O14983 (AT2A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
Short name=SERCA1
Short name=SR Ca(2+)-ATPase 1
EC=3.6.3.8

Alternative name(s):
Calcium pump 1
Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform
Endoplasmic reticulum class 1/2 Ca(2+) ATPase

Gene names

Name:

ATP2A1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1001 AA.
Sequence status	Complete.
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.
Catalytic activity	ATP + H2O + Ca2+(Side 1) = ADP + phosphate + Ca2+(Side 2).
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 By similarity.
Subunit structure	Associated with sarcolipin (SLN) and phospholamban (PLN) By similarity.
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 accounts for more than 99% of SERCA1 isoforms expressed in adult skeletal muscle, while isoform SERCA1B predominates in neo-natal skeletal muscle.
Induction	Increased contractile activity leads to a decrease in SERCA1 expression, while decreased contractile activity leads to an increase in SERCA1 expression.
Involvement in disease	Brody myopathy (BRM) [MIM:601003]: A disorder of muscle function that is characterized by painless muscle cramping and exercise-induced impairment of muscle relaxation. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily. [View classification]

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Endoplasmic reticulum Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Calcium Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic mitochondrial changes Inferred from mutant phenotype PubMed 19061639. Source: BHF-UCL blood coagulation Traceable author statement. Source: Reactome calcium ion import Inferred from mutant phenotype PubMed 8040329. Source: BHF-UCL elevation of endoplasmic reticulum calcium ion concentration Inferred from mutant phenotype PubMed 11402072. Source: BHF-UCL elevation of mitochondrial calcium ion concentration Inferred from mutant phenotype PubMed 19061639. Source: BHF-UCL intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from mutant phenotype PubMed 19061639. Source: BHF-UCL maintenance of mitochondrion location Inferred from mutant phenotype PubMed 19061639. Source: BHF-UCL negative regulation of striated muscle contraction Inferred from mutant phenotype Ref.4. Source: UniProtKB positive regulation of fast-twitch skeletal muscle fiber contraction Inferred from direct assay PubMed 12479237. Source: UniProtKB reduction of endoplasmic reticulum calcium ion concentration Inferred from mutant phenotype PubMed 11402072PubMed 19061639. Source: BHF-UCL relaxation of skeletal muscle Inferred from direct assay PubMed 8841193. Source: BHF-UCL
Cellular_component	H zone Inferred from direct assay PubMed 1329967. Source: UniProtKB I band Inferred from direct assay PubMed 1329967. Source: UniProtKB calcium channel complex Inferred by curator PubMed 11402072. Source: BHF-UCL endoplasmic reticulum membrane Inferred from direct assay PubMed 11402072. Source: UniProtKB endoplasmic reticulum-Golgi intermediate compartment Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB platelet dense tubular network membrane Traceable author statement. Source: Reactome sarcoplasmic reticulum Inferred from sequence or structural similarity. Source: UniProtKB sarcoplasmic reticulum membrane Traceable author statement PubMed 11402072. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from mutant phenotype PubMed 9405806. Source: UniProtKB calcium-transporting ATPase activity Inferred from direct assay PubMed 8729696PubMed 1329967. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform SERCA1B (identifier: O14983-1)

Also known as: ATP2A1B; 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: O14983-2)

Also known as: ATP2A1A; 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_0000046187
Regions
	Topological domain	1 – 48	48	Cytoplasmic By similarity
	Transmembrane	49 – 69	21	Helical; Name=1; By similarity
	Topological domain	70 – 89	20	Lumenal By similarity
	Transmembrane	90 – 110	21	Helical; Name=2; By similarity
	Topological domain	111 – 253	143	Cytoplasmic By similarity
	Transmembrane	254 – 273	20	Helical; Name=3; By similarity
	Topological domain	274 – 295	22	Lumenal By similarity
	Transmembrane	296 – 313	18	Helical; Name=4; By similarity
	Topological domain	314 – 757	444	Cytoplasmic By similarity
	Transmembrane	758 – 777	20	Helical; Name=5; By similarity
	Topological domain	778 – 787	10	Lumenal By similarity
	Transmembrane	788 – 808	21	Helical; Name=6; By similarity
	Topological domain	809 – 828	20	Cytoplasmic By similarity
	Transmembrane	829 – 851	23	Helical; Name=7; By similarity
	Topological domain	852 – 897	46	Lumenal By similarity
	Transmembrane	898 – 917	20	Helical; Name=8; By similarity
	Topological domain	918 – 930	13	Cytoplasmic By similarity
	Transmembrane	931 – 949	19	Helical; Name=9; By similarity
	Topological domain	950 – 964	15	Lumenal By similarity
	Transmembrane	965 – 985	21	Helical; Name=10; By similarity
	Topological domain	986 – 1001	16	Cytoplasmic By similarity
	Region	370 – 400	31	Interacts with phospholamban 1 By similarity
	Region	788 – 808	21	Interacts with phospholamban 2 By similarity
Sites
	Active site	351	1	4-aspartylphosphate intermediate By similarity
	Metal binding	304	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	305	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	307	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	309	1	Calcium 2 By similarity
	Metal binding	703	1	Magnesium By similarity
	Metal binding	707	1	Magnesium By similarity
	Metal binding	768	1	Calcium 1 By similarity
	Metal binding	771	1	Calcium 1 By similarity
	Metal binding	796	1	Calcium 2 By similarity
	Metal binding	799	1	Calcium 1 By similarity
	Metal binding	800	1	Calcium 1 By similarity
	Metal binding	800	1	Calcium 2 By similarity
	Metal binding	908	1	Calcium 1 By similarity
Amino acid modifications
	Disulfide bond	876 ↔ 888		Ref.3
Natural variations
	Alternative sequence	994 – 1001	8	DPEDERRK → G in isoform SERCA1A.		VSP_000355
	Natural variant	789	1	P → L in BRM; almost complete loss of Ca(2+) transport activity because of reduced Ca(2+) affinity. Ref.4		VAR_015588

