DB code: M00102

RLCP classification 1.15.39000.353 : Hydrolysis
CATH domain 2.70.150.10 : Calcium-transporting ATPase, cytoplasmic transduction domain A
1.20.1110.10 : Calcium-transporting ATPase, transmembrane domain
3.40.1110.10 : Calcium-transporting ATPase, cytoplasmic domain N
3.40.50.1000 : Rossmann fold Catalytic domain
E.C. 3.6.3.8
CSA 1eul
M-CSA 1eul
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1000 : Rossmann fold D00248

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04191 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
SERCA1
EC 3.6.3.8
Calcium pump 1
Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform
SR Ca(2+)-ATPase 1
Endoplasmic reticulum class 1/2 Ca(2+) ATPase
NP_001082787.1 (Protein)
NM_001089318.1 (DNA/RNA sequence)
PF00689 (Cation_ATPase_C)
PF00690 (Cation_ATPase_N)
PF00122 (E1-E2_ATPase)
PF00702 (Hydrolase)
[Graphical View]

KEGG enzyme name
Ca2+-transporting ATPase
sarcoplasmic reticulum ATPase
sarco(endo)plasmic reticulum Ca2+-ATPase
calcium pump
Ca2+-pumping ATPase
plasma membrane Ca-ATPase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04191 AT2A1_RABIT ATP + H(2)O + Ca(2+)(Cis) = ADP + phosphate + Ca(2+)(Trans). Associated with sarcolipin (SLN) (By similarity) and phospholamban (PLN). Endoplasmic reticulum membrane, Multi-pass membrane protein. Sarcoplasmic reticulum membrane, Multi-pass membrane protein.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00001 C00076 C00008 C00009 C00076
E.C.
Compound magnesium ATP H2O Ca2+(cis) ADP Orthophosphate Ca2+(trans)
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide H2O divalent metal (Ca2+, Mg2+) amine group,nucleotide phosphate group/phosphate ion divalent metal (Ca2+, Mg2+)
ChEBI 18420
 18420
 		15422
 15422
 		15377
 15377
 		29108
 29108
 		16761
 16761
 		26078
 26078
 		29108
 29108
PubChem 888
 888
 		5957
 5957
 		22247451
 962
 22247451
 962
 		271
 271
 		6022
 6022
 		1004
 22486802
 1004
 22486802
 		271
 271
1eulA01 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoA01 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoB01 Unbound Unbound Unbound Unbound Unbound Unbound
1kjuA01 Unbound Unbound Unbound Unbound Unbound Unbound
1eulA02 Unbound Unbound Bound:2x_CA Unbound Unbound Bound:2x_CA
1iwoA02 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoB02 Unbound Unbound Unbound Unbound Unbound Unbound
1kjuA02 Unbound Unbound Unbound Unbound Unbound Unbound
1eulA03 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoA03 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoB03 Unbound Unbound Unbound Unbound Unbound Unbound
1kjuA03 Unbound Unbound Unbound Unbound Unbound Unbound
1eulA04 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoA04 Unbound Unbound Unbound Unbound Unbound Unbound
1iwoB04 Unbound Unbound Unbound Unbound Unbound Unbound
1kjuA04 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot, PDB

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eulA01
1iwoA01
1iwoB01
1kjuA01
1eulA02 ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)
1iwoA02 ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)
1iwoB02 ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)
1kjuA02 ASN 768;GLU 771;THR 799;ASP 800;GLU 908(Ca-1 binding);VAL 304;ALA 305;ILE 307;GLU 309;ASN 796;ASP 800(Ca-2 binding)
1eulA03
1iwoA03
1iwoB03
1kjuA03
1eulA04 ASP 703;ASP 707(Mg binding) ASP 351(phosphorylation)
1iwoA04 ASP 703;ASP 707(Mg binding) ASP 351(phosphorylation)
1iwoB04 ASP 703;ASP 707(Mg binding) ASP 351(phosphorylation)
1kjuA04 ASP 703;ASP 707(Mg binding) ASP 351(phosphorylation)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.651-652
[4]
p.667-671, p.673-676
[8]
Fig.3 2
[9]
p.207, Fig.7 2
[11]
Fig.5, p.426-429 2
[15]
p.452-453, p.459-462

