POPDC2

Popeye domain containing 2

Identifiers

POPDC2 ; POP2

External IDs

OMIM: 605823 MGI: 1930150 HomoloGene: 11147 GeneCards: POPDC2 Gene

Gene ontology
Molecular function	• molecular_function • cAMP binding
Cellular component	• integral component of membrane
Biological process	• regulation of heart rate • biological_process • regulation of membrane potential • sinoatrial node cell development
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 3:
119.64 – 119.67 Mb

Chr 16:
38.36 – 38.38 Mb

PubMed search

Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene.^[1]^[2]

Structure

This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac muscle.^[1] The Popeye domain, which is located in the cytoplasmic part of the protein displays limited sequence homology to other proteins, while sequence conservation amongst Popeye proteins is high and amounts to approximately 40%–60%.^[2]

Function

The bacterial CAP or CRP proteins are the closest related non-Popdcproteins. CRP proteins function as cyclic nucleotide-regulated transcription factors that modulate the expression of genes encoding enzymes involved in carbohydrate metabolism. The cyclic AMP-binding domains of these proteins display approximately 25% identity and 60% similarity to the Popeye domain.^[3] Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A (PKA) and HCN channels.^[3]

Ligands

The Popeye domain binds cyclic nucleotides and has a binding affinity (IC₅₀) for cAMP of 120 nM, which is comparable to the affinities reported for PKA (100 nM) and HCN4 (240 nM).^[3] One of the interacting proteins is the two-pore potassium (K2P) channel TREK-1. In the presence of Popdc proteins, TREK-1 current is increased. This increase was based on an enhanced membrane representation of TREK-1, suggesting a modulation of channel trafficking by Popdc proteins.^[3]

Animal studies

Genetic inactivation of Popdc2 in mice resulted in bradyarrhythmia, which is strictly stress-dependent. At rest a normal ECG was observed.^[3] Gene inactivation in the zebrafish also causes a cardiac arrhythmia phenotype and defective skeletal muscle development.^[4]

References

1 2 "Entrez Gene: popeye domain containing 2".
1 2 Andrée B, Hillemann T, Kessler-Icekson G, Schmitt-John T, Jockusch H, Arnold HH, Brand T (July 2000). "Isolation and characterization of the novel popeye gene family expressed in skeletal muscle and heart". Dev. Biol. 223 (2): 371–82. doi:10.1006/dbio.2000.9751. PMID 10882522.
1 2 3 4 5 Froese A, Breher SS, Waldeyer C, Schindler RF, Nikolaev VO, Rinné S, Wischmeyer E, Schlueter J, Becher J, Simrick S, Vauti F, Kuhtz J, Meister P, Kreissl S, Torlopp A, Liebig SK, Laakmann S, Müller TD, Neumann J, Stieber J, Ludwig A, Maier SK, Decher N, Arnold HH, Kirchhof P, Fabritz L, Brand T (March 2012). "Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice". J. Clin. Invest. 122 (3): 1119–82. doi:10.1172/JCI59410. PMID 3287222.
↑ Kirchmaier BC, Poon KL, Schwerte T, Huisken J, Winkler C, Jungblut B, Stainier DY, Brand T (June 2012). "The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development.". Dev Biol. 363 (2): 438–50. doi:10.1016/j.ydbio.2012.01.015. PMID 22290329.