Molecular cloning and functional expression of the human sodium channel beta1B subunit, a novel splicing variant of the beta1 subunit.
The voltage gated sodium channel comprises a pore-forming alpha subunit and regulatory beta subunits. We report here the identification and characterization of a novel splicing variant of the human beta1 subunit, termed beta1B. The 807 bp open reading frame of the human beta1Beta subunit encodes a 268 residue protein with a calculated molecular mass of 30.4 kDa. The novel human beta1B subunit shares an identical N-terminal half (residues 1-149) with the human beta1 subunit, but contains a novel C-terminal half (residues 150-268) of less than 17% sequence identity with the human beta1 subunit. The C-terminal region of the human beta1B is also significantly different from that of the rat beta1A subunit, sharing less than 33% sequence identity. Tissue distribution studies reveal that the human beta1Beta subunit is expressed predominantly in human brain, spinal cord, dorsal root ganglion and skeletal muscle. Functional studies in oocytes demonstrate that the human beta1B subunit increases the ionic current when coexpressed with the tetrodotoxin sensitive channel, NaV1.2, without significantly changing voltage dependent kinetics and steady-state properties, thus distinguishing it from the human beta1 and rat beta1A subunits.
Qin
Ning
N
Department of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA. nquin@prdus.jnj.com
D'Andrea
Michael R
MR
Lubin
Mary-Lou
ML
Shafaee
Navid
N
Codd
Ellen E
EE
Correa
Ana M
AM
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus
D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C568251:SCN2A protein, human; C568253:Scn2A protein, rat; D015222:Sodium Channels