PMID- 10401004
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - Defective copper-induced trafficking and localization of the Menkes protein in
      patients with mild and copper-treated classical Menkes disease.
PG  - 1547-55
AB  - Menkes disease is an X-linked disorder of copper metabolism. An overall copper
      deficiency reduces the activity of copper-dependent enzymes accounting for the
      clinical presentation of affected individuals. The Menkes gene product (MNK) is a
      P-type ATPase and is considered to be the main copper efflux protein in most
      cells. The protein is located primarily at the trans -Golgi network (TGN), but
      relocalizes to the plasma membrane in elevated copper conditions to expel the
      excess copper from the cell. Here we report the first missense mutation which
      causes mild Menkes disease, a mutation in a successfully copper-treated classical
      Menkes patient and the effect of each mutation on the localization of MNK within 
      the cell. Using western blot analysis, MNK was detectable in cells from both
      patients, but appeared to be mislocalized in the treated case. In the mild Menkes
      patient, the protein appeared to be located in the TGN but failed to redistribute
      towards the cell periphery in response to copper. This is the first description
      of a mutation in a Menkes patient which affects the trafficking of MNK, and the
      loss of this process is consistent with the clinical phenotype.
FAU - Ambrosini, L
AU  - Ambrosini L
AD  - The Murdoch Institute, Royal Children's Hospital, Flemington Road, Parkville
      3052, Australia.
FAU - Mercer, J F
AU  - Mercer JF
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Carrier Proteins)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 789U1901C5 (Copper)
RN  - 9007-49-2 (DNA)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.3.54 (Copper-transporting ATPases)
RN  - EC 7.2.2.8 (ATP7A protein, human)
SB  - IM
MH  - Adenosine Triphosphatases/*genetics/metabolism
MH  - Adult
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Biological Transport/drug effects
MH  - Blotting, Western
MH  - Carrier Proteins/*genetics/metabolism
MH  - *Cation Transport Proteins
MH  - Cells, Cultured
MH  - Child
MH  - Copper/*therapeutic use
MH  - Copper-transporting ATPases
MH  - DNA/chemistry/genetics
MH  - DNA Mutational Analysis
MH  - Humans
MH  - Male
MH  - Menkes Kinky Hair Syndrome/drug therapy/*genetics
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Point Mutation
MH  - *Recombinant Fusion Proteins
MH  - Sequence Analysis, DNA
MH  - Sequence Deletion
MH  - Sequence Homology, Amino Acid
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - ddc176 [pii]
AID - 10.1093/hmg/8.8.1547 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1547-55. doi: 10.1093/hmg/8.8.1547.