ATP2A1 (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1)

Gene

• Entrez ID: 487
• Gene name: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1
• Gene symbol: ATP2A1
• Synonyms: ATP2A, SERCA1
• Chromosome: 16
• Chromosome location: 16p11.2
• Summary: This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs111266804	G>A,C	Likely-pathogenic	Splice donor variant
rs113803159	C>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs117350233	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs121918113	C>T	Pathogenic	Coding sequence variant, stop gained
rs121918114	C>A	Pathogenic	Coding sequence variant, stop gained
rs121918115	C>G,T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs398124554	C>-	Uncertain-significance, pathogenic	Frameshift variant, coding sequence variant
rs398124555	->T	Uncertain-significance, pathogenic	Frameshift variant, coding sequence variant
rs551660089	G>A	Likely-pathogenic, pathogenic	Splice donor variant
rs748241465	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs751365374	C>-,CC,CCC	Pathogenic-likely-pathogenic, likely-pathogenic, pathogenic	Frameshift variant, coding sequence variant
rs755227074	G>A	Likely-pathogenic	Splice donor variant
rs895911431	C>T	Pathogenic	Stop gained, coding sequence variant
rs897301304	C>T	Pathogenic, likely-pathogenic	Stop gained, coding sequence variant
rs972494690	G>A,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs1409892710	T>G	Pathogenic	Stop gained, coding sequence variant
rs1421005631	CT>-	Pathogenic	Frameshift variant, coding sequence variant
rs1555515558	TGTGGCTGCCAT>ACGGCATA	Pathogenic	Frameshift variant, coding sequence variant
rs1555516994	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1567479853	A>T	Likely-pathogenic	Splice acceptor variant
rs1596682330	GGT>TGG	Likely-pathogenic	Splice donor variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IBA	21873635
GO:0005388	Function	Calcium transmembrane transporter activity, phosphorylative mechanism	IDA	8729696
GO:0005509	Function	Calcium ion binding	IMP	9405806
GO:0005515	Function	Protein binding	IPI	9295312
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006816	Process	Calcium ion transport	IMP	9405806
GO:0006874	Process	Cellular calcium ion homeostasis	IBA	21873635
GO:0008553	Function	Proton-exporting ATPase activity, phosphorylative mechanism	IBA	21873635
GO:0008637	Process	Apoptotic mitochondrial changes	IMP	19061639
GO:0016021	Component	Integral component of membrane	ISS
GO:0016021	Component	Integral component of membrane	NAS	9405806
GO:0016529	Component	Sarcoplasmic reticulum	NAS	8841193
GO:0016887	Function	ATPase activity	IBA	21873635
GO:0030899	Function	Calcium-dependent ATPase activity	ISS
GO:0031095	Component	Platelet dense tubular network membrane	TAS
GO:0031448	Process	Positive regulation of fast-twitch skeletal muscle fiber contraction	IDA	12479237
GO:0032470	Process	Positive regulation of endoplasmic reticulum calcium ion concentration	IMP	11402072
GO:0032471	Process	Negative regulation of endoplasmic reticulum calcium ion concentration	IMP	11402072, 19061639
GO:0033017	Component	Sarcoplasmic reticulum membrane	IBA	21873635
GO:0033017	Component	Sarcoplasmic reticulum membrane	IC	8040329
GO:0033017	Component	Sarcoplasmic reticulum membrane	ISS
GO:0033017	Component	Sarcoplasmic reticulum membrane	TAS	11402072
GO:0034220	Process	Ion transmembrane transport	TAS
GO:0034704	Component	Calcium channel complex	IC	11402072
GO:0034976	Process	Response to endoplasmic reticulum stress	IMP	19061639
GO:0042803	Function	Protein homodimerization activity	IPI	11402072
GO:0051561	Process	Positive regulation of mitochondrial calcium ion concentration	IMP	19061639
GO:0051659	Process	Maintenance of mitochondrion location	IMP	19061639
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP	19061639
GO:0070509	Process	Calcium ion import	IMP	8040329
GO:0070588	Process	Calcium ion transmembrane transport	IBA	21873635
GO:0090076	Process	Relaxation of skeletal muscle	IDA	8841193
GO:0106134	Process	Positive regulation of cardiac muscle cell contraction	ISS
GO:1901896	Process	Positive regulation of ATPase-coupled calcium transmembrane transporter activity	ISS
GO:1902082	Process	Positive regulation of calcium ion import into sarcoplasmic reticulum	ISS
GO:1902600	Process	Proton transmembrane transport	IEA
GO:1903779	Process	Regulation of cardiac conduction	TAS
GO:1990036	Process	Calcium ion import into sarcoplasmic reticulum	ISS

Other IDs

• MIM: 108730
• HGNC: 811
• e!Ensembl: ENSG00000196296

Protein

• UniProt ID: O14983
• Protein name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) (SR Ca(2+)-ATPase 1) (EC 7.2.2.10) (Calcium pump 1) (Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase)
• Protein function: Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677).
• 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 → 528		Family
  PF00689	Cation_ATPase_C	784 → 987	Cation transporting ATPase, C-terminus	Family

• Sequence:

  MEAAHAKTTEECLAYFGVSETTGLTPDQVKRNLEKYGLNELPAEEGKTLWELVIEQFEDL
  LVRILLLAACISFVLAWFEEGEETITAFVEPFVILLILIANAIVGVWQERNAENAIEALK
  EYEPEMGKVYRADRKSVQRIKARDIVPGDIVEVAVGDKVPADIRILAIKSTTLRVDQSIL
  TGESVSVIKHTEPVPDPRAVNQDKKNMLFSGTNIAAGKALGIVATTGVGTEIGKIRDQMA
  ATEQDKTPLQQKLDEFGEQLSKVISLICVAVWLINIGHFNDPVHGGSWFRGAIYYFKIAV
  ALAVAAIPEGLPAVITTCLALGTRRMAKKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ
  MSVCKMFIIDKVDGDICLLNEFSITGSTYAPEGEVLKNDKPVRPGQYDGLVELATICALC
  NDSSLDFNEAKGVYEKVGEATETALTTLVEKMNVFNTDVRSLSKVERANACNSVIRQLMK
  KEFTLEFSRDRKSMSVYCSPAKSSRAAVGNKMFVKGAPEGVIDRCNYVRVGTTRVPLTGP
  VKEKIMAVIKEWGTGRDTLRCLALATRDTPPKREEMVLDDSARFLEYETDLTFVGVVGML
  DPPRKEVTGSIQLCRDAGIRVIMITGDNKGTAIAICRRIGIFGENEEVADRAYTGREFDD
  LPLAEQREACRRACCFARVEPSHKSKIVEYLQSYDEITAMTGDGVNDAPALKKAEIGIAM
  GSGTAVAKTASEMVLADDNFSTIVAAVEEGRAIYNNMKQFIRYLISSNVGEVVCIFLTAA
  LGLPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMDRPPRSPKEPLISGWLFFRYMAI
  GGYVGAATVGAAAWWFLYAEDGPHVNYSQLTHFMQCTEDNTHFEGIDCEVFEAPEPMTMA
  LSVLVTIEMCNALNSLSENQSLLRMPPWVNIWLLGSICLSMSLHFLILYVDPLPMIFKLR
  ALDLTQWLMVLKISLPVIGLDEILKFVARNYLEDPEDERRK

• Sequence length: 1001