P01027 · CO3_MOUSE

  • Protein
    Complement C3
  • Gene
    C3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

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.
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. The short isoform has B-cell stimulatory activity.

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.

Features

Showing features for site.

116632004006008001,0001,2001,4001,600
TypeIDPosition(s)Description
Site747-748Cleavage; by carboxypeptidases
Site748-749Cleavage; by C3 convertase
Site954-955Cleavage; by factor I
Site1303-1304Cleavage; by factor I
Site1320-1321Cleavage; by factor I
Site1663Coordinates Mg2+ for interaction with Complement factor B Bb fragment

GO annotations

AspectTerm
Cellular Componentcell surface
Cellular Componentextracellular region
Cellular Componentextracellular space
Cellular Componentprotein-containing complex
Molecular FunctionC5L2 anaphylatoxin chemotactic receptor binding
Molecular Functionendopeptidase inhibitor activity
Molecular Functionlipid binding
Biological Processamyloid-beta clearance
Biological Processcomplement activation
Biological Processcomplement activation, alternative pathway
Biological Processcomplement activation, classical pathway
Biological Processcomplement receptor mediated signaling pathway
Biological Processcomplement-dependent cytotoxicity
Biological Processcomplement-mediated synapse pruning
Biological Processfatty acid metabolic process
Biological Processinflammatory response
Biological Processneuron remodeling
Biological Processoviduct epithelium development
Biological Processpositive regulation of activation of membrane attack complex
Biological Processpositive regulation of angiogenesis
Biological Processpositive regulation of apoptotic cell clearance
Biological Processpositive regulation of developmental growth
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of G protein-coupled receptor signaling pathway
Biological Processpositive regulation of glucose transmembrane transport
Biological Processpositive regulation of lipid storage
Biological Processpositive regulation of phagocytosis
Biological Processpositive regulation of phagocytosis, engulfment
Biological Processpositive regulation of protein phosphorylation
Biological Processpositive regulation of receptor-mediated endocytosis
Biological Processpositive regulation of type IIa hypersensitivity
Biological Processpositive regulation of vascular endothelial growth factor production
Biological Processregulation of triglyceride biosynthetic process
Biological Processresponse to bacterium
Biological Processvertebrate eye-specific patterning

Keywords

Enzyme and pathway databases

    • R-MMU-173736Alternative complement activation
    • R-MMU-174577Activation of C3 and C5
    • R-MMU-198933Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
    • R-MMU-375276Peptide ligand-binding receptors
    • R-MMU-381426Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Protein family/group databases

Names & Taxonomy

Protein names

Gene names

    • Name
      C3

Organism names

  • Taxonomic identifier
  • Strain
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P01027
  • Secondary accessions
    • Q61370
    • Q80XP1

Proteomes

Organism-specific databases

Phenotypes & Variants

Disruption phenotype

Null mice displayed altered lipid metabolism and morphological changes in adipocyte distribution. There is reduced adipsin/CFD expression, increased number of smaller fat cells, decreased DGAT1 expression and activity, and less triglyceride storage capacity associated with delayed postprandial clearance. Mice on a high-fat diet exhibited no diet-induced up-regulation of adipsin/CFD expression nor adipocyte differentiation.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 93 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, modified residue, disulfide bond, glycosylation, cross-link, peptide.

TypeIDPosition(s)Description
Signal1-24
ChainPRO_000000591825-666Complement C3 beta chain
ChainPRO_000000591725-1663Complement C3
Modified residue40Phosphoserine
Disulfide bond559↔816Interchain (between beta and alpha chains)
ChainPRO_0000430431569-666C3-beta-c
Disulfide bond626↔661
Modified residue671Phosphoserine
ChainPRO_0000419936671-747Acylation stimulating protein
ChainPRO_0000005920671-748C3a anaphylatoxin
ChainPRO_0000005919671-1663Complement C3 alpha chain
Disulfide bond693↔720
Disulfide bond694↔727
Disulfide bond707↔728
ChainPRO_0000005922749-954Complement C3c alpha' chain fragment 1
ChainPRO_0000005921749-1663Complement C3b alpha' chain
Disulfide bond873↔1513
Glycosylation939N-linked (GlcNAc...) asparagine
ChainPRO_0000005924955-1001Complement C3g fragment
ChainPRO_0000005923955-1303Complement C3dg fragment
Modified residue968Phosphoserine
ChainPRO_00000059251002-1303Complement C3d fragment
Cross-link1010↔1013Isoglutamyl cysteine thioester (Cys-Gln)
Disulfide bond1101↔1158
PeptidePRO_00000059271304-1320Complement C3f fragment
Modified residue1321Phosphoserine
ChainPRO_00002739491321-1663Complement C3c alpha' chain fragment 2
Disulfide bond1358↔1489
Disulfide bond1389↔1458
Disulfide bond1506↔1511
Disulfide bond1518↔1590
Disulfide bond1537↔1661
Modified residue1573Phosphoserine
Glycosylation1617N-linked (GlcNAc...) asparagine
Disulfide bond1637↔1646

Post-translational modification

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 dietary chylomicrons.
Phosphorylated by FAM20C in the extracellular medium.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

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). Forms the pro-C3-convertase enzyme complex by interacting with Complement factor B Bb fragment (Bb), which is then stabilized by binding CFP, allowing the complex to become active (By similarity).
The interaction with Bb is dependent on Mg2+ (By similarity).
Part of a complex composed of complement component C3, CLCA1/CLCA3, A2ML1/OH and ALB/serum albumin (PubMed:30899053).
C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains). C3b interacts with CFH. C3d interacts with CFH. 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. 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
View interactors in UniProtKB
View CPX-5893 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain693-728Anaphylatoxin-like
Domain1518-1661NTR
Region1634-1659Interaction with CFP/properdin

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.

