Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
FAM20C phosphorylates FAM20C substrates
Comparative Proteomics Reveals Important Viral-Host Interactions in HCV-Infected Human Liver Cells.
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An affinity purification of HCV envelope glycoprotein E2 complexes from infected human hepatoma cells recovered 85 cellular proteins, of which alpha-fetoprotein was one of three taken forward and confirmed as an E2 binding partner.
"were further validated as novel E2 binding partners"
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The confirmation was a co-immunoprecipitation between two over-expressed proteins in 293T cells, which is weaker evidence than an assay with purified components; the paper's functional follow-up was on UGT1, not on alpha-fetoprotein.
"To this end, we subcloned AFP, UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), and Cdc2 in a Flag-tagged expression plasmid and co-transfected with a HCV E2 expression plasmid into 293T cells."
A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer.
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The alpha-fetoprotein-glypican-3 interaction was validated outside the mass-spectrometry screen using purified proteins with a negative control, so it is not a screen artefact.
"The results show that AFP pulls down GPC3, but not MUC16, a control protein"
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Binding is to the glypican-3 core protein rather than to its heparan sulfate chains, because a glypican-3 mutant lacking those chains still precipitates alpha-fetoprotein. This is why a proteoglycan-binding term would misdescribe the interaction.
"suggesting that the GPC3 core protein might bind AFP"
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The authors state the core-protein conclusion directly.
"Our results indicate that the core protein of GPC3 is involved in binding with AFP."
Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites.
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The first structure of human alpha-fetoprotein resolves four bound fatty acids and a metal-ion site formed by three histidines and an aspartate.
"We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280."
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The bound lipids were identified chemically rather than inferred from density shape, with palmitate the dominant species at 57.42 per cent of total fatty acid.
"it was identified that palmitic acid (C16:0) was the most abundant FA bound to AFP"
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The four fatty acid sites map to defined subdomains of the albumin fold.
"These FA binding sites are located in AFP substructures IIA, IIA/IIB, IIIA, and IIIB, respectively"
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The metal was acquired by the protein from its growth environment rather than added by the experimenters, which argues the site is occupied under ordinary conditions.
"the presence of metal ions was not intentionally introduced during the protein extraction process"
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The identity of the bound metal is modelled as zinc but the authors record a caveat that the density may average over more than one metal species.
"This could be due to the presence of multiple metal ions at this binding site, and the metal ion density being obtained through an averaging algorithm"
Copper(II)-binding ability of human alpha-fetoprotein.
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Alpha-fetoprotein purified from human umbilical cord serum and from hepatoma ascites binds one copper(II) ion per molecule above pH 6.
"Alpha-fetoprotein bound 1 mol of copper(II) ion per mol of protein above pH 6.0"
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The site was mapped chemically to histidine, by loss of binding on selective photooxidation of histidyl residues.
"Photooxidation of alpha-fetoprotein in the presence of methylene blue resulted in the loss of the copper(II)-binding ability of the protein in parallel with the destruction of the histidyl residues."
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The activity was reconstituted from a synthetic peptide corresponding to the protein's amino terminus, localising the site to that region.
"A synthetic amino-terminal undecapeptide of alpha-fetoprotein also bound copper(II) ion."
alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability.
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Alpha-fetoprotein from human cord serum and from hepatoma ascites binds bilirubin at 1:1 stoichiometry with sub-micromolar dissociation constants, measured by two independent methods.
"1 mol of each alpha-fetoprotein bound 1 mol of bilirubin at pH 8.3"
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The affinities were determined as dissociation constants in the 10^-7 M range for both fetal and tumour-derived protein.
"the dissociation constants of the complexes of bilirubin with fetal alpha-fetoprotein and hepatoma-derived alpha-fetoprotein were 2.6 x 10(-7) and 5.0 x 10(-7) M, respectively"
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The authors draw the carrier conclusion explicitly, by analogy with serum albumin.
"These results indicate that alpha-fetoprotein may function as a carrier protein for bilirubin as has been shown for serum albumin."
Congenital deficiency of alpha feto-protein.
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Individuals homozygous for a frameshift null allele of AFP are healthy, which places a hard ceiling on how essential any biological process annotated to this gene can be.
"The affected individuals were asymptomatic and presented normal development."
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The authors state the dispensability conclusion for development and male reproduction.
"deficiency of AFP is compatible with human normal fetal development and further reproduction in males"
A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome.
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A second, independent null allele of AFP again produced normal fetal development and birth, so the first report is not an isolated observation.
"Despite this, fetal development and birth were normal."
AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway.
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Alpha-fetoprotein and HuR were seen to colocalise in the cytoplasm of hepatoma cell lines, which is human evidence for an intracellular pool independent of the mouse orthologue transfer that GOA actually records.
"partial colocalization of AFP and HuR was observed in the cytoplasm of HuH7 and HepG2 cells"
Expression of serum albumin and of alphafetoprotein in murine normal and neoplastic primitive embryonic structures.
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In this study alpha-fetoprotein protein was not detected by immunostaining in the embryos examined; the positive protein signal was serum albumin.
"antibodies to SA gave a positive reaction in embryos of 7 days, while AFP was not detected during this period"
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In the teratocarcinomas likewise only serum albumin protein was visible by immunostaining, with alpha-fetoprotein detected as mRNA only.
"Only SA protein was detectable by immunostaining."
Production of human serum albumin by sugar starvation induced promoter and rice cell culture.
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The starvation-inducibility in this study is a property of the rice alpha-amylase 3 promoter used to drive expression; human serum albumin is the recombinant cargo protein.
"Mature form of HSA was expressed under the control of the sucrose starvation-inducible rice alpha Amy3 promoter"
Albumin prevents mitochondrial depolarization and apoptosis elicited by endoplasmic reticulum calcium depletion of neuroblastoma cells.
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Albumin was applied as a culture-medium supplement at 29-49 mg/ml and the stimulus was pharmacological release of endoplasmic reticulum calcium, not a change in nutrient levels.
"In serum-free medium, albumin (29 or 49 mg/ml) fully prevented the apoptotic effects of dotarizine, flunarizine and cyclopiazonic acid."
Recovery of rat growth and lipid profiles in adult rats subjected to fetal protein malnutrition with a fructose-rich diet.
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Serum albumin concentration was used as a readout of nutritional status; the protein is the thing being measured, not an agent participating in the response.
"there was a restoration of serum glucose, total protein, and albumin concentrations, which were reduced by fetal malnutrition"
Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility.
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The mouse knockout phenotype is sex-limited - null males are normal and fertile, null females are infertile through hypothalamic-pituitary dysfunction.
"Whereas mutant homozygous adult males are viable and fertile, AFP null females are infertile."
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The authors attribute the phenotype specifically to estrogen binding, which is the property that distinguishes rodent from human alpha-fetoprotein and the reason this phenotype must not be transferred to the human gene.
"It is most likely that AFP acts by virtue of its capacity to bind estrogen, because the infertility phenotype of the Afp knockout mice resembles that of female animals exposed perinatally to estrogens"
Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens.
A single kinase generates the majority of the secreted phosphoproteome.
UniProt entry P02771 (FETA_HUMAN), alpha-fetoprotein
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UniProt assigns the protein to the albumin family, which is the basis of the PANTHER PTHR11385 placement and of every phylogenetic inference on this gene.
"Belongs to the ALB/AFP/VDB family."
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The subcellular location is secreted, which is what makes the cytosolic and nuclear partners from high-throughput screens topologically implausible.
"SUBCELLULAR LOCATION: Secreted."
Affinage mechanistic annotation for AFP (human)