STRIT1 encodes DWORF (dwarf open reading frame), a 35-residue tail-anchored transmembrane micropeptide translated from a muscle-specific transcript formerly annotated as a long noncoding RNA. It resides in the sarcoplasmic reticulum membrane of cardiac and slow-twitch skeletal muscle, where its single C-terminal helix binds the SERCA Ca2+-ATPase at the same transmembrane groove used by the inhibitory regulins phospholamban, sarcolipin and myoregulin. DWORF displaces these inhibitors and, in studies with the human peptide, also raises SERCA activity directly, increasing the apparent Ca2+ affinity and turnover of the pump. The result is faster Ca2+ reuptake into the sarcoplasmic reticulum, larger SR Ca2+ stores and faster muscle relaxation. DWORF binds preferentially to the Ca2+-bound, phosphorylated conformations of SERCA and forms homo- and hetero-oligomers with the other regulins. Loss of Dworf in mouse slows relaxation of slow-twitch muscle, and its overexpression protects mouse hearts in models of dilated cardiomyopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:A6NM10-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:J3KQ12) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:O15529) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:O15552) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:O95279) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:O95436-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:O95858) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P11912) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P16157-17) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P19397) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P32856-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P38484) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:P48051) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q07108) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q13113) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q13323) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q13336-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q13520) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q14802-3) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q15800) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q16623) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q16653-13) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q3SXY8) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q68DC2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q6UXB8) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q6UXK2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q6ZMD2-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q7KYR7-4) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q7Z5P4) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q8NBJ4) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q8NBQ5) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q8TAZ6) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q96CE8) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q96IK0) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q96Q45-2) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9BZJ8) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9GZY8-5) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9H2H9) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9H2K0) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9HAV5) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9HDC5) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9NQQ7-3) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9NW97) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9NY72) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary yeast two-hybrid hit (UniProtKB:Q9Y624) from the HuRI human reference interactome; bare protein binding carries no functional information. Reason: Generic protein binding is uninformative and no more specific molecular function can be derived from a high-throughput Y2H pair, so the row is removed rather than rewritten. None of the 45 HuRI partners of DWORF is a SERCA pump or a regulin (PLN, SLN, MRLN), the only partners with functional support; nearly all are unrelated membrane proteins (aquaporins, tetraspanins, SLC transporters, GPCRs, syntaxins), the pattern expected when a single hydrophobic transmembrane helix is expressed in a yeast nuclear assay. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:32296183 Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs. |
