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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways.
-
Human LRP12 belongs to the LDL receptor-related family, but family membership alone does not establish LDL-particle binding or uptake.
"These results strongly suggested that ST7 was
also a novel member of the low-density lipoprotein receptor superfamily."
-
The LRP12 cytoplasmic tail interacted in yeast two-hybrid assays with RACK1, NMRK2/MIBP, and ZFYVE9/SARA.
"Use of the yeast two-hybrid
system to identify proteins that associate with ST7's cytoplasmic domain
revealed that this domain interacts with three proteins involved in signal
transduction and/or endocytosis, viz., receptor for activated protein C kinase 1
(RACK1), muscle integrin binding protein (MIBP), and SMAD anchor for receptor
activation (SARA), suggesting that ST7, like other proteins in the LDLR
superfamily, functions in these two pathways."
-
The accessible record reports endocytic and signaling motifs, not a direct cargo-internalization assay.
"Our results indicate that ST7 is a member of a subfamily of the
LDLR superfamily and that its cytoplasmic domain contains several motifs
implicated in endocytosis and signal transduction."
LRP12 silencing during brain development results in cortical dyslamination and seizure sensitization.
-
Lrp12 knockdown impaired neuronal arborization in primary mouse neurons.
"In vitro
knockdown of LRP12 in primary neurons results in impaired neuronal arborization."
-
In utero cortical Lrp12 silencing in mice caused upper-layer neuron malpositioning and cortical dyslamination.
"In vivo ablation of LRP12 by intraventricularly in utero electroporated shRNAs
elicits cortical maldevelopment, i.e. aberrant lamination by malpositioning of
upper cortical layer neurons."
Cloning and characterization of a novel gene encoding a putative transmembrane protein with altered expression in some human transformed and tumor-derived cell lines.
-
The cloned human LRP12/ST7 product is an 859-residue putative single-pass membrane protein with extracellular LDLR-like repeats and a long cytoplasmic region.
"Molecular cloning of a near full-length cDNA revealed that the novel gene
encodes a putative transmembrane protein composed of 859 amino acids: the 492
N-terminal amino acids including a fivefold cysteine-rich repeat of 40 amino
acids homologous to the ligand binding repeat of the known low density
lipoprotein receptor, a 24 hydrophobic amino acid stretch spanning the plasma
membrane, and a C-terminal domain of 343 residues."
-
The original tumor study established differential expression, not a direct tumor-suppressor or growth-regulatory mechanism.
"These studies
are a first step in characterizing a novel putative receptor protein, whose
expression is downregulated in some malignantly transformed cells, and which may
play an important role in the transformation process of these cells."
LRP12 is an endogenous transmembrane inactivator of α4 integrins.
-
Lrp12 directly binds the α4-integrin cytoplasmic tail and interferes with talin engagement, maintaining the integrin in an inactive state.
"The LRP12 cytoplasmic domain directly binds to the
integrin α4 cytoplasmic tail and inhibits talin binding to the β subunit, thus
keeping integrin inactive."
-
Lrp12 controls leading-edge nascent-adhesion turnover and restrains cell migration.
"In migrating cells, LRP12-α4 interaction induces
nascent adhesion (NA) turnover at the leading-edge protrusion. Knockdown of
LRP12 leads to increased NAs and enhanced cell migration."
Lrp12/Mig13a reveals changing patterns of preplate neuronal polarity during corticogenesis that are absent in reeler mutant mice.
-
In mouse, an Lrp12/Mig13a-expressing preplate-neuron subset undergoes tangential migration and pioneers anterior-commissure projections.
"Lrp12/Mig13a, a mammalian gene
related to the Caenorhabditis elegans neuroblast migration gene mig-13, is
expressed in a subpopulation of preplate neurons that undergo ventrally directed
tangential migrations in the preplate layer and pioneer axon projections to the
anterior commissure."
-
The reporter study describes Lrp12-positive cell behavior and Reelin-dependent patterning; it does not by itself establish an Lrp12 receptor mechanism.
