My NCBISign In

Display Settings:

Format

Send to:

Choose Destination

    C4B complement component 4B (Chido blood group) [ Homo sapiens ]

    Gene ID: 721, updated on 11-May-2012
    Help top of page

    Summary

    Official Symbol
    C4Bprovided by HGNC
    Official Full Name
    complement component 4B (Chido blood group)provided by HGNC
    Primary source
    HGNC:1324
    Locus tag
    DADB-112B14.11-001
    See related
    Ensembl:ENSG00000224389; HPRD:00402; HPRD:18631; MIM:120820; Vega:OTTHUMG00000031187
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CH; C4F; CO4; C4B1; C4B2; C4B3; C4B5; C4BD; C4B12; CPAMD3; FLJ60561; MGC164979
    Summary
    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. [provided by RefSeq, Jul 2008]
    Help top of page

    Genomic context

    Location :
    6p21.3
    Sequence :
    Chromosome: 6; NC_000006.11 (31982572..32003195)
    See C4B in Epigenomics, MapViewer

    Chromosome 6 - NC_000006.11Genomic Context describing neighboring genes Neighboring gene cytochrome P450, family 21, subfamily A, polypeptide 1 pseudogene Neighboring gene tenascin XA (pseudogene) Neighboring gene serine/threonine kinase 19 pseudogene Neighboring gene cytochrome P450, family 21, subfamily A, polypeptide 2 Neighboring gene tenascin XB Neighboring gene activating transcription factor 6 beta

    Help top of page

    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
    Helptop of page

    Bibliography

    Related articles in PubMed

    1. Inhibition of CXCL10 release by monomeric C3bi and C4b. Takeda Y, et al. Clin Exp Immunol, 2012 Jan. PMID 22132894.
    2. Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. Boteva L, et al. PLoS One, 2011. PMID 21857912.
    3. Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation. Avirutnan P, et al. J Immunol, 2011 Jul 1. PMID 21642539.
    4. C4d analysis in endomyocardial biopsies of heart transplant patients: is there a correlation with hemodynamic data? Boffini M, et al. Transplant Proc, 2011 May. PMID 21620080.
    5. Transcriptional repression of C4 complement by hepatitis C virus proteins. Banerjee A, et al. J Virol, 2011 May. PMID 21345967.

    See all (116) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Data show that in the UK cohort, total C4 GCN ranged from 2 to 6, with copy numbers from 0 to 4 observed for both C4A and C4B, while in the Spanish cohort, C4A GCN from 0 to 6 and C4B GCN from 0 to 5.
      Title: Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations.
    2. Purified C4b inhibited IFN-beta-induced CXCL10 production & STAT1 phosphorylation.
      Title: Inhibition of CXCL10 release by monomeric C3bi and C4b.
    3. Findings suggest that significant allograft dysfunction is not related to C4d positivity in heart transplant recipients.
      Title: C4d analysis in endomyocardial biopsies of heart transplant patients: is there a correlation with hemodynamic data?
    4. Flavivirus soluble nonstructural protein NS1 recruits human complement 4b-binding protein (C4BP) to the surface of cells in order to inactivate C4b on the plasma membrane.
      Title: Binding of flavivirus nonstructural protein NS1 to C4b binding protein modulates complement activation.
    5. C4 mRNA levels of the two isoforms (C4A and C4B) were significantly reduced in hepatocytes transfected with RNA from HCV genotype 1a or 2a.
      Title: Transcriptional repression of C4 complement by hepatitis C virus proteins.
    6. Data indicate that the deposition of both C4 and C3 showed a significant positive correlation with the serum concentration of Ficolin-3.
      Title: Functional analysis of Ficolin-3 mediated complement activation.
    7. Homozygous complement C4B deficiency is described in a female patient with membranoproliferative glomerulonephritis type III characterized by renal biopsies with strong complement C4 and IgG deposits.
      Title: Familial C4B deficiency and immune complex glomerulonephritis.
    8. The physiology and molecular basis of the Chido blood-group system is discussed. Review.
      Title: A review of the Chido/Rodgers blood group.
    9. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    10. C4B null allele has a significant risk for association with autism and may indicate its possible contributing role to autoimmunity in autism.
      Title: The link of C4B null allele to autism and to a family history of autoimmunity in Egyptian autistic children.
    Submit: New GeneRIF Correction See all (62)
    Help top of page

    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    C4 deficiency

    C4B deficiency

    Help top of page

    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Preincubation of HIV-1 gp41 with either factor H or properdin, and of HIV-1 gp120 with C3b or C4b affect the interaction between HIV-1 gp41 and gp120 PubMed
    env A synthetic peptide covering positions 233-251 of the HIV-1 gp120 protein binds to complement proteins C3, C4, C5, C9, and properdin PubMed
    env Complement proteins C4, C3d, C5b-9, and properdin bind to HIV-1 gp120-coated CD4+ T cells of healthy individuals when incubated in autologous serum PubMed
    env Amino acid residues 410-449 of HIV-1 gp120 are involved in its binding to C4b PubMed

