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    C4BPB complement component 4 binding protein beta [ Homo sapiens (human) ]

    Gene ID: 725, updated on 3-Apr-2024

    Summary

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    Official Symbol
    C4BPBprovided by HGNC
    Official Full Name
    complement component 4 binding protein betaprovided by HGNC
    Primary source
    HGNC:HGNC:1328
    See related
    Ensembl:ENSG00000123843 MIM:120831; AllianceGenome:HGNC:1328
    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
    C4BP
    Summary
    This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. A single, unique beta-chain encoded by this gene assembles with seven identical alpha-chains into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Alternative splicing gives rise to multiple transcript variants. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in liver (RPKM 52.4) and ovary (RPKM 16.6) See more
    Orthologs
    all
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    Genomic context

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    Location:
    1q32.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (207088860..207099993)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (206354100..206365236)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (207262205..207273338)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA U13 Neighboring gene Sharpr-MPRA regulatory region 4428 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207224117-207224687 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:207225911-207226550 Neighboring gene 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:207240869-207241100 Neighboring gene YOD1 deubiquitinase Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2439 Neighboring gene uncharacterized LOC107985251 Neighboring gene complement component 4 binding protein alpha Neighboring gene Sharpr-MPRA regulatory region 9788 Neighboring gene C4BPA pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells. Ermert D, et al. J Biol Chem, 2013 Nov 8. PMID 24064215, Free PMC Article
    2. Complement inhibitor C4b-binding protein in primary Sjögren's syndrome and its association with other disease markers. Zadura AF, et al. Scand J Immunol, 2009 Apr. PMID 19284503
    3. C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation. Trouw LA, et al. J Exp Med, 2005 Jun 20. PMID 15967823, Free PMC Article
    4. Promoter region of the human gene coding for beta-chain of C4b binding protein. Hepatocyte nuclear factor-3 and nuclear factor-I/CTF transcription factors are required for efficient expression of C4BPB in HepG2 cells. Arenzana N, et al. J Immunol, 1996 Jan 1. PMID 8598458
    5. The human C4b-binding protein beta-chain gene. Hillarp A, et al. J Biol Chem, 1993 Jul 15. PMID 8325877

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. C4BP(beta-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.
      Title: C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.
    2. Exposure to arterial blood pressure leads to a transient presence of C4bp in the saphenous vein wall.
      Title: Arterial Blood Pressure Induces Transient C4b-Binding Protein in Human Saphenous Vein Grafts.
    3. SAA, PROZ, and C4BPB may serve as new potential biomarkers for TB
      Title: Serum amyloid A, protein Z, and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis.
    4. C4BP is deposited in the diseased aortic valve, coincident with C3d expression.
      Title: C4b-Binding Protein Deposition is Induced in Diseased Aortic Heart Valves, Coinciding with C3d.
    5. C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese
      Title: An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia.
    6. Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.
      Title: Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells.
    7. crystallographic data on the structure of CD11c/CD18 and prediction of the secondary structure of the C4BP oligomerization domain, we show that epitopes bound by KIM185 in these proteins are unlikely to share any major structural similarity.
      Title: The role of higher-order protein structure in supporting binding by heteroclitic monoclonal antibodies: the monoclonal antibody KIM185 to CD18 also binds C4-binding protein.
    8. C4BP alpha7beta0 subunit [C4BP alpha7beta0 isoform lacking the beta-chain] induces a semimature, tolerogenic state on human monocyte-derived dendritic cells activated by a proinflammatory stimulus.
      Title: The α7β0 isoform of the complement regulator C4b-binding protein induces a semimature, anti-inflammatory state in dendritic cells.
    9. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b.
      Title: Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.
    10. Results demonstrate that successful secretion of complement regulatory protein C4b-binding protein beta-chains depends on intracellular complex formation with vitamin K-dependent protein S, but not on the alpha-chains.
      Title: Dependence on vitamin K-dependent protein S for eukaryotic cell secretion of the beta-chain of C4b-binding protein.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in blood coagulation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in complement activation, classical pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of complement activation, classical pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of opsonization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to symbiotic bacterium IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    C4b-binding protein beta chain

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_029386.1 RefSeqGene

      Range
      4994..16127
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_603

    mRNA and Protein(s)

