ATP2A2 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2)

Gene

• Entrez ID: 488
• Gene name: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2
• Gene symbol: ATP2A2
• Synonyms: ATP2B, DAR, DD, SERCA2
• Chromosome: 12
• Chromosome location: 12q24.11
• Summary: This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28929478	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121912731	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs121912732	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs121912733	G>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs121912734	T>C	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs121912735	C>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, synonymous variant
rs121912736	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs121912737	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs121912738	G>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs387906594	C>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs757914881	G>A,T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, stop gained
rs886041576	C>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs886041697	A>T	Pathogenic	Non coding transcript variant, initiator codon variant, missense variant
rs886041748	AT>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1057518135	G>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1057518457	A>C	Likely-pathogenic	Splice acceptor variant
rs1057520577	G>A	Pathogenic	Splice acceptor variant
rs1057520789	A>G	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1064793900	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1085307908	T>C	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1085307960	T>C	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1131691899	A>G,T	Likely-pathogenic	Non coding transcript variant, synonymous variant, missense variant, coding sequence variant
rs1555282129	G>C	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1555284765	A>G	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1555285354	->AAGA	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant, intron variant
rs1566240208	ACA>-	Pathogenic	Inframe deletion, coding sequence variant, non coding transcript variant
rs1592839705	G>A	Pathogenic	Splice donor variant
rs1592864859	T>A	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1592868802	C>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005137	hsa-miR-30a-5p	pSILAC, Proteomics;Other	18668040
MIRT005137	hsa-miR-30a-5p	HITS-CLIP	23313552
MIRT021642	hsa-miR-142-3p	Microarray	17612493
MIRT021642	hsa-miR-142-3p	HITS-CLIP	22473208
MIRT028977	hsa-miR-26b-5p	Microarray	19088304
MIRT032246	hsa-let-7b-5p	Proteomics	18668040
MIRT032246	hsa-let-7b-5p	CLASH	23622248
MIRT036518	hsa-miR-1226-3p	CLASH	23622248
MIRT036518	hsa-miR-1226-3p	HITS-CLIP	19536157
MIRT039280	hsa-miR-671-5p	CLASH	23622248
MIRT042367	hsa-miR-484	CLASH	23622248
MIRT046495	hsa-miR-15b-5p	CLASH	23622248
MIRT046967	hsa-miR-221-3p	CLASH	23622248
MIRT048071	hsa-miR-197-3p	CLASH	23622248
MIRT048397	hsa-miR-100-5p	CLASH	23622248
MIRT049871	hsa-miR-31-5p	CLASH	23622248
MIRT051398	hsa-let-7f-5p	CLASH	23622248
MIRT051808	hsa-let-7c-5p	CLASH	23622248
MIRT052513	hsa-let-7a-5p	CLASH	23622248
MIRT053291	hsa-miR-25-3p	In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	24670661
MIRT062437	hsa-miR-575	HITS-CLIP	19536157
MIRT062444	hsa-miR-4676-5p	HITS-CLIP	19536157
MIRT247419	hsa-miR-3185	HITS-CLIP	23313552
MIRT247422	hsa-miR-4781-5p	HITS-CLIP	23313552
MIRT247423	hsa-miR-4786-3p	HITS-CLIP	23313552
MIRT270215	hsa-miR-511-3p	PAR-CLIP	21572407
MIRT270215	hsa-miR-511-3p	PAR-CLIP	20371350
MIRT270216	hsa-miR-568	PAR-CLIP	21572407
MIRT270216	hsa-miR-568	PAR-CLIP	20371350
MIRT270217	hsa-miR-651-3p	PAR-CLIP	21572407
MIRT270217	hsa-miR-651-3p	PAR-CLIP	20371350
MIRT335152	hsa-miR-6884-3p	HITS-CLIP	19536157
MIRT549261	hsa-miR-223-5p	PAR-CLIP	21572407
MIRT549261	hsa-miR-223-5p	PAR-CLIP	20371350
MIRT549262	hsa-miR-944	PAR-CLIP	21572407
MIRT549262	hsa-miR-944	PAR-CLIP	20371350
MIRT618408	hsa-miR-874-3p	HITS-CLIP	23824327
MIRT618409	hsa-miR-3157-3p	HITS-CLIP	23824327
MIRT618410	hsa-miR-3941	HITS-CLIP	23824327
MIRT618411	hsa-miR-6886-3p	HITS-CLIP	23824327
MIRT618412	hsa-miR-938	HITS-CLIP	23824327
MIRT618413	hsa-miR-216b-3p	HITS-CLIP	23824327
MIRT618414	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT618415	hsa-miR-362-3p	HITS-CLIP	23824327
MIRT618416	hsa-miR-329-3p	HITS-CLIP	23824327
MIRT618417	hsa-miR-8485	HITS-CLIP	23824327
MIRT705320	hsa-miR-3171	HITS-CLIP	23313552
MIRT705321	hsa-miR-4495	HITS-CLIP	23313552
MIRT705322	hsa-miR-186-5p	HITS-CLIP	23313552
MIRT705323	hsa-miR-3133	HITS-CLIP	23313552
MIRT705324	hsa-miR-5582-3p	HITS-CLIP	23313552
MIRT705325	hsa-miR-548f-3p	HITS-CLIP	23313552
MIRT705326	hsa-miR-548e-3p	HITS-CLIP	23313552
MIRT705327	hsa-miR-548az-3p	HITS-CLIP	23313552
MIRT705328	hsa-miR-548ar-3p	HITS-CLIP	23313552
MIRT705329	hsa-miR-548a-3p	HITS-CLIP	23313552
MIRT705330	hsa-miR-30b-5p	HITS-CLIP	23313552
MIRT705331	hsa-miR-30c-5p	HITS-CLIP	23313552
MIRT705332	hsa-miR-30d-5p	HITS-CLIP	23313552
MIRT705333	hsa-miR-30e-5p	HITS-CLIP	23313552
MIRT721604	hsa-miR-4733-3p	HITS-CLIP	19536157
MIRT728260	hsa-miR-32-5p	HITS-CLIP	22473208
MIRT728261	hsa-miR-92b-3p	HITS-CLIP	22473208
MIRT728262	hsa-miR-92a-3p	HITS-CLIP	22473208

