Reviewed, UniProtKB/Swiss-Prot P04191 (AT2A1_RABIT)

Names and origin

Protein names

Recommended name:
    Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
      Short name=SERCA1
    EC=3.6.3.8
Alternative name(s):
    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

Gene names

Name:

ATP2A1

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	1001 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction By similarity.
Catalytic activity	ATP + H2O + Ca2+(Cis) = ADP + phosphate + Ca2+(Trans).
Enzyme regulation	Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN.
Subunit structure	Associated with sarcolipin (SLN) By similarity and phospholamban (PLN).
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Sarcoplasmic reticulum membrane; Multi-pass membrane protein.
Tissue specificity	Skeletal muscle, fast twitch muscle (type II) fibers.
Developmental stage	Isoform SERCA1A is predominantly found in adult and isoform SERCA1B in neonatal skeletal muscle.
Induction	Increased contractile activity leads to decrease SERCA1 expression, while decreased contractile activity leads to increase of SERCA1 expression.
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IIA subfamily.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Endoplasmic reticulum Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Ligand	ATP-binding Calcium Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	ATP biosynthetic process Inferred from electronic annotation. Source: InterPro calcium ion transport Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fast-twitch skeletal muscle fiber contraction Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW sarcoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from sequence or structural similarity. Source: UniProtKB calcium-transporting ATPase activity Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.9 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PLN	P61015	1	EBI-79241,EBI-79236

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform SERCA1B (identifier: P04191-1)

Also known as: Neonatal;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform SERCA1A (identifier: P04191-2)

Also known as: Adult;

The sequence of this isoform differs from the canonical sequence as follows:
     994-1001: DPEDERRK → G

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1001

1001

Sarcoplasmic/endoplasmic reticulum calcium ATPase 1

PRO_0000046189

Regions

Topological domain

1 – 48

48

Cytoplasmic

Transmembrane

49 – 69

21

1

Topological domain

70 – 89

20

Lumenal

Transmembrane

90 – 110

21

2

Topological domain

111 – 253

143

Cytoplasmic

Transmembrane

254 – 273

20

3

Topological domain

274 – 295

22

Lumenal

Transmembrane

296 – 313

18

4

Topological domain

314 – 757

444

Cytoplasmic

Transmembrane

758 – 777

20

5

Topological domain

778 – 787

10

Lumenal

Transmembrane

788 – 808

21

6

Topological domain

809 – 828

20

Cytoplasmic

Transmembrane

829 – 851

23

7

Topological domain

852 – 897

46

Lumenal

Transmembrane

898 – 917

20

8

Topological domain

918 – 930

13

Cytoplasmic

Transmembrane

931 – 949

19

9

Topological domain

950 – 964

15

Lumenal

Transmembrane

965 – 985

21

10

Topological domain

986 – 1001

16

Cytoplasmic

Region

370 – 400

31

Interacts with phospholamban 1

Region

788 – 808

21

Interacts with phospholamban 2

Sites

Active site

351

1

4-aspartylphosphate intermediate

Metal binding

304

1

Calcium 2; via carbonyl oxygen

Metal binding

305

1

Calcium 2; via carbonyl oxygen

Metal binding

307

1

Calcium 2; via carbonyl oxygen

Metal binding

309

1

Calcium 2

Metal binding

703

1

Magnesium By similarity

Metal binding

707

1

Magnesium By similarity

Metal binding

768

1

Calcium 1

Metal binding

771

1

Calcium 1

Metal binding

796

1

Calcium 2

Metal binding

799

1

Calcium 1

Metal binding

800

1

Calcium 1

Metal binding

800

1

Calcium 2

Metal binding

908

1

Calcium 1

Amino acid modifications

Disulfide bond

876 ↔ 888

Natural variations

Alternative sequence

994 – 1001

8

DPEDERRK → G in isoform SERCA1A.

VSP_000356

Secondary structure

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1001

Helix Strand Turn

Details...

Turn

4 – 6

3

Helix

9 – 15

7

Turn

20 – 22

3

Helix

26 – 36

11

Helix

49 – 53

5

Helix

55 – 78

24

Helix

86 – 117

32

Helix

118 – 122

5

Beta strand

128 – 133

6

Helix

142 – 144

3

Beta strand

149 – 153

5

Beta strand

161 – 168

8

Beta strand

174 – 176

3

Turn

178 – 180

3

Helix

201 – 203

3

Beta strand

213 – 216

4

Beta strand

219 – 225

7

Helix

227 – 229

3

Turn

231 – 235

5

Beta strand

236 – 241

6

Helix

248 – 273

26

Helix

276 – 278

3

Helix

282 – 284

3

Helix

290 – 306

17

Helix

311 – 328

18

Helix

337 – 343

7

Beta strand

347 – 353

7

Turn

354 – 356

3

Beta strand

362 – 373

12

Beta strand

376 – 384

9

Beta strand

388 – 391

4

Beta strand

395 – 397

3

Helix

404 – 406

3

Helix

408 – 419

12

Beta strand

424 – 428

5

Turn

429 – 432

4

Beta strand

433 – 438

6

Helix

440 – 452

13

Helix

464 – 467

4

Helix

470 – 478

9

Beta strand

479 – 488

10

Turn

489 – 492

4

Beta strand

493 – 500

8

Beta strand

511 – 516

6

Helix

518 – 523

6

Beta strand

525 – 530

6

Beta strand

533 – 536

4

Helix

539 – 554

16

Beta strand

560 – 569

10

Helix

573 – 575

3

Helix

581 – 583

3

Helix

584 – 587

4

Beta strand

590 – 600

11

Helix

607 – 616

10

Beta strand

620 – 627

8

Helix

629 – 638

10

Beta strand

651 – 654

4

Helix

655 – 659

5

Helix

663 – 672

10

Beta strand

675 – 678

4

Helix

681 – 692

12

Turn

693 – 695

3

Beta strand

698 – 702

5

Helix

705 – 707

3

Helix

708 – 713

6

Beta strand

714 – 720

7

Helix

725 – 729

5

Beta strand

732 – 737

6

Helix

740 – 781

42

Helix

789 – 799

11

Helix

802 – 807

6

Helix

831 – 856

26

Beta strand

860 – 863

4

Helix

873 – 875

3

Turn

876 – 878

3

Helix

880 – 882

3

Helix

888 – 892

5

Helix

894 – 911

18

Helix

913 – 915

3

Beta strand

916 – 919

4

Turn

922 – 924

3

Helix

927 – 929

3

Helix

931 – 949

19

Helix

952 – 956

5

Helix

964 – 974

11

Helix

976 – 991

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform SERCA1B (Neonatal) [UniParc]. Last modified March 20, 1987. Version 1. Checksum: 1F0D8C36CF975266	FASTA	1,001	110,459
	10 20 30 40 50 60 MEAAHSKSTE ECLAYFGVSE TTGLTPDQVK RHLEKYGHNE LPAEEGKSLW ELVIEQFEDL 70 80 90 100 110 120 LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAENAIEALK 130 140 150 160 170 180 EYEPEMGKVY RADRKSVQRI KARDIVPGDI VEVAVGDKVP ADIRILSIKS TTLRVDQSIL 190 200 210 220 230 240 TGESVSVIKH TEPVPDPRAV NQDKKNMLFS GTNIAAGKAL GIVATTGVST EIGKIRDQMA 250 260 270 280 290 300 ATEQDKTPLQ QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWIR GAIYYFKIAV 310 320 330 340 350 360 ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 370 380 390 400 410 420 MSVCKMFIID KVDGDFCSLN EFSITGSTYA PEGEVLKNDK PIRSGQFDGL VELATICALC 430 440 450 460 470 480 NDSSLDFNET KGVYEKVGEA TETALTTLVE KMNVFNTEVR NLSKVERANA CNSVIRQLMK 490 500 510 520 530 540 KEFTLEFSRD RKSMSVYCSP AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPMTGP 550 560 570 580 590 600 VKEKILSVIK EWGTGRDTLR CLALATRDTP PKREEMVLDD SSRFMEYETD LTFVGVVGML 610 620 630 640 650 660 DPPRKEVMGS IQLCRDAGIR VIMITGDNKG TAIAICRRIG IFGENEEVAD RAYTGREFDD 670 680 690 700 710 720 LPLAEQREAC RRACCFARVE PSHKSKIVEY LQSYDEITAM TGDGVNDAPA LKKAEIGIAM 730 740 750 760 770 780 GSGTAVAKTA SEMVLADDNF STIVAAVEEG RAIYNNMKQF IRYLISSNVG EVVCIFLTAA 790 800 810 820 830 840 LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMDRP PRSPKEPLIS GWLFFRYMAI 850 860 870 880 890 900 GGYVGAATVG AAAWWFMYAE DGPGVTYHQL THFMQCTEDH PHFEGLDCEI FEAPEPMTMA 910 920 930 940 950 960 LSVLVTIEMC NALNSLSENQ SLMRMPPWVN IWLLGSICLS MSLHFLILYV DPLPMIFKLK 970 980 990 1000 ALDLTQWLMV LKISLPVIGL DEILKFIARN YLEDPEDERR K
	Isoform SERCA1A (Adult). Checksum: 148C462A8653A3E5	FASTA	994	109,490
	10 20 30 40 50 60 MEAAHSKSTE ECLAYFGVSE TTGLTPDQVK RHLEKYGHNE LPAEEGKSLW ELVIEQFEDL 70 80 90 100 110 120 LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAENAIEALK 130 140 150 160 170 180 EYEPEMGKVY RADRKSVQRI KARDIVPGDI VEVAVGDKVP ADIRILSIKS TTLRVDQSIL 190 200 210 220 230 240 TGESVSVIKH TEPVPDPRAV NQDKKNMLFS GTNIAAGKAL GIVATTGVST EIGKIRDQMA 250 260 270 280 290 300 ATEQDKTPLQ QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWIR GAIYYFKIAV 310 320 330 340 350 360 ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 370 380 390 400 410 420 MSVCKMFIID KVDGDFCSLN EFSITGSTYA PEGEVLKNDK PIRSGQFDGL VELATICALC 430 440 450 460 470 480 NDSSLDFNET KGVYEKVGEA TETALTTLVE KMNVFNTEVR NLSKVERANA CNSVIRQLMK 490 500 510 520 530 540 KEFTLEFSRD RKSMSVYCSP AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPMTGP 550 560 570 580 590 600 VKEKILSVIK EWGTGRDTLR CLALATRDTP PKREEMVLDD SSRFMEYETD LTFVGVVGML 610 620 630 640 650 660 DPPRKEVMGS IQLCRDAGIR VIMITGDNKG TAIAICRRIG IFGENEEVAD RAYTGREFDD 670 680 690 700 710 720 LPLAEQREAC RRACCFARVE PSHKSKIVEY LQSYDEITAM TGDGVNDAPA LKKAEIGIAM 730 740 750 760 770 780 GSGTAVAKTA SEMVLADDNF STIVAAVEEG RAIYNNMKQF IRYLISSNVG EVVCIFLTAA 790 800 810 820 830 840 LGLPEALIPV QLLWVNLVTD GLPATALGFN PPDLDIMDRP PRSPKEPLIS GWLFFRYMAI 850 860 870 880 890 900 GGYVGAATVG AAAWWFMYAE DGPGVTYHQL THFMQCTEDH PHFEGLDCEI FEAPEPMTMA 910 920 930 940 950 960 LSVLVTIEMC NALNSLSENQ SLMRMPPWVN IWLLGSICLS MSLHFLILYV DPLPMIFKLK 970 980 990 ALDLTQWLMV LKISLPVIGL DEILKFIARN YLEG

References

[1]	"Two Ca2+ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences." Brandl C.J., Green N.M., Korczak B., McLennan D.H. Cell 44:597-607(1986) [PubMed: 2936465] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SERCA1B).
[2]	"Involvement of an arginyl residue in the nucleotide-binding site of Ca(2+)-ATPase from sarcoplasmic reticulum as seen by reaction with phenylglyoxal." Corbalan-Garcia S., Teruel J.A., Gomez-Fernandez J.C. Biochem. J. 318:179-185(1996) [PubMed: 8761469] [Abstract] Cited for: PROTEIN SEQUENCE OF 134-140 AND 490-495.
[3]	"Localization of E1-E2 conformational transitions of sarcoplasmic reticulum Ca-ATPase by tryptic cleavage and hydrophobic labeling." Andersen J.P., Vilsen B., Collins J.H., Jorgensen P.L. J. Membr. Biol. 93:85-92(1986) [PubMed: 2948019] [Abstract] Cited for: PROTEIN SEQUENCE OF 199-212; 335-348 AND 506-519.
[4]	"Chemical modification of the Ca(2+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum: identification of sites labeled with aryl isothiocyanates and thiol-directed conformational probes." Wawrzynow A., Collins J.H. Biochim. Biophys. Acta 1203:60-70(1993) [PubMed: 8218393] [Abstract] Cited for: PROTEIN SEQUENCE OF 335-365; 468-476; 493-502; 513-529; 606-615; 630-637 AND 668-671.
[5]	"Interaction of 4-azido-2-nitrophenyl phosphate, a pseudosubstrate, with the sarcoplasmic reticulum Ca-ATPase." Lacapere J.J., Garin J. Biochemistry 33:2586-2593(1994) [PubMed: 8117720] [Abstract] Cited for: PROTEIN SEQUENCE OF 506-513 AND 584-591.
[6]	"Adult forms of the Ca2+ATPase of sarcoplasmic reticulum. Expression in developing skeletal muscle." Brandl C.J., Deleon S., Martin D.R., McLennan D.H. J. Biol. Chem. 262:3768-3774(1987) [PubMed: 3029125] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 973-1001 (ISOFORMS SERCA1A AND SERCA1B).
[7]	"Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution." Toyoshima C., Nakasako M., Nomura H., Ogawa H. Nature 405:647-655(2000) [PubMed: 10864315] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF ISOFORM SERCA1A.
[8]	"Identification of regions in the Ca(2+)-ATPase of sarcoplasmic reticulum that affect functional association with phospholamban." Toyofuku T., Kurzydlowski K., Tada M., McLennan D.H. J. Biol. Chem. 268:2809-2815(1993) [PubMed: 8428955] [Abstract] Cited for: INTERACTION WITH PHOSPHOLAMBAN.
[9]	"Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites." Asahi M., Kimura Y., Kurzydlowski K., Tada M., McLennan D.H. J. Biol. Chem. 274:32855-32862(1999) [PubMed: 10551848] [Abstract] Cited for: INTERACTION WITH PHOSPHOLAMBAN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M12898 mRNA. Translation: AAA31165.1.
M15351 mRNA. Translation: AAA31166.1.
M15158 mRNA. Translation: AAA31167.1.

