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
Molecular and phylogenetic characterization of a novel putative membrane transporter (SLC10A7), conserved in vertebrates and bacteria.
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SLC10A7 was detected in the plasma membrane when expressed in Xenopus oocytes and HEK293 cells, but transported neither bile acids nor steroid sulfates, so the protein is not a bile acid carrier and its substrate was left unidentified.
"When expressed in Xenopus laevis oocytes and HEK293 cells, SLC10A7 was detected in the plasma membrane but revealed no transport activity for bile acids and steroid sulfates."
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SLC10A7 has a ten-transmembrane topology with intracellular N- and C-termini, unlike the seven-transmembrane architecture of the other SLC10 members.
"By immunofluorescence analysis of dual hemagglutinin (HA)- and FLAG-labeled SLC10A7 proteins in HEK293 cells, we established a topology of 10 transmembrane domains with an intracellular cis orientation of the N-terminal and C-terminal ends."
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Unlike the other SLC10 members, which are restricted to vertebrates, SLC10A7 has relatives in yeasts, plants and bacteria.
"SLC10A7-related proteins exist also in yeasts, plants, and bacteria, making SLC10A7 taxonomically the most widespread member of this carrier family."
Homo- and hetero-dimeric architecture of the human liver Na⁺-dependent taurocholate co-transporting protein.
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NTCP forms heteromeric complexes with SLC10A4 and SLC10A6 but does not co-localize with SLC10A7, consistent with SLC10A7 being the divergent family member with a different compartment.
"NTCP co-localized in U2OS cells with SLC10A4 and SLC10A6, but not with SLC10A3, SLC10A5 or SLC10A7."
Architecture of the human interactome defines protein communities and disease networks.
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Proteome-scale AP-MS survey (BioPlex 2.0) from which the IntAct SLC10A7-DPY19L4 interaction derives; the study makes no gene-specific claim about SLC10A7.
"Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome"
Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation.
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The human protein localizes to the Golgi, in contrast to its yeast ortholog.
"In contrast to yeast, human SLC10A7 localized to the Golgi."
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Patient fibroblasts mislocalize glycoproteins and fail to transport them from the Golgi to the cell membrane.
"Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane."
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Patients present with amelogenesis imperfecta, skeletal dysplasia and decreased bone mineral density.
"The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis."
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SLC10A7-deficient zebrafish show strongly reduced bone mineralization.
"Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization."
SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects.
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Homozygous SLC10A7 mutations in six individuals cause skeletal dysplasia with multiple dislocations and amelogenesis imperfecta; the Slc10a7 knockout mouse recapitulates the phenotype.
"We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype."
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Heparan sulfate is reduced about two-fold in patient fibroblasts and about 2.5-fold in knockout mouse cartilage, while chain length and sulfation pattern are unchanged, so the deficit is in the number of chains.
"indicating that HS decrease in Slc10a7−/− is mostly related to the number of HS chains, rather than to their sulfation and length."
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Loss of SLC10A7 increases calcium influx into patient fibroblasts, identifying the wild-type protein as a negative regulator of calcium entry.
"After addition of extracellular CaCl2, SLC10A7-deficient patient fibroblasts showed a significantly increased Ca2+ influx compared with control fibroblasts"
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The authors place the calcium defect upstream of the glycosaminoglycan and glycosylation defects, i.e. SLC10A7's contribution to glycosaminoglycan synthesis is indirect.
"This deregulation of Ca2+ homoeostasis due to SLC10A7 deficiency is most likely responsible for defects in GAG synthesis and glycosylation."
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The transported substrate of SLC10A7 remains unidentified.
"SLC10A7 is a 10-transmembrane-domain transporter located at the plasma membrane, with a yet unidentified substrate14."
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The plasma-membrane localization asserted in this paper rests on punctate anti-myc staining of an over-expressed tagged construct in transfected HEK293F cells.
"C-myc immunolabelling demonstrated a uniform punctate staining following transfection with wild-type SLC10A7, consistent with a cell membrane localization."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
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BioPlex 3.0 AP-MS network in which the SLC10A7-DPY19L4 interaction was re-detected; the study makes no gene-specific claim about SLC10A7.
"The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins."
The solute carrier superfamily interactome.
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Systematic AP-MS mapping of the interactomes of 396 human solute carriers, including SLC10A7, in HEK293 cells; the paper discusses other family members but makes no gene-specific claim about SLC10A7.
"We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics."
SLC10A7 sodium-site conservation against the ligand-bound NTCP cryo-EM structures
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Only 3 of the 12 NTCP sodium-contacting positions are conserved in SLC10A7, with four non-conservative substitutions including E257 to phenylalanine and N106 to alanine, while SLC10A1, SLC10A2, SLC10A6 and even the orphan SLC10A4 all retain the site. The SLC10 fold is retained (TM-score 0.766) but the ion-binding chemistry is not.
"SLC10A7 is the only human family member whose sodium site is not conserved."
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SLC10A7 also loses all three polar anchors of the NTCP bile-salt pocket (N103 to V118, N262 to T268, Q264 to A270), whereas SLC10A4 keeps all three and ASBT keeps two, making SLC10A7 the only human family member to have lost both the ion site and the substrate recognition triad.
"So SLC10A7 is the only family member to have
lost both the ion site and the substrate recognition triad."
OpenScientist focused report on the SLC10A7 translocation pathway
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Focused audit found that SLC10A7 retains the SLC10/BASS transmembrane fold and an open pathway, but not the NTCP-type sodium-coordination machinery.
"The NTCP Na⁺-coordination sphere is degraded, not conserved"