Transcription factors

Transcription factor	Regulation	Reference
ATF6	Unknown	11595740
HAX1	Repression	18971376
PPARG	Unknown	22240811
SP1	Activation	17597815
SP1	Unknown	14613864
SP3	Unknown	14613864

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002026	Process	Regulation of the force of heart contraction	IEA
GO:0003009	Process	Skeletal muscle contraction	IEA
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IBA	21873635
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IDA	16402920
GO:0005509	Function	Calcium ion binding	IDA	16402920
GO:0005515	Function	Protein binding	IPI	17526652, 20528919, 22084111, 24764305, 25661196, 25996873, 28298427, 31735293
GO:0005524	Function	ATP binding	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	16081076, 30188326
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	11402072
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	2844796
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0006874	Process	Cellular calcium ion homeostasis	IMP	18068335
GO:0006984	Process	ER-nucleus signaling pathway	IEA
GO:0006996	Process	Organelle organization	IEA
GO:0007155	Process	Cell adhesion	TAS	10080178
GO:0008544	Process	Epidermis development	TAS	10080178
GO:0008553	Function	Proton-exporting ATPase activity, phosphorylative mechanism	IBA	21873635
GO:0010460	Process	Positive regulation of heart rate	TAS	22679139
GO:0010882	Process	Regulation of cardiac muscle contraction by calcium ion signaling	IBA	21873635
GO:0012506	Component	Vesicle membrane	IEA
GO:0014883	Process	Transition between fast and slow fiber	IEA
GO:0014898	Process	Cardiac muscle hypertrophy in response to stress	IEA
GO:0016020	Component	Membrane	IDA	22375059
GO:0016529	Component	Sarcoplasmic reticulum	IDA	12804600
GO:0016887	Function	ATPase activity	IBA	21873635
GO:0019899	Function	Enzyme binding	IPI	21903937
GO:0031095	Component	Platelet dense tubular network membrane	TAS
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IEA
GO:0031775	Function	Lutropin-choriogonadotropic hormone receptor binding	IEA
GO:0032469	Process	Endoplasmic reticulum calcium ion homeostasis	IDA	16402920
GO:0032470	Process	Positive regulation of endoplasmic reticulum calcium ion concentration	IDA	16402920
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0033017	Component	Sarcoplasmic reticulum membrane	IBA	21873635
GO:0033017	Component	Sarcoplasmic reticulum membrane	TAS	19095005
GO:0033292	Process	T-tubule organization	IEA
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0034599	Process	Cellular response to oxidative stress	IEA
GO:0034605	Process	Cellular response to heat	IEA
GO:0034976	Process	Response to endoplasmic reticulum stress	ISS
GO:0044325	Function	Ion channel binding	IPI	18068335
GO:0044548	Function	S100 protein binding	IPI	12804600
GO:0045822	Process	Negative regulation of heart contraction	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0055119	Process	Relaxation of cardiac muscle	IEA
GO:0061831	Component	Apical ectoplasmic specialization	IEA
GO:0070296	Process	Sarcoplasmic reticulum calcium ion transport	TAS	19095005, 22679139
GO:0070588	Process	Calcium ion transmembrane transport	IBA	21873635
GO:0070588	Process	Calcium ion transmembrane transport	IDA	16402920
GO:0086036	Process	Regulation of cardiac muscle cell membrane potential	IC	16402920
GO:0086036	Process	Regulation of cardiac muscle cell membrane potential	ISS
GO:0086036	Process	Regulation of cardiac muscle cell membrane potential	TAS	22679139
GO:0086039	Function	Calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential	IBA	21873635
GO:0086039	Function	Calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential	IC	16402920
GO:0086039	Function	Calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential	ISS
GO:0086039	Function	Calcium-transporting ATPase activity involved in regulation of cardiac muscle cell membrane potential	TAS	22679139
GO:0097470	Component	Ribbon synapse	IEA
GO:0098909	Process	Regulation of cardiac muscle cell action potential involved in regulation of contraction	ISS
GO:0120025	Component	Plasma membrane bounded cell projection	IEA
GO:1900121	Process	Negative regulation of receptor binding	IMP	18068335
GO:1902600	Process	Proton transmembrane transport	IEA
GO:1903233	Process	Regulation of calcium ion-dependent exocytosis of neurotransmitter	IEA
GO:1903515	Process	Calcium ion transport from cytosol to endoplasmic reticulum	IDA	16402920
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1990036	Process	Calcium ion import into sarcoplasmic reticulum	IC	16402920
GO:1990036	Process	Calcium ion import into sarcoplasmic reticulum	ISS

