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P0C0L5

- CO4B_HUMAN

UniProt

P0C0L5 - CO4B_HUMAN

Protein

Complement C4-B

Gene

C4B

more
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 2 (03 Apr 2013)
      Previous versions | rss
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    Functioni

    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.

    GO - Molecular functioni

    1. carbohydrate binding Source: BHF-UCL
    2. complement binding Source: BHF-UCL
    3. endopeptidase inhibitor activity Source: InterPro

    GO - Biological processi

    1. complement activation Source: BHF-UCL
    2. complement activation, classical pathway Source: UniProtKB-KW
    3. detection of molecule of bacterial origin Source: BHF-UCL
    4. inflammatory response Source: UniProtKB-KW
    5. innate immune response Source: Reactome
    6. opsonization Source: BHF-UCL
    7. positive regulation of apoptotic cell clearance Source: BHF-UCL
    8. regulation of complement activation Source: Reactome

    Keywords - Molecular functioni

    Blood group antigen

    Keywords - Biological processi

    Complement pathway, Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_118707. Regulation of Complement cascade.
    REACT_7972. Activation of C3 and C5.
    REACT_8024. Initial triggering of complement.

    Protein family/group databases

    MEROPSiI39.951.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Complement C4-B
    Alternative name(s):
    Basic complement C4
    C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3
    Cleaved into the following 6 chains:
    Gene namesi
    Name:C4B
    Synonyms:CO4, CPAMD3
    AND
    Name:C4B_2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:1324. C4B.
    HGNC:42398. C4B_2.

    Subcellular locationi

    GO - Cellular componenti

    1. blood microparticle Source: UniProt
    2. extracellular region Source: Reactome
    3. extracellular space Source: BHF-UCL
    4. extracellular vesicular exosome Source: UniProt
    5. other organism cell Source: BHF-UCL
    6. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1120 – 11201L → P: No effect on hemolytic activity, nor on C1-dependent binding to IgG. 1 Publication
    Mutagenesisi1121 – 11211S → C: 30-40% decrease in hemolytic activity and C1-dependent binding to IgG. 1 Publication
    Mutagenesisi1124 – 11241I → A: 50-60% decrease in hemolytic activity and C1-dependent binding to IgG. 1 Publication
    Mutagenesisi1125 – 11251H → A: 20% decrease in hemolytic activity, 2-fold increase in C1-dependent binding to IgG. 1 Publication
    Mutagenesisi1125 – 11251H → D: 2.5-3 fold-decrease in hemolytic activity, 3-fold increase in C1-dependent binding to IgG. 1 Publication

    Keywords - Diseasei

    Systemic lupus erythematosus

    Organism-specific databases

    MIMi152700. phenotype.
    614374. phenotype.
    614379. phenotype.
    Orphaneti169147. Immunodeficiency due to an early component of complement deficiency.
    536. Systemic lupus erythematosus.
    PharmGKBiPA25904.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Add
    BLAST
    Chaini20 – 675656Complement C4 beta chainPRO_0000042699Add
    BLAST
    Propeptidei676 – 67941 PublicationPRO_0000042700
    Chaini680 – 1446767Complement C4-B alpha chainPRO_0000042701Add
    BLAST
    Chaini680 – 75677C4a anaphylatoxinPRO_0000042702Add
    BLAST
    Chaini757 – 1446690C4b-BPRO_0000042703Add
    BLAST
    Chaini957 – 1336380C4d-BPRO_0000042704Add
    BLAST
    Propeptidei1447 – 14537PRO_0000042705
    Chaini1454 – 1744291Complement C4 gamma chainPRO_0000042706Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi226 – 2261N-linked (GlcNAc...)1 Publication
    Disulfide bondi702 ↔ 728By similarity
    Disulfide bondi703 ↔ 735By similarity
    Disulfide bondi716 ↔ 736By similarity
    Glycosylationi862 – 8621N-linked (GlcNAc...)Sequence Analysis
    Cross-linki1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)
    Glycosylationi1328 – 13281N-linked (GlcNAc...)1 Publication
    Glycosylationi1391 – 13911N-linked (GlcNAc...)1 Publication
    Modified residuei1417 – 14171Sulfotyrosine1 Publication
    Modified residuei1420 – 14201Sulfotyrosine1 Publication
    Modified residuei1422 – 14221Sulfotyrosine1 Publication
    Disulfide bondi1595 ↔ 1673By similarity
    Disulfide bondi1618 ↔ 1742By similarity

    Post-translational modificationi

    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.

