SARCO_RABIT
ID SARCO_RABIT Reviewed; 31 AA.
AC P42532;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Sarcolipin;
GN Name=SLN;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Odermatt A., Maclennan D.H.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=1416990; DOI=10.1016/0003-9861(92)90457-8;
RA Wawrzynow A., Theibert J.L., Murphy C., Jona I., Martonosi A.,
RA Collins J.H.;
RT "Sarcolipin, the 'proteolipid' of skeletal muscle sarcoplasmic reticulum,
RT is a unique, amphipathic, 31-residue peptide.";
RL Arch. Biochem. Biophys. 298:620-623(1992).
RN [3]
RP PROTEIN SEQUENCE OF 1-12 AND 28-31.
RX PubMed=6450618; DOI=10.1016/0005-2795(80)90208-1;
RA Ohnoki S., Martonosi A.;
RT "Purification and characterization of the proteolipid of rabbit
RT sarcoplasmic reticulum.";
RL Biochim. Biophys. Acta 626:170-178(1980).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=9575189; DOI=10.1074/jbc.273.20.12360;
RA Odermatt A., Becker S., Khanna V.K., Kurzydlowski K., Leisner E., Pette D.,
RA MacLennan D.H.;
RT "Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal
RT muscle sarcoplasmic reticulum Ca2+-ATPase.";
RL J. Biol. Chem. 273:12360-12369(1998).
RN [5]
RP FUNCTION, INTERACTION WITH ATP2A1, SUBCELLULAR LOCATION, TOPOLOGY,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF VAL-26; ARG-27;
RP SER-28; TYR-29; GLN-30 AND TYR-31.
RX PubMed=23362265; DOI=10.1074/jbc.m112.446161;
RA Gorski P.A., Glaves J.P., Vangheluwe P., Young H.S.;
RT "Sarco(endo)plasmic reticulum calcium ATPase (SERCA) inhibition by
RT sarcolipin is encoded in its luminal tail.";
RL J. Biol. Chem. 288:8456-8467(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH ATP2A1, AND
RP INTERACTION WITH ATP2A1.
RX PubMed=23455422; DOI=10.1038/nature11899;
RA Toyoshima C., Iwasawa S., Ogawa H., Hirata A., Tsueda J., Inesi G.;
RT "Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1
RT state.";
RL Nature 495:260-264(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH ATP2A1, AND
RP INTERACTION WITH ATP2A1.
RX PubMed=23455424; DOI=10.1038/nature11900;
RA Winther A.M., Bublitz M., Karlsen J.L., Moller J.V., Hansen J.B.,
RA Nissen P., Buch-Pedersen M.J.;
RT "The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the
RT cytoplasm.";
RL Nature 495:265-269(2013).
CC -!- FUNCTION: Reversibly inhibits the activity of ATP2A1 and ATP2A2 in
CC sarcoplasmic reticulum by decreasing the apparent affinity of the
CC ATPase for Ca(2+). Modulates calcium re-uptake during muscle relaxation
CC and plays an important role in calcium homeostasis in muscle
CC (PubMed:23362265, PubMed:9575189). Required for muscle-based, non-
CC shivering thermogenesis (By similarity). {ECO:0000250|UniProtKB:Q9CQD6,
CC ECO:0000269|PubMed:23362265, ECO:0000269|PubMed:9575189}.
CC -!- SUBUNIT: Interacts with calcium ATPase ATP2A1/SERCA1 (PubMed:23362265,
CC PubMed:23455422, PubMed:23455424). Interact with ATP2A2; the inhibition
CC decreases ATP2A1 Ca(2+) affinity. Interacts with VMP1; VMP1 competes
CC with PLN and SLN to prevent them from forming an inhibitory complex
CC with ATP2A2 (By similarity). {ECO:0000250|UniProtKB:O00631,
CC ECO:0000269|PubMed:23362265, ECO:0000269|PubMed:23455422,
CC ECO:0000269|PubMed:23455424}.
