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Aliases for C4A Gene

Aliases for C4A Gene

  • Complement Component 4A (Rodgers Blood Group) 2 3
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 2 3 4
  • Acidic Complement C4 3 4
  • CPAMD2 3 4
  • C4AD 3 6
  • CO4 3 4
  • C4S 3 6
  • Complement Component 4A 2
  • Rodgers Form Of C4 3
  • C4A Anaphylatoxin 3
  • Complement C4-A 3
  • EC 2.1.1.144 64
  • Acidic C4 3
  • EC 2.7.11 64
  • C4A2 3
  • C4A3 3
  • C4A4 3
  • C4A6 3
  • C4 3
  • RG 3

External Ids for C4A Gene

Summaries for C4A Gene

Entrez Gene Summary for C4A Gene

  • This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

GeneCards Summary for C4A Gene

C4A (Complement Component 4A (Rodgers Blood Group)) is a Protein Coding gene. Diseases associated with C4A include c4a deficiency and adult respiratory distress syndrome. Among its related pathways are Complement and coagulation cascades and Staphylococcus aureus infection. GO annotations related to this gene include endopeptidase inhibitor activity. An important paralog of this gene is CD109.

UniProtKB/Swiss-Prot for C4A Gene

  • Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens

  • Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes

Gene Wiki entry for C4A Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for C4A Gene

Genomics for C4A Gene

Genomic Location for C4A Gene

Start:
31,982,024 bp from pter
End:
32,002,681 bp from pter
Size:
20,658 bases
Orientation:
Plus strand

Genomic View for C4A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for C4A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Regulatory Elements for C4A Gene

Proteins for C4A Gene

  • Protein details for C4A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P0C0L4-CO4A_HUMAN
    Recommended name:
    Complement C4-A
    Protein Accession:
    P0C0L4
    Secondary Accessions:
    • A6H8M8
    • A6NHJ5
    • A7E2V2
    • B0QZR6
    • B0V2C8
    • B2RUT6
    • B7ZVZ6
    • P01028
    • P78445
    • Q13160
    • Q13906
    • Q14033
    • Q14835
    • Q4LE82
    • Q5JNX2
    • Q5JQM8
    • Q6P4R1
    • Q6U2E5
    • Q6U2E8
    • Q6U2F0
    • Q6U2F3
    • Q6U2F4
    • Q6U2F6
    • Q6U2F8
    • Q6U2G0
    • Q96EG2
    • Q96SA8
    • Q9NPK5
    • Q9UIP5

    Protein attributes for C4A Gene

    Size:
    1744 amino acids
    Molecular mass:
    192785 Da
    Quaternary structure:
    • Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain
    SequenceCaution:
    • Sequence=AAB59537.1; Type=Miscellaneous discrepancy; Note=During cDNA synthesis, the 5 end has been inverted (PubMed:3838531).; Evidence={ECO:0000305 PubMed:3838531}; Sequence=BAE06071.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for C4A Gene

    Alternative splice isoforms for C4A Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for C4A Gene

Proteomics data for C4A Gene at MOPED

Selected DME Specific Peptides for C4A Gene

Post-translational modifications for C4A Gene

  • N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan.
  • Prior to secretion, the single-chain precursor is enzymatically cleaved to yield non-identical chains alpha, beta and gamma. During activation, the alpha chain is cleaved by C1 into C4a and C4b, and C4b stays linked to the beta and gamma chains. Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase. The proteolytic cleavages often are incomplete so that many structural forms can be found in plasma
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn226, Asn862, Thr1244, Asn1328, and Asn1391

Other Protein References for C4A Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for C4A Gene

Gene Families for C4A Gene

HGNC:

UniProtKB/Swiss-Prot:

CO4A_HUMAN
Domain:
  • Contains 1 anaphylatoxin-like domain.:
    • P0C0L4
  • Contains 1 NTR domain.:
    • P0C0L4
genes like me logo Genes that share domains with C4A: view