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Sulfation, Thioester bond

    Proteomic databases

    MaxQBiP0C0L5.
    PaxDbiP0C0L5.
    PRIDEiP0C0L5.

    2D gel databases

    SWISS-2DPAGEP0C0L5.

    PTM databases

    PhosphoSiteiP0C0L5.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Gene expression databases

    GenevestigatoriP0C0L5.

    Interactioni

    Subunit structurei

    Circulates in blood as a disulfide-linked trimer of alpha, beta and gamma chains.

    Protein-protein interaction databases

    BioGridi107182. 1 interaction.
    DIPiDIP-47260N.
    IntActiP0C0L5. 2 interactions.
    STRINGi9606.ENSP00000412786.

    Structurei

    3D structure databases

    ProteinModelPortaliP0C0L5.
    SMRiP0C0L5. Positions 20-670, 681-1420, 1455-1744.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini702 – 73635Anaphylatoxin-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini1595 – 1742148NTRPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 anaphylatoxin-like domain.PROSITE-ProRule annotation
    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG2373.
    HOVERGENiHBG107123.
    InParanoidiP0C0L5.
    KOiK03989.
    OMAiYAPRQTV.
    PhylomeDBiP0C0L5.
    TreeFamiTF313285.

    Family and domain databases

    Gene3Di1.20.91.20. 1 hit.
    1.50.10.20. 1 hit.
    2.60.40.690. 1 hit.
    InterProiIPR009048. A-macroglobulin_rcpt-bd.
    IPR011626. A2M_comp.
    IPR002890. A2M_N.
    IPR011625. A2M_N_2.
    IPR000020. Anaphylatoxin/fibulin.
    IPR018081. Anaphylatoxin_comp_syst.
    IPR001840. Anaphylatoxn_comp_syst_dom.
    IPR001599. Macroglobln_a2.
    IPR019742. MacrogloblnA2_CS.
    IPR019565. MacrogloblnA2_thiol-ester-bond.
    IPR001134. Netrin_domain.
    IPR018933. Netrin_module_non-TIMP.
    IPR008930. Terpenoid_cyclase/PrenylTrfase.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view]
    PfamiPF00207. A2M. 1 hit.
    PF07678. A2M_comp. 1 hit.
    PF01835. A2M_N. 1 hit.
    PF07703. A2M_N_2. 1 hit.
    PF07677. A2M_recep. 1 hit.
    PF01821. ANATO. 1 hit.
    PF01759. NTR. 1 hit.
    PF10569. Thiol-ester_cl. 1 hit.
    [Graphical view]
    PRINTSiPR00004. ANAPHYLATOXN.
    SMARTiSM00104. ANATO. 1 hit.
    SM00643. C345C. 1 hit.
    [Graphical view]
    SUPFAMiSSF47686. SSF47686. 1 hit.
    SSF48239. SSF48239. 1 hit.
    SSF49410. SSF49410. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEiPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
    PS01177. ANAPHYLATOXIN_1. 1 hit.
    PS01178. ANAPHYLATOXIN_2. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P0C0L5-1 [UniParc]FASTAAdd to Basket