References
[1]
Resource
Comments X-ray crystallography (2.6 Angstroms)
Medline ID 20320311
PubMed ID 10864315
Journal Nature
Year 2000
Volume 405
Pages 647-655
Authors Toyoshima C, Nakasako M, Nomura H, Ogawa H
Title Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10998362
Journal Biochem J
Year 2000
Volume 351
Pages 195-205
Authors Negash S, Yao Q, Sun H, Li J, Bigelow DJ, Squier TC
Title Phospholamban remains associated with the Ca2+- and Mg2+-dependent ATPase following phosphorylation by cAMP-dependent protein kinase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 11311132
Journal Biochem J
Year 2001
Volume 355
Pages 699-706
Authors Sharma P, Patchell VB, Gao Y, Evans JS, Levine BA
Title Cytoplasmic interactions between phospholamban residues 1-20 and the calcium-activated ATPase of the sarcoplasmic reticulum.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11389676
Journal Biochem J
Year 2001
Volume 356
Pages 665-83
Authors Lee AG, East JM
Title What the structure of a calcium pump tells us about its mechanism.
Related PDB
Related UniProtKB
[5]
Resource
Comments mutation analysis
Medline ID
PubMed ID 11438551
Journal J Biol Chem
Year 2001
Volume 276
Pages 35741-35750
Authors Clausen JD, McIntosh DB, Woolley DG, Andersen JP
Title Importance of Thr-353 of the conserved phosphorylation loop of the sarcoplasmic reticulum Ca2+-ATPase in MgATP binding and catalytic activity.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11526231
Journal Proc Natl Acad Sci U S A
Year 2001
Volume 98
Pages 10061-6
Authors Asahi M, Green NM, Kurzydlowski K, Tada M, MacLennan DH
Title Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11544263
Journal J Biol Chem
Year 2001
Volume 276
Pages 42793-800
Authors Reis M, Farage M, de Souza AC, de Meis L
Title Correlation between uncoupled ATP hydrolysis and heat production by the sarcoplasmic reticulum Ca2+-ATPase: coupling effect of fluoride.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11557055
Journal FEBS Lett
Year 2001
Volume 505
Pages 129-35
Authors Danko S, Yamasaki K, Daiho T, Suzuki H, Toyoshima C
Title Organization of cytoplasmic domains of sarcoplasmic reticulum Ca(2+)-ATPase in E(1)P and E(1)ATP states: a limited proteolysis study.
Related PDB
Related UniProtKB
[9]
Resource
Comments structural model, catalysis
Medline ID
PubMed ID 11829513
Journal J Mol Biol
Year 2002
Volume 316
Pages 201-211
Authors Xu C, Rice WJ, He W, Stokes DL
Title A structural model for the catalytic cycle of Ca(2+)-ATPase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11841218
Journal Biochemistry
Year 2002
Volume 41
Pages 2264-72
Authors Hua S, Ma H, Lewis D, Inesi G, Toyoshima C
Title Functional role of "N" (nucleotide) and "P" (phosphorylation) domain interactions in the sarcoplasmic reticulum (SERCA) ATPase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12051918
Journal J Mol Biol
Year 2002
Volume 319
Pages 421-31
Authors Wang W, Cho HS, Kim R, Jancarik J, Yokota H, Nguyen HH, Grigoriev IV, Wemmer DE, Kim SH
Title Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12163080
Journal Curr Opin Struct Biol
Year 2002
Volume 12
Pages 547-54
Authors Lee AG
Title A calcium pump made visible.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12167852
Journal Nature
Year 2002
Volume 418
Pages 605-11
Authors Toyoshima C, Nomura H
Title Structural changes in the calcium pump accompanying the dissociation of calcium.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 12172642
Journal J Membr Biol
Year 2002
Volume 188
Pages 1-9
Authors de Meis L
Title Ca2+-ATPases (SERCA): energy transduction and heat production in transport ATPases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 12598367
Journal Annu Rev Biophys Biomol Struct
Year 2003
Volume 32
Pages 445-68
Authors Stokes DL, Green NM
Title Structure and function of the calcium pump.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 12829699
Journal J Biol Chem
Year 2003
Volume 278
Pages 35798-804
Authors Padanyi R, Paszty K, Penheiter AR, Filoteo AG, Penniston JT, Enyedi A
Title Intramolecular interactions of the regulatory region with the catalytic core in the plasma membrane calcium pump.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 14630328
Journal FEBS Lett
Year 2003
Volume 555
Pages 106-10
Authors Toyoshima C, Nomura H, Sugita Y
Title Structural basis of ion pumping by Ca(2+)-ATPase of sarcoplasmic reticulum.
Related PDB
Related UniProtKB

Comments
This belongs to the cation transport ATPases family (E1-E2 ATPases).
Although the catalytic mechanism of the homologous enzyme of this ATPase, phosphoserine phosphatase, have been elucidated and considered to be similar to its own mechanism, the corresponding residues to general acid/base are not found [11].
However, Asp351 acts as a nucleophile to form phosho-aspartyl enzyme intermediate through associative mechanism (SN2-like reaction) ([15] & [22]). During this reaction, magnesium ion, which might be ligated to Asp351 and transferred phosphate group, may assist the nucleophilic attack, according to the literature for the homologous enzyme, phosphoserine phosphatase [22].
At the next stage, a water molecule will attack the acyl-phosphate. However, the general base, which will activate the hydrolytic water, has not been reported.

Created Updated
2002-07-09 2009-02-26