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Aliases for C4B_2 Gene

Aliases for C4B_2 Gene

  • Complement Component 4B (Chido Blood Group), Copy 2 2 3
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 3 4
  • Basic Complement C4 4
  • EC 2.1.1.144 61
  • C4B C4B_2 4
  • EC 2.7.11 61
  • CPAMD3 4
  • CO4 4

External Ids for C4B_2 Gene

Previous GeneCards Identifiers for C4B_2 Gene

  • GC06Po31872
  • GC06P031985
  • GC06P8U3282

Summaries for C4B_2 Gene

Entrez Gene Summary for C4B_2 Gene

  • This gene encodes the basic 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 may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. 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. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. This GeneID and its associated RefSeq record represent a second copy of C4B found on ALT_REF_LOCI_7. [provided by RefSeq, Jul 2011]

GeneCards Summary for C4B_2 Gene

C4B_2 (Complement Component 4B (Chido Blood Group), Copy 2) is a Protein Coding gene. Diseases associated with C4B_2 include C4b Deficiency. Among its related pathways are Innate Immune System and Creation of C4 and C2 activators.

UniProtKB/Swiss-Prot for C4B_2 Gene

  • Non-enzymatic component of the 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.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for C4B_2 Gene

Genomics for C4B_2 Gene

Regulatory Elements for C4B_2 Gene

Enhancers for C4B_2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06G003279 1.1 Ensembl ENCODE 0.7 -3.4 -3446 0.4 PKNOX1 RB1 ARNT WRNIP1 ARID4B ZNF2 RAD21 RFX5 SCRT2 ZNF143 TUBB2B PSMG4 ENSG00000228170 C4B_2 PIR47461
GH06G003280 0.9 Ensembl ENCODE 0.7 -1.3 -1265 2.4 JUND GATA2 JUN SIN3A FOS NFE2 NFE2L2 NR2F2 PSMG4 TUBB2B ENSG00000228170 C4B_2 PIR47461
GH06G003269 0.6 ENCODE 0.4 -12.8 -12826 1.4 PAF1 SSRP1 POLR2A CEBPB FEZF1 CREM PSMG4 TUBB2B BPHL ENSG00000228170 PIR47461 C4B_2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around C4B_2 on UCSC Golden Path with GeneCards custom track

Genomic Location for C4B_2 Gene

Chromosome:
6
Start:
3,283,246 bp from pter
End:
3,303,870 bp from pter
Size:
20,625 bases
Orientation:
Plus strand

Genomic View for C4B_2 Gene

Genes around C4B_2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
  • 6p21.3 alternate reference locus by HGNC
GeneLoc Logo Gene Density

RefSeq DNA sequence for C4B_2 Gene

Proteins for C4B_2 Gene

  • Protein details for C4B_2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P0C0L5-CO4B_HUMAN
    Recommended name:
    Complement C4-B
    Protein Accession:
    P0C0L5
    Secondary Accessions:
    • A2BHY4
    • P01028
    • P78445
    • Q13160
    • Q13906
    • Q14033
    • Q14835
    • Q6U2E9
    • Q6U2G1
    • Q6U2I5
    • Q6U2L1
    • Q6U2L7
    • Q6U2L9
    • Q6U2M5
    • Q6VCV8
    • Q96SA7
    • Q9NPK5
    • Q9UIP5

    Protein attributes for C4B_2 Gene

    Size:
    1744 amino acids
    Molecular mass:
    192751 Da
    Quaternary structure:
    • Circulates in blood as a disulfide-linked trimer of alpha, beta and gamma chains.
    • Circulates in blood as a disulfide-linked trimer of alpha, beta and gamma chains.
    SequenceCaution:
    • Sequence=AAA99717.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for C4B_2 Gene

neXtProt entry for C4B_2 Gene

Selected DME Specific Peptides for C4B_2 Gene

P0C0L5:
  • GPGGGDS
  • DLGCGPG

Post-translational modifications for C4B_2 Gene

  • 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.
  • Glycosylation at posLast=226226, posLast=862862, Asn1328, and posLast=13911391
  • Modification sites at PhosphoSitePlus

Other Protein References for C4B_2 Gene

REFSEQ proteins:

Domains & Families for C4B_2 Gene

No data available for Gene Families , Suggested Antigen Peptide Sequences and UniProtKB/Swiss-Prot for C4B_2 Gene

Function for C4B_2 Gene

Molecular function for C4B_2 Gene

UniProtKB/Swiss-Prot Function:
Non-enzymatic component of the 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 C4B_2 Gene

Animal Model Products

No data available for Gene Ontology (GO) - Molecular Function , Phenotypes , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for C4B_2 Gene

Localization for C4B_2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for C4B_2 Gene

Secreted. Cell junction, synapse. Cell projection, axon. Cell projection, dendrite.

