Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
A reference map of the human binary protein interactome.
STARS, a striated muscle activator of Rho signaling and serum response factor-dependent transcription.
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The founding description of the protein: a striated-muscle actin-binding protein that localises to the sarcomeric I-band and to actin filaments, activates Rho signalling events, and stimulates SRF-dependent transcription in a manner requiring its actin binding. This one paper is the experimental basis for the actin binding, actin cytoskeleton, actin cytoskeleton organization and Rho signalling annotations on the human record, all of them reaching human by transfer from the mouse ortholog.
"STARS binds to the I-band of the sarcomere and to actin filaments in transfected cells, where it activates Rho-signaling events."
Muscle-specific signaling mechanism that links actin dynamics to serum response factor.
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Establishes the mechanism: STARS activates SRF by inducing nuclear translocation of the MRTFs, the process requires RhoA and actin polymerisation, and the actin-binding domain is necessary and sufficient. Includes loss-of-function evidence, so the conclusion does not rest on overexpression alone.
"Here we show that STARS activates SRF by inducing the nuclear translocation of MRTFs."
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Knockdown of endogenous STARS reduces SRF activity in differentiated C2C12 myotubes and cardiac myocytes.
"A knockdown of endogenous STARS expression by using small interfering RNA significantly reduced SRF activity in differentiated C2C12 skeletal muscle cells and cardiac myocytes."
Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with STARS and directly bind F-actin.
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ABLIM2 and ABLIM3 were identified with STARS as bait, bind F-actin, and synergistically enhance STARS-dependent SRF activation; ABLIM knockdown blunts SRF-dependent transcription in C2C12 cells. This paper is the source of the mouse IDA and three IGI rows behind the human positive-regulation-of-transcription IBA.
"these novel ABLIM proteins strongly bind F-actin, are localized to actin stress fibers, and synergistically enhance STARS-dependent activation of SRF"
Modulation of adverse cardiac remodeling by STARS, a mediator of MEF2 signaling and SRF activity.
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Describes STARS as Z-disc localised and as activating SRF-dependent transcription by inducing nuclear translocation of MRTF-A and MRTF-B; places STARS transcription downstream of MEF2 and shows that cardiac overexpression sensitises the heart to hypertrophic stress.
"activates serum response factor-dependent (SRF-dependent) transcription by inducing nuclear translocation of the myocardin-related SRF coactivators MRTF-A and -B"
STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.
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Morpholino knockdown of zebrafish STARS disrupts cardiac chamber dimensions and contractile function, and the phenotype is rescued by co-injected SRF mRNA, placing the requirement for STARS upstream of SRF in vivo.
"Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown"
Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.
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STARS overexpression enhances C2C12 myotube differentiation, and blocking MRTF-A nuclear translocation with CCG-1423 does not abolish the effect, indicating an output that the canonical STARS-RhoA-MRTF-SRF axis does not account for.
"had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism"
Actin-binding rho activating protein (Abra) is essential for fluid shear stress-induced arteriogenesis.
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Abra is strongly upregulated by fluid shear stress in growing collateral vessels, its induction is nitric-oxide-dependent, it drives smooth muscle cell proliferation through a Rho-dependent mechanism, and targeted deletion in mice impairs arteriogenesis.
"targeted deletion of Abra in CL57BL/6 mice led to impaired arteriogenesis"
Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy.
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In human quadriceps biopsies, STARS and its downstream pathway members rise with hypertrophy-inducing resistance training and return to baseline after de-training, alongside coordinated changes in SRF target genes.
"Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy."
Striated muscle activator of Rho signalling (STARS) is reduced in ageing human skeletal muscle and targeted by miR-628-5p.
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STARS protein is lower in skeletal muscle of older than of younger humans, and miR-628-5p binds the STARS 3'UTR and downregulates it.
"we established that miR-628-5p, a miRNA regulated by age and exercise, binds to the STARS 3'UTR to directly downregulate its transcription"
Costars, a Dictyostelium protein similar to the C-terminal domain of STARS, regulates the actin cytoskeleton and motility.
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The Costars protein is 82 residues and resembles only the C-terminal region of STARS; its loss in Dictyostelium disturbs the actin cytoskeleton and motility, and the defects are rescued by the small human counterpart protein. The human counterpart of that 82-residue protein is ABRACL, not ABRA.
"The 82 amino acid Costars protein sequence appears highly conserved among diverse species, and significantly resembles the C-terminal region of the striated muscle activator of Rho signaling (STARS)"
Where does the human ABRA GO record come from, and does its one plasma-membrane call have any support?
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Fourteen of ABRA's sixteen GOA rows are transfers, and mouse Abra alone accounts for eight of them under four different identifier styles, which makes the record look better-sourced than it is. Only two rows are experimental, and neither concerns what the protein does.
"fourteen of the sixteen rows trace to two rodent proteins, and the mouse entry supplies eight of them under four different identifier styles, which makes the record look better-sourced than it is"
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The human GO:0005886 plasma membrane call has been projected back into the mouse ortholog by two separate pipelines, both citing the human accession, so a single GFP-fusion overexpression image is the sole origin of a plasma-membrane annotation in two species.
"The single human GFP-overexpression image is the sole origin of a plasma-membrane annotation in two species."
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PANTHER PTHR22739 contains four reviewed members, all named ABRA and all in subfamily SF20, so the IBA and ISS transfers carry no paralog hazard; and Pfam PF14705 is carried in human only by ABRA and by the 81-residue ABRACL, which is why Costars-domain phenotypes cannot be attributed to ABRA.
"Exactly two reviewed human proteins carry the Costars domain `PF14705`"
Affinage mechanistic annotation for ABRA (human)
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Machine-fetched Affinage record (trust gates passed, all twelve citations resolvable numeric PMIDs). Its mechanistic narrative of the STARS-RhoA-MRTF-SRF axis and of the transcriptional control of ABRA itself is accurate and matches the primary abstracts.
"It localizes to the sarcomeric Z disc/I-band, binds actin filaments, and activates Rho-GTPase signaling, which in turn drives nuclear translocation of the MRTF-A/MRTF-B co-activators to stimulate SRF-dependent transcription"