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P0C0L5 (CO4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C4-B
Alternative name(s):
Basic complement C4
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3
Gene names
Name:C4B
Synonyms:CO4, CPAMD3
AND
Name:C4B_2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1744 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.16 Ref.17

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. Ref.16 Ref.17

Subunit structure

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

Subcellular location

Secreted.

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. Ref.19

Post-translational modification

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.

Polymorphism

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 (Ref.19).

Involvement in disease

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. Ref.15 Ref.18 Ref.24

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. Ref.15

Sequence similarities

Contains 1 anaphylatoxin-like domain.

Contains 1 NTR domain.

Sequence caution

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

Ontologies

Keywords
   Biological processComplement pathway
Immunity
Inflammatory response
Innate immunity
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseSystemic lupus erythematosus
   DomainSignal
   Molecular functionBlood group antigen
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Sulfation
Thioester bond
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcomplement activation

Inferred from genetic interaction PubMed 19302245. Source: BHF-UCL

complement activation, classical pathway

Inferred from electronic annotation. Source: UniProtKB-KW

detection of molecule of bacterial origin

Inferred from direct assay PubMed 22333221. Source: BHF-UCL

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

opsonization

Traceable author statement PubMed 22333221. Source: BHF-UCL

positive regulation of apoptotic cell clearance

Inferred from genetic interaction PubMed 19302245. Source: BHF-UCL

regulation of complement activation

Traceable author statement. Source: Reactome

   Cellular_componentblood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 22333221Ref.16. Source: BHF-UCL

other organism cell

Inferred from direct assay PubMed 22333221. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncarbohydrate binding

Inferred from direct assay Ref.16. Source: BHF-UCL

complement binding

Inferred from direct assay Ref.16. Source: BHF-UCL

endopeptidase inhibitor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Chain20 – 675656Complement C4 beta chain
PRO_0000042699
Propeptide676 – 6794
PRO_0000042700
Chain680 – 1446767Complement C4-B alpha chain
PRO_0000042701
Chain680 – 75677C4a anaphylatoxin
PRO_0000042702
Chain757 – 1446690C4b-B
PRO_0000042703
Chain957 – 1336380C4d-B
PRO_0000042704
Propeptide1447 – 14537
PRO_0000042705
Chain1454 – 1744291Complement C4 gamma chain
PRO_0000042706

Regions

Domain702 – 73635Anaphylatoxin-like
Domain1595 – 1742148NTR

Amino acid modifications

Modified residue14171Sulfotyrosine Ref.14
Modified residue14201Sulfotyrosine Ref.14
Modified residue14221Sulfotyrosine Ref.14
Glycosylation2261N-linked (GlcNAc...) Ref.20
Glycosylation8621N-linked (GlcNAc...) Potential
Glycosylation13281N-linked (GlcNAc...) Ref.22
Glycosylation13911N-linked (GlcNAc...) Ref.21
Disulfide bond702 ↔ 728 By similarity
Disulfide bond703 ↔ 735 By similarity
Disulfide bond716 ↔ 736 By similarity
Disulfide bond1595 ↔ 1673 By similarity
Disulfide bond1618 ↔ 1742 By similarity
Cross-link1010 ↔ 1013Isoglutamyl cysteine thioester (Cys-Gln)

Natural variations

Natural variant3471S → Y in allotype C4B-long. Ref.2 Ref.4
Corresponds to variant rs139889867 [ dbSNP | Ensembl ].
VAR_023729
Natural variant4781P → L in allotype C4B1-hi.
VAR_069160
Natural variant9071T → A in allotype C4B-long and allotype C4B2. Ref.2 Ref.3 Ref.4
VAR_023730
Natural variant10731G → D in allotype C4B2 and allotype C4B5-Rg1. Ref.3 Ref.7
VAR_023731
Natural variant11761S → N in allotype C4B1a. Ref.12
Corresponds to variant rs2746414 [ dbSNP | Ensembl ].
VAR_023732
Natural variant12071A → V in allotype C4B5-Rg1. Ref.12
Corresponds to variant rs200888163 [ dbSNP | Ensembl ].
VAR_023734
Natural variant12101R → L in allotype C4B5-Rg1. Ref.12
Corresponds to variant rs112683215 [ dbSNP | Ensembl ].
VAR_023735
Natural variant13171I → F in allotype C4B1-SC01. Ref.1
VAR_069161