CC -!- INTERACTION:
CC P42532; B6CAM1; NbExp=2; IntAct=EBI-16039445, EBI-16039422;
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:1416990, ECO:0000269|PubMed:23362265,
CC ECO:0000269|PubMed:9575189}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23362265}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Skeletal muscle (at protein level).
CC {ECO:0000269|PubMed:1416990}.
CC -!- SIMILARITY: Belongs to the sarcolipin family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U96091; AAB86979.1; -; mRNA.
DR PIR; S27112; S27112.
DR RefSeq; NP_001075856.1; NM_001082387.1.
DR RefSeq; XP_017196242.1; XM_017340753.1.
DR PDB; 3W5A; X-ray; 3.01 A; C=1-31.
DR PDB; 4H1W; X-ray; 3.10 A; B=1-31.
DR PDBsum; 3W5A; -.
DR PDBsum; 4H1W; -.
DR AlphaFoldDB; P42532; -.
DR BMRB; P42532; -.
DR SMR; P42532; -.
DR DIP; DIP-60212N; -.
DR IntAct; P42532; 1.
DR STRING; 9986.ENSOCUP00000010204; -.
DR iPTMnet; P42532; -.
DR SwissPalm; P42532; -.
DR Ensembl; ENSOCUT00000011874; ENSOCUP00000010204; ENSOCUG00000011876.
DR GeneID; 100009246; -.
DR KEGG; ocu:100009246; -.
DR CTD; 6588; -.
DR eggNOG; ENOG502TD27; Eukaryota.
DR HOGENOM; CLU_221275_0_0_1; -.
DR InParanoid; P42532; -.
DR Proteomes; UP000001811; Chromosome 1.
DR Bgee; ENSOCUG00000011876; Expressed in skeletal muscle tissue and 14 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IDA:BHF-UCL.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:BHF-UCL.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:1901877; P:negative regulation of calcium ion binding; IDA:BHF-UCL.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IDA:BHF-UCL.
DR GO; GO:1901020; P:negative regulation of calcium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:BHF-UCL.
DR GO; GO:0043242; P:negative regulation of protein-containing complex disassembly; IDA:BHF-UCL.
DR GO; GO:1901881; P:positive regulation of protein depolymerization; IDA:BHF-UCL.
DR GO; GO:1901894; P:regulation of ATPase-coupled calcium transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:1901077; P:regulation of relaxation of muscle; ISS:UniProtKB.
DR GO; GO:0070296; P:sarcoplasmic reticulum calcium ion transport; ISS:UniProtKB.
DR InterPro; IPR008028; Sarcolipin.
DR Pfam; PF05366; Sarcolipin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum; Membrane;
KW Reference proteome; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix.
FT PEPTIDE 1..31
FT /note="Sarcolipin"
FT /id="PRO_0000045900"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT TRANSMEM 8..26
FT /note="Helical"
FT TOPO_DOM 27..31
FT /note="Lumenal"
FT MUTAGEN 26
FT /note="V->A: Slightly reduces inhibition of ATP2A1-mediated
FT calcium uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT MUTAGEN 27
FT /note="R->A: Nearly abolishes inhibition of ATP2A1-mediated
FT calcium uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT MUTAGEN 28
FT /note="S->A: Reduces inhibition of ATP2A1-mediated calcium
FT uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT MUTAGEN 29
FT /note="Y->A: Reduces inhibition of ATP2A1-mediated calcium
FT uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT MUTAGEN 30
FT /note="Q->A: Reduces inhibition of ATP2A1-mediated calcium
FT uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT MUTAGEN 31
FT /note="Y->A: Nearly abolishes inhibition of ATP2A1-mediated
FT calcium uptake."
FT /evidence="ECO:0000269|PubMed:23362265"
FT HELIX 4..30
FT /evidence="ECO:0007829|PDB:3W5A"
SQ SEQUENCE 31 AA; 3774 MW; 6E3725560658481B CRC64;
MERSTRELCL NFTVVLITVI LIWLLVRSYQ Y