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    MRLLWGLIWA SSFFTLSLQK PRLLLFSPSV VHLGVPLSVG VQLQDVPRGQ     50
    VVKGSVFLRN PSRNNVPCSP KVDFTLSSER DFALLSLQVP LKDAKSCGLH 100
    QLLRGPEVQL VAHSPWLKDS LSRTTNIQGI NLLFSSRRGH LFLQTDQPIY 150
    NPGQRVRYRV FALDQKMRPS TDTITVMVEN SHGLRVRKKE VYMPSSIFQD 200
    DFVIPDISEP GTWKISARFS DGLESNSSTQ FEVKKYVLPN FEVKITPGKP 250
    YILTVPGHLD EMQLDIQARY IYGKPVQGVA YVRFGLLDED GKKTFFRGLE 300
    SQTKLVNGQS HISLSKAEFQ DALEKLNMGI TDLQGLRLYV AAAIIESPGG 350
    EMEEAELTSW YFVSSPFSLD LSKTKRHLVP GAPFLLQALV REMSGSPASG 400
    IPVKVSATVS SPGSVPEVQD IQQNTDGSGQ VSIPIIIPQT ISELQLSVSA 450
    GSPHPAIARL TVAAPPSGGP GFLSIERPDS RPPRVGDTLN LNLRAVGSGA 500
    TFSHYYYMIL SRGQIVFMNR EPKRTLTSVS VFVDHHLAPS FYFVAFYYHG 550
    DHPVANSLRV DVQAGACEGK LELSVDGAKQ YRNGESVKLH LETDSLALVA 600
    LGALDTALYA AGSKSHKPLN MGKVFEAMNS YDLGCGPGGG DSALQVFQAA 650
    GLAFSDGDQW TLSRKRLSCP KEKTTRKKRN VNFQKAINEK LGQYASPTAK 700
    RCCQDGVTRL PMMRSCEQRA ARVQQPDCRE PFLSCCQFAE SLRKKSRDKG 750
    QAGLQRALEI LQEEDLIDED DIPVRSFFPE NWLWRVETVD RFQILTLWLP 800
    DSLTTWEIHG LSLSKTKGLC VATPVQLRVF REFHLHLRLP MSVRRFEQLE 850
    LRPVLYNYLD KNLTVSVHVS PVEGLCLAGG GGLAQQVLVP AGSARPVAFS 900
    VVPTAATAVS LKVVARGSFE FPVGDAVSKV LQIEKEGAIH REELVYELNP 950
    LDHRGRTLEI PGNSDPNMIP DGDFNSYVRV TASDPLDTLG SEGALSPGGV 1000
    ASLLRLPRGC GEQTMIYLAP TLAASRYLDK TEQWSTLPPE TKDHAVDLIQ 1050
    KGYMRIQQFR KADGSYAAWL SRGSSTWLTA FVLKVLSLAQ EQVGGSPEKL 1100
    QETSNWLLSQ QQADGSFQDL SPVIHRSMQG GLVGNDETVA LTAFVTIALH 1150
    HGLAVFQDEG AEPLKQRVEA SISKASSFLG EKASAGLLGA HAAAITAYAL 1200
    TLTKAPADLR GVAHNNLMAM AQETGDNLYW GSVTGSQSNA VSPTPAPRNP 1250
    SDPMPQAPAL WIETTAYALL HLLLHEGKAE MADQAAAWLT RQGSFQGGFR 1300
    STQDTVIALD ALSAYWIASH TTEERGLNVT LSSTGRNGFK SHALQLNNRQ 1350
    IRGLEEELQF SLGSKINVKV GGNSKGTLKV LRTYNVLDMK NTTCQDLQIE 1400
    VTVKGHVEYT MEANEDYEDY EYDELPAKDD PDAPLQPVTP LQLFEGRRNR 1450
    RRREAPKVVE EQESRVHYTV CIWRNGKVGL SGMAIADVTL LSGFHALRAD 1500
    LEKLTSLSDR YVSHFETEGP HVLLYFDSVP TSRECVGFEA VQEVPVGLVQ 1550
    PASATLYDYY NPERRCSVFY GAPSKSRLLA TLCSAEVCQC AEGKCPRQRR 1600
    ALERGLQDED GYRMKFACYY PRVEYGFQVK VLREDSRAAF RLFETKITQV 1650
    LHFTKDVKAA ANQMRNFLVR ASCRLRLEPG KEYLIMGLDG ATYDLEGHPQ 1700
    YLLDSNSWIE EMPSERLCRS TRQRAACAQL NDFLQEYGTQ GCQV 1744
    Length:1,744
    Mass (Da):192,751
    Last modified:April 3, 2013 - v2
    Checksum:iE724B85F7FA673C5
    GO

