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C3 Gene

protein-coding   GIFtS: 73
GCID: GC19M006677

Complement Component 3

Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Complement Component 31 2     ASP2
C3a Anaphylatoxin1 2     C3a2
Complement Component C3a1 2     C3b2
Complement Component C3b1 2     HEL-S-62p2
prepro-C31 2     Acylation-Stimulating Protein Cleavage Product2
CPAMD12 3     Complement C32
C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 12 3     Complement Component C32
AHUS52 5     Epididymis Secretory Sperm Binding Protein Li 62p2
ARMD92 5     

External Ids:    HGNC: 13181   Entrez Gene: 7182   Ensembl: ENSG000001257307   OMIM: 1207005   UniProtKB: P010243   

Export aliases for C3 gene to outside databases

Previous GC identifers: GC19M006772 GC19M006617 GC19M006628 GC19M006440


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for C3 Gene:
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. People with C3 deficiency are susceptible to
bacterial infection. (provided by RefSeq, Feb 2009)

GeneCards Summary for C3 Gene:
C3 (complement component 3) is a protein-coding gene. Diseases associated with C3 include c3 deficiency, autosomal recessive, and hemolytic uremic syndrome, atypical 5. GO annotations related to this gene include C5L2 anaphylatoxin chemotactic receptor binding and receptor binding. An important paralog of this gene is A2M.

UniProtKB/Swiss-Prot: CO3_HUMAN, P01024
Function: C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is
the central reaction in both classical and alternative complement pathways. After activation C3b can bind
covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates
Function: Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local
inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes
histamine release from mast cells and basophilic leukocytes
Function: Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and
glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears
to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes
the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2

summary for C3 Gene:
The complement system is a biochemical pathway involved in both innate and adaptive immune responses. There
are four main functions of the complement system; lysis of microorganisms, promotion of phagocytosis,
triggering inflammation and immune clearance. There are three pathways that can activate the complement
system; the classical complement pathway (in response to IgG- or IgM-antigen complexes), the alternative
complement pathway (spontaneous activation) and the mannose-binding lectin pathway (in response to lectin
residues on pathogen cell surface membranes). All three pathway generate variants of C3 convertase, which
cleaves C3 into C3a and C3b. C3a and C3b activate a series of further cleavage events that activates the
complement cascade. This leads to immune defence responses such as degranulation of mast cells, increasing
vascular permeability and initiation of the membrane attack pathway. Deregulation of the complement system
would be extremely damaging to the host, so it is tightly regulated by complement control proteins. These
regulatory proteins are found in much higher concentrations that complement proteins themselves and prevent
complement system activation in 'self' tissues. The complement system has been implicated in many autoimmune
disorders, including systemic lupus erythematosus, multiple sclerosis and arthritis, and more recently has
been suggested to have a pathophysiological role in Alzheimer's and other neurodegenerative disorders.

Gene Wiki entry for C3 (Complement component 3) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000019.10  NC_018930.2  NT_011295.12  
Regulatory elements:
   Regulatory transcription factor binding sites in the C3 gene promoter:
         PPAR-gamma1   AP-1   ATF-2   STAT3   PPAR-gamma2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): C3 promoter sequence
   Search Chromatin IP Primers for C3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat C3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.3-p13.2   Ensembl cytogenetic band:  19p13.3   HGNC cytogenetic band: 19p13.3-p13.2

C3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
C3 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19M006677:  view genomic region     (about GC identifiers)

Start:
6,677,715 bp from pter      End:
6,730,573 bp from pter
Size:
52,859 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: CO3_HUMAN, P01024 (See protein sequence)
Recommended Name: Complement C3 precursor  
Size: 1663 amino acids; 187148 Da
Subunit: C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha,
linked by a disulfide bond. C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin
and generating C3b (beta chain + alpha' chain). C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and
2). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2.
Interacts with VSIG4. C3b interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 2 (HHV-2)
envelope glycoprotein C; this interaction inhibits the activation of the complement system. Interacts with
S.aureus immunoglobulin-binding protein sbi, this prevents interaction between C3dg and CR2. Interacts with
S.aureus fib. Interacts (both C3a and ASP) with C5AR2; the interaction occurs with higher affinity for ASP,
enhancing the phosphorylation and activation of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis
of GRP77
Caution: According to PubMed:21527715, the interaction surface between C3 and CR2 reported in PubMed:11387479 is
artifactual and can be ascribed to the presence of zinc acetate in the buffer
Selected PDB 3D structures from and Proteopedia for C3 (see all 34):
1C3D (3D)        1GHQ (3D)        1W2S (3D)        2A73 (3D)        2A74 (3D)        2GOX (3D)    
Secondary accessions: A7E236