| GO:0008047 enzyme activator activity | ISS GO_REF:0000024 | MODIFY | Summary: DWORF increases SERCA Ca-ATPase activity (displacing PLN/SLN/MRLN and, per human-sequence studies, also activating SERCA directly). The activity is correct but the term is too general. Reason: The ISS transfer from mouse Dworf (P0DN83) is sound, and human DWORF itself has direct experimental support: human DWORF raises the apparent Ca affinity of human SERCA2a in HEK293 homogenates, P15/W22 are needed (PMID:33581112), and purified recombinant human DWORF raises the turnover of reconstituted SERCA1a (PMID:34075877). The target, SERCA, is a P-type ATPase and a transporter, so the matched specific terms are ATPase activator activity (GO:0001671) and transporter activator activity (GO:0141109). Comparator check: human PLN, the inhibitory regulin, carries the mirror terms ATPase inhibitor activity (GO:0042030) and transporter inhibitor activity (GO:0141110) by IDA, and the mouse Pln GO-CAM (62f58d8800005094) uses ATPase inhibitor activity. Whether DWORF activates directly or only by relieving inhibition is disputed (PMID:26816378, PMID:30299255 vs PMID:33581112, PMID:34075877), but either way the net molecular effect is increased pump activity. Proposed replacements: ATPase activator activity transporter activator activity Supporting Evidence: PMID:33581112 gene was similarly fused to the N terminus of the human DWORF or PLB gene PMID:33581112 We observed that DWORF activates SERCA2a directly, in the absence of PLB, by enhancing the Ca-ATPase apparent calcium affinity PMID:33581112 In our model, DWORF binds to SERCA2a, displacing PLB, and activates SERCA via two distinct mechanisms: (a) DWORF displaces the inhibitory PLB and (b) DWORF activates SERCA directly, above the level of SERCA in the absence of both DWORF and PLB. PMID:34075877 Recombinant human DWORF was expressed as a maltose-binding protein (MBP) fusion with a TEV cleavage site for removal of MBP. PMID:34075877 Here, we show that DWORF is a direct activator of SERCA, increasing its turnover rate in the absence of phospholamban. PMID:26816378 Based on gain- and loss-of-function studies, our results demonstrate that DWORF enhances SR Ca2+ uptake and myocyte contractility through its displacement of the inhibitory peptides PLN, SLN, and MLN from SERCA (Fig. 4C). |
| GO:0031449 regulation of slow-twitch skeletal muscle fiber contraction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Mouse Dworf knockout soleus relaxes more slowly after tetanic stimulation; this is a downstream physiological consequence of reduced SERCA activity in slow-twitch fibres. Reason: The evidence (mouse KO; PMID:26816378) supports a role in slow-twitch fibre relaxation, and DWORF is enriched in slow-twitch muscle. The effect is modest (only post-tetanic relaxation was altered, peak force unchanged) and follows from the core activity on SERCA, so it is retained as a non-core physiological process. This InterPro2GO mapping (IPR044529 DWORF family) is appropriate for the family. Supporting Evidence: PMID:26816378 however, at tetanus-inducing frequencies, relaxation rates were significantly slowed in Dworf KO muscles after tetanus (Fig. 3F). PMID:26816378 Analysis of homogenates from the soleus muscle of Dworf KO mice revealed a decreased apparent affinity of SERCA for Ca2+ as compared with homogenates from WT muscles (Fig. 4B and table S3). |
| GO:0031449 regulation of slow-twitch skeletal muscle fiber contraction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Dworf knockout soleus relaxes more slowly after tetanic stimulation; this is a downstream physiological consequence of reduced SERCA activity in slow-twitch fibres. Reason: The evidence (mouse KO; PMID:26816378) supports a role in slow-twitch fibre relaxation, and DWORF is enriched in slow-twitch muscle. The effect is modest (only post-tetanic relaxation was altered, peak force unchanged) and follows from the core activity on SERCA, so it is retained as a non-core physiological process. ISS transfer from mouse is reasonable. Supporting Evidence: PMID:26816378 however, at tetanus-inducing frequencies, relaxation rates were significantly slowed in Dworf KO muscles after tetanus (Fig. 3F). PMID:26816378 Analysis of homogenates from the soleus muscle of Dworf KO mice revealed a decreased apparent affinity of SERCA for Ca2+ as compared with homogenates from WT muscles (Fig. 4B and table S3). |
| GO:0033017 sarcoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: DWORF is a tail-anchored single-pass membrane peptide of the sarcoplasmic reticulum, where it colocalizes with SERCA. Reason: Mouse GFP-DWORF shows SR striations in skeletal muscle fibres (PMID:26816378); human DWORF has a single C-terminal transmembrane helix and functions on SERCA in ER/SR membranes. Human expression is muscle-restricted, so SR membrane is the appropriate location. Supporting Evidence: PMID:26816378 GFP-DWORF localizes in an alternating pattern with myosin (Fig. 2A), a distribution consistent with the location of the SR. PMID:28436536 phospholamban, sarcolipin, myoregulin and DWORF are expressed in the membrane of the sarcoplasmic reticulum of muscle cells, where they regulate the sarco/endoplasmic reticulum Ca 2+ βATPase (SERCA). |