    Sequence cautioni

    The sequence AAA99717.1 differs from that shown. Reason: Erroneous gene model prediction.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti714 – 7141R → S in AAR89101. 1 PublicationCurated
    Sequence conflicti729 – 7291R → Q in AAR89127. 1 PublicationCurated
    Sequence conflicti980 – 9812VT → LQ in AAA99717. (PubMed:8575831)Curated
    Sequence conflicti1013 – 10131Q → E AA sequence (PubMed:6978711)Curated
    Sequence conflicti1013 – 10131Q → E AA sequence (PubMed:3696167)Curated
    Sequence conflicti1013 – 10131Q → E AA sequence (PubMed:6950384)Curated
    Sequence conflicti1109 – 11102SQ → IA AA sequence (PubMed:3696167)Curated
    Sequence conflicti1271 – 12711H → V AA sequence (PubMed:3696167)Curated
    Sequence conflicti1271 – 12711H → V AA sequence (PubMed:6832377)Curated
    Sequence conflicti1300 – 13001R → V AA sequence (PubMed:3696167)Curated
    Sequence conflicti1300 – 13001R → V AA sequence (PubMed:6832377)Curated
    Sequence conflicti1654 – 16541T → RA in AAA99717. (PubMed:8575831)Curated
    Sequence conflicti1698 – 16981H → Q in AAA99717. (PubMed:8575831)Curated

    Polymorphismi

    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 [MIMi: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).1 Publication

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti347 – 3471S → Y in allotype C4B-long. 2 Publications
    Corresponds to variant rs139889867 [ dbSNP | Ensembl ].
    VAR_023729
    Natural varianti478 – 4781P → L in allotype C4B1-hi.
    VAR_069160
    Natural varianti907 – 9071T → A in allotype C4B-long and allotype C4B2. 3 Publications
    VAR_023730
    Natural varianti1073 – 10731G → D in allotype C4B2 and allotype C4B5-Rg1. 2 Publications
    VAR_023731
    Natural varianti1176 – 11761S → N in allotype C4B1a. 1 Publication
    Corresponds to variant rs2746414 [ dbSNP | Ensembl ].
    VAR_023732
    Natural varianti1207 – 12071A → V in allotype C4B5-Rg1. 1 Publication
    Corresponds to variant rs200888163 [ dbSNP | Ensembl ].
    VAR_023734
    Natural varianti1210 – 12101R → L in allotype C4B5-Rg1. 1 Publication
    Corresponds to variant rs112683215 [ dbSNP | Ensembl ].
    VAR_023735
    Natural varianti1317 – 13171I → F in allotype C4B1-SC01. 1 Publication
    VAR_069161

