Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule.
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A targeted yeast two-hybrid study identified the TPR-containing MegBP as an LRP2/megalin-associated scaffold and mapped binding to a proline-rich region near the N terminus of the receptor tail.
"Using yeast two-hybrid screens, we identified a novel
scaffold protein with tetratrico peptide repeats, the megalin-binding protein
(MegBP) that associates with the receptor. The binding site of MegBP was mapped
to an N-terminal region on the receptor tail harboring a proline-rich peptide
element."
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MegBP association did not inhibit megalin endocytosis in the reported assay, whereas MegBP overexpression caused cellular lethality.
"MegBP binding did not block the endocytic activity of the receptor;
however, overexpression resulted in cellular lethality."
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Additional screens recovered transcriptional regulators as candidate MegBP partners, motivating—but not establishing—a model connecting the megalin tail to transcriptional regulation.
"MegBP-interacting partners included several transcriptional
regulators such as the SKI-interacting protein (SKIP), a co-activator of the
vitamin D receptor. These finding suggest a model whereby megalin directly
participates in transcriptional regulation through controlled sequestration or
release of transcription factors via MegBP."
Architecture of the human interactome defines protein communities and disease networks.
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BioPlex 2.0 reports candidate protein co-associations from affinity-purification mass spectrometry rather than necessarily direct binary interactions.
"With more than 56,000 candidate interactions"
A reference map of the human binary protein interactome.
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HuRI interactions arose from repeated proteome-scale yeast two-hybrid screening with pairwise retesting and sequence confirmation.
"To map the reference interactome, we performed nine screens of Space III, followed by pairwise verification by quadruplicate retesting and sequence confirmation."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 and a second HCT116 network were designed as cell-line-specific AP-MS interaction maps, so individual associations remain context-dependent candidates.
"The first, BioPlex 3.0, results from affinity purification"
UniProtKB/Swiss-Prot record for human LRP2BP (Q9P2M1)
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The reviewed human record treats LRP2BP as a candidate adapter for LRP2 and records a direct LRP2 interaction from PMID:12508107.
"CC -!- FUNCTION: May act as an adapter that regulates LRP2 function.
CC -!- SUBUNIT: Interacts with LRP2. {ECO:0000269|PubMed:12508107}."
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Human LRP2BP is recorded in the cytoplasm with vesicular staining near the plasma membrane and throughout the cytoplasm.
"CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12508107}.
CC Note=Detected in a vesicular staining pattern close to the plasma
CC membrane and throughout the cytoplasm."
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The reviewed record contains two named splice isoforms; isoform 2 differs by the small VSP_030664 insertion at residue 35.
"CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P2M1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P2M1-2; Sequence=VSP_030664;"
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The 347-residue canonical protein contains one annotated TPR followed by six annotated Sel1-like repeats.
"FT REPEAT 59..92
FT /note="TPR"
FT REPEAT 93..125
FT /note="Sel1-like 1"
FT REPEAT 133..168
FT /note="Sel1-like 2"
FT REPEAT 173..206
FT /note="Sel1-like 3"
FT REPEAT 207..242
FT /note="Sel1-like 4"
FT REPEAT 243..277
FT /note="Sel1-like 5"
FT REPEAT 297..332
FT /note="Sel1-like 6""
PANTHER PTHR44554 LRP2-binding protein family entries
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The fetched PANTHER member table places human LRP2BP in the LRP2-binding protein subfamily PTHR44554:SF1.
"Q9P2M1,LRP2-binding protein,protein,9606,Homo sapiens,Homo sapiens (Human),LRP2BP,347,PTHR44554:SF1,LRP2-BINDING PROTEIN,True"
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Mouse Lrp2bp is assigned to the same PTHR44554:SF1 subfamily, supporting an exact vertebrate orthology boundary rather than paralog transfer.
"Q9D4C6,LRP2-binding protein,protein,10090,Mus musculus,Mus musculus (Mouse),Lrp2bp,346,PTHR44554:SF1,LRP2-BINDING PROTEIN,True"