Other IDs

• MIM: 108740
• HGNC: 812
• e!Ensembl: ENSG00000174437

Protein

• UniProt ID: P16615
• Protein name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase)
• Protein function: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). ; [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation.
• PDB: 5ZTF, 6JJU, 6LLE, 6LLY, 6LN5, 6LN6, 6LN7, 6LN8, 6LN9, 7BT2
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00690	Cation_ATPase_N	4 → 72	Cation transporter/ATPase, N-terminus	Domain
  PF00122	E1-E2_ATPase	121 → 329		Family
  PF13246	Cation_ATPase	418 → 527		Family
  PF00689	Cation_ATPase_C	783 → 986	Cation transporting ATPase, C-terminus	Family

• Sequence:

  MENAHTKTVEEVLGHFGVNESTGLSLEQVKKLKERWGSNELPAEEGKTLLELVIEQFEDL
  LVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILVANAIVGVWQERNAENAIEALK
  EYEPEMGKVYRQDRKSVQRIKAKDIVPGDIVEIAVGDKVPADIRLTSIKSTTLRVDQSIL
  TGESVSVIKHTDPVPDPRAVNQDKKNMLFSGTNIAAGKAMGVVVATGVNTEIGKIRDEMV
  ATEQERTPLQQKLDEFGEQLSKVISLICIAVWIINIGHFNDPVHGGSWIRGAIYYFKIAV
  ALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ
  MSVCRMFILDRVEGDTCSLNEFTITGSTYAPIGEVHKDDKPVNCHQYDGLVELATICALC
  NDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTELKGLSKIERANACNSVIKQLMK
  KEFTLEFSRDRKSMSVYCTPNKPSRTSMSKMFVKGAPEGVIDRCTHIRVGSTKVPMTSGV
  KQKIMSVIREWGSGSDTLRCLALATHDNPLRREEMHLEDSANFIKYETNLTFVGCVGMLD
  PPRIEVASSVKLCRQAGIRVIMITGDNKGTAVAICRRIGIFGQDEDVTSKAFTGREFDEL
  NPSAQRDACLNARCFARVEPSHKSKIVEFLQSFDEITAMTGDGVNDAPALKKAEIGIAMG
  SGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAAL
  GFPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMNKPPRNPKEPLISGWLFFRYLAIG
  CYVGAATVGAAAWWFIAADGGPRVSFYQLSHFLQCKEDNPDFEGVDCAIFESPYPMTMAL
  SVLVTIEMCNALNSLSENQSLLRMPPWENIWLVGSICLSMSLHFLILYVEPLPLIFQITP
  LNVTQWLMVLKISLPVILMDETLKFVARNYLEPGKECVQPATKSCSFSACTDGISWPFVL
  LIMPLVIWVYSTDTNFSDMFWS

• Sequence length: 1042