SERCA2a: a key protein in the Ca2+ cycle of the heart failure

  • Liu Zhihao
  • Ni Jingyu
  • Li Lan
  • Sarhene Michael
  • Guo Rui
  • Bian Xiyun
  • Liu Xiaozhi
  • Fan GuanweiEmail author


Calcium ion (Ca2+) cycle plays a crucial role in the contraction and relaxation of cardiomyocytes. The sarcoplasmic reticulum (SR) acts as an organelle for storing Ca2+, which mediated the release and re-uptake of Ca2+ during contraction and relaxation. Disorders of SR function lead to the dysfunction of Ca2+ cycle and myocardial cell function. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) acts as a subtype of SERCA expressed in the heart, which mediates the contraction of cardiomyocytes and Ca2+ in the cytoplasm to re-enter into the SR. The rate of uptake of Ca2+ by the SR determines the rate of myocardial relaxation. The regulation of SERCA2a activity controls the contractility and relaxation of the heart, affecting cardiac function. The expression and activity of SERCA2a are reduced in failing hearts. Gene therapy by increasing the expression of SERCA2a in the heart has been proven effective. In addition, SERCA2a is regulated by a variety of factors, including transmembrane micropeptides, protein kinases, and post-translational modifications (PTMs). In this review, we discuss the regulatory factors of SERCA2a and provide new insights into future treatments and the direction of heart failure research. In addition, gene therapy for SERCA2a has recently emerged as therapeutic option and hence will be discussed in this review.


SERCA2a Transmembrane micropeptides PTM Gene therapy 



adeno-associated vector type 1




calcium ion


calcium/calmodulin-dependent protein kinase II


dwarf open reading frame




heart failure


lysine acetyltransferases


lysine deacetylase


L-type Ca2+ channel








cAMP-dependent protein kinase


protein phosphatase 1


post-translational modification


ryanodine receptor 2


sarco/endoplasmic reticulum Ca2+ ATPase 2a




striated muscle–specific protein kinase


sarcoplasmic reticulum


small ubiquitin-like modifier


Funding information

This study is supported by grants from the Tianjin Outstanding Youth Science Foundation (17JCJQJC46200), the National Natural Science Foundation of China (NSFC 81774050), the Natural Science Foundation of Tianjin (17JCYBJC29000), and the Ministry of Education of People’s Republic of China “Program for Innovative Research Team in University” (No. IRT_16R54).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Authors and Affiliations

  • Liu Zhihao
    • 1
    • 2
  • Ni Jingyu
    • 1
    • 2
  • Li Lan
    • 1
    • 2
  • Sarhene Michael
    • 1
    • 2
  • Guo Rui
    • 1
    • 2
  • Bian Xiyun
    • 3
  • Liu Xiaozhi
    • 3
  • Fan Guanwei
    • 1
    • 2
    Email author
  1. 1.Tianjin Laboratory of Translational Research of TCM Prescription and SyndromeFirst Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  2. 2.State Key Laboratory of Modern Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  3. 3.Central LaboratoryThe Fifth Central Hospital of TianjinTianjinPeople’s Republic of China

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