Explore the universe of human proteins at neXtProt for C3: NX_P01024

Explore proteomics data for C3 at MOPED

Post-translational modifications: 

  • C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is
    released. Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 +
    alpha' chain fragment 2), C3dg and C3f. Other proteases produce other fragments such as C3d or C3g. C3a is
    further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation
    stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by insulin
    and dietary chylomicrons1
  • Phosphorylation sites are present in the extracellular medium1
  • Glycosylation2 at Asn85, Asn939, Asn1617
  • Modification sites at PhosphoSitePlus

  • See C3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_000055.2  
    ENSEMBL proteins: 
     ENSP00000245907   ENSP00000469482   ENSP00000471384   ENSP00000469744   ENSP00000472044  
    Reactome Protein details: P01024

    C3 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for C3 (Complement Component C3a)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for C3
    OriGene Protein Over-expression Lysate for C3
    OriGene MassSpec for C3
    OriGene Custom Protein Services for C3
    GenScript Custom Purified and Recombinant Proteins Services for C3
    Novus Biologicals C3 Proteins
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for C3
    Cloud-Clone Corp. Proteins for C3

    C3 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of C3
    R&D Systems Antibodies for C3 (Complement Component C3a, Complement Component C3d)
    OriGene Antibodies for C3
    OriGene Custom Antibody Services for C3
    Novus Biologicals C3 Antibodies
    Abcam antibodies for C3
    Cloud-Clone Corp. Antibodies for C3
    ThermoFisher Antibody for C3
    LSBio Antibodies in human, mouse, rat for C3

    C3 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for C3
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for C3
    Enzo Life Sciences assays for C3
    Cloud-Clone Corp. ELISAs for C3
    Cloud-Clone Corp. CLIAs for C3


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ENDOLIG: Endogenous ligands
    complement: Complement system

    Selected InterPro protein domains (see all 14):
     IPR008993 TIMP-like_OB-fold
     IPR001599 Macroglobln_a2
     IPR011626 A2M_comp
     IPR002890 A2M_N
     IPR009048 A-macroglobulin_rcpt-bd

    Graphical View of Domain Structure for InterPro Entry P01024

    ProtoNet protein and cluster: P01024

    5 Blocks protein domains:
    IPB001134 Netrin
    IPB001599 Alpha-2-macroglobulin
    IPB001840 Anaphylatoxin domain signature
    IPB002890 Alpha-2-macroglobulin
    IPB009048 Alpha-macroglobulin


    UniProtKB/Swiss-Prot: CO3_HUMAN, P01024
    Similarity: Contains 1 anaphylatoxin-like domain
    Similarity: Contains 1 NTR domain


    C3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CO3_HUMAN, P01024
    Function: C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is
    the central reaction in both classical and alternative complement pathways. After activation C3b can bind
    covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates
    Function: Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local
    inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes
    histamine release from mast cells and basophilic leukocytes
    Function: Acylation stimulating protein (ASP): adipogenic hormone that stimulates triglyceride (TG) synthesis and
    glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears
    to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes
    the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2

         Genatlas biochemistry entry for C3:
    complement component 3,glycoprotein,180kDa,activated by classical or alternative pathway with two forms,C3a
    (anaphylatoxin),C3b (opsonin)

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004866endopeptidase inhibitor activity IEA--
    GO:0005102receptor binding TAS9164946
    GO:0005515protein binding IPI11705926
    GO:0031715C5L2 anaphylatoxin chemotactic receptor binding IDA15833747
         
    C3 for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for C3:
     Increased gamma-H2AX phosphory 

         Selected MGI mutant phenotypes (inferred from 4 alleles(MGI details for C3) (see all 21):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  digestive/alimentary 
     embryogenesis  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  liver/biliary system  mortality/aging  muscle  nervous system 

    C3 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for C3: C3tm1Pkna C3tm1Crr C3tm1Hrc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for C3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for C3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for C3
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for C3

    miRNA
    Products:
        
    miRTarBase miRNAs that target C3:
    hsa-mir-26b-5p (MIRT030181), hsa-mir-98-5p (MIRT027814)

    Block miRNA regulation of human, mouse, rat C3 using miScript Target Protectors
    1 qRT-PCR Assays for microRNA that regulate C3:
    hsa-miR-127-5p
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for C3
    Predesigned siRNA for gene silencing in human, mouse, rat C3

