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3.A.3.2.7
The sarco/endoplasmic reticulum Ca2+ -ATPase, SERCA2b or ATP2A2 is encoded by the ATP2A2 gene.  Mutatioins give rise to Darier''s disease; the spectrum of mutations have been related to patients' phenotypes (Ahn et al., 2003; Godic et al. 2010).  SERCA1 functions as a heat generator in mitochondria of brown adipose tissue (de Meis et al., 2006). It normally functions as a Ca2+:H+ antiporter (Karjalainen et al., 2007). Capsaicin converts SERCA to a Ca2+ non-transporting ATPase that generates heat, and is thus a natural drug that augments uncoupled SERCA, resulting in thermogenesis (Mahmmoud, 2008b). Oligomeric interactions of the N-terminus of sarcolipin with the Ca-ATPase have been documented (Autry et al., 2011), and these interactions uncouple ATP hydrolysis from Ca2+ transport (Sahoo et al. 2015) resulting in thermogenesis.  TMS 11, absent in SERCA1a and SERCA2a, functions in regulation (Gorski et al. 2012). The bovine SERCA has also been crystallized (2.9Å resolution; Sacchetto et al., 2012).  These enzymes are regulated differentially by phospholamban (PLN; 1.A.50.1.1) and sarcolipin (SLN; 1.A.50.2.1) as noted above (Gorski et al. 2013).  SERCA2 is regulated by TMEM64 (9.B.27.5.1), a 380 aa 6 TMS membrane protein of the DedA family (TC# 9.B.27) which regulates Ca2+ oscillations by direct interaction with CIRCA2, modulating its activity and influencing osteoblast differentiation (Kim et al. 2013).  Animal SERCAs are inhibited by three short single (C-terminal) TMS membrane proteins, phospholamban (TC# 1.A.50.1), sarcolipin (1.A.50.2) and myoregulin (1.A.50.3), and the inhibitory actions of these peptides on SERCA are counteracted by a peptide called DWORF (Dwarf ORF) (Nelson et al. 2016; Anderson et al. 2015). Small ankyrin 1 (sAnk1; TC#8.A.28.1.2) and sarcolipin (TC# 1.A.50.2.1) interact in their transmembrane domains to regulate SERCA (Desmond et al. 2017).

Accession Number:P16615
Protein Name:ATP2A2 aka ATP2B aka SERCA2
Length:1042
Molecular Weight:114757.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate Ca2+

Cross database links:

Genevestigator: P16615
eggNOG: prNOG08565
HEGENOM: HBG456486
RefSeq: NP_001129237.1    NP_001672.1    NP_733765.1   
Entrez Gene ID: 488   
Pfam: PF00689    PF00690    PF00122    PF00702   
OMIM: 101900  phenotype
108740  gene
124200  phenotype
KEGG: hsa:488   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005792 C:microsome
GO:0033017 C:sarcoplasmic reticulum membrane
GO:0005524 F:ATP binding
GO:0005388 F:calcium-transporting ATPase activity
GO:0046872 F:metal ion binding
GO:0008022 F:protein C-terminus binding
GO:0048155 F:S100 alpha binding
GO:0006754 P:ATP biosynthetic process
GO:0007155 P:cell adhesion
GO:0008544 P:epidermis development
GO:0070296 P:sarcoplasmic reticulum calcium ion transport

References (16)

[1] “Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene.”  Lytton J.et.al.   2844796
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis.”  Stefanovic B.et.al.   14749390
[4] “Large-scale characterization of HeLa cell nuclear phosphoproteins.”  Beausoleil S.A.et.al.   15302935
[5] “Detection of sequence-specific tyrosine nitration of manganese SOD and SERCA in cardiovascular disease and aging.”  Xu S.et.al.   16399855
[6] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[7] “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.”  Daub H.et.al.   18691976
[8] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[9] “The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival.”  Vafiadaki E.et.al.   18971376
[10] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[11] “Lysine acetylation targets protein complexes and co-regulates major cellular functions.”  Choudhary C.et.al.   19608861
[12] “Spectrum of novel ATP2A2 mutations in patients with Darier's disease.”  Sakuntabhai A.et.al.   10441323
[13] “ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class.”  Ruiz-Perez V.L.et.al.   10441324
[14] “ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes.”  Jacobsen N.J.O.et.al.   10441325
[15] “Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease.”  Sakuntabhai A.et.al.   10080178
[16] “Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease.”  Dhitavat J.et.al.   12542527

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FASTA formatted sequence
1:	MENAHTKTVE EVLGHFGVNE STGLSLEQVK KLKERWGSNE LPAEEGKTLL ELVIEQFEDL 
61:	LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILVA NAIVGVWQER NAENAIEALK 
121:	EYEPEMGKVY RQDRKSVQRI KAKDIVPGDI VEIAVGDKVP ADIRLTSIKS TTLRVDQSIL 
181:	TGESVSVIKH TDPVPDPRAV NQDKKNMLFS GTNIAAGKAM GVVVATGVNT EIGKIRDEMV 
241:	ATEQERTPLQ QKLDEFGEQL SKVISLICIA VWIINIGHFN DPVHGGSWIR GAIYYFKIAV 
301:	ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 
361:	MSVCRMFILD RVEGDTCSLN EFTITGSTYA PIGEVHKDDK PVNCHQYDGL VELATICALC 
421:	NDSALDYNEA KGVYEKVGEA TETALTCLVE KMNVFDTELK GLSKIERANA CNSVIKQLMK 
481:	KEFTLEFSRD RKSMSVYCTP NKPSRTSMSK MFVKGAPEGV IDRCTHIRVG STKVPMTSGV 
541:	KQKIMSVIRE WGSGSDTLRC LALATHDNPL RREEMHLEDS ANFIKYETNL TFVGCVGMLD 
601:	PPRIEVASSV KLCRQAGIRV IMITGDNKGT AVAICRRIGI FGQDEDVTSK AFTGREFDEL 
661:	NPSAQRDACL NARCFARVEP SHKSKIVEFL QSFDEITAMT GDGVNDAPAL KKAEIGIAMG 
721:	SGTAVAKTAS EMVLADDNFS TIVAAVEEGR AIYNNMKQFI RYLISSNVGE VVCIFLTAAL 
781:	GFPEALIPVQ LLWVNLVTDG LPATALGFNP PDLDIMNKPP RNPKEPLISG WLFFRYLAIG 
841:	CYVGAATVGA AAWWFIAADG GPRVSFYQLS HFLQCKEDNP DFEGVDCAIF ESPYPMTMAL 
901:	SVLVTIEMCN ALNSLSENQS LLRMPPWENI WLVGSICLSM SLHFLILYVE PLPLIFQITP 
961:	LNVTQWLMVL KISLPVILMD ETLKFVARNY LEPGKECVQP ATKSCSFSAC TDGISWPFVL 
1021:	LIMPLVIWVY STDTNFSDMF WS