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U24578 Genomic DNA. Translation: AAA99717.1. Sequence problems.
    AF019413 Genomic DNA. Translation: AAB67980.1.
    AY379860 Genomic DNA. Translation: AAR89087.1.
    AY379862 Genomic DNA. Translation: AAR89089.1.
    AY379864 Genomic DNA. Translation: AAR89091.1.
    AY379866 Genomic DNA. Translation: AAR89093.1.
    AY379868 Genomic DNA. Translation: AAR89095.1.
    AY379870 Genomic DNA. Translation: AAR89097.1.
    AY379872 Genomic DNA. Translation: AAR89099.1.
    AY379874 Genomic DNA. Translation: AAR89101.1.
    AY379876 Genomic DNA. Translation: AAR89103.1.
    AY379878 Genomic DNA. Translation: AAR89105.1.
    AY379880 Genomic DNA. Translation: AAR89107.1.
    AY379882 Genomic DNA. Translation: AAR89109.1.
    AY379884 Genomic DNA. Translation: AAR89111.1.
    AY379886 Genomic DNA. Translation: AAR89113.1.
    AY379888 Genomic DNA. Translation: AAR89115.1.
    AY379890 Genomic DNA. Translation: AAR89117.1.
    AY379892 Genomic DNA. Translation: AAR89119.1.
    AY379894 Genomic DNA. Translation: AAR89121.1.
    AY379896 Genomic DNA. Translation: AAR89123.1.
    AY379898 Genomic DNA. Translation: AAR89125.1.
    AY379900 Genomic DNA. Translation: AAR89127.1.
    AY379902 Genomic DNA. Translation: AAR89130.1.
    AY379904 Genomic DNA. Translation: AAR89132.1.
    AY379906 Genomic DNA. Translation: AAR89134.1.
    AY379908 Genomic DNA. Translation: AAR89136.1.
    AY379910 Genomic DNA. Translation: AAR89138.1.
    AY379912 Genomic DNA. Translation: AAR89139.1.
    AY379914 Genomic DNA. Translation: AAR89142.1.
    AY379916 Genomic DNA. Translation: AAR89144.1.
    AY379918 Genomic DNA. Translation: AAR89145.1.
    AY379920 Genomic DNA. Translation: AAR89148.1.
    AY379922 Genomic DNA. Translation: AAR89150.1.
    AY379924 Genomic DNA. Translation: AAR89151.1.
    AY379959
    , AY379936, AY379937, AY379938, AY379939, AY379940, AY379941, AY379942, AY379943, AY379944, AY379945, AY379946, AY379947, AY379948, AY379949, AY379950, AY379951, AY379952, AY379953, AY379954, AY379955, AY379956, AY379957, AY379958 Genomic DNA. Translation: AAR89163.1.
    AL049547 Genomic DNA. Translation: CAB89302.1.
    BX679671 Genomic DNA. No translation available.
    K02404 mRNA. Translation: AAA59651.1.
    U77887 Genomic DNA. Translation: AAK49811.1.
    AY343497 Genomic DNA. Translation: AAQ99144.1.
    CCDSiCCDS47405.1.
    PIRiB20807.
    RefSeqiNP_001002029.3. NM_001002029.3.
    NP_001229752.1. NM_001242823.2.
    UniGeneiHs.534847.
    Hs.720022.

    Genome annotation databases

    EnsembliENST00000375177; ENSP00000364321; ENSG00000228454.
    ENST00000411583; ENSP00000407942; ENSG00000228267.
    ENST00000435363; ENSP00000415941; ENSG00000224389.
    ENST00000435500; ENSP00000412786; ENSG00000233312.
    ENST00000449788; ENSP00000414200; ENSG00000236625.
    GeneIDi100293534.
    721.
    KEGGihsa:100293534.
    hsa:721.
    UCSCiuc011doy.2. human.

    Polymorphism databases

    DMDMi476007828.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    dbRBC/BGMUT

    Blood group antigen gene mutation database

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U24578 Genomic DNA. Translation: AAA99717.1 . Sequence problems.
    AF019413 Genomic DNA. Translation: AAB67980.1 .
    AY379860 Genomic DNA. Translation: AAR89087.1 .
    AY379862 Genomic DNA. Translation: AAR89089.1 .
    AY379864 Genomic DNA. Translation: AAR89091.1 .
    AY379866 Genomic DNA. Translation: AAR89093.1 .
    AY379868 Genomic DNA. Translation: AAR89095.1 .
    AY379870 Genomic DNA. Translation: AAR89097.1 .
    AY379872 Genomic DNA. Translation: AAR89099.1 .
    AY379874 Genomic DNA. Translation: AAR89101.1 .
    AY379876 Genomic DNA. Translation: AAR89103.1 .
    AY379878 Genomic DNA. Translation: AAR89105.1 .
    AY379880 Genomic DNA. Translation: AAR89107.1 .
    AY379882 Genomic DNA. Translation: AAR89109.1 .
    AY379884 Genomic DNA. Translation: AAR89111.1 .
    AY379886 Genomic DNA. Translation: AAR89113.1 .
    AY379888 Genomic DNA. Translation: AAR89115.1 .
    AY379890 Genomic DNA. Translation: AAR89117.1 .
    AY379892 Genomic DNA. Translation: AAR89119.1 .
    AY379894 Genomic DNA. Translation: AAR89121.1 .
    AY379896 Genomic DNA. Translation: AAR89123.1 .
    AY379898 Genomic DNA. Translation: AAR89125.1 .
    AY379900 Genomic DNA. Translation: AAR89127.1 .
    AY379902 Genomic DNA. Translation: AAR89130.1 .
    AY379904 Genomic DNA. Translation: AAR89132.1 .
    AY379906 Genomic DNA. Translation: AAR89134.1 .
    AY379908 Genomic DNA. Translation: AAR89136.1 .
    AY379910 Genomic DNA. Translation: AAR89138.1 .
    AY379912 Genomic DNA. Translation: AAR89139.1 .
    AY379914 Genomic DNA. Translation: AAR89142.1 .
    AY379916 Genomic DNA. Translation: AAR89144.1 .
    AY379918 Genomic DNA. Translation: AAR89145.1 .
    AY379920 Genomic DNA. Translation: AAR89148.1 .
    AY379922 Genomic DNA. Translation: AAR89150.1 .
    AY379924 Genomic DNA. Translation: AAR89151.1 .
    AY379959
    , AY379936 , AY379937 , AY379938 , AY379939 , AY379940 , AY379941 , AY379942 , AY379943 , AY379944 , AY379945 , AY379946 , AY379947 , AY379948 , AY379949 , AY379950 , AY379951 , AY379952 , AY379953 , AY379954 , AY379955 , AY379956 , AY379957 , AY379958 Genomic DNA. Translation: AAR89163.1 .
    AL049547 Genomic DNA. Translation: CAB89302.1 .
    BX679671 Genomic DNA. No translation available.
    K02404 mRNA. Translation: AAA59651.1 .
    U77887 Genomic DNA. Translation: AAK49811.1 .
    AY343497 Genomic DNA. Translation: AAQ99144.1 .
    CCDSi CCDS47405.1.
    PIRi B20807.
    RefSeqi NP_001002029.3. NM_001002029.3.
    NP_001229752.1. NM_001242823.2.
    UniGenei Hs.534847.
    Hs.720022.

