UNIPROT:P02749 - FACTA Search

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Query: UNIPROT:P02749 (beta2-glycoprotein I)
836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein H (apoH, protein; APOH, gene) has been implicated as a necessary cofactor for the binding of certain autoimmune antiphospholipid antibodies to anionic phospholipids. APOH exhibits genetically determined structural polymorphism with the occurrence of four alleles. Recently three IgG1k monoclonal antibodies (mAb) to human apoH, designated 3G9, 1B4, and 3D11, have been produced. The mAb 3D11 does not recognize apoH bound to anionic phospholipids in contrast to mAb 3G9 and 1B4, which recognize free and phospholipid-bound apoH. In this investigation we have determined the reactivity of the three mAb with four APOH allele products and the binding ability of these allele products with anionic phospholipids. The mAb 3G9 and 1B4, like the polyclonal anti-apoH, were equally reactive with all four allelic products, but the 3D11 recognized only the APOH*3 allele product. In the 159 APOH*3 carriers tested from five ethnic groups, the reactivity of mAb 3D11 was observed with all the Chinese but none of the African blacks. For the U.S. whites and Polynesians 89% and 75%, respectively, of the APOH*3 allele products were recognized by 3D11, while 87% of the U.S. blacks with this allele had no 3D11 reactivity. These data show that the APOH*3 allele, originally identified as a single entity by the polyclonal anti-apoH, is heterogeneous with at least one distinct variation based on mAb 3D11 reactivity. Our data also demonstrate that the apoH from certain homozygous APOH*3 individuals is unable to bind to anionic phospholipids. Such ethnic-specific apoH variations could play a significant role in the binding properties of autoimmune antiphospholipid antibodies to anionic phospholipids.
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PMID:Heterogeneity of the apolipoprotein H*3 allele and its role in affecting the binding of apolipoprotein H (beta 2-glycoprotein I) to anionic phospholipids. 770 32

In this study, we describe a two-allelic RsaI restriction fragment length polymorphism identified by Southern blot analysis and by allele-specific polymerase chain reaction amplification for the human beta 2-glycoprotein I (beta 2-I; apolipoprotein H = APOH) gene. This polymorphism, which segregates in a co-dominant fashion, leads to a valine-leucine amino acid exchange at amino acid position 247. The allele frequency has been established in 34 unrelated parents of the Centre d'Etude du Polymorphisme Humain family panel and was found to be 0.76 for valine and 0.23 for leucine. The Val-Leu polymorphism described in this study does not correlate with the four isoelectric focusing alleles previously described, indicating that other variants are responsible for this polymorphism.
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PMID:Human beta 2-glycoprotein I: molecular analysis of DNA and amino acid polymorphism. 809 61

Apolipoprotein H (apoH, protein; APOH, gene) is considered to be an essential cofactor for the binding of certain antiphospholipid autoantibodies to anionic phospholipids. APOH exhibits a genetically determined structural polymorphism due to the presence of three common alleles (APOH*1, APOH*2 and APOH*3) detectable by isoelectric focusing (IEF) and immunoblotting. The APOH*3 allele can be further characterized into two subtypes, APOH*3w and APOH*3B, based upon its reactivity with monoclonal antibody 3D11. In this study we have determined the molecular basis of the APOH protein polymorphism and its distribution in three large U.S. population samples comprising 661 non-Hispanic whites, 444 Hispanics and 422 blacks. By direct DNA sequencing of PCR amplified fragments corresponding to the eight APOH exons, we identified two missense mutations that correspond to the APOH*1 and APOH*3w alleles. A missense mutation (G-->A) in exon 3, which alters amino acid Ser to Asn at codon 88 and creates a restriction site for TSP509 I, was present in all APOH*1 allele carriers. A second missense mutation (G-->C) at codon 316 in exon 8, which replaces amino acid Trp with Ser and creates a restriction site for BSTBI, was present in all APOH*3w carriers. The distribution of the Ser 88 Asn and Trp 316 Ser mutations was significantly different between the three racial groups. The frequency of the Asn-88 allele was 0.011, 0.043, and 0.056 in blacks. Hispanics and non-Hispanic whites, respectively. While the Ser-316 allele was observed sporadically in blacks (0.008), it was present at a polymorphic frequency in Hispanics (0.027) and non-Hispanic whites (0.059). The identification of the molecular basis of the APOH protein polymorphism will help to elucidate the structural-functional relationship of apoH in the production of antiphospholipid autoantibodies.
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PMID:Molecular basis of the apolipoprotein H (beta 2-glycoprotein I) protein polymorphism. 922 69

Apolipoprotein H (apoH, protein; APOH, gene) is a single chain glycoprotein that exists in plasma both in a free form and in combination with lipoprotein particles. ApoH has been implicated in several physiologic pathways, including lipid metabolism, coagulation, and the production of antiphospholipid antibodies. The wide range of interindividual variation in plasma apoH levels is thought to be under genetic control, but its molecular basis is unknown. APOH displays a common structural polymorphism with the occurrence of three common alleles (APOH*1, APOH*2, and APOH*3), the APOH*2 allele being the most frequent in all populations. The relationship between the APOH polymorphism and plasma apoH levels is unknown. In this study, we have determined the impact of this APOH polymorphism on apoH levels in 455 normoglycemic non-Hispanic Whites (220 men and 235 women) from the San Luis Valley, Colorado. Mean plasma apoH levels, determined by capture enzyme-linked immunosorbent assay, were 20.0 +/- 0.2 mg/dl (range: 3.4-31.2 mg/dl) with no significant difference between men and women. In women, but not in men, age had a significant effect on plasma apoH levels explaining 3.4% of its phenotypic variance. ApoH levels also correlated positively with cholesterol (P = 0.015), HDL-cholesterol (P = 0.044), and triglyceride (P = 0.037) in women, but not in men. An analysis of variance (ANOVA) of adjusted plasma apoH levels showed significant association with the APOH polymorphism in both men and women (P < 0.0001), and the APOH polymorphism accounted for 11.4% and 13.6% of the variation in apoH levels in men and women, respectively. Compared with the APOH*1 and APOH*2 alleles, the APOH*3 allele was associated with significantly lower plasma apoH levels. At the molecular level, APOH*3 can be further subdivided into two distinct forms, called APOH*3W and APOH*3B. The APOH*3W form is more common in US Whites and is the result of a missense mutation at codon 316. An ANOVA for the codon 316 polymorphism revealed that this polymorphism is a major determinant of plasma apoH variation (P < 0.0001). This study indicates that common genetic variation in the APOH gene is a significant determinant of plasma apoH levels in non-Hispanics Whites and should be useful in evaluating the role of the APOH genetic variation in various metabolic pathways in which apoH has been implicated.
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PMID:Genetic variation in the apolipoprotein H (beta2-glycoprotein I) gene affects plasma apolipoprotein H concentrations. 1048 Mar 57

Apolipoprotein H (apoH, protein; APOH, gene) is a required cofactor for the production of antiphospholipid antibodies (APA). In this study we have examined whether genetic variation in the APOH gene affects variation in risk for systemic lupus erythematosus (SLE), occurrence of antiphospholipid antibodies (APA), anti-apoH, and plasma apoH concentrations. A total of 222 white SLE women were screened for four APOH polymorphisms (codons 88, 247, 306, and 316) by polymerase chain reaction, and for plasma apoH concentrations by ELISA. Of these, 29.3% were positive for APA (APA-positive group) and 31.1% for anti-apoH. None of the four APOH polymorphisms were significantly associated with variation in risk for SLE. The codons 306 and 316 polymorphisms showed significant, gene-dosage effects on plasma apoH concentrations (P<0.0001) and explained 30% and 13%, respectively, of the residual variation in apoH concentrations. No significant association was observed between anti-apoH status and APOH polymorphisms or plasma apoH levels. However, plasma apoH concentrations were significantly higher in patients positive for APA than in patients negative for APA (18.5+/-4.0 mg/dl vs 17.1+/-3. 8 mg/dl; P=0.02). The distribution of the Trp316Ser polymorphism was significantly different between the APA-positive and APA-negative groups. The frequency of the mutant allele (Ser316) was significantly lower in the APA-positive group than the APA-negative group (3.1% vs 12.1% P<0.04), indicating that the Ser316 mutation is protective against the production of phospholipid-apoH dependent APA. Our data indicate that common genetic variation in the APOH gene is a significant determinant of plasma apoH variation in SLE patients, and the Trp316Ser polymorphism appears to provide protection against the production of APA in SLE patients.
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PMID:Genetic variation in apolipoprotein H (beta2-glycoprotein I) affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus. 1060 47

Apolipoprotein H (apoH, protein; APOH, gene) binds to negatively charged phospholipids, which triggers the production of a subset of autoantibodies against phospholipid in patients with autoimmune diseases. We have demonstrated that two naturally occurring missense mutations in the fifth domain of apoH, Trp316Ser and Cys306Gly, disrupt the binding of native apoH to phosphatidylserine [Sanghera, D. K., Wagenknecht, D. R., McIntyre, J. A. & Kamboh, M. I. (1997) Hum. Mol. Genet. 6, 311-316]. To confirm whether these are functional mutations, we mutagenized APOH cDNAs and transiently expressed them in COS-1 cells. The cardiolipin ELISA of wild-type and mutant recombinant apoH confirmed that the Gly306 and Ser316 mutations are responsible for abolishing the binding of recombinant apoH to cardiolipin. These mutations, however, had no effect on the levels of expression or secretion of recombinant apoH in transfected COS-1 cells. While the Cys306Gly mutation disrupts a disulfide bond between Cys306 and Cys281, which appears to be critical for clustering positively charged amino acids, the Trp316Ser mutation affects the integrity of an evolutionarily conserved hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp), which is hypothesized to interact with anionic phospholipid. To test this hypothesis, we exchanged the remaining three hydrophobic amino acids with neutral amino acids by site-directed mutagenesis (Leu313Gly, Ala314Ser and Phe315Ser). Binding of the Leu313Gly and Phe315Ser mutants to cardiolipin was significantly reduced to 25% and 13%, respectively, of that of the wild-type. On the other hand, the Ala314Ser mutation showed normal cardiolipin binding. Taken together with our previous findings, these results strongly suggest that the configuration of the fifth domain of apoH, as well as the integrity of the highly conserved hydrophobic amino acids at positions 313-316, is essential for the binding of apoH to anionic phospholipid.
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PMID:A hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp) in the fifth domain of apolipoprotein H (beta2-glycoprotein I) is crucial for cardiolipin binding. 1071 9

Apolipoprotein H (apoH, protein; APOH, gene) is a 50-kDa glycoprotein that binds to negatively charged substrates, including phospholipids. ApoH is a main target antigen for the binding of antiphospholipid antibodies that are associated with thrombotic events. We have previously characterized the structural organization of the human APOH gene. Because of the significant structural homology between the human and chimpanzee genomes, we have employed oligonucleotides from the human APOH gene sequence to amplify chimpanzee DNA covering the entire transcribed region together with flanking sequence in the 5' region. As in humans, the chimpanzee APOH gene consists of eight exons and seven introns and encodes for a 326-amino-acid protein. The deduced amino acid and nucleotide sequence show 99.4% and 99.6% similarity between human and chimpanzee APOH, respectively. Using isoelectric focusing (IEF) and immunoblotting, we screened 155 chimpanzees (128 unrelated captured parents and 27 captive-born offspring) for the apoH protein polymorphism. The most common IEF pattern in chimpanzees was identical to a previously described APOH*3 allele in humans. In addition, an anodally shifted pattern was observed in chimpanzees with an allele frequency of 0.168, and the corresponding allele was designated as APOH*4. DNA sequencing of APOH*4 carriers revealed a missense mutation in exon 6 (A-->G) at codon 210, which replaces the amino acid lysine by glutamic acid. This mutation does not affect the binding of apoH to cardiolipin as revealed by cardiolipin/enzyme-linked immunosorbent assay (ELISA). We also evaluated the prevalence of anti-apoH antibodies in chimpanzee plasma by using human-apoH-based ELISA and the association of the Lys210Glu mutation with the occurrence of anti-apoH antibodies. The prevalence of anti-apoH antibodies in chimpanzees (64%) was found to be unusually high compared with that found in humans. However, the Lys210Glu mutation showed no association with the occurrence of anti-apoH antibodies. The prevalence of anti-apoH antibodies in chimpanzees may serve as a useful animal model for the human antiphospholipid syndrome, where these antibodies are associated with clinical manifestations.
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PMID:Chimpanzee apolipoprotein H (beta2-glycoprotein I): report on the gene structure, a common polymorphism, and a high prevalence of antiphospholipid antibodies. 1147 37

Apolipoprotein polymorphisms are emerging as suitable markers for the study of the formation of human populations. In contrast to the data available for apolipoprotein E, the data regarding apolipoprotein H (protein, apoH; gene, APOH) variations are only beginning to accumulate. By blood plasma isoelectric focusing and immunoblotting, we analyzed the distribution of apoH phenotypes in 397 individuals (192 males; 205 females) from seven villages of an autochthonous population of the eastern Adriatic island of Krk. APOH allele frequencies were: APOH*2 = 0.877, APOH*3 = 0.098, APOH*1 = 0.025, with the majority of the sample being homozygous. No significant differences between villages were observed. When these data were compared to those of other populations studied so far, a significant association between APOH allele frequencies and latitude was observed. We hypothesize that this association reflects differences in diet composition across different climatic zones.
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PMID:Apolipoprotein H genetic variability in the population of Krk Island, Croatia. 1237 81

This study characterized the human apolipoprotein H [APOH; beta(2)-glycoprotein I (beta(2)GPI)] promoter and its variants by in vitro functional experiments and investigated their relationship with human plasma beta(2)GPI levels. We examined the individual effects of 12 APOH promoter single nucleotide polymorphisms in the 5' flanking region of APOH (approximately 1.4 kb) on luciferase activity in COS-1 cells and HepG2 cells and their impact on plasma beta(2)GPI levels in 799 American White people, the DNA binding properties of the APOH promoter using an electrophoretic mobility shift assay in HepG2 cells, the effects of serial deletion analysis of the APOH 5' flanking region in COS-1 and HepG2 cells and cross-species conservation of the APOH promoter sequence. The variant alleles of three single nucleotide polymorphisms (-1219G>A, -643T>C and -32C>A) showed significantly lower luciferase expression (51, 40 and 37%, respectively) as compared with the wild-type allele. The electrophoretic mobility shift assay demonstrated that these three variants specifically bind with protein(s) from HepG2 cell nuclear extracts. Three-site haplotype analysis (-1219G>A, -643T>C and -32C>A) revealed one haplotype carrying -32A (allele frequency = 0.075) to be significantly associated with decreased plasma beta(2)GPI levels (P < 0.001). Deletion analysis localized the core APOH promoter to approximately 160 bp upstream of ATG codon with the presence of critical cis-acting elements between -166 and -65. Cross-species conservation analysis of the APOH promoters of seven species indicated that basic promoter elements are highly conserved across species. In conclusion, we have characterized the functional promoter of APOH and identified functional variants that affect the transcriptional activity of the APOH promoter.
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PMID:Functional and genetic characterization of the promoter region of apolipoprotein H (beta2-glycoprotein I). 2008 41

Fat deposition influences both meat quality and animal productivity. However, it is not clear how fat development is regulated in growing and fattening beef cattle. This study characterized proteomic changes in subcutaneous adipose tissue from steers fed a high-grain diet in an effort to understand the molecular mechanisms of fat development during feedlot production. Eight British-Continental crossbred steers had two subcutaneous adipose tissue biopsies at 12 and 15 mo of age. Protein expression in fat samples was profiled using liquid chromatography-tandem mass spectrometry (LC-MS/MS). During the finishing period, steers increased subcutaneous adipose tissue mass with concomitant changes in the proteome profile, but the nature of these changes varied among steers. The expression of 123 out of 627 identified proteins differed (P <: 0.05) between 2 ages. Functional analyses on differentially expressed proteins revealed that 20.2% of them were associated with cellular growth and proliferation of adipose tissue. There were 17 out of 108 differentially expressed proteins associated with lipid metabolism, which were acyl-CoA synthetase medium-chain family member 1 (ACSM1), annexin A1 (ANXA1), apolipoprotein C-III (APOC3), apolipoprotein H (beta-2-glycoprotein I; APOH), EH-domain containing 1 (EHD1), coagulation factor II (thrombin; F2), gelsolin (GSN), lamin A/C (LMNA), mitogen-activated protein kinase kinase 1 (MAP2K1), myosin, heavy chain 9, non-muscle (MYH9), orosomucoid 1 (ORM1), protein disulfide isomerase family A, member 3 (PDIA3), retinol binding protein 4, plasma (RBP4), renin binding protein (RENBP), succinate dehydrogenase complex, subunit A, flavoprotein (Fp; SDHA), serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1), and serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 (SERPING1). Further analysis of the expression levels of proteins associated with lipid metabolism indicated a downregulation in the synthesis of fatty acids at the cellular level at 15 compared to 12 mo of age. These results suggest that even though adipose tissue expanded, fat anabolism was reduced in adipocytes during growth, revealing a coordinated balance between subcutaneous fat mass and the cellular abundance of lipogenic proteins to control the rate of fat deposition in growing beef cattle. The findings observed in this study expand our understanding on how proteome of bovine adipose tissue is regulated during growth, which might help the development in the future of new strategies to manipulate adiposity in beef cattle in a manner that improves meat quality and animal productivity.
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PMID:Effect of age on bovine subcutaneous fat proteome: molecular mechanisms of physiological variations during beef cattle growth. 2489 5

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