"These changes in
neuronal polarity do not occur in reeler mutant mice, revealing the earliest
known defect in reeler cortical patterning and suggesting that the alignment of
preplate neurons into a pseudolayer facilitates the movement of later-born
radially migrating neurons into the emerging cortical plate."
Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance.
-
LRP12 promoter methylation correlated inversely with expression and predicted carboplatin response in NSCLC cohorts.
"This
analysis led to the identification of a promoter CpG island methylation of LDL
receptor-related protein 12 (LRP12) associated with increased resistance to
carboplatin. Validation in an independent patient cohort (n = 35) confirmed that
LRP12 methylation status is predictive for therapeutic response of NSCLC
patients to platin therapy with a sensitivity of 80% and a specificity of 84%
(p < 0.01)."
LRP12 promotes gastric cancer progression through AKT/mTOR signaling and M2 macrophage-mediated immunosuppression.
-
In gastric-cancer models, LRP12 perturbation altered proliferation and invasion, and knockdown reduced xenograft growth.
"Functional studies using
both overexpression and knockdown showed that LRP12 promotes GC cell
proliferation and invasion, while xenografts of LRP12-knockdown cells exhibited
reduced tumor growth."
-
LRP12 overexpression increased AKT and mTOR phosphorylation in the tested gastric-cancer context.
"Mechanistically, LRP12 overexpression activated the
AKT/mTOR pathway, reflected by increased phosphorylation of AKT and mTOR."
Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease.
-
A noncoding CGG-repeat expansion in LRP12 was identified as the cause of oculopharyngodistal myopathy 1.
"we identified similar noncoding CGG repeat expansions in two
other diseases: oculopharyngeal myopathy with leukoencephalopathy and
oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively."
CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.
-
LRP12 CGG expansions of 61-100 repeats were found in ALS, whereas most LRP12-OPDM expansions contained 100-200 repeats.
"We identify CGG
repeat expansion in LRP12 in five families and two simplex individuals. These
ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM
individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200
repeats."
-
Expanded-repeat disease showed RNA foci and phenotype-dependent Muscleblind-like 1 aggregation.
"RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS
than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM
muscle."
-
Repeat length determines whether the LRP12 expansion presents predominantly as ALS or OPDM.
"In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM,
depending on the length of the repeat. Our findings provide insight into the
repeat length-dependent switching of phenotypes."
UniProtKB reviewed entry for human low-density lipoprotein receptor-related protein 12
-
The reviewed human canonical entry is an 859-residue type-I single-pass membrane protein with extracellular residues 33-492 and a cytoplasmic tail spanning residues 514-859.
"FT TOPO_DOM 33..492
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 493..513
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 514..859
FT /note="Cytoplasmic""
-
UniProt curates two named isoforms; isoform 2 lacks residues 27-45 of the canonical sequence.
"CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y561-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y561-2; Sequence=VSP_040992;"
-
The record has an AlphaFold prediction but no experimental PDB cross-reference.
"DR AlphaFoldDB; Q9Y561; -."
-
OPDM1 is caused by a heterozygous CGG expansion in the LRP12 5-prime untranslated region, usually exceeding 100 repeats.
"CC disease is caused by variants affecting the gene represented in this
CC entry. The causative mutation is a heterozygous trinucleotide repeat
CC expansion (CGG) in the 5-prime untranslated region of the gene
CC (PubMed:31332380, PubMed:37339631). The number of repeats in OPDM1
CC patients is usually greater than 100 (PubMed:37339631)."
-
ALS28 is caused by a heterozygous LRP12 5-prime-UTR CGG expansion of 61-100 repeats.
"CC disease is caused by variants affecting the gene represented in this
CC entry. The causative mutation is a heterozygous trinucleotide repeat
CC expansion (CGG) in the 5-prime untranslated region of the gene. The
CC number of repeats in ALS28 patients is between 61 and 100."