Sequences

	Sequence		Length	Mass (Da)
	Isoform SERCA1B (ATP2A1B) (Neonatal) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: C8F33809B56FDDEE	FASTA	1,001	110,252
	10 20 30 40 50 60 MEAAHAKTTE ECLAYFGVSE TTGLTPDQVK RNLEKYGLNE LPAEEGKTLW ELVIEQFEDL 70 80 90 100 110 120 LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAENAIEALK 130 140 150 160 170 180 EYEPEMGKVY RADRKSVQRI KARDIVPGDI VEVAVGDKVP ADIRILAIKS TTLRVDQSIL 190 200 210 220 230 240 TGESVSVIKH TEPVPDPRAV NQDKKNMLFS GTNIAAGKAL GIVATTGVGT EIGKIRDQMA 250 260 270 280 290 300 ATEQDKTPLQ QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWFR GAIYYFKIAV 310 320 330 340 350 360 ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 370 380 390 400 410 420 MSVCKMFIID KVDGDICLLN EFSITGSTYA PEGEVLKNDK PVRPGQYDGL VELATICALC 430 440 450 460 470 480 NDSSLDFNEA KGVYEKVGEA TETALTTLVE KMNVFNTDVR SLSKVERANA CNSVIRQLMK 490 500 510 520 530 540 KEFTLEFSRD RKSMSVYCSP AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPLTGP 550 560 570 580 590 600 VKEKIMAVIK EWGTGRDTLR CLALATRDTP PKREEMVLDD SARFLEYETD LTFVGVVGML 610 620 630 640 650 660 DPPRKEVTGS 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 AAAWWFLYAE DGPHVNYSQL THFMQCTEDN THFEGIDCEV FEAPEPMTMA 910 920 930 940 950 960 LSVLVTIEMC NALNSLSENQ SLLRMPPWVN IWLLGSICLS MSLHFLILYV DPLPMIFKLR 970 980 990 1000 ALDLTQWLMV LKISLPVIGL DEILKFVARN YLEDPEDERR K
	Isoform SERCA1A (ATP2A1A) (Adult) [UniParc]. Checksum: 3C07972DB585C083	FASTA	994	109,283
	10 20 30 40 50 60 MEAAHAKTTE ECLAYFGVSE TTGLTPDQVK RNLEKYGLNE LPAEEGKTLW ELVIEQFEDL 70 80 90 100 110 120 LVRILLLAAC ISFVLAWFEE GEETITAFVE PFVILLILIA NAIVGVWQER NAENAIEALK 130 140 150 160 170 180 EYEPEMGKVY RADRKSVQRI KARDIVPGDI VEVAVGDKVP ADIRILAIKS TTLRVDQSIL 190 200 210 220 230 240 TGESVSVIKH TEPVPDPRAV NQDKKNMLFS GTNIAAGKAL GIVATTGVGT EIGKIRDQMA 250 260 270 280 290 300 ATEQDKTPLQ QKLDEFGEQL SKVISLICVA VWLINIGHFN DPVHGGSWFR GAIYYFKIAV 310 320 330 340 350 360 ALAVAAIPEG LPAVITTCLA LGTRRMAKKN AIVRSLPSVE TLGCTSVICS DKTGTLTTNQ 370 380 390 400 410 420 MSVCKMFIID KVDGDICLLN EFSITGSTYA PEGEVLKNDK PVRPGQYDGL VELATICALC 430 440 450 460 470 480 NDSSLDFNEA KGVYEKVGEA TETALTTLVE KMNVFNTDVR SLSKVERANA CNSVIRQLMK 490 500 510 520 530 540 KEFTLEFSRD RKSMSVYCSP AKSSRAAVGN KMFVKGAPEG VIDRCNYVRV GTTRVPLTGP 550 560 570 580 590 600 VKEKIMAVIK EWGTGRDTLR CLALATRDTP PKREEMVLDD SARFLEYETD LTFVGVVGML 610 620 630 640 650 660 DPPRKEVTGS 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 AAAWWFLYAE DGPHVNYSQL THFMQCTEDN THFEGIDCEV FEAPEPMTMA 910 920 930 940 950 960 LSVLVTIEMC NALNSLSENQ SLLRMPPWVN IWLLGSICLS MSLHFLILYV DPLPMIFKLR 970 980 990 ALDLTQWLMV LKISLPVIGL DEILKFVARN YLEG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of cDNA and genomic DNA encoding SERCA1, the Ca(2+)-ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its elimination as a candidate gene for Brody disease." Zhang Y., Fujii J., Phillips M.S., Chen H.-S., Karpati G., Yee W.-C., Schrank B., Cornblath D.R., Boylan K.B., Maclennan D.H. Genomics 30:415-424(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SERCA1A AND SERCA1B). Tissue: Skeletal muscle.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SERCA1A). Tissue: Tongue.