Function for C4A Gene

Molecular function for C4A Gene

GENATLAS Biochemistry: complement component 4A,primarily expressed in liver and to a lesser extent in immune cells,including the ZA transcript,embedded in intron 35 and overlapping exon 36 (?and others) in the same orientation,expressed specifically in adrenals,under the control of a putative promoter,embedded in intron 35 and containing a potential binding site for steroidogenic factor 1
UniProtKB/Swiss-Prot Function: Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens
UniProtKB/Swiss-Prot Function: Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes

Enzyme Numbers (IUBMB) for C4A Gene

Gene Ontology (GO) - Molecular Function for C4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001849 complement component C1q binding IDA 2395880
GO:0004866 endopeptidase inhibitor activity IEA --
GO:0005515 protein binding --
genes like me logo Genes that share ontologies with C4A: view

No data available for Phenotypes , Animal Models , miRNA , Transcription Factor Targeting and HOMER Transcription for C4A Gene

Localization for C4A Gene

Subcellular locations from UniProtKB/Swiss-Prot for C4A Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for C4A Gene COMPARTMENTS Subcellular localization image for C4A gene
Compartment Confidence
extracellular 5
plasma membrane 4
cytosol 1
mitochondrion 1
nucleus 1

Gene Ontology (GO) - Cellular Components for C4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space --
GO:0005886 plasma membrane TAS --
GO:0070062 extracellular exosome IDA 23533145
GO:0072562 blood microparticle IDA 22516433
genes like me logo Genes that share ontologies with C4A: view

Pathways for C4A Gene

genes like me logo Genes that share pathways with C4A: view

Gene Ontology (GO) - Biological Process for C4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response IEA --
GO:0006956 complement activation TAS --
GO:0006958 complement activation, classical pathway IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0030449 regulation of complement activation TAS --
genes like me logo Genes that share ontologies with C4A: view

Compounds for C4A Gene

(1) Drugbank Compounds for C4A Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Intravenous Immunoglobulin
  • Ig alpha-2 chain C region
9007-83-4 target binder

(11) Novoseek inferred chemical compound relationships for C4A Gene

Compound -log(P) Hits PubMed IDs
anaphylatoxin 71.1 1
bamhi 46.9 1
steroid 29.8 11
hind iii 24.8 2
agarose 16.8 3
genes like me logo Genes that share compounds with C4A: view

Transcripts for C4A Gene

mRNA/cDNA for C4A Gene

(3) REFSEQ mRNAs :
(15) Additional mRNA sequences :
(17) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for C4A Gene

Complement component 4A (Rodgers blood group):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for C4A Gene

No ASD Table

Relevant External Links for C4A Gene

GeneLoc Exon Structure for
C4A
ECgene alternative splicing isoforms for
C4A

Expression for C4A Gene

mRNA expression in normal human tissues for C4A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for C4A Gene

This gene is overexpressed in Liver (18.2) and Adrenal Gland (5.0).

Integrated Proteomics: protein expression from ProteomicsDB, MOPED, and MaxQB for C4A Gene

SOURCE GeneReport for Unigene cluster for C4A Gene Hs.534847

mRNA Expression by UniProt/SwissProt for C4A Gene

P0C0L4-CO4A_HUMAN
Tissue specificity: Complement component C4 is expressed at highest levels in the liver, at moderate levels in the adrenal cortex, adrenal medulla, thyroid gland,and the kidney, and at lowest levels in the heart, ovary, small intestine, thymus, pancreas and spleen. The extra-hepatic sites of expression may be important for the local protection and inflammatory response.
genes like me logo Genes that share expressions with C4A: view

Orthologs for C4A Gene

This gene was present in the common ancestor of chordates.

