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complement C3 OKDB#: 2516
 Symbols: C3 Species: human
 Synonyms: ASP, C3a, C3b, AHUS5, ARMD9, CPAMD1, HEL-S-62p  Locus: 19p13.3 in Homo sapiens

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General Comment NCBI Summary: Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]
General function
Cellular localization
Comment Serum complement C3 has a stronger association with insulin resistance than high-sensitivity C-reactive protein in women with polycystic ovary syndrome. Yang S et al. (2011) To compare the association of complement C3 (C3) versus high-sensitivity C-reactive protein (hs-CRP) with insulin resistance (IR) in women with polycystic ovary syndrome (PCOS). Cross-sectional analysis. Clinical research center in China. One hundred thirty-three women with PCOS and 116 healthy, age-matched controls were recruited. None. One hundred one women with PCOS and 20 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as an M value. Compared with controls, women with PCOS had a lower M value and higher C3 (1.37 ± 0. 34 vs. 1.10 ± 0.22 g/L) and hs-CRP levels (1.46 ± 2.29 vs. 0.49 ± 0.88 mg/L). In women with PCOS, C3 and hs-CRP negatively correlated with M value (r = -0.61 and r = -0.47, respectively). By regression analysis, C3 was found to have a greater impact on the M value (standardized coefficient β = -0.24) than did hs-CRP (standardized coefficient β = -0.13). After adjusting for body mass index (BMI), women with PCOS in the upper quartile were 4.30 times more likely to exhibit IR compared with those in the lower quartiles, whereas hs-CRP was not a statistically significant predictor of IR in women with PCOS. Compared with hs-CRP, serum C3 might be a stronger inflammatory marker of IR in women with PCOS.//////////////////
Ovarian function Ovulation, Oocyte maturation
Comment Effects of Complement Component 3 Derivatives on Pig Oocyte Maturation, Fertilization and Early Embryo Development In Vitro. Georgiou A et al. Complement component 3 (C3) has well-established roles within immune system, but its roles outside of immune system are less characterized. The extensive presence of C3 throughout the female reproductive tract, and its temporal, and gamete-specific regulation of expression suggest a potential role for C3 in reproduction. In the present investigation, the effects of C3, C3b and iC3b on porcine oocyte maturation, fertilization and embryonic development were examined. We identified the ability of iC3b to positively influence oocyte maturation. No effects on fertilization efficiency, penetration rates, polyspermy and blastocyst formation were observed. However, C3, C3b and iC3b presence in embryo culture medium resulted in fewer total cells in test blastocysts compared to control blastocysts. The results of this study indicate a potential function for iC3b in oocyte maturation. Furthermore, it was demonstrated that the presence of either C3, C3b or iC3b has a negative influence on early embryonic development in the porcine species.
Expression regulated by LH
Comment Endocrine Society 2004 [P2-252] Involvement of Complement System in the Ovulation. Giyoun Na, Mary C Gieske, CheMyong Ko, Yongbum Koo. Sch of Biotechnology and Biomed Sci, Inje Univ, Gimhae, Republic of Korea; Clin Scis, Univ of Kentucky, Lexington, KY It is well known that the ovulation is an inflammatory-like process, which may involve the activation of complement system. Complement system is composed of various proteins that are sequentially activated by inflammatory signal resulting in the formation of membrane attack complex (MAC), which disrupts various types of cell membranes. At the site of inflammatory reaction, on the other hand, host cells produce regulators of complement systems which inhibit the MAC formation. In order to see whether complement system is involved in the ovulatory process, expression patterns of the membrane bound forms of regulators of complement activation (RCA) were examined in the periovulatory stage ovaries. For this purpose, a rat ovarian gene expression database (rOGED) was used. rOGED provides quantitative temporal mRNA expression profiles of 31,000 genes at ovarian (OVA), granulosa cell (GC), and non-granulosa/oocyte ovarian tissue (NGO) levels at various stages of follicular development (Abstract #852214). Of the three main types of RCAs, rOGED detected the expressions of mRNAs for membrane inhibitor of reactive lysis (CD59) and decay accelerating factor (DAF; CD55), but not membrane co-factor protein (MCP). CD59 mRNA was expressed both in GC and NGO all over the time points examined, with the peak expression at 12 h post treatment hCG. Expression of DAF mRNA was dramatically, yet transiently increased at 6 h post hCG treatment. Ten fold higher expression of DAF mRNA was detected in NGO than in GC at all time points examined. Northern blot analyses have confirmed the tissue- and time-dependent expression patterns of the rOGED data. We further examined the expression patterns of the various components of complement system. Surprisingly, within 6 hours of hCG treatment, two fold increase in mRNA expression was observed in the mRNAs for C1q , C3 and C4 proteins. Interestingly, those components were detected only in the NGO, except C1 that is expressed both in GC and NGO. The ovulatory inflammatory reaction is known to facilitate the process of follicle rupture. The inflammatory reaction, however, may give serious damages to the growing follicles, ovulated follicles and other important ovarian tissues. Present study strongly indicates that complement system may be involved in the ovulatory inflammation and the RCAs are expressed to protect ruptured follicles as well as other parts of the ovarian tissues from the potential attack by the complement system.
Ovarian localization Oocyte, Follicular Fluid
Comment A Proteomic Analysis of Human Follicular Fluid: Comparison between Younger and Older Women with Normal FSH Levels. Hashemitabar M 2014 et al. The follicular fluid (FF) is produced during folliculogenesis and contains a variety of proteins that play important roles in follicle development and oocyte maturation. Age-related infertility is usually considered as a problem that can be solved by assisted reproduction technology. Therefore, the identi?cation of novel biomarkers that are linked to reproductive aging is the subject of this study. FF was obtained from healthy younger (20-32 years old) and older (38-42 years old) women undergoing intracytoplasmic sperm injection (ICSI) due to male factor infertility. The FF was analyzed by two-dimensional gel electrophoresis (2-DE). The power of two-dimensional gel electrophoresis and the identi?cation of proteins were exploited using matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry. Twenty three protein spots showed reproducible and significant changes in the aged compared to the young group. Of these, 19 protein spots could be identified using MALDI-TOF-TOF-MS. As a result of MASCOT search, five unique downregulated proteins were identified in the older group. These were identified as serotransferrin, hemopexin precursor, complement C3, C4 and kininogen. A number of protein markers were found that may help develop diagnostic methods of infertility. ///////////////////////// A proteomic analysis of IVF follicular fluid in women Estes SJ et al. OBJECTIVE: To address the lack of predictors of IVF success by using proteomic biometrics. DESIGN: Experimental study of follicular fluid specimens from a prospective cohort of IVF patients. SETTING: Academic research laboratory and IVF program. PATIENT(S): Women or=11 oocytes and live birth (10 pairs). Year of cycle start and IVF down-regulation protocol were also matched. INTERVENTION(S): Follicular fluid was separated by two-dimensional polyacrylamide gel electrophoresis followed by Sypro Ruby staining and comparison with PDQuest software. Logistic regression was incorporated to calculate the likelihood of live birth in relation to the protein spot of interest. MAIN OUTCOME MEASURE(S): Protein markers. RESULT(S): Liquid chromatography-tandem mass spectrometry and searching of sequence databases revealed 11 potential protein candidates. Haptoglobin alpha, predominantly fetal expressed T1 domain, mitochondrial integrity genome (ATPase), apolipoprotein H (beta-2 glycoprotein I), dihydrolipoyl dehydrogenase, lyzozyme C, fibrinogen alpha-chain, and immunoglobulin heavy chain V-III (region BRO) were found to have increased expression in the live birth group, whereas antithrombin, vitamin D-binding protein, and complement 3 were decreased. An ELISA confirmed a significantly lower level of antithrombin. CONCLUSION(S): Proteomic evaluation of follicular fluid is able to identify potential biomarkers of good versus poor responders in matched pairs of IVF patients. Receptor-mediated transport and deposition of complement component C3 into developing chicken oocytes Recheis B, et al . Immunological resistance of the chick embryo is dependent upon IgG present in the yolk of the layed egg. Here we show that complement factor 3 (C3), a key component of the humoral complement system, is a yolk component of chicken eggs. C3 is transported into oocytes by LR8-mediated endocytosis. LR8 also binds and transports other major yolk components such as vitellogenin, very-low-density lipoprotein, and alpha(2)-macroglobulin. Expression studies of LR8 during chicken development and oocyte maturation, in combination with studies on the uptake of individual yolk components, suggest the following model for oocyte maturation in the chicken: all oocytes present in the ovary contain high levels of LR8 mRNA and protein long before the onset of oocyte maturation. Selected oocytes gain access to yolk precursors, and LR8 binds, internalizes, and deposits the major yolk components in the ratio of their relative abundance in the accessible pool.
Follicle stages
Comment Preliminary proteomic analysis on the alterations in follicular fluid proteins from women undergoing natural cycles or controlled ovarian hyperstimulation. Wu YT et al. (2015) To study the differences in protein expression profiles of follicular fluid (FF) between controlled ovarian hyperstimulation (COH) and natural ovulatory cycles. Twelve infertile women undergoing in vitro fertilization and embryo transfer (IVF-ET), with matched clinical information, were retrospectively recruited in the IVF center of our university hospital, including six undergoing COH and another six with natural cycles. FF was sampled from dominant follicles with mature oocytes. Protein expression profiles in each FF sample were analyzed respectively using two-dimensional gel electrophoresis. Differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and validated by western blotting. Differentially expressed proteins were further analyzed using Ingenuity Pathway Analysis (IPA) software. Two proteins were downregulated and 11 proteins were upregulated (change ≥1.5-fold, P < 0.05) in the COH group. We identified one down-egulated and seven upregulated proteins using MALDI-TOF MS. Four differentially expressed proteins, including transferrin, complement component C3 (C3), haptoglobin and alpha-1-antitrypsin (AAT), were further validated by rate nephelometry and western blotting analyses. The IPA analysis revealed a significant network involved in the humoral immune and inflammatory responses. The eight differentially expressed proteins were related to immune and inflammatory responses in the ovary. Our results provide new insights into the influence of COH on follicular (spp) development and IVF outcomes.//////////////////
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: mouse
Mutation name:
type: null mutation
fertility: fertile
Comment: Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Circolo A et al. (1999) Genetic deficiencies of the complement protein C3 occur naturally in humans and animal models and have been induced in mice by targeted deletion of the C3 gene. The study of these deficiencies has provided evidence for C3 functions in immune responses. C3 deficient mice were generated by replacing the 5'-flanking region of the C3 gene with the neomycin-resistance (neo) gene. Serum from these mice had no detectable C3 protein or complement activity. Challenge with Streptococcus pneumoniae revealed approximately 2000-fold increase in bacteremia as compared to littermate controls. C3 mRNA was absent in the liver, but it was detected in the lung, kidney, fat tissue, heart and spleen. Metabolic labeling of the lung tissue and peritoneal macrophages showed synthesis of pro-C3, but no post-synthetic intracellular processing of the protein and no secretion of mature C3. cDNA analysis at the cap site indicated that extrahepatic transcription of the targeted gene was initiated in the neo cassette, close to the C3/neo junction and predicted a primary translation product lacking the leader peptide. The data indicate that these mice provide a good animal model for the study of complete C3 deficiencies and a potential probe for tissue-specific C3 gene regulatory elements.//////////////////

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created: June 22, 2004, 5:20 p.m. by: hsueh   email:
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last update: May 7, 2021, 4:18 p.m. by: hsueh    email:

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