No data available for Subcellular locations from COMPARTMENTS and Gene Ontology (GO) - Cellular Components for C4B_2 Gene

Pathways & Interactions for C4B_2 Gene

genes like me logo Genes that share pathways with C4B_2: view

Pathways by source for C4B_2 Gene

Interacting Proteins for C4B_2 Gene

Selected Interacting proteins: P0C0L5-CO4B_HUMAN for C4B_2 Gene via IID

Gene Ontology (GO) - Biological Process for C4B_2 Gene

None

No data available for SIGNOR curated interactions for C4B_2 Gene

Drugs & Compounds for C4B_2 Gene

No Compound Related Data Available

Transcripts for C4B_2 Gene

mRNA/cDNA for C4B_2 Gene

(1) REFSEQ mRNAs :

Alternative Splicing Database (ASD) splice patterns (SP) for C4B_2 Gene

No ASD Table

Relevant External Links for C4B_2 Gene

GeneLoc Exon Structure for
C4B_2
ECgene alternative splicing isoforms for
C4B_2

Expression for C4B_2 Gene

Protein differential expression in normal tissues from HIPED for C4B_2 Gene

This gene is overexpressed in Synovial fluid (25.9) and Vitreous humor (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for C4B_2 Gene



Protein tissue co-expression partners for C4B_2 Gene

NURSA nuclear receptor signaling pathways regulating expression of C4B_2 Gene:

C4B_2

mRNA Expression by UniProt/SwissProt for C4B_2 Gene:

P0C0L5-CO4B_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.

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for C4B_2 Gene

Orthologs for C4B_2 Gene

No data available for Orthologs and Evolution for C4B_2 Gene

Paralogs for C4B_2 Gene

(4) SIMAP similar genes for C4B_2 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with C4B_2: view

No data available for Paralogs for C4B_2 Gene

Variants for C4B_2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for C4B_2 Gene

CO4B_HUMAN-P0C0L5
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. The second copy of C4B gene present in some individuals has been called C4B_2 by the HUGO Gene Nomenclature Committee (HGNC). 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). Common copy-number variants of C4A and C4B affecting expression of complement component C4 in the brain have been associated with schizophrenia risk (PubMed:26814963).

Sequence variations from dbSNP and Humsavar for C4B_2 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs1000726010 -- 31,995,990(+) TTTGG(C/T)CCAGG reference, missense
rs1001158549 -- 31,980,963(+) CTTGA(A/G)CCTAG intron-variant, upstream-variant-2KB
rs1001324282 -- 31,998,009(+) CCAGG(A/C)CTCTT intron-variant
rs1002089632 -- 31,996,854(+) GTCAC(C/T)GGTTC reference, synonymous-codon
rs1004522192 -- 31,996,675(+) GAGGG(A/C)GAGGC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for C4B_2 Gene