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for C3

    Clone
    Products:
         
    OriGene clones in human, mouse for C3 (see all 5)
    OriGene ORF clones in mouse, rat for C3
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): C3 (NM_182962)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for C3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat C3

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for C3
    Browse ESI BIO Cell Lines and PureStem Progenitors for C3 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for C3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CO3_HUMAN, P01024: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    plasma membrane4
    cytosol3
    nucleus3
    endoplasmic reticulum2
    cytoskeleton1
    mitochondrion1
    peroxisome1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--
    GO:0005615extracellular space IDA--
    GO:0005886plasma membrane TAS--
    GO:0070062extracellular vesicular exosome IDA--
    GO:0072562blood microparticle IDA--

    C3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for C3 About   (see all 18)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Complement Pathway
    Immune response Lectin Induced complement pathway0.56
    Classical Complement Pathway0.00
    Immune response Classic complement pathway0.56
    Activation of C3 and C50.00
    Immune response Alternative complement pathway0.56
    Lectin Induced Complement Pathway0.00
    Regulation of Complement cascade0.48
    Alternative Complement Pathway0.00
    2Complement and coagulation cascades
    Complement and coagulation cascades0.71
    Complement Activation, Classical Pathway0.00
    Complement and Coagulation Cascades0.71
    3Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    Peptide ligand-binding receptors0.60
    GPCR ligand binding0.71
    G alpha (i) signalling events0.44
    4Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    5Creation of C4 and C2 activators
    Initial triggering of complement0.85
    Alternative complement activation0.00
    Complement cascade0.68

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for C3
        Alternative Complement Pathway
    Classical Complement Pathway
    Lectin Induced Complement Pathway
    Complement Pathway
    Phagocytosis of Microbes

    3 GeneGo (Thomson Reuters) Pathways for C3
        Immune response Alternative complement pathway
    Immune response Classical complement pathway
    Immune response Lectin induced complement pathway

    2 BioSystems Pathways for C3
        Complement Activation, Classical Pathway
    Complement and Coagulation Cascades

    Selected Reactome Pathways for C3 (see all 6)
        Peptide ligand-binding receptors
    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
    Alternative complement activation
    G alpha (i) signalling events
    Regulation of Complement cascade


    Selected Kegg Pathways  (Kegg details for C3) (see all 11):
        Phagosome
    Complement and coagulation cascades
    Pertussis
    Legionellosis
    Leishmaniasis


    C3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including C3 (see all 9): 
              Innate & Adaptive Immune Responses in human mouse rat
              Estrogen Receptor Signaling in human mouse rat
              NFKB Signaling Targets in human mouse rat
              Obesity in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for C3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for C3 (P010241, 2, 3 ENSP000002459074) via UniProtKB, MINT, STRING, and/or I2D (see all 211)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000231543P066813, ENSP000004079614I2D: score=1 STRING: ENSP00000407961
    C2P066813, ENSP000002993674I2D: score=1 STRING: ENSP00000299367
    ENSG00000204364P066813I2D: score=1 
    ENSG00000206372P066813I2D: score=1 
    ENSG00000226560P066813I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001798positive regulation of type IIa hypersensitivity IEA--
    GO:0001934positive regulation of protein phosphorylation IDA15833747
    GO:0001970positive regulation of activation of membrane attack complex IEA--
    GO:0006631fatty acid metabolic process IEA--
    GO:0006954inflammatory response IEA--

    C3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for C3 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Compstatin C3-binding protein, inhibits complement activation [206645-99-0]
    Compstatin control peptideControl peptide for Compstatin (Cat. No. 2585)[301544-78-5]
    NDT 9513727 Potent, selective human C5a receptor antagonist [439571-48-9]

    2 DrugBank Compounds for C3    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Intravenous ImmunoglobulinIg alpha-2 chain C region (see all 3)9007-83-4targetbinder17351760 20441428 17911465
    S-Hydroxycysteine-- --target--17139284 17016423 10592235

