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POPDC2

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POPDC2
Identifiers
AliasesPOPDC2, POP2, popeye domain containing 2
External IDsOMIM: 605823; MGI: 1930150; HomoloGene: 11147; GeneCards: POPDC2; OMA:POPDC2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001308333
NM_022135
NM_001369919

NM_001081984
NM_022318

RefSeq (protein)

NP_001295262
NP_071418
NP_001356848

NP_001075453
NP_071713

Location (UCSC)Chr 3: 119.64 – 119.67 MbChr 16: 38.18 – 38.2 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene.[5][6]

Structure

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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.[5] 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%.[6]

Function

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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.[7] Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A (PKA) and HCN channels.[7]

Ligands

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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).[7] 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.[7]

Animal studies

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Genetic inactivation of Popdc2 in mice resulted in bradyarrhythmia, which is strictly stress-dependent. At rest a normal ECG was observed.[7] Gene inactivation in the zebrafish also causes a cardiac arrhythmia phenotype and defective skeletal muscle development.[8]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121577Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022803Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: popeye domain containing 2".
  6. ^ a b 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". Developmental Biology. 223 (2): 371–382. doi:10.1006/dbio.2000.9751. PMID 10882522.
  7. ^ a b c d e 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" (PDF). The Journal of Clinical Investigation. 122 (3): 1119–1130. doi:10.1172/JCI59410. PMC 3287222. PMID 22354168.
  8. ^ Kirchmaier BC, Poon KL, Schwerte T, Huisken J, Winkler C, Jungblut B, Stainier DY, Brand T (March 2012). "The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development". Developmental Biology. 363 (2): 438–450. doi:10.1016/j.ydbio.2012.01.015. PMC 3677075. PMID 22290329.