[3]	"Mutations of either or both Cys876 and Cys888 residues of sarcoplasmic reticulum Ca2+-ATPase result in a complete loss of Ca2+ transport activity without a loss of Ca2+-dependent ATPase activity. Role of the Cys876-Cys888 disulfide bond." Daiho T., Yamasaki K., Saino T., Kamidochi M., Satoh K., Iizuka H., Suzuki H. J. Biol. Chem. 276:32771-32778(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BOND.
[4]	"The mutation of Pro(789) to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA1) and is associated with Brody disease." Odermatt A., Barton K., Khanna V.K., Mathieu J., Escolar D., Kuntzer T., Karpati G., MacLennan D.H. Hum. Genet. 106:482-491(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BRM LEU-789.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U96781 , U96773, U96774, U96775, U96776, U96777, U96778, U96779, U96780 Genomic DNA. Translation: AAB53113.1. U96781 , U96773, U96774, U96775, U96776, U96777, U96778, U96779, U96780 Genomic DNA. Translation: AAB53112.1. AK291314 mRNA. Translation: BAF84003.1.
IPI	IPI00024804. IPI00396118.
RefSeq	NP_004311.1. NM_004320.4. NP_775293.1. NM_173201.3.
UniGene	Hs.657344.
3D structure databases
ProteinModelPortal	O14983.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14983. 3 interactions.
MINT	MINT-1158140.
STRING	9606.ENSP00000349595.
PTM databases
PhosphoSite	O14983.
Proteomic databases
PaxDb	O14983.
PRIDE	O14983.
Protocols and materials databases
DNASU	487.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357084; ENSP00000349595; ENSG00000196296. ENST00000395503; ENSP00000378879; ENSG00000196296.
GeneID	487.
KEGG	hsa:487.
UCSC	uc002drn.1. human. uc002dro.1. human.
Organism-specific databases
CTD	487.
GeneCards	GC16P028889.
HGNC	HGNC:811. ATP2A1.
HPA	CAB032706.
MIM	108730. gene. 601003. phenotype.
neXtProt	NX_O14983.
Orphanet	53347. Brody myopathy.
PharmGKB	PA25105.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0474.
HOGENOM	HOG000265621.
HOVERGEN	HBG105648.
KO	K05853.
OMA	LENSNIM.
OrthoDB	EOG4SXNBQ.
PhylomeDB	O14983.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	O14983.
Bgee	O14983.
CleanEx	HS_ATP2A1.
Genevestigator	O14983.
GermOnline	ENSG00000196296. Homo sapiens.
Family and domain databases
Gene3D	1.20.1110.10. 2 hits. 2.70.150.10. 2 hits. 3.40.1110.10. 1 hit.
InterPro	IPR005782. ATPase_P-typ_Ca-transp_IIA. IPR006068. ATPase_P-typ_cation-transptr_C. IPR004014. ATPase_P-typ_cation-transptr_N. IPR023299. ATPase_P-typ_cyto_domN. IPR018303. ATPase_P-typ_P_site. IPR023298. ATPase_P-typ_TM_dom. IPR008250. ATPase_P-typ_transduc_dom_A. IPR001757. Cation_transp_P_typ_ATPase. IPR023214. HAD-like_dom. [Graphical view]
PANTHER	PTHR24093. PTHR24093. 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.
SMART	SM00831. Cation_ATPase_N. 1 hit. [Graphical view]
SUPFAM	SSF81660. ATPase_cation_domN. 1 hit. SSF56784. HAD-like_dom. 1 hit.
TIGRFAMs	TIGR01116. ATPase-IIA1_Ca. 1 hit. TIGR01494. ATPase_P-type. 2 hits.
PROSITE	PS00154. ATPASE_E1_E2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O14983.
ChEMBL	CHEMBL3136.
GenomeRNAi	487.
NextBio	2023.
SOURCE	Search...

Entry information

Entry name

AT2A1_HUMAN

Accession

Primary (citable) accession number: O14983
Secondary accession number(s): A8K5J9, O14984

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.