    Selected Novoseek inferred chemical compound relationships for C3 gene (see all 30)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    anaphylatoxin 72.2 7 1431125 (1), 11037838 (1), 11487475 (1), 19687018 (1) (see all 6)
    triacylglycerol 61.6 36 8582446 (4), 9555951 (4), 8492712 (3), 8068623 (3) (see all 17)
    fatty acid 46.6 34 11108729 (3), 14703506 (3), 8574269 (2), 20416070 (1) (see all 19)
    glucose 42.8 100 9059512 (8), 8492712 (6), 9130021 (5), 15043507 (3) (see all 36)
    lipid 37 49 11836332 (3), 16302015 (3), 17372315 (2), 19022911 (2) (see all 26)
    oleic acid 33.4 10 18004729 (2), 8492712 (1), 9034195 (1), 14703506 (1)
    cholesterol 32.8 42 11714853 (3), 18206145 (2), 18075846 (2), 16302015 (2) (see all 16)
    neopterin 27.5 3 8925815 (1), 7702398 (1), 7874897 (1)
    glycerol 3-phosphate 13.9 2 8582446 (1), 1943492 (1)
    steroid 9.97 4 18615583 (2), 18671285 (1)



    C3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for C3 gene: 
    NM_000064.2  

    Unigene Cluster for C3:

    Complement component 3
    Hs.529053  [show with all ESTs]
    Unigene Representative Sequence: BC063852
    18 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000245907(uc002mfm.3) ENST00000601475 ENST00000599899 ENST00000602229
    ENST00000599668 ENST00000601008 ENST00000596548 ENST00000596179 ENST00000596238
    ENST00000598805 ENST00000594005 ENST00000602053 ENST00000600763 ENST00000594270
    ENST00000597442 ENST00000595577 ENST00000594936 ENST00000600744
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Block miRNA regulation of human, mouse, rat C3 using miScript Target Protectors
    1 qRT-PCR Assays for microRNA that regulate C3:
    hsa-miR-127-5p
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for C3
    Predesigned siRNA for gene silencing in human, mouse, rat C3
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    OriGene clones in human, mouse for C3 (see all 5)
    OriGene ORF clones in mouse, rat for C3
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): C3 (NM_182962)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for C3
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat C3
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for C3
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat C3
      QuantiTect SYBR Green Assays in human, mouse, rat C3
      QuantiFast Probe-based Assays in human, mouse, rat C3

    Additional mRNA sequence: 

    AK094728.1 AK304071.1 AY927485.1 BC022897.1 BC063852.1 BC150179.1 BC150200.1 BC150299.1 
    K02765.1 

    Selected DOTS entries (see all 36):

    DT.95200471  DT.100805138  DT.95212039  DT.100642455  DT.95288012  DT.92469022  DT.100865720  DT.92469028 
    DT.121504652  DT.100642643  DT.95365044  DT.100668443  DT.86844052  DT.92068615  DT.100668436  DT.92469035 
    DT.121504611  DT.100668437  DT.40256655  DT.95347307  DT.95356787  DT.95365047  DT.95365050  DT.121504605 

    Selected AceView cDNA sequences (see all 731):

    BM696828 CD607280 BQ652672 BF525480 AA427448 BF340032 BF032613 CB154110 
    AI093026 BQ723278 NM_000064 AA343381 AA166723 CB154335 CB267825 AA337584 
    T60995 AA319129 BG542872 AA344123 CK429838 BQ641572 CA447572 AA343382 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for C3 (see all 7)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
    SP1:                                                                          -                                         -                                       
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 24 ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30 ^ 31 ^ 32 ^ 33a · 33b ^ 34a · 34b ^ 35a · 35b ^ 36 ^ 37 ^ 38a · 38b ^ 39 ^ 40 ^ 41 ^ 42a · 42b
    SP1:                                -                                         -     -                             -                                 
    SP2:                                                                                                                                                
    SP3:                                                                                                                                                
    SP4:                                                                                                                                                
    SP5:                                                                                                                                                


    ECgene alternative splicing isoforms for C3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    C3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    C3 Expression
    About this image


    C3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 8) fully expand
     
     Lung (Respiratory System)
             Alveolar type II cells
     
     Liver (Hepatobiliary System)
             Mature Mesothelial Cells Hepatic Mesenchyme
     
     Epithelial Cells
             Adult Retinal Pigmented Epithelium Cells Retinal Pigmented Epithelium
     
     Eye (Sensory Organs)
             Adult Retinal Pigmented Epithelium Cells Retinal Pigmented Epithelium
     
     Heart (Cardiovascular System)
             Mature Cardiac Fibroblasts Myocardium
    C3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    C3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.529053

    UniProtKB/Swiss-Prot: CO3_HUMAN, P01024
    Tissue specificity: Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into
    the plasma during both the fasting and postprandial periods

        Pathway & Disease-focused RT2 Profiler PCR Arrays including C3 (see all 9): 
              Innate & Adaptive Immune Responses in human mouse rat
              Estrogen Receptor Signaling in human mouse rat
              NFKB Signaling Targets in human mouse rat
              Obesity in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for C3

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of chordates.

