JPH2

JPH2
Identifiers
Aliases	JPH2, CMH17, JP-2, JP2, junctophilin 2, CMD2E
External IDs	OMIM: 605267; MGI: 1891496; HomoloGene: 10714; GeneCards: JPH2; OMA:JPH2 - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.12 Start 44,106,590 bp[1] End 44,187,188 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 H3 Start 163,178,162 bp[2] End 163,239,913 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in myocardium of left ventricle Skeletal muscle tissue of rectus abdominis tibialis anterior muscle cardiac muscle tissue of right atrium muscle of thigh Skeletal muscle tissue of biceps brachii apex of heart quadriceps femoris muscle vastus lateralis muscle popliteal artery Top expressed in muscle of thigh triceps brachii muscle sternocleidomastoid muscle temporal muscle skeletal muscle tissue ankle digastric muscle interventricular septum myocardium of ventricle extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatidic acid binding phosphatidylinositol-4-phosphate binding phosphatidylinositol-5-phosphate binding phosphatidylserine binding phosphatidylinositol-3,4,5-trisphosphate binding protein binding phosphatidylinositol-3,5-bisphosphate binding phosphatidylinositol-4,5-bisphosphate binding phosphatidylinositol-3-phosphate binding calcium-release channel activity DNA binding Cellular component integral component of membrane sarcoplasmic reticulum sarcoplasmic reticulum membrane junctional membrane complex membrane endoplasmic reticulum plasma membrane junctional sarcoplasmic reticulum membrane Z disc endoplasmic reticulum membrane nucleus Biological process regulation of cardiac muscle tissue development calcium ion transport into cytosol positive regulation of cytosolic calcium ion concentration positive regulation of ryanodine-sensitive calcium-release channel activity calcium ion homeostasis regulation of ryanodine-sensitive calcium-release channel activity release of sequestered calcium ion into cytosol multicellular organism development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57158 59091 Ensembl ENSG00000149596 ENSMUSG00000017817 UniProt Q9BR39 Q9ET78 RefSeq (mRNA) NM_020433 NM_175913 NM_001205076 NM_021566 NM_197984 RefSeq (protein) NP_065166 NP_787109 NP_001192005 NP_067541 Location (UCSC) Chr 20: 44.11 – 44.19 Mb Chr 2: 163.18 – 163.24 Mb PubMed search [3] [4]
Wikidata
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Junctophilin 2, also known as JPH2, is a protein which in humans is encoded by the JPH2 gene.^[5][6][7] Alternative splicing has been observed at this locus and two variants encoding distinct isoforms 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 hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic 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, and JPH4) and is the predominant isoform in cardiac tissue, but is also expressed with JPH1 in skeletal muscle.^[8] 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.^[5] 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.^[9]

Role in Disease

Mutations in JPH2 were identified in a cohort of patients with hypertrophic cardiomyopathy who lacked the traditional mutations in sarcomere proteins.^[10] 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