Orthologs for C4A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia -- 37
  • 99 (a)
ManyToMany
-- 37
  • 99 (a)
ManyToMany
C4A 36
  • 99.33 (n)
  • 98.97 (a)
cow
(Bos Taurus)
Mammalia -- 37
  • 75 (a)
ManyToMany
-- 37
  • 80 (a)
ManyToMany
C4A 36
  • 83.71 (n)
  • 80.24 (a)
dog
(Canis familiaris)
Mammalia -- 37
  • 82 (a)
OneToMany
C4A 36
  • 83.97 (n)
  • 82.21 (a)
mouse
(Mus musculus)
Mammalia C4a 16
C4b 36
  • 79.01 (n)
  • 76.44 (a)
C4b 37
  • 77 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 37
  • 67 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 66 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia C4a 36
  • 80.8 (n)
  • 79.67 (a)
chicken
(Gallus gallus)
Aves C4 36
  • 51.99 (n)
  • 39.64 (a)
C4 37
  • 39 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 37
  • 44 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia c4a 36
  • 49.53 (n)
  • 41.99 (a)
zebrafish
(Danio rerio)
Actinopterygii si:dkey-8k3.2 36
  • 46.95 (n)
  • 37.13 (a)
si:dkey-8k3.2 37
  • 34 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 21 (a)
ManyToMany
CSA.4097 37
  • 22 (a)
ManyToMany
Species with no ortholog for C4A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for C4A Gene

ENSEMBL:
Gene Tree for C4A (if available)
TreeFam:
Gene Tree for C4A (if available)

Paralogs for C4A Gene

Paralogs for C4A Gene

Selected SIMAP similar genes for C4A Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with C4A: view

Variants for C4A Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for C4A Gene

P0C0L4-CO4A_HUMAN
The complement component C4 is the most polymorphic protein of the complement system. It is the product of 2 closely linked and highly homologous genes, C4A and C4B. Once polymorphic variation is discounted, the 2 isotypes differ by only 4 amino acids at positions 1120-1125: PCPVLD for C4A and LSPVIH for C4B. The 2 isotypes bear several antigenic determinants defining Chido/Rodgers blood group system [MIM:614374]. Rodgers determinants are generally associated with C4A allotypes, and Chido with C4B. Variations at these loci involve not only nucleotide polymorphisms, but also gene number and gene size. Some individuals may lack either C4A, or C4B gene. Partial deficiency of C4A or C4B is the most commonly inherited immune deficiency known in humans with a combined frequency over 31% in the normal Caucasian population (PubMed:11367523). C4A6 allotype is deficient in hemolytic activity. Allotype C4A13 is infrequent.

Sequence variations from dbSNP and Humsavar for C4A Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs56157548 -- 31,996,099(+) ATACA(C/T)AGGAG reference, synonymous-codon
rs112683215 -- 31,996,553(+) CCTGC(G/T)GGGTG missense, reference
rs113822282 -- 31,996,097(+) TGATA(C/G)ATAGG missense, reference
rs147162052 - 31,995,782(+) ACGGG(A/G)CAGCA reference, missense
rs201016130 - 31,997,008(+) AGGCT(G/T)CGGCC missense, reference

