Gene Ontology annotation through association of InterPro records with GO terms
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.
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Human and C. elegans HRG-1 co-localize, bind heme and transport heme; hrg-1 knockdown in zebrafish causes erythropoietic defects rescued by worm HRG-1.
"Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1"
Heme-binding protein HRG-1 is induced by insulin-like growth factor I and associates with the vacuolar H+-ATPase to control endosomal pH and receptor trafficking.
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HRG-1 binds the V-ATPase c subunit and supports V-ATPase activity and endosomal acidification; found in endosomes and at the plasma membrane but not in LAMP1-positive lysosomes in HeLa cells.
"HRG-1 interacts with the c subunit of the V-ATPase and enhances V-ATPase activity in isolated yeast vacuoles."
Topologically conserved residues direct heme transport in HRG-1-related proteins.
HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis.
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Hrg1 is recruited to Lamp1-positive phagolysosomal membranes during erythrophagocytosis and is needed for heme-dependent responses; human P36L variant is transport-defective.
"Hrg1 was recruited to the phagolysosomal membranes specifically during phagocytosis of RBCs but not latex beads"
HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to cytosolic/extracellular pH gradient regulation by the vacuolar-H(+) ATPase.
A proteome-scale map of the human interactome network.
Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney.
Hemozoin produced by mammals confers heme tolerance.
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Slc48a1-null mice sequester heme as hemozoin in enlarged LAMP1-positive lysosomes of RES macrophages.
"These animals are heme tolerant because they sequester heme within enlarged lysosomes in the RES macrophages and form crystalline hemozoin"
A reference map of the human binary protein interactome.
Normal Iron Homeostasis Requires the Transporter SLC48A1 for Efficient Heme-Iron Recycling in Mammals.
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SLC48A1-deficient mice cannot move heme from RES phagolysosomes into the cytoplasm; hemozoin appears from postnatal day 8.
"SLC48A1-deficient mice are unable to transport heme from RES phagolysosomes into the cytoplasm."
Oligodendrocyte Slc48a1 (Hrg1) encodes a functional heme transporter required for myelin integrity.
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Hrg1 is highly expressed in myelinating oligodendrocytes; Hrg1-null mice show myelin defects and oligodendrocytes import heme.
"Together these findings indicate OL Hrg1 encodes a functional heme transporter required for myelin integrity"
UniProtKB entry Q6P1K1 (HRG1_HUMAN)