Browse C3

Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted.
Domain PF00207 Alpha-2-macroglobulin family
PF07678 A-macroglobulin complement component
PF01835 MG2 domain
PF07703 Alpha-2-macroglobulin family N-terminal region
PF07677 A-macroglobulin receptor
PF01821 Anaphylotoxin-like domain
PF01759 UNC-6/NTR/C345C module
PF10569 Alpha-macro-globulin thiol-ester bond-forming region
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. 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. ; FUNCTION: C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation. ; 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).

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001794 type IIa hypersensitivity
GO:0001796 regulation of type IIa hypersensitivity
GO:0001798 positive regulation of type IIa hypersensitivity
GO:0001819 positive regulation of cytokine production
GO:0001905 activation of membrane attack complex
GO:0001969 regulation of activation of membrane attack complex
GO:0001970 positive regulation of activation of membrane attack complex
GO:0002250 adaptive immune response
GO:0002437 inflammatory response to antigenic stimulus
GO:0002438 acute inflammatory response to antigenic stimulus
GO:0002443 leukocyte mediated immunity
GO:0002444 myeloid leukocyte mediated immunity
GO:0002445 type II hypersensitivity
GO:0002449 lymphocyte mediated immunity
GO:0002455 humoral immune response mediated by circulating immunoglobulin
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002524 hypersensitivity
GO:0002526 acute inflammatory response
GO:0002673 regulation of acute inflammatory response
GO:0002675 positive regulation of acute inflammatory response
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B cell mediated immunity
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002861 regulation of inflammatory response to antigenic stimulus
GO:0002863 positive regulation of inflammatory response to antigenic stimulus
GO:0002864 regulation of acute inflammatory response to antigenic stimulus
GO:0002866 positive regulation of acute inflammatory response to antigenic stimulus
GO:0002883 regulation of hypersensitivity
GO:0002885 positive regulation of hypersensitivity
GO:0002886 regulation of myeloid leukocyte mediated immunity
GO:0002888 positive regulation of myeloid leukocyte mediated immunity
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0002892 regulation of type II hypersensitivity
GO:0002894 positive regulation of type II hypersensitivity
GO:0002920 regulation of humoral immune response
GO:0002922 positive regulation of humoral immune response
GO:0006631 fatty acid metabolic process
GO:0006638 neutral lipid metabolic process
GO:0006639 acylglycerol metabolic process
GO:0006641 triglyceride metabolic process
GO:0006909 phagocytosis
GO:0006956 complement activation
GO:0006957 complement activation, alternative pathway
GO:0006958 complement activation, classical pathway
GO:0006959 humoral immune response
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0008643 carbohydrate transport
GO:0008645 hexose transport
GO:0010466 negative regulation of peptidase activity
GO:0010573 vascular endothelial growth factor production
GO:0010574 regulation of vascular endothelial growth factor production
GO:0010575 positive regulation of vascular endothelial growth factor production
GO:0010827 regulation of glucose transport
GO:0010828 positive regulation of glucose transport
GO:0010866 regulation of triglyceride biosynthetic process
GO:0010876 lipid localization
GO:0010883 regulation of lipid storage
GO:0010884 positive regulation of lipid storage
GO:0010951 negative regulation of endopeptidase activity
GO:0010954 positive regulation of protein processing
GO:0015749 monosaccharide transport
GO:0015758 glucose transport
GO:0016064 immunoglobulin mediated immune response
GO:0016485 protein processing
GO:0019216 regulation of lipid metabolic process
GO:0019432 triglyceride biosynthetic process
GO:0019724 B cell mediated immunity
GO:0019915 lipid storage
GO:0030100 regulation of endocytosis
GO:0030449 regulation of complement activation
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0043277 apoptotic cell clearance
GO:0045017 glycerolipid biosynthetic process
GO:0045745 positive regulation of G-protein coupled receptor protein signaling pathway
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0045807 positive regulation of endocytosis
GO:0045861 negative regulation of proteolysis
GO:0045862 positive regulation of proteolysis
GO:0045917 positive regulation of complement activation
GO:0046460 neutral lipid biosynthetic process
GO:0046463 acylglycerol biosynthetic process
GO:0046486 glycerolipid metabolic process
GO:0046890 regulation of lipid biosynthetic process
GO:0048514 blood vessel morphogenesis
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050764 regulation of phagocytosis
GO:0050766 positive regulation of phagocytosis
GO:0051235 maintenance of location
GO:0051346 negative regulation of hydrolase activity
GO:0051604 protein maturation
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060627 regulation of vesicle-mediated transport
GO:0070613 regulation of protein processing
GO:0072376 protein activation cascade
GO:0090207 regulation of triglyceride metabolic process
GO:1901342 regulation of vasculature development
GO:1903317 regulation of protein maturation
GO:1903319 positive regulation of protein maturation
GO:1904018 positive regulation of vasculature development
GO:2000257 regulation of protein activation cascade
GO:2000259 positive regulation of protein activation cascade
GO:2000425 regulation of apoptotic cell clearance
GO:2000427 positive regulation of apoptotic cell clearance
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0004175 endopeptidase activity
GO:0004252 serine-type endopeptidase activity
GO:0004857 enzyme inhibitor activity
GO:0004866 endopeptidase inhibitor activity
GO:0008236 serine-type peptidase activity
GO:0017171 serine hydrolase activity
GO:0030414 peptidase inhibitor activity
GO:0031714 C5a anaphylatoxin chemotactic receptor binding
GO:0031715 C5L2 anaphylatoxin chemotactic receptor binding
GO:0061134 peptidase regulator activity
GO:0061135 endopeptidase regulator activity
Cellular Component GO:0072562 blood microparticle
> KEGG and Reactome Pathway
 
