PMID- 10555956
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20191210
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 38
IP  - 45
DP  - 1999 Nov 9
TI  - The Na,K-ATPase alpha4 gene (Atp1a4) encodes a ouabain-resistant alpha subunit
      and is tightly linked to the alpha2 gene (Atp1a2) on mouse chromosome 1.
PG  - 14746-51
AB  - We have isolated and characterized cDNA clones encoding the murine homologue of a
      putative fourth Na,K-ATPase alpha subunit isoform (alpha4). The predicted
      polypeptide is 1032 amino acids in length and exhibits 75% amino acid sequence
      identity to the rat alpha1, alpha2, and alpha3 subunits. Within the first
      extracellular loop, the alpha4 subunit is highly divergent from other Na,K-ATPase
      alpha subunits. Because this region of Na,K-ATPase is a major determinant of
      ouabain sensitivity, we tested the ability of the rodent alpha4 subunit to
      transfer ouabain resistance in a transfection protocol. We find that a cDNA
      containing the complete rodent alpha4 ORF is capable of conferring low levels of 
      ouabain resistance upon HEK 293 cells, an indication that the alpha4 subunit can 
      substitute for the endogenous ouabain-sensitive alpha subunit of human cells.
      Nucleotide sequences specific for the murine alpha4 subunit were used to identify
      the chromosomal position of the alpha4 subunit gene. By hybridizing an alpha4
      probe with a series of BACs, we localized the alpha4 subunit gene (Atp1a4) to the
      distal portion of mouse chromosome 1, in very close proximity to the murine
      Na,K-ATPase alpha2 subunit gene. In adult mouse tissues, we detected expression
      of the alpha4 subunit gene almost exclusively in testis, with low levels of
      expression in epididymis. The close similarities in the organization and
      expression pattern of the murine and human alpha4 subunit genes suggest that
      these two genes are orthologous. Together, our studies indicate that the alpha4
      subunit represents a functional Na,K-ATPase alpha subunit isoform.
FAU - Underhill, D A
AU  - Underhill DA
AD  - Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
FAU - Canfield, V A
AU  - Canfield VA
FAU - Dahl, J P
AU  - Dahl JP
FAU - Gros, P
AU  - Gros P
FAU - Levenson, R
AU  - Levenson R
LA  - eng
SI  - GENBANK/AA184055
SI  - GENBANK/AA509743
GR  - HL-39263/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 5ACL011P69 (Ouabain)
RN  - EC 3.6.1.- (ATP1A2 protein, human)
RN  - EC 3.6.1.- (ATP1A4 protein, human)
RN  - EC 3.6.1.- (Atp1a2 protein, mouse)
RN  - EC 3.6.1.- (Atp1a2 protein, rat)
RN  - EC 3.6.1.- (Atp1a4 protein, mouse)
RN  - EC 3.6.1.- (Atp1a4 protein, rat)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Chromosomes
MH  - Cloning, Molecular
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Ouabain/*pharmacology
MH  - Phenotype
MH  - Protein Conformation
MH  - Rats
MH  - Sodium-Potassium-Exchanging ATPase/*genetics
MH  - Transfection
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - bi9916168 [pii]
AID - 10.1021/bi9916168 [doi]
PST - ppublish
SO  - Biochemistry. 1999 Nov 9;38(45):14746-51. doi: 10.1021/bi9916168.