    3D structure databases

    ProteinModelPortali P0C0L5.
    SMRi P0C0L5. Positions 20-670, 681-1420, 1455-1744.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107182. 1 interaction.
    DIPi DIP-47260N.
    IntActi P0C0L5. 2 interactions.
    STRINGi 9606.ENSP00000412786.

    Protein family/group databases

    MEROPSi I39.951.

    PTM databases

    PhosphoSitei P0C0L5.

    Polymorphism databases

    DMDMi 476007828.

    2D gel databases

    SWISS-2DPAGE P0C0L5.

    Proteomic databases

    MaxQBi P0C0L5.
    PaxDbi P0C0L5.
    PRIDEi P0C0L5.

    Protocols and materials databases

    DNASUi 721.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000375177 ; ENSP00000364321 ; ENSG00000228454 .
    ENST00000411583 ; ENSP00000407942 ; ENSG00000228267 .
    ENST00000435363 ; ENSP00000415941 ; ENSG00000224389 .
    ENST00000435500 ; ENSP00000412786 ; ENSG00000233312 .
    ENST00000449788 ; ENSP00000414200 ; ENSG00000236625 .
    GeneIDi 100293534.
    721.
    KEGGi hsa:100293534.
    hsa:721.
    UCSCi uc011doy.2. human.

    Organism-specific databases

    CTDi 100293534.
    721.
    GeneCardsi GC06P031982.
    GC06P031985.
    H-InvDB HIX0164690.
    HIX0164691.
    HIX0166073.
    HIX0166340.
    HIX0166869.
    HIX0167127.
    HIX0167359.
    HIX0167360.
    HGNCi HGNC:1324. C4B.
    HGNC:42398. C4B_2.
    MIMi 120820. gene.
    152700. phenotype.
    614374. phenotype.
    614379. phenotype.
    neXtProti NX_P0C0L5.
    Orphaneti 169147. Immunodeficiency due to an early component of complement deficiency.
    536. Systemic lupus erythematosus.
    PharmGKBi PA25904.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2373.
    HOVERGENi HBG107123.
    InParanoidi P0C0L5.
    KOi K03989.
    OMAi YAPRQTV.
    PhylomeDBi P0C0L5.
    TreeFami TF313285.

    Enzyme and pathway databases

    Reactomei REACT_118707. Regulation of Complement cascade.
    REACT_7972. Activation of C3 and C5.
    REACT_8024. Initial triggering of complement.

    Miscellaneous databases

    GeneWikii Complement_component_4B.
    NextBioi 20783275.
    PROi P0C0L5.
    SOURCEi Search...

