TISIDB

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
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 [ TOP ]
Subcellular Location	Cell membrane Multi-pass membrane protein Cytoplasmic vesicle Note=Phosphorylated C5aR colocalizes with ARRB1 and ARRB2 in cytoplasmic vesicles.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471, PubMed:9553099, PubMed:10636859, PubMed:15153520, PubMed:29300009). The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production (PubMed:10636859, PubMed:15153520).

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0001525 angiogenesis GO:0001819 positive regulation of cytokine production GO:0002237 response to molecule of bacterial origin GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002430 complement receptor mediated signaling pathway GO:0002526 acute inflammatory response GO:0002673 regulation of acute inflammatory response GO:0002685 regulation of leukocyte migration GO:0002687 positive regulation of leukocyte migration GO:0002688 regulation of leukocyte chemotaxis GO:0002690 positive regulation of leukocyte chemotaxis GO:0002697 regulation of immune effector process GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002920 regulation of humoral immune response GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006956 complement activation GO:0006959 humoral immune response GO:0006968 cellular defense response GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007202 activation of phospholipase C activity GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0009299 mRNA transcription GO:0010517 regulation of phospholipase activity GO:0010518 positive regulation of phospholipase 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:0010758 regulation of macrophage chemotaxis GO:0010759 positive regulation of macrophage chemotaxis GO:0010863 positive regulation of phospholipase C activity GO:0016485 protein processing GO:0021534 cell proliferation in hindbrain GO:0030335 positive regulation of cell migration GO:0030449 regulation of complement activation GO:0030593 neutrophil chemotaxis GO:0030595 leukocyte chemotaxis GO:0030902 hindbrain development GO:0031099 regeneration GO:0031100 animal organ regeneration GO:0032103 positive regulation of response to external stimulus GO:0032147 activation of protein kinase activity GO:0032494 response to peptidoglycan GO:0032496 response to lipopolysaccharide GO:0033674 positive regulation of kinase activity GO:0038178 complement component C5a signaling pathway GO:0040017 positive regulation of locomotion GO:0042742 defense response to bacterium GO:0042789 mRNA transcription from RNA polymerase II promoter GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043523 regulation of neuron apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045860 positive regulation of protein kinase activity GO:0048246 macrophage chemotaxis GO:0048514 blood vessel morphogenesis GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050679 positive regulation of epithelial cell proliferation GO:0050727 regulation of inflammatory response GO:0050830 defense response to Gram-positive bacterium GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051272 positive regulation of cellular component movement GO:0051402 neuron apoptotic process GO:0051480 regulation of cytosolic calcium ion concentration GO:0051604 protein maturation GO:0055074 calcium ion homeostasis GO:0060191 regulation of lipase activity GO:0060193 positive regulation of lipase activity GO:0060326 cell chemotaxis GO:0061351 neural precursor cell proliferation GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0070613 regulation of protein processing GO:0070997 neuron death GO:0071621 granulocyte chemotaxis GO:0071622 regulation of granulocyte chemotaxis GO:0071624 positive regulation of granulocyte chemotaxis GO:0071674 mononuclear cell migration GO:0071675 regulation of mononuclear cell migration GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072376 protein activation cascade GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0090022 regulation of neutrophil chemotaxis GO:0090023 positive regulation of neutrophil chemotaxis GO:0097529 myeloid leukocyte migration GO:0097530 granulocyte migration GO:0098542 defense response to other organism GO:1900274 regulation of phospholipase C activity GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death GO:1901342 regulation of vasculature development GO:1902622 regulation of neutrophil migration GO:1902624 positive regulation of neutrophil migration GO:1903317 regulation of protein maturation GO:1904018 positive regulation of vasculature development GO:1990266 neutrophil migration GO:2000147 positive regulation of cell motility GO:2000257 regulation of protein activation cascade
Molecular Function	GO:0001847 opsonin receptor activity GO:0001848 complement binding GO:0001856 complement component C5a binding GO:0004875 complement receptor activity GO:0004878 complement component C5a receptor activity
Cellular Component	GO:0016323 basolateral plasma membrane GO:0045177 apical part of cell

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04080 Neuroactive ligand-receptor interaction hsa04610 Complement and coagulation cascades
Reactome	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-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

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04080 Neuroactive ligand-receptor interaction
hsa04610 Complement and coagulation cascades

Reactome

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-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
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between C5AR1 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

[ TOP ]

Literatures describing the relation between C5AR1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27297552	Melanoma; Lung carcinoma; Breast carcinoma; liver carcinoma	Inhibit immunity	Our findings suggest that complement receptors C3aR and C5aR expressed on CD8(+) TILs represent a novel class of immune checkpoints that could be targeted for tumor immunotherapy.
24786787	Breast Carcinoma	Inhibit immunity (T cell function)	In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8(+) and CD4(+) T-cell responses in the lungs. Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulation of TGFβ and IL10 production in these cells. TGFβ and IL10 favored generation of T regulatory cells (Treg) and Th2-oriented responses that rendered CD8(+) T cells dysfunctional. Importantly, pharmacologic blockade of C5aR or its genetic ablation in C5aR-deficient mice were sufficient to reduce lung metastases. In contrast to previous findings, we observed that C5aR signaling promoted Treg generation and suppressed T-cell responses in organs where metastases arose.

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
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

[ TOP ]

Statistical results of C5AR1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
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

[ TOP ]

Points in the above scatter plot represent the expression difference of C5AR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.066	0.856
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.058	0.965
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.071	0.942
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.07	0.907
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.163	0.439
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.322	0.536
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.165	0.764
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.284	0.826
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.04	0.978
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.186	0.235
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.454	0.356
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.308	0.106

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of C5AR1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of C5AR1. 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 [ TOP ]

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of C5AR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by C5AR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of C5AR1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of C5AR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between C5AR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	C5AR1
Name	complement component 5a receptor 1
Aliases	C5AR; CD88; C5R1; complement component 5 receptor 1 (C5a ligand); C5a anaphylatoxin receptor; C5a ligand; C5 ......
Chromosomal Location	19q13.3-q13.4
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting C5AR1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse C5AR1