (= C176), C182 (≠ H181)

1z05A Crystal structure of the rok family transcriptional regulator, homolog of e.Coli mlc protein.
26% identity, 70% coverage: 54:278/320 of query aligns to 128:347/396 of 1z05A

query
sites
1z05A

T

T

D

Y

A

A

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Q

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L

D

D

P

-

T

-

A

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C

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x
C

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binding zinc ion: H236 (= H163), C246 (= C174), C248 (= C176), C253 (≠ H181)

3vovB Crystal structure of rok hexokinase from thermus thermophilus (see paper)
33% identity, 77% coverage: 66:310/320 of query aligns to 60:290/298 of 3vovB

query
sites
3vovB

A

A

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G

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T

binding zinc ion: H157 (= H163), C167 (= C174), C169 (= C176), C174 (≠ H181)

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 26 papers)
28% identity, 86% coverage: 3:278/320 of query aligns to 408:686/722 of Q9Y223

query
sites
Q9Y223

S

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G

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T

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R

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V

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A

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M

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G

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I

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G

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R

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E

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E

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D

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G
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K

H
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-
x
G

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x
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M
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L

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I

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G
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G

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I

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G
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H

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x
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L
x
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x
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G

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x
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D
x
S

G
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A

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E

A
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G

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H

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D

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C

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C

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A

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N
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D
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A

D
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K

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G

D
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A

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x
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A
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L

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M
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H

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P

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x
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G

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A

L
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Q

D413 (= D8) binding Mg(2+); to Y: in THC12; likely pathogenic; dbSNP:rs1280775456
G416 (= G11) binding an N-acyl-D-mannosamine 6-phosphate
T417 (= T12) binding ADP; to M: in THC12; likely pathogenic; dbSNP:rs1554659711
N418 (= N13) binding ADP
R420 (= R15) binding ADP; to Q: in THC12; likely pathogenic; dbSNP:rs780092539
I472 (= I69) to T: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity
G475 (≠ A72) to F: in THC12; likely pathogenic; requires 2 nucleotide substitutions
G476 (= G73) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
R477 (= R74) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
V485 (= V82) to R: in THC12; uncertain significance; reduced protein abundance in homozygous patient cells; requires 2 nucleotide substitutions
L486 (≠ E83) to P: in THC12; uncertain significance; dbSNP:rs774867424
T489 (≠ N86) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
N516 (≠ K111) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
D517 (= D112) 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 (≠ A114) to S: in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs1554658910
A524 (≠ G119) 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 (≠ H123) to C: in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs986773986
T544 (≠ S138) to R: in THC12; uncertain significance; reduced protein abundance in homozygous patient cells
G545 (= G139) binding an N-acyl-D-mannosamine 6-phosphate
C563 (≠ N157) to Y: in THC12; likely pathogenic; results in severely decreased cell surface sialylation
E566 (= E160) binding an N-acyl-D-mannosamine
H569 (= H163) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate; binding Zn(2+)
V572 (= V166) to L: in NM and THC12; likely pathogenic; mildly decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity corresponding to less than 10% of wild-type activity; does not affect homohexamers formation; dbSNP:rs121908632
G576 (= G170) to E: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs121908625
C579 (= C174) binding Zn(2+)
C581 (= C176) binding Zn(2+)
C586 (≠ H181) binding Zn(2+)
I587 (≠ W182) to T: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; decreased N-acylmannosamine kinase activity; dbSNP:rs748949603
E588 (= E183) binding an N-acyl-D-mannosamine; binding an N-acyl-D-mannosamine 6-phosphate
A630 (≠ N224) to T: in NM; decreased N-acylmannosamine kinase activity; does not affect homohexamers formation; dbSNP:rs1382191649
A631 (≠ D225) to V: in NM; does not affect homohexamers formation; dbSNP:rs62541771

Sites not aligning to the query:

13 C → S: in NM; decreased UDP-N-acetylglucosamine 2-epimerase 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; impaired homohexamers formation
157 H → Y: in THC12; likely pathogenic
176 D → V: in NM; decreased UDP-N-acetylglucosamine 2-epimerase 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; impaired homohexamers formation; dbSNP:rs539332585
200 I → F: in NM; uncertain significance; 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; requires 2 nucleotide substitutions; dbSNP:rs121908633
307 binding UDP
321 binding UDP
331 V → A: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; no effect on N-acylmannosamine kinase activity; impaired homohexamers formation
378 D → Y: in NM; decreased UDP-N-acetylglucosamine 2-epimerase activity; impaired homohexamers formation; dbSNP:rs199877522
420:722 natural variant: Missing (in THC12; likely pathogenic)
704 P → R: in THC12; likely pathogenic; the orthologous mutation in mouse embryos results in cerebrospinal hemorrhages and defective angiogenesis; results in loss of cell surface sialylation
708 G → S: in NM and THC12; likely pathogenic; decreased UDP-N-acetylglucosamine 2-epimerase activity; severely decreased N-acylmannosamine kinase activity; dbSNP:rs1554657922
712 M → T: in NM; decreased N-acylmannosamine kinase activity; dbSNP:rs28937594

Q91WG8 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 Mus musculus (Mouse) (see paper)
28% identity, 86% coverage: 3:278/320 of query aligns to 408:686/722 of Q91WG8

query
sites
Q91WG8

S

S

Y

A

A

L

G

A

V

V

D

D

L

L

G

G

T

T

N

N

L

L

R

R

V

V

V

A

V

I

A

V

D

S

A

M

D

K

G

G

N

E

I

I

D

V

G

K

S

K

D

Y

R

T

R

Q

E

F

A

N

P

P

R

K

G

T

P

Y

N

E

G

-

L

-

A

E

V

R

T

I

E

S

A

L

I

I

L

L

E

Q

S

M

L

C

R

V

E

E

A

A

T

A

D

A

A

E

A

A

G

V

V

K

D

L

P

N

T

C

A

R

I

I

T

L

A

G

V

V

G

G

I

I

A

S

A

T

A

G

G

G

R

R

L

V

D

N

L

P

T

Q

E

E

G

G

L

V

V

V

E

L

P

H

T

S

N

T

I

K

P

L

V

I

G

Q

E

E

-

W

-

N

-

S

V

V

P

D

L

L

R

R

G

T

P

P

V

L

S

S

N

D

L

T

L

L

D

H

T

L

E

P

E

-

V

V

Y

W

L

V

H

D

K

N

D

D

V

G

A

N

A

C

G

A

V

A

I

M

G

A

E

E

R

R

Y

K

H

F

A

G

E

Q

-

G

R

K

N

G

P

Q

D

E

D

N

M

F

V

V

Y

T

L

L

T

I

I

T

S

G

S

T

G

G

I

I

G

G

A

G

G

G

V

I

A

I

V

H

D

Q

G

H

N

E

I

L

L

I

G

H

G

G

W

S

D

S

G

F

N
x
C

A

A

G

A

E

E

A

L

G

G

H

H

L

L

T

V

V

V

D

S

P

L

K

D

G

G

R

P

M

-

D

D

C

C

G

S

C

C

G

G

K

S

E

H

G

G

H

C

W

I

E

E

A

A

Y

Y

C

A

A

S

G

G

T

M

N

A

I

L

P

Q

E

R

Y

E

A

A

R

K

L

K

L

L

W

H

D

D

D

E

E

D

G

L

Q

L

P

L

E

V

T

E

A

G

L

M

P

S

I

V

-

P

E

K

T

D

E

E

G

A

F

V

T

G

A

A

V

L

D

H

V

L

F

I

E

Q

N

A

D

A

D

K

-

L

-

G

D

N

E

V

F

K

A

A

N

Q

H

S

V

I

V

L

G

R

R

T

L

A

A

G

D

T

W

A

N

L

A

G

L

L

G

G

M

V

A

V

D

N

I

I

V

L

H

H

A

T

Y

M

A

N

P

P

L

S

V

L

V

V

S

I

V

L

G

S

G

G

A

V

V

L

A

A

L

S

N

H

N

Y

E

I

A

H

R

I

V

V

V

K

D

D

P

V

M

I

R

R

E

Q

R

Q

C563 (≠ N157) mutation to Y: Loss-of-function mutant resulting in impaired sialic acid biosynthesis.