    Gene expression databases

    Genevestigatori P0C0L5.

    Family and domain databases

    Gene3Di 1.20.91.20. 1 hit.
    1.50.10.20. 1 hit.
    2.60.40.690. 1 hit.
    InterProi IPR009048. A-macroglobulin_rcpt-bd.
    IPR011626. A2M_comp.
    IPR002890. A2M_N.
    IPR011625. A2M_N_2.
    IPR000020. Anaphylatoxin/fibulin.
    IPR018081. Anaphylatoxin_comp_syst.
    IPR001840. Anaphylatoxn_comp_syst_dom.
    IPR001599. Macroglobln_a2.
    IPR019742. MacrogloblnA2_CS.
    IPR019565. MacrogloblnA2_thiol-ester-bond.
    IPR001134. Netrin_domain.
    IPR018933. Netrin_module_non-TIMP.
    IPR008930. Terpenoid_cyclase/PrenylTrfase.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view ]
    Pfami PF00207. A2M. 1 hit.
    PF07678. A2M_comp. 1 hit.
    PF01835. A2M_N. 1 hit.
    PF07703. A2M_N_2. 1 hit.
    PF07677. A2M_recep. 1 hit.
    PF01821. ANATO. 1 hit.
    PF01759. NTR. 1 hit.
    PF10569. Thiol-ester_cl. 1 hit.
    [Graphical view ]
    PRINTSi PR00004. ANAPHYLATOXN.
    SMARTi SM00104. ANATO. 1 hit.
    SM00643. C345C. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47686. SSF47686. 1 hit.
    SSF48239. SSF48239. 1 hit.
    SSF49410. SSF49410. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEi PS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
    PS01177. ANAPHYLATOXIN_1. 1 hit.
    PS01178. ANAPHYLATOXIN_2. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype."
      Ulgiati D., Townend D.C., Christiansen F.T., Dawkins R.L., Abraham L.J.
      Immunogenetics 43:250-252(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-1317.
      Tissue: Blood.
    2. "Sequence determination of 300 kilobases of the human class III MHC locus."
      Rowen L., Dankers C., Baskin D., Faust J., Loretz C., Ahearn M.E., Banta A., Swartzell S., Smith T.M., Spies T., Hood L.
      Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-347 AND ALA-907.
    3. "Molecular genetics of complement C4: implications for MHC evolution and disease susceptibility gene mapping."
      Sayer D., Puschendorf M., Wetherall J.
      Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-907 AND ASP-1073.
    4. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS TYR-347 AND ALA-907.
    5. "Complete primary structure of human C4a anaphylatoxin."
      Moon K.E., Gorski J.P., Hugli T.E.
      J. Biol. Chem. 256:8685-8692(1981) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 680-756.
    6. "Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein."
      Hessing M., van 't Veer C., Hackeng T.M., Bouma B.N., Iwanaga S.
      FEBS Lett. 271:131-136(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 757-771 AND 980-990.
    7. "The structural basis of the multiple forms of human complement component C4."
      Belt K.T., Carroll M.C., Porter R.R.
      Cell 36:907-914(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 956-1336, VARIANT ASP-1073.
      Tissue: Liver.
    8. "Amino acid sequence around the thiol and reactive acyl groups of human complement component C4."
      Campbell R.D., Gagnon J., Porter R.R.
      Biochem. J. 199:359-370(1981) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 957-1044.
    9. "The chemical structure of the C4d fragment of the human complement component C4."
      Chakravarti D.N., Campbell R.D., Porter R.R.
      Mol. Immunol. 24:1187-1197(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 957-1336.
    10. "Sequence determination of the thiolester site of the fourth component of human complement."
      Harrison R.A., Thomas M.L., Tack B.F.
      Proc. Natl. Acad. Sci. U.S.A. 78:7388-7392(1981) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 990-1037.
    11. "C4d DNA sequences of two infrequent human allotypes (C4A13 and C4B12) and the presence of signal sequences enhancing recombination."
      Martinez-Quiles N., Paz-Artal E., Moreno-Pelayo M.A., Longas J., Ferre-Lopez S., Rosal M., Arnaiz-Villena A.
      J. Immunol. 161:3438-3443(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1055-1225 (ALLOTYPE C4B12).
    12. "C4d DNA sequence of complement C4B93 and recombination mechanisms for its generation."