    Orthologs for C3 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia C31 , 5 complement component 31, 5 79.06(n)1
    77.11(a)1
      17 (29.72 cM)5
    122661  NM_009778.21  NP_033908.21 
     572039705 
    chicken
    (Gallus gallus)
    Aves C31 complement component 3 63.12(n)
    54.86(a)
      396370  NM_205405.1  NP_990736.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    (see all 4)
    Uncharacterized protein
    (see all 4)
    53(a)
    53(a)
    (see all 4)
    1 ↔ many
    1 ↔ many
    (see all 4)
    2(75798369-75880702)
    2(77547966-77615105)
    African clawed frog
    (Xenopus laevis)
    Amphibia BX851366.12   -- 72.79(n)    BX851366.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BC055564.12   -- 75.23(n)   321046  BC055564.1 


    ENSEMBL Gene Tree for C3 (if available)
    TreeFam Gene Tree for C3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for C3 gene
    A2M2  C52  C4B2  C4A2  A2ML12  PZP2  CPAMD82  CD1092  
    6 SIMAP similar genes for C3 using alignment to 5 protein entries:     CO3_HUMAN (see all proteins):
    C4B    ZA    C4B_2    C5    OVOS2    C4A

    C3 for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for C3
    PGOHUM00000250593


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    CO3_HUMAN, P01024: There are two alleles: C3S (C3 slow), the most common allele in all races and C3F (C3 fast),
    relatively frequent in Caucasians, less common in Black Americans, extremely rare in Orientals


    Selected SNPs for C3 (see all 1597)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1177935401,2,,4
    C,FHemolytic uremic syndrome atypical 5 (AHUS5)4 --6707129(+) CCGCCG/ACAGCT 2 /R /W mis12Minor allele frequency- A:0.00NA EU 4841
    VAR_0632194
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632192 Q K mis40--------
    VAR_0632134
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632132 R Q mis40--------
    VAR_0632184
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632182 C W mis40--------
    VAR_0632204
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632202 H D mis40--------
    VAR_0636554
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0636552 R L mis40--------
    VAR_0019854
    Complement component 3 deficiency (C3D)4--see VAR_0019852 D N mis40--------
    VAR_0632174
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632172 D N mis40--------
    VAR_0636544
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0636542 F V mis40--------
    VAR_0632164
    Hemolytic uremic syndrome atypical 5 (AHUS5)4--see VAR_0632162 A V mis40--------

    HapMap Linkage Disequilibrium report for C3 (6677715 - 6730573 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for C3 (see all 19):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2677585CNV Deletion23128226
    esv2718067CNV Deletion23290073
    esv2265092CNV Deletion18987734
    esv5110CNV Deletion18987735
    esv2718068CNV Deletion23290073
    esv2718070CNV Deletion23290073
    esv2718069CNV Deletion23290073
    dgv14e196CNV Duplication17116639
    nsv470120CNV Loss18288195
    dgv3703n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): C3
    Locus Specific Mutation Databases (LSDB): C3

    Site Specific Mutation Identification with PCR Assays
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    DNA2.0 Custom Variant and Variant Library Synthesis for C3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 120700   
    OMIM disorders: 613779  612925  611378  
    UniProtKB/Swiss-Prot: CO3_HUMAN, P01024
  • Complement component 3 deficiency (C3D) [MIM:613779]: A rare defect of the complement classical pathway.
    Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some
    patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and
    membranoproliferative glomerulonephritis. Note=The disease is caused by mutations affecting the gene represented
    in this entry
  • Macular degeneration, age-related, 9 (ARMD9) [MIM:611378]: A form of age-related macular degeneration, a
    multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most
    patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid
    that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch
    membrane. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
  • Hemolytic uremic syndrome atypical 5 (AHUS5) [MIM:612925]: An atypical form of hemolytic uremic syndrome.
    It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal
    failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome,
    atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal
    disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Other genes may play a role in modifying the phenotype
  • Note=Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and
    coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage

  • Selected diseases for C3 (see all 135):    
    About MalaCards
    c3 deficiency, autosomal recessive    hemolytic uremic syndrome, atypical 5    autoimmune disease of central nervous system    c3-related atypical hemolytic-uremic syndrome
    c3 deficiency    age-related macular degeneration 9    c4a deficiency    hyperapobetalipoproteinemia
    complement deficiency    arteriolosclerosis    pneumococcal meningitis    retinal drusen
    capillary leak syndrome    dense deposit disease    multiple sclerosis    lupus erythematosus
    hemolytic-uremic syndrome    atypical hemolytic-uremic syndrome    pediatric systemic lupus erythematosus    age related macular degeneration

    7 diseases from the University of Copenhagen DISEASES database for C3:
    C3 deficiency     Nephritis     Lupus erythematosus     Connective tissue disease
    Age related macular degeneration     Proteinuria     Vascular disease

    C3 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for C3 gene (see all 37)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    afibrinogenemia 65.7 1 1966986 (1)
    complement deficiency 65.6 3 18667363 (1)
    hyperlipidemia familial combined 55.9 3 11979403 (2), 11348883 (1)
    lipodystrophy 51.2 2 12942374 (1)
    glomerulonephritis membranoproliferative 48.8 1 8395463 (1)
    insulin resistance 48.1 19 17595349 (3), 16302015 (2), 18206145 (1), 12679444 (1) (see all 10)
    obesity 47.2 31 15853826 (3), 8574269 (2), 1885258 (2), 14564690 (2) (see all 16)
    dyslipidemia 38.8 7 18253759 (1), 11836332 (1), 20173020 (1), 20069551 (1) (see all 6)
    meningococcal diseases 38.2 1 9844044 (1)
    insulin sensitivity 33.1 10 11397716 (1), 12679444 (1), 15809665 (1), 18702682 (1) (see all 8)

    Genatlas disease: C3
    glomerulonephritis,pyogenic recurrent infections,lupus systemic syndrome

    Genetic Association Database (GAD): C3
    Human Genome Epidemiology (HuGE) Navigator: C3 (142 documents)

    Export disorders for C3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for C3 gene, integrated from 10 sources (see all 638):
    (articles sorted by number of sources associating them with C3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (PubMed id 20513133)1, 2, 4 Maga T.K.... Smith R.J.H. (Hum. Mutat. 2010)
    2. Complement C3 variant and the risk of age-related macular degeneration. (PubMed id 17634448)1, 2, 4 Yates J.R.W....Moore A.T. (N. Engl. J. Med. 2007)
    3. Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line. (PubMed id 9059512)1, 2, 9 Tao Y....Germinario R.J. (Biochim. Biophys. Acta 1997)
    4. Inherited human complement C3 deficiency. An amino acid substitution in the beta-chain (Asp549 to Asn) impairs C3 secretion. (PubMed id 7961791)1, 2, 9 Singer L....Wetsel R.A. (J. Biol. Chem. 1994)
    5. Acylation stimulating protein but not complement C3 associates with metabolic syndrome components in Chinese children and adolescents. (PubMed id 18805911)1, 2, 9 Wamba P.C....Cianflone K. (Eur. J. Endocrinol. 2008)
    6. C5L2 is a functional receptor for acylation-stimulating protein. (PubMed id 15833747)1, 2, 9 Kalant D....Cianflone K. (J. Biol. Chem. 2005)
    7. Acylation-stimulating protein (ASP): structure-function determinants of cell surface binding and triacylglycerol synthetic activity. (PubMed id 10432298)1, 2, 9 Murray I.... Cianflone K. (Biochem. J. 1999)
    8. Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. (PubMed id 9555951)1, 2, 9 Saleh J....Frayn K.N. (J. Lipid Res. 1998)
    9. Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma. (PubMed id 15278436)1, 4, 9 Hasegawa K....Suzuki Y. (Hum. Genet. 2004)
    10. Systemic complement activation in age-related macular degeneration. (PubMed id 18596911)1, 4, 9 Scholl H.P....Oppermann M. (PLoS ONE 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 718 HGNC: 1318 AceView: C3andTNFSF14 Ensembl:ENSG00000125730 euGenes: HUgn718
    ECgene: C3 Kegg: 718 H-InvDB: C3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for C3 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for C3 Genetics and Cytogenetics in Oncology and Haematology
    C3basehttp://bioinf.uta.fi/C3base/
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=C3[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/Complement_c3
    SeattleSNPshttp://pga.gs.washington.edu/data/c3/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for C3 gene:
    Search GeneIP for patents involving C3

    Licensable Technologies for C3 gene:
    Weizmann Institute:Synthetic Peptides for Treatment of Allergies
    GeneCards and IP:
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    The GeneCards human gene database gene index: 1 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 


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