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sarcoplasmic/endoplasmic reticulum Ca+2 ATPase 2; Ca+2 ATPase of endoplasmic/sarcoplasmic reticulum; Ca+2 ATPase slow-twitch (SERCA2)

Sarcoplasmic & endoplasmic reticulum Ca+2-ATPase of slow twitch skeletal muscle & cardiac muscle. Function: - catalyzes hydrolysis of ATP coupled with translocation of Ca+2 from cytosol to sarcoplasmic reticulum lumen - SERCA2A isoform involved in regulation of contraction- relaxation cycle - associates with phospholamban - reversibly inhibited by phospholamban at low Ca+2 concentrations - dephosphorylated phospholamban decreases apparent affinity of the ATPase for Ca+2 - inhibition is regulated by the phosphorylation of phospholamban (putative) Compartment: - endoplasmic reticulum membrane - sarcoplasmic reticulum membrane Alternative splicing: named isoforms=2; SERCA2A, SERCA2B Expression: - isoform SERCA2A is highly expressed in heart & slow twitch skeletal muscle - isoform SERCA2B is widely expressed, in smooth muscle & nonmuscle tissues including adult skin epidermis - expression inhibited by miR-25 [5] Pathology: - defects associated with a) Darier's disease b) acrokeratosis verruciformis (Hopf disease) - lower levels associated with heart failure [5] Genetics: gene locus: 12q23-q24.1

Interactions

molecular events

Related

ATP2A2 or ATP2B gene

General

sarcoplasmic/endoplasmic reticulum calcium ATPase; P-type ATPase subfamily IIA (SERCA)

Properties

SIZE: entity length = 1042 aa MW = 115 kD COMPARTMENT: smooth endoplasmic reticulum MOTIF: cytoplasmic domain {1-48} transmembrane domain {49-69} exoplasmic loop {70-89} transmembrane domain {90-110} cytoplasmic loop {111-253} transmembrane domain {254-273} exoplasmic loop {274-295} transmembrane domain {296-313} MOTIF: Ca+2-binding site SITE: 304-304 Ca+2-binding site SITE: 305-305 Ca+2-binding site SITE: 307-307 Ca+2-binding site SITE: 309-309 cytoplasmic loop {314-756} MOTIF: aspartate residue {D351} phospholamban interaction {370-400} Thr phosphorylation site {T537} Ser phosphorylation site {S663} Mg+2-binding site SITE: 702-702 Mg+2-binding site SITE: 706-706 transmembrane domain {757-776} MOTIF: Ca+2-binding site SITE: 767-767 Ca+2-binding site SITE: 770-770 exoplasmic loop {777-786} transmembrane domain {787-807} MOTIF: phospholamban interaction {787-807} Ca+2-binding site SITE: 795-795 Ca+2-binding site SITE: 798-798 Ca+2-binding site SITE: 799-799 cytoplasmic loop {808-827} transmembrane domain {828-850} exoplasmic loop {851-896} transmembrane domain {897-916} MOTIF: Ca+2-binding site SITE: 907-907 cytoplasmic loop {917-929} transmembrane domain {930-948} exoplasmic loop {949-963} transmembrane domain {964-984} cytoplasmic domain {985-1042}

Database Correlations

OMIM correlations MORBIDMAP 108740 UniProt P16615 PFAM correlations Entrez Gene 488 Kegg hsa/hsa04020 ENZYME 3.6.3.8

References

  1. Carafoli E. Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme. FASEB J. 1994 Oct;8(13):993-1002. Review. PMID: 7926378
  2. OMIM :accession 108740
  3. UniProt :accession P16615
  4. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=ATP2A2
  5. Wahlquist C et al. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 2014 Apr 24; 508:531. PMID: 24670661