Junctophilin 2, also known as JPH2, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
which in humans is encoded by the ''JPH2''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
has been observed at this locus and two variants encoding distinct
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
are described.
Function
Junctional complexes between the plasma membrane and
endoplasmic/
sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular
ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
ic membrane occupation and recognition nexus (MORN) domain that shows specific affinity for the plasma membrane. JPH2 is a member of the junctophilin gene family (the other members of the family are
JPH1,
JPH3
Junctophilin-3 is a protein that in humans, is encoded by the ''JPH3'' gene. The gene is approximately 97 kilobases long and is located at position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexe ...
, and
JPH4
Junctophilin 4 is a protein in humans that is encoded by the JPH4 gene.
This gene encodes a member of the junctophilin family of transmembrane proteins that are involved in the formation of the junctional membrane complexes between the plasma ...
) and is the predominant isoform in cardiac tissue, but is also expressed with JPH1 in skeletal muscle. The JPH2 protein product plays a critical role in maintaining the spacing a geometry of the cardiac dyad - the space between the
plasma membrane and sarcoplasmic reticulum.
These cardiac dyads also known as junctional membrane complexes or calcium release units are thought to play a key role in calcium induced calcium release by approximating L-type calcium channels on the plasma membrane and ryanodine receptor type 2 on the sarcoplasmic reticulum. JPH2 also contains an evolutionarily conserved nuclear localization signal and a DNA binding domain. During (heart) disease, stress-activated calpain converts the full length JPH2 into fragments. The N-terminal fragment (including nuclear localization signal and DNA binding domain) is translocated to nucleus and regulates gene transcription.
Role in Disease
Mutations in JPH2 were identified in a cohort of patients with hypertrophic cardiomyopathy who lacked the traditional mutations in sarcomere proteins.
JPH2 has been shown to be downregulated in several animal models of heart failure. A JPH2 knock-out mouse model is lethal at embryonic day 10.5, which is around the time when cardiac contractility should initiate. These mice showed abnormal cardiac calcium handling, cardiomyopathy, and altered junctional membrane complex formation.
References
Further reading
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