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C4B_2 Gene

protein-coding   GIFtS: 24
GCID: GC06P8U3282

Complement Component 4B (Chido Blood Group), Copy 2

  See C4B_2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Complement Component 4B (Chido Blood Group), Copy 21 2     Basic Complement C43
Complement C4-B-Like2     C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 33
CO43     EC 2.1.1.1448
CPAMD33     EC 2.7.118

External Ids:    HGNC: 423981   Entrez Gene: 1002935342   Ensembl: ENSG000002333127   UniProtKB: P0C0L53   

Export aliases for C4B_2 gene to outside databases

Previous GC identifers: GC06Po31872 GC06P031985


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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, and sle susceptibility.

UniProtKB/Swiss-Prot: CO4B_HUMAN, P0C0L5
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
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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for C4B_2
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for C4B_2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat C4B_2


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_SSTOp21.33   HGNC cytogenetic band: 6p21.3 alternate reference locus

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06P8U3282:       (about GC identifiers)

Start:
3,282,544 bp from pter      End:
3,303,168 bp from pter
Size:
20,625 bases      Orientation:
unknown strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CO4B_HUMAN, P0C0L5 (See protein sequence)
Recommended Name: Complement C4-B precursor  
Size: 1744 amino acids; 192751 Da
Subunit: Circulates in blood as a disulfide-linked trimer of alpha, beta and gamma chains
Sequence caution: Sequence=AAA99717.1; Type=Erroneous gene model prediction;
Secondary accessions: A2BHY4 P01028 P78445 Q13160 Q13906 Q14033 Q14835 Q6U2E9 Q6U2G1 Q6U2I5
Q6U2L1 Q6U2L7 Q6U2L9 Q6U2M5 Q6VCV8 Q96SA7 Q9NPK5 Q9UIP5

Explore the universe of human proteins at neXtProt for C4B_2: NX_P0C0L5

Explore proteomics data for C4B_2 at MOPED

Post-translational modifications: 

  • 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
    plasma1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • 2 DME Specific Peptides for C4B_2 (P0C0L5)
     DLGCGPG  GPGGGDS 


    See C4B_2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_001229752.1  
    ENSEMBL proteins: 
     ENSP00000412786   ENSP00000449433  
    Reactome Protein details: P0C0L5

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 14):
     IPR008993 TIMP-like_OB-fold
     IPR001599 Macroglobln_a2
     IPR011626 A2M_comp
     IPR002890 A2M_N
     IPR009048 A-macroglobulin_rcpt-bd

    Graphical View of Domain Structure for InterPro Entry P0C0L5

    ProtoNet protein and cluster: P0C0L5

    5 Blocks protein domains:
    IPB001134 Netrin
    IPB001599 Alpha-2-macroglobulin
    IPB001840 Anaphylatoxin domain signature
    IPB002890 Alpha-2-macroglobulin
    IPB009048 Alpha-macroglobulin


    UniProtKB/Swiss-Prot: CO4B_HUMAN, P0C0L5
    Similarity: Contains 1 anaphylatoxin-like domain
    Similarity: Contains 1 NTR domain


    Find genes that share domains with C4B_2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CO4B_HUMAN, P0C0L5
    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
    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): EC 2.1.1.1442 EC 2.7.112

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004866endopeptidase inhibitor activity ----
    GO:0005515protein binding ----
         
    Find genes that share ontologies with C4B_2           About GenesLikeMe


    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for C4B_2

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CO4B_HUMAN, P0C0L5: Secreted

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region ----
    GO:0005615extracellular space ----
    GO:0005886plasma membrane ----

    Find genes that share ontologies with C4B_2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Find genes that share SuperPaths with C4B_2           About GenesLikeMe

    Pathways by sourceSee SuperPaths
    Show all pathways


    3 Reactome Pathways for C4B_2
        Regulation of Complement cascade
    Activation of C3 and C5
    Initial triggering of complement


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for C4B_2
    Interactions:

        Search GeneGlobe Interaction Network for C4B_2

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    Selected Interacting proteins for C4B_2 (P0C0L53 ENSP000004127864) via UniProtKB, MINT, STRING, and/or I2D (see all 9)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    C2P066813I2D: score=1 
    ENSG00000204364P066813I2D: score=1 
    ENSG00000206372P066813I2D: score=1 
    ENSG00000226560P066813I2D: score=1 
    ENSG00000231543P066813I2D: score=1 
    About this table

    Gene Ontology (GO): 5 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006954inflammatory response ----
    GO:0006956complement activation ----
    GO:0006958complement activation, classical pathway ----
    GO:0030449regulation of complement activation ----
    GO:0045087innate immune response ----

    Find genes that share ontologies with C4B_2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for C4B_2 (CO4B)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for C4B_2 gene: 
    NM_001242823.2  

    14 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000435500(uc011jpd.2 uc011jpe.2) ENST00000488382 ENST00000497344
    ENST00000487248 ENST00000467180 ENST00000475110 ENST00000465720 ENST00000487105
    ENST00000485492 ENST00000466864 ENST00000496446(uc011jpg.2) ENST00000463341
    ENST00000492701 ENST00000552464(uc011jpf.1)
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    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --

    C4B_2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    C4B_2 Protein Expression

    UniProtKB/Swiss-Prot: CO4B_HUMAN, P0C0L5
    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

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    In Situ
    Assay Products:
     

     
    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for C4B_2

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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      --

    ENSEMBL Gene Tree for C4B_2 (if available)
    TreeFam Gene Tree for C4B_2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for C4B_2 gene
    4 SIMAP similar genes for C4B_2 using alignment to 1 protein entry:     CO4B_HUMAN:
    C4A    C4B    C3    OVOS2

    Find genes that share paralogs with C4B_2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    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)

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    UniProtKB/Swiss-Prot: CO4B_HUMAN, P0C0L5
  • 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. 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
  • 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. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 4 diseases for C4B_2:    
    About MalaCards
    c4b deficiency    sle susceptibility    systemic lupus erythematosus    lupus erythematosus


    Find genes that share disorders with C4B_2           About GenesLikeMe


    Export disorders for C4B_2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for C4B_2 gene, integrated from 10 sources (see all 29):
    (articles sorted by number of sources associating them with C4B_2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Linkage analysis of the C4A/C4B copy number variation and polymorphisms of the adjacent steroid 21-hydroxylase gene in a healthy population. (PubMed id 19505723)1, 3 Blasko B.... Szilagyi A. (Mol. Immunol. 2009)
    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. (PubMed id 17503323)1, 2 Yang Y.... Yu C.Y. (Am. J. Hum. Genet. 2007)
    3. Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. (PubMed id 2431902)1, 2 Yu C.Y.... Porter R.R. (EMBO J. 1986)
    4. The structural basis of the multiple forms of human complement component C4. (PubMed id 6546707)1, 2 Belt K.T.... Porter R.R. (Cell 1984)
    5. A review of the Chido/Rodgers blood group. (PubMed id 20795316)1 Mougey R. (Immunohematology 2010)
    6. Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. (PubMed id 18032375)1 BlaskA^ B....Arason G.J. (Int. Immunol. 2008)
    7. Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. (PubMed id 16740002)2 Ramachandran P....Loo J.A. (J. Proteome Res. 2006)
    8. C4d DNA sequence of complement C4B93 and recombination mechanisms for its generation. (PubMed id 14989716)2 Lopez-Goyanes A.... Paz-Artal E. (Tissue Antigens 2004)
    9. Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. (PubMed id 14760718)2 Bunkenborg J.... Wisniewski J.R. (Proteomics 2004)
    10. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. (PubMed id 12754519)2 Zhang H.... Aebersold R. (Nat. Biotechnol. 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 100293534 HGNC: 42398 Ensembl:ENSG00000233312 euGenes: HUgn100293534 ECgene: C4B_2
    H-InvDB: C4B_2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for C4B_2 Pharmacogenomics, SNPs, Pathways
    dbRBC/BGMUThttp://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=chrg

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for C4B_2 gene:
    Search GeneIP for patents involving C4B_2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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