Sites not aligning to the query:

704 P→R: Homozygous embryos exhibit cerebrospinal hemorrhages and defective angiogenesis in the diencephalon at 11 dpc, and become non-viable between 11.5 and 12.5 dpc. Loss-of-function mutant resulting in impaired sialic acid biosynthesis.

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, 86% coverage: 3:278/320 of query aligns to 408:686/722 of O35826

query
sites
O35826

S
|
S

Y
x
A

A
x
L

G
x
A

V
|
V

D
|
D

L
|
L

G
|
G

T
|
T

N
|
N

L
|
L

R
|
R

V
|
V

V
x
A

V
x
I

A
x
V

D
x
S

A
x
M

D
x
K

G
|
G

N
x
E

I
|
I

D
x
V

G
x
K

S
x
K

D
x
Y

R
x
T

R
x
Q

E
x
F

A
x
N

P
|
P

R
x
K

G
x
T

P
x
Y

N
x
E

G

-

L

-

A
x
E

V
x
R

T
x
I

E
x
S

A
x
L

I
|
I

L
|
L

E
x
Q

S
x
M

L
x
C

R
x
V

E
|
E

A
|
A

T
x
A

D
x
A

A
x
E

A
|
A

G
x
V

V
x
K

D
x
L

P
x
N

T
x
C

A
x
R

I
|
I

T
x
L

A
x
G

V
|
V

G
|
G

I
|
I

A
x
S

A
x
T

A
x
G

G
|
G

R
|
R

L
x
V

D
x
N

L
x
P

T
x
Q

E
|
E

G
|
G

L
x
V

V
|
V

E
x
L

P
x
H

T
x
S

N
x
T

I
x
K

P
x
L

V
x
I

G
x
Q

E
|
E

-
x
W

-
x
N

-
x
S

V
|
V

P
x
D

L
|
L

R
|
R

G
x
T

P
|
P

V
x
L

S
|
S

N
x
D

L
x
T

L
|
L

D
x
H

T
x
L

E
x
P

E

-

V
|
V

Y
x
W

L
x
V

H
x
D

K
x
N

D
|
D

V
x
G

A
x
N

A
x
C

G
x
A

V
x
A

I
x
M

G
x
A

E
|
E

R
|
R

Y
x
K

H
x
F

A
x
G

E
x
Q

-
x
G

R
x
K

N
x
G

P
x
Q

D
x
E

D
x
N

M
x
F

V
|
V

Y
x
T

L
|
L

T
x
I

I
x
T

S
x
G

S
x
T

G
|
G

I
|
I

G
|
G

A
x
G

G
|
G

V
x
I

A
x
I

V
x
H

D
x
Q

G
x
H

N
x
E

I
x
L

L
x
I

G
x
H

G
|
G

W
x
S

D
x
S

G
x
F

N
x
C

A
|
A

G
x
A

E
|
E

A
x
L

G
|
G

H
|
H

L
|
L

T
x
V

V
|
V

D
x
S

P
x
L

K
x
D

G
|
G

R
x
P

M

-

D
|
D

C
|
C

G
x
S

C
|
C

G
|
G

K
x
S

E
x
H

G
|
G

H
x
C

W
x
I

E
|
E

A
|
A

Y
|
Y

C
x
A

A
x
S

G
|
G

T
x
M

N
x
A

I
x
L

P
x
Q

E
x
R

Y
x
E

A
|
A

R
x
K

L
x
K

L
|
L

W
x
H

D
|
D

D
x
E

E
x