PIR

PWRBFC. A01075.

RefSeq

NP_001082787.1.

UniGene

Ocu.1829
Ocu.6937

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FQU	model	-	A	1-993	[»]
1IWO	X-ray	3.10	A/B	1-993	[»]
1KJU	electron microscopy	6.00	A	1-993	[»]
1SU4	X-ray	2.40	A	1-993	[»]
1T5S	X-ray	2.60	A	1-993	[»]
1T5T	X-ray	2.90	A	1-993	[»]
1VFP	X-ray	2.90	A/B	1-993	[»]
1WPG	X-ray	2.30	A/B/C/D	1-993	[»]
1XP5	X-ray	3.00	A	1-993	[»]
2AGV	X-ray	2.40	A/B	1-993	[»]
2BY4	X-ray	3.30	A	1-993	[»]
2C88	X-ray	3.10	A	1-993	[»]
2C8K	X-ray	2.80	A	1-993	[»]
2C8L	X-ray	3.10	A	1-993	[»]
2C9M	X-ray	3.00	A/B	1-993	[»]
2DQS	X-ray	2.50	A	1-993	[»]
2EAR	X-ray	3.10	A	1-993	[»]
2EAS	X-ray	3.40	A	1-993	[»]
2EAT	X-ray	2.90	A	1-993	[»]
2EAU	X-ray	2.80	A	1-993	[»]
2O9J	X-ray	2.65	A	1-993	[»]
2OA0	X-ray	3.40	A	1-993	[»]
2ZBD	X-ray	2.40	A	1-993	[»]
2ZBE	X-ray	3.80	A/B	1-993	[»]
2ZBF	X-ray	2.40	A	1-993	[»]
2ZBG	X-ray	2.55	A	1-993	[»]
3B9B	X-ray	2.65	A	1-993	[»]
3B9R	X-ray	3.00	A/B	1-993	[»]
3BA6	X-ray	2.80	A	1-993	[»]
3FGO	X-ray	2.50	A/B	1-993	[»]
3FPB	X-ray	2.55	A	1-993	[»]
3FPS	X-ray	3.20	A	1-993	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P04191. 1 interaction.

Genome annotation databases

GeneID

100037716.

Phylogenomic databases

HOVERGEN

P04191.

Enzyme and pathway databases

BRENDA

3.6.3.8. 255.

Family and domain databases

InterPro

IPR008250. ATPase_P-typ_ATPase-assoc-reg.
IPR005782. ATPase_P-typ_Ca-transp.
IPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR000695. ATPase_P-typ_H-transp.
IPR001757. ATPase_P-typ_ion-transptr.
IPR018303. ATPase_P-typ_phosphor_site.
IPR005834. Dehalogen-like_hydro.
[Graphical view]

PANTHER

PTHR11939. ATPase_P. 1 hit.

Pfam

PF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]

PRINTS

PR00119. CATATPASE.
PR00120. HATPASE.

TIGRFAMs

TIGR01116. ATPase-IIA1_Ca. 1 hit.
TIGR01494. ATPase_P-type. 4 hits.

PROSITE

PS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

AT2A1_RABIT

Accession

Primary (citable) accession number: P04191
Secondary accession number(s): P11719

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	March 20, 1987
Last modified:	June 16, 2009
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)