PMID- 10642508
OWN - NLM
STAT- MEDLINE
DCOM- 20000323
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 345 Pt 3
DP  - 2000 Feb 1
TI  - Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1
      binds to Na+-channel subunits.
PG  - 503-9
AB  - The epithelial Na(+) channel (ENaC) regulates Na(+) absorption in epithelial
      tissues including the lung, colon and sweat gland, and in the distal nephrons of 
      the kidney. When Na(+)-channel function is disrupted, salt and water homoeostasis
      is affected. The cytoplasmic regions of the Na(+)-channel subunits provide
      binding sites for other proteins to interact with and potentially regulate
      Na(+)-channel activity. Previously we showed that a proline-rich region of the
      alpha subunit of the Na(+) channel bound to a protein of 116 kDa from human lung 
      cells. Here we report the identification of this protein as human Nedd4, a
      ubiquitin-protein ligase that binds to the Na(+)-channel subunits via its WW
      domains. Further, we show that WW domains 2, 3 and 4 of human Nedd4 bind to the
      alpha, beta and gamma Na(+)-channel subunits but not to a mutated beta subunit.
      In addition, when co-expressed in Xenopus oocytes, human Nedd4 down-regulates
      Na(+)-channel activity.
FAU - Farr, T J
AU  - Farr TJ
AD  - School of Biological Sciences, Victoria University, P.O. Box 600, Wellington
      6004, New Zealand.
FAU - Coddington-Lawson, S J
AU  - Coddington-Lawson SJ
FAU - Snyder, P M
AU  - Snyder PM
FAU - McDonald, F J
AU  - McDonald FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sodium Channels)
RN  - 0 (Xenopus Proteins)
RN  - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases)
RN  - EC 2.3.2.26 (Nedd4 protein, Xenopus)
RN  - EC 2.3.2.26 (Nedd4 protein, human)
RN  - EC 2.3.2.26 (nedd4l protein, Xenopus)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - COS Cells/metabolism
MH  - Calcium-Binding Proteins/*genetics/*metabolism
MH  - Cloning, Molecular
MH  - Dogs
MH  - Endosomal Sorting Complexes Required for Transport
MH  - Epithelial Sodium Channels
MH  - Humans
MH  - *Ligases
MH  - Molecular Sequence Data
MH  - Nedd4 Ubiquitin Protein Ligases
MH  - Oocytes/metabolism
MH  - RNA, Messenger
MH  - Recombinant Proteins/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Sodium Channels/*metabolism
MH  - *Ubiquitin-Protein Ligases
MH  - Xenopus
MH  - Xenopus Proteins
MH  - src Homology Domains
PMC - PMC1220784
EDAT- 2000/01/22 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/01/22 09:00
PHST- 2000/01/22 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/01/22 09:00 [entrez]
PST - ppublish
SO  - Biochem J. 2000 Feb 1;345 Pt 3:503-9.