DWORF_MOUSE
ID DWORF_MOUSE Reviewed; 34 AA.
AC P0DN83;
DT 16-MAR-2016, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF {ECO:0000305};
DE Short=SERCA regulator DWORF {ECO:0000305};
DE AltName: Full=Dwarf open reading frame {ECO:0000303|PubMed:26816378};
DE Short=DWORF {ECO:0000303|PubMed:26816378};
DE AltName: Full=Small transmembrane regulator of ion transport 1 {ECO:0000312|MGI:MGI:5593461};
GN Name=Strit1 {ECO:0000312|MGI:MGI:5593461};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH
RP ATP2A1, AND DISRUPTION PHENOTYPE.
RX PubMed=26816378; DOI=10.1126/science.aad4076;
RA Nelson B.R., Makarewich C.A., Anderson D.M., Winders B.R., Troupes C.D.,
RA Wu F., Reese A.L., McAnally J.R., Chen X., Kavalali E.T., Cannon S.C.,
RA Houser S.R., Bassel-Duby R., Olson E.N.;
RT "Muscle physiology. A peptide encoded by a transcript annotated as long
RT noncoding RNA enhances SERCA activity in muscle.";
RL Science 351:271-275(2016).
RN [3]
RP SUBUNIT, FUNCTION, AND INTERACTION WITH ATP2A1.
RX PubMed=30299255; DOI=10.7554/elife.38319;
RA Makarewich C.A., Munir A.Z., Schiattarella G.G., Bezprozvannaya S.,
RA Raguimova O.N., Cho E.E., Vidal A.H., Robia S.L., Bassel-Duby R.,
RA Olson E.N.;
RT "The DWORF micropeptide enhances contractility and prevents heart failure
RT in a mouse model of dilated cardiomyopathy.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic
CC reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a
CC key regulator of skeletal muscle activity (PubMed:26816378,
CC PubMed:30299255). Does not directly stimulate SERCA pump activity
CC (PubMed:26816378). Enhances sarcoplasmic reticulum Ca(2+) uptake and
CC myocyte contractility by displacing the SERCA inhibitory peptides
CC sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN)
CC (PubMed:26816378, PubMed:30299255). {ECO:0000269|PubMed:26816378,
CC ECO:0000269|PubMed:30299255}.
CC -!- SUBUNIT: Monomer (PubMed:30299255). Interacts with ATP2A1/SERCA1
CC (PubMed:26816378, PubMed:30299255). {ECO:0000269|PubMed:26816378,
CC ECO:0000269|PubMed:30299255}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26816378}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart (at protein level).
CC Detected in heart and soleus, a postural muscle group of the hindlimb
CC containing the highest enrichment of slow-twitch muscle fibers. Also
CC expressed in diaphragm, which contains some slow-twitch fibers. Not
CC detected in the quadriceps, a fast-twitch muscle group, or in cardiac
CC atrial muscle. Not expressed in the prenatal heart but gradually
CC increases in abundance postnatally. {ECO:0000269|PubMed:26816378}.
CC -!- DISRUPTION PHENOTYPE: Mice produce offspring at expected Mendelian
CC ratios. Slow-twitch skeletal muscle fibers display delayed Ca(2+)
CC clearance and relaxation and reduced SERCA activity. No significant
CC differences are observed in peak muscle force and no differences are
CC observed in relaxation rates at low, non-tetanic stimulation
CC frequencies. However at tetanus-inducing frequencies, relaxation rates
CC are significantly slowed after tetanus. {ECO:0000269|PubMed:26816378}.
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; GL456099; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS89629.1; -.
DR AlphaFoldDB; P0DN83; -.
DR SMR; P0DN83; -.
DR Ensembl; ENSMUST00000192926; ENSMUSP00000147363; ENSMUSG00000103476.
DR MGI; MGI:5593461; Strit1.
DR VEuPathDB; HostDB:ENSMUSG00000103476; -.
DR GeneTree; ENSGT01050000245741; -.
DR PRO; PR:P0DN83; -.
DR Proteomes; UP000000589; Chromosome 3.
DR Bgee; ENSMUSG00000103476; Expressed in striatum and 15 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0090280; P:positive regulation of calcium ion import; IMP:MGI.
DR GO; GO:1902082; P:positive regulation of calcium ion import into sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0106134; P:positive regulation of cardiac muscle cell contraction; IMP:UniProtKB.
DR GO; GO:1901894; P:regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0031449; P:regulation of slow-twitch skeletal muscle fiber contraction; IDA:UniProtKB.
DR CDD; cd20247; DWORF; 1.
DR InterPro; IPR044529; DWORF.
PE 1: Evidence at protein level;
KW Membrane; Reference proteome; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..34
FT /note="Sarcoplasmic/endoplasmic reticulum calcium ATPase
FT regulator DWORF"
FT /id="PRO_0000435803"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 34 AA; 3815 MW; BC5F9BC7E8AA6F7A CRC64;
MAEKESTSPH LIVPILLLVG WIVGCIIVIY IVFF