| GO:0033017 sarcoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: DWORF is a tail-anchored single-pass membrane peptide of the sarcoplasmic reticulum, where it colocalizes with SERCA. Reason: Mouse GFP-DWORF shows SR striations in skeletal muscle fibres (PMID:26816378); human DWORF has a single C-terminal transmembrane helix and functions on SERCA in ER/SR membranes. Human expression is muscle-restricted, so SR membrane is the appropriate location. Supporting Evidence: PMID:26816378 GFP-DWORF localizes in an alternating pattern with myosin (Fig. 2A), a distribution consistent with the location of the SR. PMID:28436536 phospholamban, sarcolipin, myoregulin and DWORF are expressed in the membrane of the sarcoplasmic reticulum of muscle cells, where they regulate the sarco/endoplasmic reticulum Ca 2+ βATPase (SERCA). |
| GO:1901894 regulation of ATPase-coupled calcium transmembrane transporter activity | ISS GO_REF:0000024 | MODIFY | Summary: DWORF increases SERCA Ca2+-ATPase activity; the direction of regulation is known, so the positive-regulation child is more informative. Reason: Mouse (PMID:26816378) and human-sequence (PMID:33581112, PMID:34075877) studies all report that DWORF increases, never decreases, SERCA activity (by raising apparent Ca2+ affinity or turnover). The positive child GO:1901896 is therefore preferred; mouse Dworf already carries it by IMP. Proposed replacements: positive regulation of ATPase-coupled calcium transmembrane transporter activity Supporting Evidence: PMID:33581112 We observed that DWORF activates SERCA2a directly, in the absence of PLB, by enhancing the Ca-ATPase apparent calcium affinity PMID:34075877 Here, we show that DWORF is a direct activator of SERCA, increasing its turnover rate in the absence of phospholamban. PMID:26816378 Analysis of homogenates from the soleus muscle of Dworf KO mice revealed a decreased apparent affinity of SERCA for Ca2+ as compared with homogenates from WT muscles (Fig. 4B and table S3). |
| GO:1902082 positive regulation of calcium ion import into sarcoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: DWORF enhances Ca2+ uptake into the SR by activating SERCA; this is the core process. Reason: Cardiomyocytes overexpressing DWORF show faster cytosolic Ca2+ decay and higher SR Ca2+ load, and DWORF KO muscle shows reduced SERCA Ca2+ affinity (PMID:26816378). Human DWORF accelerates SERCA2a-dependent Ca2+ uptake in cell assays (PMID:33581112, PMID:34075877). DWORF does the regulatory work of the process directly through binding the pump. Supporting Evidence: PMID:26816378 Based on gain- and loss-of-function studies, our results demonstrate that DWORF enhances SR Ca2+ uptake and myocyte contractility through its displacement of the inhibitory peptides PLN, SLN, and MLN from SERCA (Fig. 4C). PMID:26816378 The pacing-induced Ca2+ transient decay rate was significantly enhanced in the Tg myocytes of both Ξ±MHC-DWORF Tg lines (Fig. 3E and fig. S12), which suggested that SERCA is more active in these cells (i.e., has a lower tau value). PMID:33581112 We observed that DWORF activates SERCA2a directly, in the absence of PLB, by enhancing the Ca-ATPase apparent calcium affinity |
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Download this section (compressed HTML)Q: Does DWORF activate SERCA directly, or only by displacing phospholamban/sarcolipin/myoregulin? The Olson lab (mouse peptide; PMID:26816378, PMID:30299255) saw no effect without inhibitor, while studies using human DWORF (PMID:33581112, PMID:34075877) report direct activation. Is the discrepancy due to species sequence, expression ratio or assay?
Q: Should human STRIT1 receive direct (IDA) GO annotations from PMID:33581112 and PMID:34075877, which used the human peptide? At present every human functional row is an ISS transfer from mouse.
Q: What are the endogenous DWORF protein levels in human heart and slow skeletal muscle, and are they reduced in human heart failure as the mRNA is?
Experiment: Co-reconstitute purified human DWORF with human SERCA2a in proteoliposomes at defined lipid-to-protein ratios, with and without PLN, and measure Ca2+-dependent ATPase activity and Ca2+ transport; include P15A/W22A mutants as negative controls.
Hypothesis: Human DWORF directly increases SERCA2a turnover independent of phospholamban.
Type: in vitro reconstitution enzyme assay
Experiment: Knock out or knock down STRIT1 in human iPSC-derived ventricular cardiomyocytes and measure Ca2+ transient decay, SR Ca2+ load (caffeine) and oxalate-supported SERCA Ca2+ uptake, with a human-DWORF-specific antibody to confirm loss of protein.
Hypothesis: Endogenous DWORF contributes to SR Ca2+ reuptake in human cardiomyocytes.
Type: loss-of-function in human cells
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