KEGG hsa04145 Phagosome
hsa04610 Complement and coagulation cascades
Reactome R-HSA-174577: Activation of C3 and C5
R-HSA-1280218: Adaptive Immune System
R-HSA-173736: Alternative complement activation
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-166658: Complement cascade
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-166663: Initial triggering of complement
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-977606: Regulation of Complement cascade
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between C3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between C3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27297552Melanoma; Lung carcinoma; Breast carcinoma; liver carcinomaInhibit immunityHowever, CD8(+) TILs do not routinely express IL10, as autocrine complement C3 inhibits IL10 production through complement receptors C3aR and C5aR. CD8(+) TILs from C3-deficient mice, however, express IL10 and exhibit enhanced effector function. C3-deficient mice are resistant to tumor development in a T-cell- and IL10-dependent manner; human TILs expanded with IL2 plus IL10 increase the killing of primary tumors in vitro compared with IL2-treated TILs.
29118090Lung CarcinomaInhibit immunityNotably, growth of primary tumors and metastases was both strongly inhibited in C3-deficient mice (C3-/-mice), with tumors undetectable in many subjects. Similarly, antagonists of the C3a or C5a receptors inhibited tumor growth.
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of C3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of C3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1370.869
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2920.914
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0490.977
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1260.837
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1070.972
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1490.969
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.9350.303
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.6890.385
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2270.929
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8360.798
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3840.94
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4130.0818
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of C3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.16.84.30.443
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.16.84.30.673
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.3014.30.238
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8637.5037.50.209
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.112.5-1.41
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 472514.310.71
1329033130MelanomaallAnti-PD-1 (nivolumab) 382710.53.76.80.393
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.17.71.41
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161412.5012.50.485
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of C3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of C3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by C3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of C3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of C3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between C3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolC3
Namecomplement component 3
Aliases CPAMD1; ARMD9; C3a; C3b; C3a anaphylatoxin; complement component C3a; complement component C3b; prepro-C3; A ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting C3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting C3.
ID Name Drug Type Targets #Targets
DB00028Immune Globulin HumanBiotechC3, C4A, C4B, C5, FCGR1A, FCGR1B, FCGR2A, FCGR2B, FCGR2C, FCGR3A, ......11
DB01593ZincSmall MoleculeA1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......119
DB01915S-HydroxycysteineSmall MoleculeACAT2, C3, GSTA1, GSTP1, PMP25
DB06492MirococeptBiotechC31
DB09130CopperSmall MoleculeA1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......141