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Protein

C5a anaphylatoxin chemotactic receptor 1

Gene

C5AR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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). 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).6 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Chemotaxis

Enzyme and pathway databases

BioCyciZFISH:G66-32295-MONOMER.
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

HGNCiHGNC:1338. C5AR1.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein Sequence analysis
  • Cytoplasmic vesicle 1 Publication

  • Note: Phosphorylated C5aR colocalizes with ARRB1 and ARRB2 in cytoplasmic vesicles.1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37ExtracellularSequence analysisAdd BLAST37
Transmembranei38 – 60Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini61 – 71CytoplasmicSequence analysisAdd BLAST11
Transmembranei72 – 94Helical; Name=2Sequence analysisAdd BLAST23
Topological domaini95 – 110ExtracellularSequence analysisAdd BLAST16
Transmembranei111 – 132Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini133 – 153CytoplasmicSequence analysisAdd BLAST21
Transmembranei154 – 174Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini175 – 200ExtracellularSequence analysisAdd BLAST26
Transmembranei201 – 226Helical; Name=5Sequence analysisAdd BLAST26
Topological domaini227 – 242CytoplasmicSequence analysisAdd BLAST16
Transmembranei243 – 265Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini266 – 282ExtracellularSequence analysisAdd BLAST17
Transmembranei283 – 303Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini304 – 350CytoplasmicSequence analysisAdd BLAST47

GO - Cellular componenti

  • apical part of cell Source: UniProtKB
  • basolateral plasma membrane Source: UniProtKB
  • cell surface Source: Ensembl
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

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...)Sequence analysis1
Modified residuei11Sulfotyrosine1 Publication1
Modified residuei14Sulfotyrosine1 Publication1
Disulfide bondi109 ↔ 188PROSITE-ProRule annotation
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.

PTM databases

iPTMnetiP21730.
PhosphoSitePlusiP21730.

Expressioni

Gene expression databases

BgeeiENSG00000197405.
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

Protein-protein interaction databases

BioGridi107189. 5 interactors.
IntActiP21730. 1 interactor.
STRINGi9606.ENSP00000347197.

Chemistry databases

BindingDBiP21730.

Structurei

3D structure databases

ProteinModelPortaliP21730.
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.
OMAiIWCQNFR.
OrthoDBiEOG091G0DT8.
PhylomeDBiP21730.
TreeFamiTF330976.

Family and domain databases

InterProiIPR001274. Anaphtx_C5AR1/C5AR2.
IPR002234. Anphylx_rcpt.
IPR000826. Formyl_rcpt-rel.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24225. PTHR24225. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01104. ANPHYLATOXNR.
PR00426. C5ANPHYLTXNR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0493772D → N.6 PublicationsCorresponds to variant rs4467185dbSNPEnsembl.1
Natural variantiVAR_049378279K → N.5 PublicationsCorresponds to variant rs11880097dbSNPEnsembl.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

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

ProteinModelPortaliP21730.
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.

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.
GeneCardsiC5AR1.
HGNCiHGNC:1338. C5AR1.
HPAiCAB002720.
HPA014520.
MIMi113995. gene.
neXtProtiNX_P21730.
OpenTargetsiENSG00000197405.
PharmGKBiPA25920.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-32295-MONOMER.
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.
PROiP21730.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197405.
CleanExiHS_C5AR1.
ExpressionAtlasiP21730. baseline and differential.
GenevisibleiP21730. HS.

Family and domain databases

InterProiIPR001274. Anaphtx_C5AR1/C5AR2.
IPR002234. Anphylx_rcpt.
IPR000826. Formyl_rcpt-rel.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24225. PTHR24225. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01104. ANPHYLATOXNR.
PR00426. C5ANPHYLTXNR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiC5AR1_HUMAN
AccessioniPrimary (citable) accession number: P21730
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: November 2, 2010
Last modified: November 30, 2016
This is version 166 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.