      Lopez-Goyanes A., Moreno M.A., Ferre S., Paz-Artal E.
      Tissue Antigens 63:260-262(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1055-1225, VARIANTS ASN-1176; VAL-1207 AND LEU-1210.
    13. "Amino acid sequence of a polymorphic segment from fragment C4d of human complement component C4."
      Chakravarti D.N., Campbell R.D., Gagnon J.
      FEBS Lett. 154:387-390(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1199-1304.
    14. "Identification of the site of sulfation of the fourth component of human complement."
      Hortin G., Sims H., Strauss A.W.
      J. Biol. Chem. 261:1786-1793(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1405-1431, SULFATION AT TYR-1417; TYR-1420 AND TYR-1422.
    15. "Complete C4B deficiency in black Americans with systemic lupus erythematosus."
      Wilson W.A., Perez M.C.
      J. Rheumatol. 15:1855-1858(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN C4BD AND SLE.
    16. "Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A."
      Carroll M.C., Fathallah D.M., Bergamaschini L., Alicot E.M., Isenman D.E.
      Proc. Natl. Acad. Sci. U.S.A. 87:6868-6872(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INVOLVEMENT OF HIS-1125 IN IMMUNOGLOBULIN-BINDING AND HEMOLYSIS, MUTAGENESIS OF LEU-1120; SER-1121; ILE-1124 AND HIS-1125.
    17. "The reaction mechanism of the internal thioester in the human complement component C4."
      Dodds A.W., Ren X.D., Willis A.C., Law S.K.
      Nature 379:177-179(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    18. "Deficiency of human complement protein C4 due to identical frameshift mutations in the C4A and C4B genes."
      Lokki M.L., Circolo A., Ahokas P., Rupert K.L., Yu C.Y., Colten H.R.
      J. Immunol. 162:3687-3693(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SLE.
    19. "Genetic, structural and functional diversities of human complement components C4A and C4B and their mouse homologues, Slp and C4."
      Blanchong C.A., Chung E.K., Rupert K.L., Yang Y., Yang Z., Zhou B., Moulds J.M., Yu C.Y.
      Int. Immunopharmacol. 1:365-392(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW, DESCRIPTION OF ALLOTYPES, TISSUE SPECIFICITY.
    20. "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
      Zhang H., Li X.-J., Martin D.B., Aebersold R.
      Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-226.
    21. "Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
      Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
      Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1391.
      Tissue: Plasma.
    22. "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry."
      Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.
      J. Proteome Res. 5:1493-1503(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1328.
      Tissue: Saliva.
    23. "Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity."
      Yu C.Y., Belt K.T., Giles C.M., Campbell R.D., Porter R.R.
      EMBO J. 5:2873-2881(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURAL BASIS OF POLYMORPHISM.
    24. "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."
      Yang Y., Chung E.K., Wu Y.L., Savelli S.L., Nagaraja H.N., Zhou B., Hebert M., Jones K.N., Shu Y., Kitzmiller K., Blanchong C.A., McBride K.L., Higgins G.C., Rennebohm R.M., Rice R.R., Hackshaw K.V., Roubey R.A., Grossman J.M.
      , Tsao B.P., Birmingham D.J., Rovin B.H., Hebert L.A., Yu C.Y.
      Am. J. Hum. Genet. 80:1037-1054(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SLE.

    Entry informationi

    Entry nameiCO4B_HUMAN
    AccessioniPrimary (citable) accession number: P0C0L5
    Secondary accession number(s): A2BHY4
    , P01028, P78445, Q13160, Q13906, Q14033, Q14835, Q6U2E9, Q6U2G1, Q6U2I5, Q6U2L1, Q6U2L7, Q6U2L9, Q6U2M5, Q6VCV8, Q96SA7, Q9NPK5, Q9UIP5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: April 3, 2013
    Last modified: October 1, 2014
    This is version 100 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Blood group antigen proteins
      Nomenclature of blood group antigens and list of entries
    2. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3