Cloning and characterization of the entire cDNA encoded by ATP1AL1 — a member of the human Na,K/H,K‐ATPase gene family

Abstract

The cDNA for ATPlALl -the fifth member of the human Na,K-/H,K-ATPase gene family ~ was cloned and sequenced. The deduced primary ATPlALl translation product is 1,039 amino acids in length and has M, of 114,543. The encoded protein has all of the structural features common to known catalytic subunits of P-type membrane ion-transporting ATPases and is equally distant (63-64% of identity) from the Na,K-ATPase isofonns and the gastric H,K-ATPase.The ATPl AL1 encoded protein was proposed to represent a new separate group within the family of human potassium-dependent ion pumps.

The α-Subunit of the Colonic H+,K+-ATPase Assembles with β1-Na+,K+-ATPase in Kidney and Distal Colon

“…Two rabbits were injected and bled according to standard protocols. The peptide was tested for similarity to different X ϩ ,K ϩ -ATPases, and the maximum identity (69%) of the peptide was with the human ATP1AL1 (or HK␣ 4 ) protein which is known to be expressed in brain, skin, and kidney (14), whereas the most divergence was with rat HK␣ 1 (23% identity) (15).…”

Functional Expression of the Colonic H+,K+-ATPase α-Subunit

“…The X ϩ ,K ϩ -ATPases, which also include the Na ϩ ,K ϩ -ATPase isozymes, share a common catalytic cycle, the ability to extrude a cation (Na ϩ or H ϩ , respectively) from the cell in exchange for K ϩ , and an apparent requirement for heterodimeric structure (2)(3)(4). To date, cDNAs encoding homologous H ϩ ,K ϩ -ATPase ␣-subunits have been cloned from gastric parietal cells (␣ G or HK␣1) (5,6), rat and guinea pig distal colon (␣ C or HK␣2) (7,8), toad urinary bladder (␣ bl or HK␣3) (9), and human skin (ATP1AL1 or HK␣4) (10). Although these H ϩ ,K ϩ -ATPase isoforms share approximately 60 -70% amino acid identity, they exhibit distinct kinetic and pharmacological properties when expressed in heterologous systems (9,11,12).…”

A Novel N-terminal Splice Variant of the Rat H+-K+-ATPase α2 Subunit

“…, was cloned from a human skin cDNA library (20), and transcripts encoding this gene product were also detected in human brain and kidney but not colon (20). Coexpression of the ATP1AL1 subunit and the rabbit gastric H ϩ -K ϩ -ATPase ␤ subunit (HK␤ g ) in Xenopus oocytes (21) or HEK 293 cells (22) resulted in the expression of functional H ϩ -K ϩ pumps that were partially sensitive to both Sch 28080 and ouabain.…”

“…These distinguishing features include the contrasting tissue distributions (20), differences in pharmacological profile (16,18,19,21,22), and greater degree of sequence divergence when compared with the interspecies differences of the other human and rat X ϩ -K ϩ -ATPase ␣ subunit isoforms. As additional structure-function and structure-regulation correlations for these genes are identified, their evolutionary relationship should come into clearer focus.…”