Structural Variations from Database of Genomic Variants (DGV) for C4A Gene

Variant ID Type Subtype PubMed ID
dgv1928e1 CNV Complex 17122850
nsv428141 CNV Gain+Loss 18775914
dgv1929e1 CNV Complex 17122850
dgv6604n71 CNV Loss 21882294
nsv884514 CNV Loss 21882294
nsv284 CNV Loss 15895083
nsv5247 CNV Loss 18451855
dgv6607n71 CNV Loss 21882294
dgv6608n71 CNV Gain 21882294
dgv6609n71 CNV Loss 21882294
dgv6610n71 CNV Gain 21882294
dgv6611n71 CNV Gain 21882294
dgv6612n71 CNV Loss 21882294
dgv6613n71 CNV Loss 21882294
dgv6614n71 CNV Gain 21882294
dgv6615n71 CNV Gain 21882294
dgv6616n71 CNV Gain+Loss 21882294
esv28110 CNV Gain+Loss 19812545
dgv6617n71 CNV Gain+Loss 21882294
nsv10824 CNV Gain+Loss 18304495
nsv884551 CNV Loss 21882294
nsv884553 CNV Gain 21882294
dgv6618n71 CNV Gain+Loss 21882294
dgv6619n71 CNV Gain 21882294
nsv884566 CNV Loss 21882294
dgv6620n71 CNV Gain 21882294
nsv821566 CNV Deletion 20802225
nsv515035 CNV Complex 21397061
nsv819957 CNV Loss 19587683
dgv6621n71 CNV Gain 21882294
dgv6622n71 CNV Gain+Loss 21882294
nsv884617 CNV Gain 21882294
dgv20n31 CNV Duplication 19718026
nsv884626 CNV Loss 21882294
nsv884627 CNV Loss 21882294
dgv6623n71 CNV Loss 21882294
dgv6624n71 CNV Loss 21882294
dgv6625n71 CNV Gain 21882294
nsv823506 CNV Loss 20364138
nsv823507 CNV Loss 20364138
esv32938 CNV Gain 17666407
dgv6626n71 CNV Gain+Loss 21882294
dgv6627n71 CNV Gain 21882294
dgv6628n71 CNV Loss 21882294
dgv6629n71 CNV Loss 21882294
nsv884657 CNV Gain 21882294
dgv6630n71 CNV Gain+Loss 21882294
dgv6631n71 CNV Loss 21882294
nsv823508 CNV Gain 20364138
nsv884663 CNV Gain 21882294
nsv884664 CNV Gain 21882294
nsv285 CNV Loss 15895083
esv2731825 CNV Deletion 23290073
nsv884665 CNV Loss 21882294
nsv471443 CNV Duplication 19718026
nsv510023 CNV Loss 20534489
nsv511870 CNV Loss 21212237
dgv6632n71 CNV Loss 21882294
nsv499146 CNV Loss 21111241
dgv6633n71 CNV Gain 21882294
nsv884671 CNV Gain 21882294
dgv6634n71 CNV Loss 21882294
nsv433379 CNV Gain 18776910
dgv6635n71 CNV Loss 21882294
dgv6636n71 CNV Loss 21882294
nsv884677 CNV Gain 21882294
nsv5248 CNV Insertion 18451855
dgv6637n71 CNV Gain 21882294

Relevant External Links for C4A Gene

HapMap Linkage Disequilibrium report
C4A
Human Gene Mutation Database (HGMD)
C4A
Blood Group Antigen Gene Mutation Database (BGMUT)
Blood Group

Disorders for C4A Gene

(3) OMIM Diseases for C4A Gene (120810)

UniProtKB/Swiss-Prot

CO4A_HUMAN
  • Complement component 4A deficiency (C4AD) [MIM:614380]: A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. {ECO:0000269 PubMed:8473511}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269 PubMed:10092831, ECO:0000269 PubMed:17503323}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.

(18) Novoseek inferred disease relationships for C4A Gene

Disease -log(P) Hits PubMed IDs
lupus erythematosus systemic 57.9 15
adrenal hyperplasia congenital 54.6 1
feltys syndrome 52.7 1
autoimmune diseases 45.9 3
iga deficiency 43 3

Relevant External Links for C4A

Genetic Association Database (GAD)
C4A
Human Genome Epidemiology (HuGE) Navigator
C4A
genes like me logo Genes that share disorders with C4A: view

Publications for C4A Gene

  1. The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect. (PMID: 1573268) Anderson M.J. … Campbell R.D. (J. Immunol. 1992) 3 4 23
  2. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression. (PMID: 8473511) Barba G. … Schneider P.M. (J. Clin. Invest. 1993) 3 4 23
  3. Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes. (PMID: 10092831) Lokki M.L. … Colten H.R. (J. Immunol. 1999) 3 4 23
  4. Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE). (PMID: 11168010) Dragon-Durey M.A. … Weiss L. (Clin. Exp. Immunol. 2001) 3 23 49
  5. Genetic, structural and functional diversities of human complement components C4A and C4B and their mouse homologues, Slp and C4. (PMID: 11367523) Blanchong C.A. … Yu C.Y. (Int. Immunopharmacol. 2001) 3 4 23

Products for C4A Gene

Sources for C4A Gene

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