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C3 Gene(Protein Coding)

Complement C3

GCID:
GC19M006677
GIFtS:
55
Genes Participants
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Aliases for C3 Gene

Aliases for C3 Gene

  • Complement C3 2 3 3 5
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 1 3 4
  • Complement Component C3a 2 3
  • Complement Component C3b 2 3
  • Complement Component 3 2 3
  • C3a Anaphylatoxin 2 3
  • Prepro-C3 2 3
  • CPAMD1 3 4
  • Epididymis Secretory Sperm Binding Protein Li 62p 3
  • Acylation-Stimulating Protein Cleavage Product 3
  • HEL-S-62p 3
  • AHUS5 3
  • ARMD9 3
  • ASP 3
  • C3a 3
  • C3b 3

External Ids for C3 Gene

Previous GeneCards Identifiers for C3 Gene

  • GC19M006772
  • GC19M006617
  • GC19M006628
  • GC19M006440

Summaries for C3 Gene

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. 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]

GeneCards Summary for C3 Gene

C3 (Complement C3) is a Protein Coding gene. Diseases associated with C3 include Complement Component 3 Deficiency, Autosomal Recessive and Hemolytic Uremic Syndrome, Atypical 5. Among its related pathways are Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and C5L2 anaphylatoxin chemotactic receptor binding. An important paralog of this gene is C4B.

UniProtKB/Swiss-Prot for C3 Gene

  • 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.

  • Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.

  • C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.

  • Acylation stimulating protein: 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 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).

Tocris 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.

Gene Wiki entry for C3 Gene

Additional gene information for C3 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for C3 Gene

Genomics for C3 Gene

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  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for C3 Gene

Promoters and enhancers for C3 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH19J006765 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE dbSUPER 650.3 -36.7 -36720 4.5 HDGF PKNOX1 ARID4B SIN3A ZNF207 ZNF143 FOS KLF13 SP3 SP5 SH2D3A C3 DUS3L XAB2 ZNF557 FLJ25758 MBD3L5 MBD3L3 LOC390877 RPL21P129
GH19J006728 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 650.7 +0.8 839 3.2 HDGF PKNOX1 FOXA2 ARID4B SIN3A YY1 SLC30A9 POLR2B ZNF143 SP5 C3 GPR108 ENSG00000276980
GH19J006717 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 650.4 +9.4 9404 6.4 HDGF PKNOX1 FOXA2 MLX ARID4B YBX1 DMAP1 ZNF2 YY1 SLC30A9 C3 XAB2 GPR108 ZNF557 RANBP3 DUS3L FLJ25758 MBD3L5 LOC390877 MBD3L3
GH19J006731 Enhancer 0.3 dbSUPER 650.7 -1.5 -1539 0.9 ZBTB33 C3 GPR108 MIR6791
GH19J006674 Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 12.1 +55.5 55455 1.1 HDGF PKNOX1 SMAD1 YBX1 IRF4 ARID2 ZNF207 ZNF143 ZNF548 FOS TNFSF14 XAB2 ZNF557 KHSRP DUS3L DENND1C C3 TRIP10 GPR108 RANBP3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around C3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the C3 gene promoter:
  • AP-1
  • c-Jun
  • ATF-2
  • PPAR-gamma2
  • PPAR-gamma1
  • STAT3

Genomic Locations for C3 Gene

Genomic Locations for C3 Gene
chr19:6,677,704-6,730,562
(GRCh38/hg38)
Size:
52,859 bases
Orientation:
Minus strand
chr19:6,677,715-6,730,573
(GRCh37/hg19)
Size:
52,859 bases
Orientation:
Minus strand

Genomic View for C3 Gene

Genes around C3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
C3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for C3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for C3 Gene

Proteins for C3 Gene

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  2. Protein
  3. Assay

  • Protein details for C3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01024-CO3_HUMAN
    Recommended name:
    Complement C3
    Protein Accession:
    P01024
    Secondary Accessions:
    • A7E236

    Protein attributes for C3 Gene

    Size:
    1663 amino acids
    Molecular mass:
    187148 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for C3 Gene

neXtProt entry for C3 Gene

Protein Expression for C3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for C3 Gene

  • 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 chylomicrons.
  • Phosphorylated by FAM20C in the extracellular medium.
  • Glycosylation at Asn1617, Asn939, and Asn85
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • CO3_HUMAN (110)

Other Protein References for C3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for C3 (Complement Component C3a)
  • R&D Systems Antibodies for C3 (Complement Component C3d)

Assay Products

  • Abcam assays for C3

No data available for DME Specific Peptides for C3 Gene

Domains & Families for C3 Gene

Gene Families for C3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Candidate cardiovascular disease genes
  • Disease related genes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for C3 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for C3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with C3: view

No data available for UniProtKB/Swiss-Prot for C3 Gene

Function for C3 Gene

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  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for C3 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Function:
Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
UniProtKB/Swiss-Prot Function:
C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.
UniProtKB/Swiss-Prot Function:
Acylation stimulating protein: 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 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).
GENATLAS Biochemistry:
complement component 3,glycoprotein,180kDa,activated by classical or alternative pathway with two forms,C3a (anaphylatoxin),C3b (opsonin)

