Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

C5a anaphylatoxin chemotactic receptor 1

Gene

C5AR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).7 Publications

GO - Molecular functioni

  • complement component C5a binding Source: Ensembl
  • complement component C5a receptor activity Source: UniProtKB
  • G protein-coupled receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processChemotaxis

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-6798695 Neutrophil degranulation
R-HSA-977606 Regulation of Complement cascade
SignaLinkiP21730
SIGNORiP21730

Names & Taxonomyi

Protein namesi
Recommended name:
C5a anaphylatoxin chemotactic receptor 1
Alternative name(s):
C5a anaphylatoxin chemotactic receptor
Short name:
C5a-R
Short name:
C5aR
CD_antigen: CD88
Gene namesi
Name:C5AR1
Synonyms:C5AR, C5R1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000197405.7
HGNCiHGNC:1338 C5AR1
MIMi113995 gene
neXtProtiNX_P21730

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37Extracellular1 PublicationAdd BLAST37
Transmembranei38 – 64Helical; Name=11 PublicationAdd BLAST27
Topological domaini65 – 69Cytoplasmic1 Publication5
Transmembranei70 – 93Helical; Name=21 PublicationAdd BLAST24
Topological domaini94 – 110Extracellular1 PublicationAdd BLAST17
Transmembranei111 – 132Helical; Name=31 PublicationAdd BLAST22
Topological domaini133 – 153Cytoplasmic1 PublicationAdd BLAST21
Transmembranei154 – 174Helical; Name=41 PublicationAdd BLAST21
Topological domaini175 – 200Extracellular1 PublicationAdd BLAST26
Transmembranei201 – 226Helical; Name=51 PublicationAdd BLAST26
Topological domaini227 – 242Cytoplasmic1 PublicationAdd BLAST16
Transmembranei243 – 265Helical; Name=61 PublicationAdd BLAST23
Topological domaini266 – 282Extracellular1 PublicationAdd BLAST17
Transmembranei283 – 303Helical; Name=71 PublicationAdd BLAST21
Topological domaini304 – 350Cytoplasmic1 PublicationAdd BLAST47

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2 – 30Missing : Strongly impairs C5a binding (45,000-fold). 1 PublicationAdd BLAST29
Mutagenesisi2 – 22Missing : Impairs C5a binding. Strongly impairs C5a binding; when associated with A-27. 1 PublicationAdd BLAST21
Mutagenesisi10D → A: Strongly impairs C5a binding; when associated with A-15; A-16; A-18 and A-21 (PubMed:8182049). Moderately impairs CHIPS binding (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-15 (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-18 (PubMed:15542591). 2 Publications1
Mutagenesisi11Y → F: Weakly impairs CHIPS binding. Loss of CHIPS binding; when associated with F-14. 1 Publication1
Mutagenesisi12G → A: Moderately impairs CHIPS binding. 1 Publication1
Mutagenesisi14Y → F: Weakly impairs CHIPS binding (PubMed:15542591). Strongly impairs CHIPS binding (PubMed:21706042). Loss of CHIPS binding; when associated with F-11 (PubMed:21706042). 2 Publications1
Mutagenesisi15D → A: Strongly impairs C5a binding; when associated with A-10; A-16; A-18 and A-21 (PubMed:8182049). Moderately impairs CHIPS binding (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-10 (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-18 (PubMed:15542591). 2 Publications1
Mutagenesisi16D → A: Strongly impairs C5a binding; when associated with A-10; A-15; A-18 and A-21. 1 Publication1
Mutagenesisi18D → A: Strongly impairs C5a binding; when associated with A-10; A-15; A-16 and A-21 (PubMed:8182049). Impairs CHIPS binding (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-10 (PubMed:15542591). Strongly impairs CHIPS binding; when associated with A-15 (PubMed:15542591). 2 Publications1
Mutagenesisi21D → A: Strongly impairs C5a binding; when associated with A-10; A-15; A-16 and A-18. 1 Publication1
Mutagenesisi27D → A: Strongly impairs C5a binding; when associated with 2-D--L-22 Del. 1 Publication1
Mutagenesisi144C → S: Fails to homodimerize. 1 Publication1
Mutagenesisi157C → S: No effect on homodimer formation. 1 Publication1
Mutagenesisi199E → Q: Impairs C5a binding (10-fold reduction) and C5a-induced 5-HT secretion. 1 Publication1
Mutagenesisi221C → S: No effect on homodimer formation. 1 Publication1