This entry describes 2 isoforms produced by Alternative initiation.

P01027-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    Long
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    1,663
  • Mass (Da)
    186,484
  • Last updated
    2011-07-27 v3
  • Checksum
    7E5546CC7C314779
MGPASGSQLLVLLLLLASSPLALGIPMYSIITPNVLRLESEETIVLEAHDAQGDIPVTVTVQDFLKRQVLTSEKTVLTGASGHLRSVSIKIPASKEFNSDKEGHKYVTVVANFGETVVEKAVMVSFQSGYLFIQTDKTIYTPGSTVLYRIFTVDNNLLPVGKTVVILIETPDGIPVKRDILSSNNQHGILPLSWNIPELVNMGQWKIRAFYEHAPKQIFSAEFEVKEYVLPSFEVRVEPTETFYYIDDPNGLEVSIIAKFLYGKNVDGTAFVIFGVQDGDKKISLAHSLTRVVIEDGVGDAVLTRKVLMEGVRPSNADALVGKSLYVSVTVILHSGSDMVEAERSGIPIVTSPYQIHFTKTPKFFKPAMPFDLMVFVTNPDGSPASKVLVVTQGSNAKALTQDDGVAKLSINTPNSRQPLTITVRTKKDTLPESRQATKTMEAHPYSTMHNSNNYLHLSVSRMELKPGDNLNVNFHLRTDPGHEAKIRYYTYLVMNKGKLLKAGRQVREPGQDLVVLSLPITPEFIPSFRLVAYYTLIGASGQREVVADSVWVDVKDSCIGTLVVKGDPRDNHLAPGQQTTLRIEGNQGARVGLVAVDKGVFVLNKKNKLTQSKIWDVVEKADIGCTPGSGKNYAGVFMDAGLAFKTSQGLQTEQRADLECTKPAARRRRSVQLMERRMDKAGQYTDKGLRKCCEDGMRDIPMRYSCQRRARLITQGENCIKAFIDCCNHITKLREQHRRDHVLGLARSELEEDIIPEEDIISRSHFPQSWLWTIEELKEPEKNGISTKVMNIFLKDSITTWEILAVSLSDKKGICVADPYEIRVMQDFFIDLRLPYSVVRNEQVEIRAVLFNYREQEELKVRVELLHNPAFCSMATAKNRYFQTIKIPPKSSVAVPYVIVPLKIGQQEVEVKAAVFNHFISDGVKKTLKVVPEGMRINKTVAIHTLDPEKLGQGGVQKVDVPAADLSDQVPDTDSETRIILQGSPVVQMAEDAVDGERLKHLIVTPAGCGEQNMIGMTPTVIAVHYLDQTEQWEKFGIEKRQEALELIKKGYTQQLAFKQPSSAYAAFNNRPPSTWLTAYVVKVFSLAANLIAIDSHVLCGAVKWLILEKQKPDGVFQEDGPVIHQEMIGGFRNAKEADVSLTAFVLIALQEARDICEGQVNSLPGSINKAGEYIEASYMNLQRPYTVAIAGYALALMNKLEEPYLGKFLNTAKDRNRWEEPDQQLYNVEATSYALLALLLLKDFDSVPPVVRWLNEQRYYGGGYGSTQATFMVFQALAQYQTDVPDHKDLNMDVSFHLPSRSSATTFRLLWENGNLLRSEETKQNEAFSLTAKGKGRGTLSVVAVYHAKLKSKVTCKKFDLRVSIRPAPETAKKPEEAKNTMFLEICTKYLGDVDATMSILDISMMTGFAPDTKDLELLASGVDRYISKYEMNKAFSNKNTLIIYLEKISHTEEDCLTFKVHQYFNVGLIQPGSVKVYSYYNLEESCTRFYHPEKDDGMLSKLCHSEMCRCAEENCFMQQSQEKINLNVRLDKACEPGVDYVYKTELTNIELLDDFDEYTMTIQQVIKSGSDEVQAGQQRKFISHIKCRNALKLQKGKKYLMWGLSSDLWGEKPNTSYIIGKDTWVEHWPEAEECQDQKYQKQCEELGAFTESMVVYGCPN

P01027-2

  • Name
    Short
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
H3BKW9H3BKW9_MOUSEC3185
H3BL60H3BL60_MOUSEC3102

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0187081-1128in isoform Short
Sequence conflict137in Ref. 6; AAA37339
Sequence conflict858in Ref. 1; AAC42013
Sequence conflict1553in Ref. 1; AAC42013 and 10; AAA37336

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
K02782
EMBL· GenBank· DDBJ
AAC42013.1
EMBL· GenBank· DDBJ
mRNA
BC043338
EMBL· GenBank· DDBJ
AAH43338.1
EMBL· GenBank· DDBJ
mRNA
M35659
EMBL· GenBank· DDBJ
AAA37339.1
EMBL· GenBank· DDBJ
mRNA
M33032
EMBL· GenBank· DDBJ
AAA37378.1
EMBL· GenBank· DDBJ
mRNA
J00369
EMBL· GenBank· DDBJ
AAA37336.1
EMBL· GenBank· DDBJ
Genomic DNA
J00367
EMBL· GenBank· DDBJ
AAA37336.1
EMBL· GenBank· DDBJ
Genomic DNA
Z37998
EMBL· GenBank· DDBJ
CAA86099.2
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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