    1. NM_000716.3 → NP_000707.1  C4b-binding protein beta chain isoform 1 precursor

      See identical proteins and their annotated locations for NP_000707.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as A19, represents the longest transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC005378, BM987840, L11245
      Consensus CDS
      CCDS1476.1
      UniProtKB/Swiss-Prot
      A5JYP8, D3DT81, P20851, Q5VVR0, Q9BS25
      Related
      ENSP00000243611.5, ENST00000243611.9
      Conserved Domains (1) summary
      cd00033
      Location:81 → 135
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    2. NM_001017364.1 → NP_001017364.1  C4b-binding protein beta chain isoform 2 precursor

      See identical proteins and their annotated locations for NP_001017364.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate, in-frame splice site in the 5' coding region, compared to variant 1. Variants 2 and 4 encode isoform 2, which has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      BC005378, BM987840
      Consensus CDS
      CCDS31005.1
      UniProtKB/Swiss-Prot
      P20851
      Related
      ENSP00000356043.3, ENST00000367076.7
      Conserved Domains (1) summary
      cl27761
      Location:46 → 207
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    3. NM_001017365.3 → NP_001017365.1  C4b-binding protein beta chain isoform 1 precursor

      See identical proteins and their annotated locations for NP_001017365.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as A12, differs in the 5' UTR compared to variant 1. Variants 1, 3 and 5 encode the same isoform (1).
      Source sequence(s)
      BG568018, BM987840, L11244
      Consensus CDS
      CCDS1476.1
      UniProtKB/Swiss-Prot
      A5JYP8, D3DT81, P20851, Q5VVR0, Q9BS25
      Related
      ENSP00000356045.3, ENST00000367078.8
      Conserved Domains (1) summary
      cd00033
      Location:81 → 135
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    4. NM_001017366.3 → NP_001017366.1  C4b-binding protein beta chain isoform 2 precursor

      See identical proteins and their annotated locations for NP_001017366.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate, in-frame splice site in the 5' coding region compared to variant 1. Variants 2 and 4 encode isoform 2, which has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      BG568018, BM987840, L11244
      Consensus CDS
      CCDS31005.1
      UniProtKB/Swiss-Prot
      P20851
      Conserved Domains (1) summary
      cl27761
      Location:46 → 207
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    5. NM_001017367.1 → NP_001017367.1  C4b-binding protein beta chain isoform 1 precursor

      See identical proteins and their annotated locations for NP_001017367.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 1. Variants 1, 3 and 5 encode the same isoform (1).
      Source sequence(s)
      BM987840, H63461, L11245
      Consensus CDS
      CCDS1476.1
      UniProtKB/Swiss-Prot
      A5JYP8, D3DT81, P20851, Q5VVR0, Q9BS25
      Related
      ENSP00000375790.1, ENST00000391923.1
      Conserved Domains (1) summary
      cd00033
      Location:81 → 135
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      207088860..207099993
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047429635.1 → XP_047285591.1  C4b-binding protein beta chain isoform X2

    2. XM_005273254.6 → XP_005273311.1  C4b-binding protein beta chain isoform X1

      See identical proteins and their annotated locations for XP_005273311.1

      UniProtKB/Swiss-Prot
      A5JYP8, D3DT81, P20851, Q5VVR0, Q9BS25
      Conserved Domains (1) summary
      cd00033
      Location:81 → 135
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    3. XM_024449464.2 → XP_024305232.1  C4b-binding protein beta chain isoform X2

      Conserved Domains (1) summary
      cl27761
      Location:46 → 207
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    4. XM_005273255.3 → XP_005273312.1  C4b-binding protein beta chain isoform X3

      UniProtKB/TrEMBL
      B4DDY0
      Conserved Domains (1) summary
      cd00033
      Location:80 → 134
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      206354100..206365236
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054338584.1 → XP_054194559.1  C4b-binding protein beta chain isoform X2

    2. XM_054338583.1 → XP_054194558.1  C4b-binding protein beta chain isoform X1

      UniProtKB/Swiss-Prot
      A5JYP8, D3DT81, P20851, Q5VVR0, Q9BS25

    3. XM_054338585.1 → XP_054194560.1  C4b-binding protein beta chain isoform X2

    4. XM_054338586.1 → XP_054194561.1  C4b-binding protein beta chain isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20851.1 GenPept UniProtKB/Swiss-Prot:P20851

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