Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Targeting of human catalase to peroxisomes is dependent upon a novel COOH-terminal peroxisomal targeting sequence.
[neonatal adrenoleukodystrophy]
We
have
identified
a
novel
peroxisomal
targeting
sequence
(
PTS
)
at
the
extreme
COOH
terminus
of
human
catalase
.
The
last
four
amino
acids
of
this
protein
(
-
KANL
)
are
necessary
and
sufficient
to
effect
targeting
to
peroxisomes
in
both
human
fibroblasts
and
Saccharomyces
cerevisiae
,
when
appended
to
the
COOH
terminus
of
the
reporter
protein
,
chloramphenicol
acetyl
transferase
.
However
,
this
PTS
differs
from
the
extensive
family
of
COOH-terminal
PTS
tripeptides
collectively
termed
PTS
1
in
two
major
aspects
.
First
,
the
presence
of
the
uncharged
amino
acid
,
asparagine
,
at
the
penultimate
residue
of
the
human
catalase
PTS
is
highly
unusual
,
in
that
a
basic
residue
at
this
position
has
been
previously
found
to
be
a
common
and
critical
feature
of
PTS
1
signals
.
Nonetheless
,
this
asparagine
residue
appears
to
constitute
an
important
component
of
the
catalase
PTS
,
in
that
replacement
with
aspartate
abolished
peroxisomal
targeting
(
as
did
deletion
of
the
COOH-terminal
four
residues
)
.
Second
,
the
human
catalase
PTS
comprises
more
than
the
COOH-terminal
three
amino
acids
,
in
that
COOH-terminal-ANL
can
not
functionally
replace
the
PTS
1
signal-
SKL
in
targeting
a
chloramphenicol
acetyl
transferase
fusion
protein
to
peroxisomes
.
The
critical
nature
of
the
fourth
residue
from
the
COOH
terminus
of
the
catalase
PTS
(
lysine
)
is
emphasized
by
the
fact
that
substitution
of
this
residue
with
a
variety
of
other
amino
acids
abolished
or
reduced
peroxisomal
targeting
.
Targeting
was
not
reduced
when
this
lysine
was
replaced
with
arginine
,
suggesting
that
a
basic
amino
acid
at
this
position
is
required
for
maximal
functional
activity
of
this
PTS
.
In
spite
of
these
unusual
features
,
human
catalase
is
sorted
by
the
PTS
1
pathway
,
both
in
yeast
and
human
cells
.
Disruption
of
the
PAS
10
gene
encoding
the
S
.
cerevisiae
PTS
1
receptor
resulted
in
a
cytosolic
location
of
chloramphenicol
acetyl
transferase
appended
with
the
human
catalase
PTS
,
as
did
expression
of
this
protein
in
cells
from
a
neonatal
adrenoleukodystrophy
patient
specifically
defective
in
PTS
1
import
.
Furthermore
,
through
the
use
of
the
two
-hybrid
system
,
it
was
demonstrated
that
both
the
PAS
10
gene
product
(
Pas
10
p
)
and
the
human
PTS
1
receptor
can
interact
with
the
COOH-terminal
region
of
human
catalase
,
but
that
this
interaction
is
abolished
by
substitutions
at
the
penultimate
residue
(
asparagine-
to
-
aspartate
)
and
at
the
fourth
residue
from
the
COOH
terminus
(
lysine-
to
-glycine
)
which
abolish
PTS
functionality
.
We
have
found
no
evidence
of
additional
targeting
information
elsewhere
in
the
human
catalase
protein
.
An
internal
tripeptide
(
-
SHL-
,
which
conforms
to
the
mammalian
PTS
1
consensus
)
located
nine
to
eleven
residues
from
the
COOH
terminus
has
been
excluded
as
a
functional
PTS
.
Additionally
,
in
contrast
to
the
situation
for
S
.
cerevisiae
catalase
A
,
which
contains
an
internal
PTS
in
addition
to
a
COOH-terminal
PTS
1
,
human
catalase
lacks
such
a
redundant
PTS
,
as
evidenced
by
the
exclusive
cytosolic
location
of
human
catalase
mutated
in
the
COOH-terminal
PTS
.
Consistent
with
this
species
difference
,
fusions
between
catalase
A
and
human
catalase
which
include
the
catalase
A
internal
PTS
are
targeted
,
at
least
in
part
,
to
peroxisomes
regardless
of
whether
the
COOH-terminal
human
catalase
PTS
is
intact
.
Diseases
Validation
Diseases presenting
"asparagine"
symptom
neonatal adrenoleukodystrophy
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom