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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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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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