Organism-specific databases

DisGeNETi728
OpenTargetsiENSG00000197405
PharmGKBiPA25920

Chemistry databases

ChEMBLiCHEMBL2373
GuidetoPHARMACOLOGYi32

Polymorphism and mutation databases

BioMutaiC5AR1
DMDMi311033355

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692091 – 350C5a anaphylatoxin chemotactic receptor 1Add BLAST350

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi5N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei11Sulfotyrosine1 Publication1
Modified residuei14Sulfotyrosine1 Publication1
Disulfide bondi109 ↔ 188PROSITE-ProRule annotationCombined sources1 Publication
Modified residuei314Phosphoserine1 Publication1
Modified residuei317Phosphoserine2 Publications1
Modified residuei327Phosphoserine2 Publications1
Modified residuei332Phosphoserine2 Publications1
Modified residuei334Phosphoserine2 Publications1
Modified residuei338Phosphoserine2 Publications1

Post-translational modificationi

Sulfation plays a critical role in the association of C5aR with C5a, but no significant role in the ability of the receptor to transduce a signal and mobilize calcium in response to a small a small peptide agonist (PubMed:11342590). Sulfation at Tyr-14 is important for CHIPS binding (PubMed:21706042).1 Publication1 Publication
Phosphorylated on serine residues in response to C5a binding, resulting in internalization of the receptor and short-term desensitization to the ligand. The key residues involved in this process are Ser-334 and Ser-338.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation

Proteomic databases

PaxDbiP21730
PeptideAtlasiP21730
PRIDEiP21730
ProteomicsDBi53893

PTM databases

iPTMnetiP21730
PhosphoSitePlusiP21730

Expressioni

Gene expression databases

BgeeiENSG00000197405 Expressed in 166 organ(s), highest expression level in blood
CleanExiHS_C5AR1
ExpressionAtlasiP21730 baseline and differential
GenevisibleiP21730 HS

Organism-specific databases

HPAiCAB002720
HPA014520

Interactioni

Subunit structurei

Homodimer. May also form higher-order oligomers (PubMed:12835319). Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of C5aR (PubMed:12464600). Interacts (via N-terminal domain) with S.aureus chemotaxis inhibitory protein (CHIPS); the interaction blocks the receptor and may thus inhibit the immune response (PubMed:15153520, PubMed:15542591, PubMed:21706042).1 Publication5 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107189, 5 interactors
IntActiP21730, 1 interactor
STRINGi9606.ENSP00000347197

Chemistry databases

BindingDBiP21730

Structurei

Secondary structure

1350
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP21730
SMRiP21730
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni10 – 18Required for CHIPS binding1 Publication9
Regioni21 – 30Involved in C5a binding1 Publication10

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF0K Eukaryota
ENOG410Y9HH LUCA
GeneTreeiENSGT00760000118990
HOGENOMiHOG000234122
HOVERGENiHBG107547
InParanoidiP21730
KOiK04010
OMAiNPIWCQN
OrthoDBiEOG091G0DT8
PhylomeDBiP21730
TreeFamiTF330976

Family and domain databases

InterProiView protein in InterPro
IPR001274 Anaphtx_C5AR1/C5AR2
IPR002234 Anphylx_rcpt
IPR000826 Formyl_rcpt-rel
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24225 PTHR24225, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01104 ANPHYLATOXNR
PR00426 C5ANPHYLTXNR
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P21730-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDSFNYTTPD YGHYDDKDTL DLNTPVDKTS NTLRVPDILA LVIFAVVFLV
60 70 80 90 100
GVLGNALVVW VTAFEAKRTI NAIWFLNLAV ADFLSCLALP ILFTSIVQHH
110 120 130 140 150
HWPFGGAACS ILPSLILLNM YASILLLATI SADRFLLVFK PIWCQNFRGA
160 170 180 190 200
GLAWIACAVA WGLALLLTIP SFLYRVVREE YFPPKVLCGV DYSHDKRRER
210 220 230 240 250
AVAIVRLVLG FLWPLLTLTI CYTFILLRTW SRRATRSTKT LKVVVAVVAS
260 270 280 290 300
FFIFWLPYQV TGIMMSFLEP SSPTFLLLKK LDSLCVSFAY INCCINPIIY
310 320 330 340 350
VVAGQGFQGR LRKSLPSLLR NVLTEESVVR ESKSFTRSTV DTMAQKTQAV
Length:350
Mass (Da):39,336
Last modified:November 2, 2010 - v2
Checksum:i9334BB39A2C96D3D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QZK7M0QZK7_HUMAN
C5a anaphylatoxin chemotactic recep...
C5AR1
17Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0493772D → N6 PublicationsCorresponds to variant dbSNP:rs4467185Ensembl.1
Natural variantiVAR_049378279K → N5 PublicationsCorresponds to variant dbSNP:rs11880097Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62505 mRNA Translation: AAA62831.1
X57250 mRNA Translation: CAA40530.1
X58674 Genomic DNA Translation: CAB37830.1
AY221091 Genomic DNA Translation: AAO65969.1
BT007358 mRNA Translation: AAP36022.1
AC099491 Genomic DNA No translation available.
BC008982 mRNA Translation: AAH08982.1
S56556, S56557 Genomic DNA Translation: AAD14919.1
CCDSiCCDS33063.1
PIRiA37963
RefSeqiNP_001727.1, NM_001736.3
UniGeneiHs.2161