Variant ID Type Subtype PubMed ID
dgv10403n54 CNV loss 21841781
dgv10404n54 CNV loss 21841781
dgv10463n54 CNV loss 21841781
dgv10466n54 CNV loss 21841781
dgv10467n54 CNV loss 21841781
dgv10468n54 CNV loss 21841781
dgv10469n54 CNV loss 21841781
dgv10470n54 CNV loss 21841781
dgv10471n54 CNV loss 21841781
dgv10472n54 CNV loss 21841781
dgv10473n54 CNV loss 21841781
dgv10474n54 CNV gain 21841781
dgv10475n54 CNV loss 21841781
dgv10476n54 CNV loss 21841781
dgv10477n54 CNV loss 21841781
dgv10478n54 CNV loss 21841781
dgv10479n54 CNV loss 21841781
dgv10480n54 CNV loss 21841781
dgv10481n54 CNV loss 21841781
dgv10482n54 CNV loss 21841781
dgv10483n54 CNV loss 21841781
dgv10484n54 CNV loss 21841781
dgv20n31 CNV gain 19718026
dgv3474e59 CNV duplication 20981092
dgv3475e59 CNV duplication 20981092
dgv3476e59 CNV duplication 20981092
esv2731825 CNV deletion 23290073
esv2759415 CNV gain+loss 17122850
esv28110 CNV gain+loss 19812545
esv3270051 CNV deletion 24192839
esv32938 CNV gain 17666407
esv3333985 CNV duplication 20981092
esv3334092 CNV duplication 20981092
esv3340418 CNV duplication 20981092
esv3358357 CNV duplication 20981092
esv3413736 CNV duplication 20981092
esv3417384 CNV duplication 20981092
esv3431334 CNV duplication 20981092
esv3450518 CNV duplication 20981092
esv3890824 CNV loss 25118596
esv3890825 CNV loss 25118596
esv3890827 CNV gain+loss 25118596
esv3890828 CNV loss 25118596
nsv1073969 CNV deletion 25765185
nsv10824 CNV gain+loss 18304495
nsv1112900 CNV deletion 24896259
nsv1126749 CNV deletion 24896259
nsv284 CNV deletion 15895083
nsv285 CNV deletion 15895083
nsv428141 CNV gain+loss 18775914
nsv433379 CNV gain 18776910
nsv471443 CNV gain 19718026
nsv499146 CNV loss 21111241
nsv510023 OTHER sequence alteration 20534489
nsv511870 CNV loss 21212237
nsv515035 CNV gain+loss 21397061
nsv5247 CNV deletion 18451855
nsv5248 CNV insertion 18451855
nsv601971 CNV gain 21841781
nsv601988 CNV gain 21841781
nsv601990 CNV loss 21841781
nsv601991 CNV loss 21841781
nsv602004 CNV gain+loss 21841781
nsv602030 CNV loss 21841781
nsv602034 CNV loss 21841781
nsv602038 CNV loss 21841781
nsv602041 CNV loss 21841781
nsv602045 CNV gain 21841781
nsv602050 CNV loss 21841781
nsv602072 CNV loss 21841781
nsv602073 CNV loss 21841781
nsv602074 CNV loss 21841781
nsv602075 CNV loss 21841781
nsv602095 CNV loss 21841781
nsv819957 CNV loss 19587683
nsv821566 CNV deletion 20802225
nsv823506 CNV loss 20364138
nsv823507 CNV loss 20364138
nsv823508 CNV gain 20364138
nsv950155 CNV deletion 24416366
nsv981129 CNV duplication 23825009

Relevant External Links for C4B_2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
C4B_2

No data available for Variation tolerance for C4B_2 Gene

Disorders for C4B_2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for C4B_2 Gene - From: GeneCards

Disorder Aliases PubMed IDs
c4b deficiency
  • complement component 4b deficiency
- elite association - COSMIC cancer census association via MalaCards
Search C4B_2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CO4B_HUMAN
  • Complement component 4B deficiency (C4BD) [MIM:614379]: 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:3265961}. 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.

Relevant External Links for C4B_2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
C4B_2
genes like me logo Genes that share disorders with C4B_2: view

No data available for Genatlas for C4B_2 Gene

Publications for C4B_2 Gene

  1. Linkage analysis of the C4A/C4B copy number variation and polymorphisms of the adjacent steroid 21-hydroxylase gene in a healthy population. (PMID: 19505723) Blasko B. … Szilagyi A. (Mol. Immunol. 2009) 2 3 64
  2. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. (PMID: 17503323) Yang Y. … Yu C.Y. (Am. J. Hum. Genet. 2007) 3 4 64
  3. Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. (PMID: 2431902) Yu C.Y. … Porter R.R. (EMBO J. 1986) 3 4 64
  4. The structural basis of the multiple forms of human complement component C4. (PMID: 6546707) Belt K.T. … Porter R.R. (Cell 1984) 3 4 64
  5. Schizophrenia risk from complex variation of complement component 4. (PMID: 26814963) Sekar A. … McCarroll S.A. (Nature 2016) 4 64

Products for C4B_2 Gene

Sources for C4B_2 Gene

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