    Go to the HIV-1, Human Protein Interaction Database

    Help top of page

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Complement component 4B, telomeric P04003 C4BPA    HPRD  PubMed  
    BioGRID:107182 BioGRID:107178 C2    BioGRID  PubMed Reconstituted Complex 
    Help top of page

    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Complement Activation, Classical Pathway, organism-specific biosystem (from WikiPathways)
      Complement Activation, Classical Pathway, organism-specific biosystemThe complement system is a biochemical cascade that helps, or ???complements???, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immun...
    • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
      Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Complement and coagulation cascades, conserved biosystem (from KEGG)
      Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
    • Pertussis, organism-specific biosystem (from KEGG)
      Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
    • Pertussis, conserved biosystem (from KEGG)
      Pertussis, conserved biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
    • SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
      SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
    • Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
      Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
    • Staphylococcus aureus infection, conserved biosystem (from KEGG)
      Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
    • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
      Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
    • Systemic lupus erythematosus, conserved biosystem (from KEGG)
      Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    endopeptidase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    complement activation TAS
    Traceable Author Statement
    more info
    		  
    complement activation, classical pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    inflammatory response IEA
    Inferred from Electronic Annotation
    more info
    		  
    innate immune response TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    extracellular region TAS
    Traceable Author Statement
    more info
    		  
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    complement C4-B
    Names
    complement C4-B
    Chido form of C4
    complement C4B1a
    basic complement C4
    C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3
    Help top of page

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011639.1 RefSeqGene

      Range
      5002..25625
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_138

    mRNA and Protein(s)

    1. NM_001002029.3 → NP_001002029.3  complement C4-B preproprotein

      Status: REVIEWED

      Source sequence(s)
      BC151204, BM672834, BQ960796, CD624022, DA395398, DA918359, K02404
      Consensus CDS
      CCDS47405.1
      UniProtKB/TrEMBL
      A7E2V2
      UniProtKB/Swiss-Prot
      P0C0L5
      UniProtKB/TrEMBL
      Q6U2E9
      Related
      ENSP00000415941, OTTHUMP00000029269, ENST00000435363, OTTHUMT00000076368
      Conserved Domains (10) summary
      cd00017
      Location:686 – 750
      Blast Score: 211
      ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...
      cd02896
      Location:996 – 1315
      Blast Score: 857
      complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...
      COG2373
      Location:141 – 482
      Blast Score: 173
      COG2373; Large extracellular alpha-helical protein [General function prediction only]
      cd03584
      Location:1588 – 1742
      Blast Score: 628
      NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...
      pfam00207
      Location:782 – 869
      Blast Score: 306
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:140 – 233
      Blast Score: 228
      A2M_N; MG2 domain
      pfam07677
      Location:1481 – 1570
      Blast Score: 355
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1051 – 1317
      Blast Score: 686
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:478 – 610
      Blast Score: 265
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam11974
      Location:20 – 90
      Blast Score: 91
      MG1; Alpha-2-macroglobulin MG1 domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000006.11 Reference GRCh37.p5 Primary Assembly

      Range
      31982572..32003195
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.2 Reference GRCh37.p5 ALT_REF_LOCI_2

      Range
      3459590..3473846
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.1 Reference GRCh37.p5 ALT_REF_LOCI_3

      Range
      3268155..3282411
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.1

      Range
      3362383..3383040
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_003403595.1 → XP_003403643.1  

      UniProtKB/TrEMBL
      B0V2C8
      Conserved Domains (10) summary
      cd00017
      Location:686 – 750
      Blast Score: 210
      ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...
      cd02896
      Location:996 – 1315
      Blast Score: 845
      complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...
      COG2373
      Location:141 – 482
      Blast Score: 171
      COG2373; Large extracellular alpha-helical protein [General function prediction only]
      cd03584
      Location:1588 – 1742
      Blast Score: 627
      NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...
      pfam00207
      Location:782 – 869
      Blast Score: 306
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:140 – 233
      Blast Score: 228
      A2M_N; MG2 domain
      pfam07677
      Location:1481 – 1570
      Blast Score: 355
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1051 – 1317
      Blast Score: 676
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:478 – 610
      Blast Score: 265
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam11974
      Location:20 – 90
      Blast Score: 91
      MG1; Alpha-2-macroglobulin MG1 domain

    2. XM_003403596.1 → XP_003403644.1  

      UniProtKB/TrEMBL
      F8VZD8
      Conserved Domains (10) summary
      cd00017
      Location:686 – 750
      Blast Score: 211
      ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...
      cd02896
      Location:996 – 1315
      Blast Score: 845
      complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...
      COG2373
      Location:141 – 482
      Blast Score: 171
      COG2373; Large extracellular alpha-helical protein [General function prediction only]
      cd03584
      Location:1542 – 1696
      Blast Score: 627
      NTR_complement_C4; NTR/C345C domain, complement C4 subfamily; The NTR domain found in complement C4 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C4 is a key player in the activation of the component classical ...
      pfam00207
      Location:782 – 869
      Blast Score: 306
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:140 – 233
      Blast Score: 228
      A2M_N; MG2 domain
      pfam07677
      Location:1457 – 1524
      Blast Score: 270
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1051 – 1317
      Blast Score: 676
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:478 – 610
      Blast Score: 266
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      pfam11974
      Location:20 – 90
      Blast Score: 91
      MG1; Alpha-2-macroglobulin MG1 domain