Genome annotation databases

EnsembliENST00000355085; ENSP00000347197; ENSG00000197405
GeneIDi728
KEGGihsa:728
UCSCiuc002pgj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M62505 mRNA Translation: AAA62831.1
X57250 mRNA Translation: CAA40530.1
X58674 Genomic DNA Translation: CAB37830.1
AY221091 Genomic DNA Translation: AAO65969.1
BT007358 mRNA Translation: AAP36022.1
AC099491 Genomic DNA No translation available.
BC008982 mRNA Translation: AAH08982.1
S56556, S56557 Genomic DNA Translation: AAD14919.1
CCDSiCCDS33063.1
PIRiA37963
RefSeqiNP_001727.1, NM_001736.3
UniGeneiHs.2161

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5O9HX-ray2.70A/B31-333[»]
6C1QX-ray2.90B30-331[»]
6C1RX-ray2.20B30-331[»]
ProteinModelPortaliP21730
SMRiP21730
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107189, 5 interactors
IntActiP21730, 1 interactor
STRINGi9606.ENSP00000347197

Chemistry databases

BindingDBiP21730
ChEMBLiCHEMBL2373
GuidetoPHARMACOLOGYi32

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP21730
PhosphoSitePlusiP21730

Polymorphism and mutation databases

BioMutaiC5AR1
DMDMi311033355

Proteomic databases

PaxDbiP21730
PeptideAtlasiP21730
PRIDEiP21730
ProteomicsDBi53893

Protocols and materials databases

DNASUi728
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355085; ENSP00000347197; ENSG00000197405
GeneIDi728
KEGGihsa:728
UCSCiuc002pgj.2 human

Organism-specific databases

CTDi728
DisGeNETi728
EuPathDBiHostDB:ENSG00000197405.7
GeneCardsiC5AR1
HGNCiHGNC:1338 C5AR1
HPAiCAB002720
HPA014520
MIMi113995 gene
neXtProtiNX_P21730
OpenTargetsiENSG00000197405
PharmGKBiPA25920
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF0K Eukaryota
ENOG410Y9HH LUCA
GeneTreeiENSGT00760000118990
HOGENOMiHOG000234122
HOVERGENiHBG107547
InParanoidiP21730
KOiK04010
OMAiNPIWCQN
OrthoDBiEOG091G0DT8
PhylomeDBiP21730
TreeFamiTF330976

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-6798695 Neutrophil degranulation
R-HSA-977606 Regulation of Complement cascade
SignaLinkiP21730
SIGNORiP21730

Miscellaneous databases

ChiTaRSiC5AR1 human
GeneWikiiC5a_receptor
GenomeRNAii728
PROiPR:P21730
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197405 Expressed in 166 organ(s), highest expression level in blood
CleanExiHS_C5AR1
ExpressionAtlasiP21730 baseline and differential
GenevisibleiP21730 HS

Family and domain databases

InterProiView protein in InterPro
IPR001274 Anaphtx_C5AR1/C5AR2
IPR002234 Anphylx_rcpt
IPR000826 Formyl_rcpt-rel
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR24225 PTHR24225, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01104 ANPHYLATOXNR
PR00426 C5ANPHYLTXNR
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiC5AR1_HUMAN
AccessioniPrimary (citable) accession number: P21730
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: November 2, 2010
Last modified: November 7, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  8. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again