Phenotypes From GWAS Catalog for C3 Gene

Gene Ontology (GO) - Molecular Function for C3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity TAS --
GO:0004866 endopeptidase inhibitor activity IEA --
GO:0005102 signaling receptor binding TAS 9164946
GO:0005515 protein binding IPI,IEA 7483825
GO:0031715 C5L2 anaphylatoxin chemotactic receptor binding IDA 15833747
genes like me logo Genes that share ontologies with C3: view
genes like me logo Genes that share phenotypes with C3: view

Human Phenotype Ontology for C3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for C3 Gene

MGI Knock Outs for C3:
  • C3 C3<tm1Crr>
  • C3 C3<tm1Hrc>
  • C3 C3<tm1.1(KOMP)Vlcg>
  • C3 C3<tm1Pkna>

Animal Model Products

miRNA for C3 Gene

miRTarBase miRNAs that target C3

Clone Products

  • Addgene plasmids for C3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for C3 Gene

Localization for C3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for C3 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for C3 gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
lysosome 5
nucleus 3
cytosol 3
cytoskeleton 2
mitochondrion 1
peroxisome 1
endosome 1

Gene Ontology (GO) - Cellular Components for C3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
GO:0005615 extracellular space IEA,IDA 25645918
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005886 plasma membrane TAS --
GO:0032991 protein-containing complex IEA --
genes like me logo Genes that share ontologies with C3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for C3 Gene

Pathways & Interactions for C3 Gene

genes like me logo Genes that share pathways with C3: view

Gene Ontology (GO) - Biological Process for C3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001798 positive regulation of type IIa hypersensitivity IEA --
GO:0001934 positive regulation of protein phosphorylation IDA 15833747
GO:0001970 positive regulation of activation of membrane attack complex IEA --
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
genes like me logo Genes that share ontologies with C3: view

No data available for SIGNOR curated interactions for C3 Gene

Drugs & Compounds for C3 Gene

Products:

  1. Drug

(25) Drugs for C3 Gene - From: DrugBank, PharmGKB, DGIdb, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma Target 202
Immune Globulin Human Approved, Investigational Pharma Target, binder 0
Zinc Approved, Investigational Pharma Target 2430
Clozapine Approved Pharma Antagonist, Positive, Allosteric regulator, Full agonist, Agonist, Inverse agonist Antipsychotic medication 121
Cyclo-Tetrametavanadate Experimental Pharma Target 0

(18) Additional Compounds for C3 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Compstatin
206645-99-0
NDT 9513727
439571-48-9
PMX 53
219639-75-5
W 54011
405098-33-1

(5) Tocris Compounds for C3 Gene

Compound Action Cas Number
Compstatin C3-binding protein, inhibits complement activation 206645-99-0
NDT 9513727 Potent, selective human C5a receptor antagonist 439571-48-9
PMX 205 Potent C5a receptor peptide antagonist 514814-49-4
PMX 53 Potent C5a receptor antagonist 219639-75-5
W 54011 High affinity C5a receptor antagonist 405098-33-1
genes like me logo Genes that share compounds with C3: view

Drug Products

Transcripts for C3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for C3 Gene

(1) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(731) Selected AceView cDNA sequences:
(18) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for C3 Gene

Complement component 3:
Representative Sequences:

Clone Products

  • Addgene plasmids for C3

Alternative Splicing Database (ASD) splice patterns (SP) for C3 Gene

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:
SP6:
SP7:

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:
SP6:
SP7:

Relevant External Links for C3 Gene

GeneLoc Exon Structure for
C3
ECgene alternative splicing isoforms for
C3

Expression for C3 Gene

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  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for C3 Gene

mRNA expression in normal human tissues for C3 Gene
mRNA expression by BioGPS for C3 GenemRNA expression by GTEx for C3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for C3 Gene

This gene is overexpressed in Liver (x20.3).

Protein differential expression in normal tissues from HIPED for C3 Gene

This gene is overexpressed in Synovial fluid (16.2), Plasma (15.9), and Lavage (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for C3 Gene



Protein tissue co-expression partners for C3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of C3 Gene:

C3

SOURCE GeneReport for Unigene cluster for C3 Gene:

Hs.529053

mRNA Expression by UniProt/SwissProt for C3 Gene:

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

Evidence on tissue expression from TISSUES for C3 Gene

  • Liver(5)
  • Blood(4.8)
  • Bone marrow(4.3)
  • Lung(4.3)
  • Nervous system(4.3)
  • Intestine(3.6)
  • Kidney(3.6)
  • Heart(3.5)
  • Thyroid gland(3.3)
  • Eye(3.2)
  • Gall bladder(3.1)
  • Muscle(2.9)
  • Skin(2.8)
  • Lymph node(2.7)
  • Spleen(2.7)
  • Stomach(2.7)
  • Pancreas(2.4)
  • Adrenal gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for C3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • urinary
Regions:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
  • lung
Abdomen:
  • kidney
  • liver
  • pancreas
Pelvis:
  • ureter
  • urinary bladder
General:
  • blood
  • blood vessel
  • coagulation system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with C3: view