    Reference GRCh37.p5 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.1 Reference GRCh37.p5 ALT_REF_LOCI_7

      Range
      3315282..3335906
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. NW_001841922.1 Alternate HuRef

      Range
      1..5389, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01138727.1 (2591..9318) None
    genomic AF019413.1 AAB67980.1
    genomic AF092085.1 AAC98380.1
    genomic AL049547.10 CAB89302.1
    genomic AL645922.12 (111059..131682) None
    genomic AL662849.8 (68222..82477) None
    genomic AL929593.6 (2000..5339) None
    genomic AY343497.1 AAQ99144.1
    genomic AY379860.1 AAR89087.1
    genomic AY379861.1 AAR89088.1
    genomic AY379862.1 AAR89089.1
    genomic AY379863.1 AAR89090.1
    genomic AY379865.1 AAR89092.1
    genomic AY379867.1 AAR89094.1
    genomic AY379868.1 AAR89095.1
    genomic AY379869.1 AAR89096.1
    genomic AY379870.1 AAR89097.1
    genomic AY379871.1 AAR89098.1
    genomic AY379872.1 AAR89099.1
    genomic AY379873.1 AAR89100.1
    genomic AY379874.1 AAR89101.1
    genomic AY379875.1 AAR89102.1
    genomic AY379876.1 AAR89103.1
    genomic AY379877.1 AAR89104.1
    genomic AY379878.1 AAR89105.1
    genomic AY379879.1 AAR89106.1
    genomic AY379884.1 AAR89111.1
    genomic AY379886.1 AAR89113.1
    genomic AY379901.1 AAR89128.1
    genomic AY379903.1 AAR89129.1
    genomic AY379905.1 AAR89131.1
    genomic AY379907.1 AAR89133.1
    genomic AY379909.1 AAR89135.1
    genomic AY379910.1 AAR89138.1
    genomic AY379911.1 AAR89137.1
    genomic AY379924.1 AAR89151.1
    genomic AY379925.1 AAR89152.1
    genomic AY379926.1 AAR89153.1
    genomic AY379927.1 AAR89154.1
    genomic AY379959.1 AAR89163.1
    genomic BX679671.7 (42685..63309) None
    genomic CR753845.11 CAQ10919.1
    genomic U24578.1 AAA99717.1
    genomic U77886.1 AAK49810.1
    genomic U77887.1 AAK49811.1
    mRNA AK304564.1 BAG65356.1
    mRNA BM672834.1 None
    mRNA BQ960796.1 None
    mRNA CD624022.1 None
    mRNA DA395398.1 None
    mRNA DA918359.1 None
    mRNA K02404.1 AAA59651.1
    other-genetic BC172377.1 AAI72377.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P0C0L5.1 GenPept UniProtKB/Swiss-Prot:P0C0L5
    Q6U2E0 GenPept UniProtKB/TrEMBL:Q6U2E0
    Q6U2E5 GenPept UniProtKB/TrEMBL:Q6U2E5
    Q6U2F3 GenPept UniProtKB/TrEMBL:Q6U2F3
    Q6U2F4 GenPept UniProtKB/TrEMBL:Q6U2F4
    Q6U2F6 GenPept UniProtKB/TrEMBL:Q6U2F6
    Q6U2G0 GenPept UniProtKB/TrEMBL:Q6U2G0
    Q6U2G1 GenPept UniProtKB/TrEMBL:Q6U2G1
    Q6U2H4 GenPept UniProtKB/TrEMBL:Q6U2H4
    Q6U2I5 GenPept UniProtKB/TrEMBL:Q6U2I5
    Q6U2L1 GenPept UniProtKB/TrEMBL:Q6U2L1
    Q6U2L6 GenPept UniProtKB/TrEMBL:Q6U2L6
    Q6U2L7 GenPept UniProtKB/TrEMBL:Q6U2L7
    Q6U2L9 GenPept UniProtKB/TrEMBL:Q6U2L9
    Q6U2M2 GenPept UniProtKB/TrEMBL:Q6U2M2
    Q6U2M5 GenPept UniProtKB/TrEMBL:Q6U2M5
    Q6VCV8 GenPept UniProtKB/TrEMBL:Q6VCV8
    Q6XMI6 GenPept UniProtKB/TrEMBL:Q6XMI6
    Q96SA7 GenPept UniProtKB/TrEMBL:Q96SA7
    Q96SA8 GenPept UniProtKB/TrEMBL:Q96SA8
    Q9UMV1 GenPept UniProtKB/TrEMBL:Q9UMV1
    Q9UNU2 GenPept UniProtKB/TrEMBL:Q9UNU2
    Help top of page

    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Miscellaneous

      Supplemental Content

      Table of contents

      Links

      Links to other resources

      General information

      Related sites

      Feedback

      Subscription

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...