Experimental info

Mutagenesis11201L → P: No effect on hemolytic activity, nor on C1-dependent binding to IgG. Ref.16
Mutagenesis11211S → C: 30-40% decrease in hemolytic activity and C1-dependent binding to IgG. Ref.16
Mutagenesis11241I → A: 50-60% decrease in hemolytic activity and C1-dependent binding to IgG. Ref.16
Mutagenesis11251H → A: 20% decrease in hemolytic activity, 2-fold increase in C1-dependent binding to IgG. Ref.16
Mutagenesis11251H → D: 2.5-3 fold-decrease in hemolytic activity, 3-fold increase in C1-dependent binding to IgG. Ref.16
Sequence conflict7141R → S in AAR89101. Ref.3
Sequence conflict7291R → Q in AAR89127. Ref.3
Sequence conflict980 – 9812VT → LQ in AAA99717. Ref.1
Sequence conflict10131Q → E AA sequence Ref.8
Sequence conflict10131Q → E AA sequence Ref.9
Sequence conflict10131Q → E AA sequence Ref.10
Sequence conflict1109 – 11102SQ → IA AA sequence Ref.9
Sequence conflict12711H → V AA sequence Ref.9
Sequence conflict12711H → V AA sequence Ref.13
Sequence conflict13001R → V AA sequence Ref.9
Sequence conflict13001R → V AA sequence Ref.13
Sequence conflict16541T → RA in AAA99717. Ref.1
Sequence conflict16981H → Q in AAA99717. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P0C0L5 [UniParc].

Last modified April 3, 2013. Version 2.
Checksum: E724B85F7FA673C5

FASTA1,744192,751
        10         20         30         40         50         60 
MRLLWGLIWA SSFFTLSLQK PRLLLFSPSV VHLGVPLSVG VQLQDVPRGQ VVKGSVFLRN 

        70         80         90        100        110        120 
PSRNNVPCSP KVDFTLSSER DFALLSLQVP LKDAKSCGLH QLLRGPEVQL VAHSPWLKDS 

       130        140        150        160        170        180 
LSRTTNIQGI NLLFSSRRGH LFLQTDQPIY NPGQRVRYRV FALDQKMRPS TDTITVMVEN 

       190        200        210        220        230        240 
SHGLRVRKKE VYMPSSIFQD DFVIPDISEP GTWKISARFS DGLESNSSTQ FEVKKYVLPN 

       250        260        270        280        290        300 
FEVKITPGKP YILTVPGHLD EMQLDIQARY IYGKPVQGVA YVRFGLLDED GKKTFFRGLE 

       310        320        330        340        350        360 
SQTKLVNGQS HISLSKAEFQ DALEKLNMGI TDLQGLRLYV AAAIIESPGG EMEEAELTSW 

       370        380        390        400        410        420 
YFVSSPFSLD LSKTKRHLVP GAPFLLQALV REMSGSPASG IPVKVSATVS SPGSVPEVQD 

       430        440        450        460        470        480 
IQQNTDGSGQ VSIPIIIPQT ISELQLSVSA GSPHPAIARL TVAAPPSGGP GFLSIERPDS 

       490        500        510        520        530        540 
RPPRVGDTLN LNLRAVGSGA TFSHYYYMIL SRGQIVFMNR EPKRTLTSVS VFVDHHLAPS 

       550        560        570        580        590        600 
FYFVAFYYHG DHPVANSLRV DVQAGACEGK LELSVDGAKQ YRNGESVKLH LETDSLALVA 

       610        620        630        640        650        660 
LGALDTALYA AGSKSHKPLN MGKVFEAMNS YDLGCGPGGG DSALQVFQAA GLAFSDGDQW 

       670        680        690        700        710        720 
TLSRKRLSCP KEKTTRKKRN VNFQKAINEK LGQYASPTAK RCCQDGVTRL PMMRSCEQRA 

       730        740        750        760        770        780 
ARVQQPDCRE PFLSCCQFAE SLRKKSRDKG QAGLQRALEI LQEEDLIDED DIPVRSFFPE 

       790        800        810        820        830        840 
NWLWRVETVD RFQILTLWLP DSLTTWEIHG LSLSKTKGLC VATPVQLRVF REFHLHLRLP 

       850        860        870        880        890        900 
MSVRRFEQLE LRPVLYNYLD KNLTVSVHVS PVEGLCLAGG GGLAQQVLVP AGSARPVAFS 

       910        920        930        940        950        960 
VVPTAATAVS LKVVARGSFE FPVGDAVSKV LQIEKEGAIH REELVYELNP LDHRGRTLEI 

       970        980        990       1000       1010       1020 
PGNSDPNMIP DGDFNSYVRV TASDPLDTLG SEGALSPGGV ASLLRLPRGC GEQTMIYLAP 

      1030       1040       1050       1060       1070       1080 
TLAASRYLDK TEQWSTLPPE TKDHAVDLIQ KGYMRIQQFR KADGSYAAWL SRGSSTWLTA 

      1090       1100       1110       1120       1130       1140 
FVLKVLSLAQ EQVGGSPEKL QETSNWLLSQ QQADGSFQDL SPVIHRSMQG GLVGNDETVA 

      1150       1160       1170       1180       1190       1200 
LTAFVTIALH HGLAVFQDEG AEPLKQRVEA SISKASSFLG EKASAGLLGA HAAAITAYAL 

      1210       1220       1230       1240       1250       1260 
TLTKAPADLR GVAHNNLMAM AQETGDNLYW GSVTGSQSNA VSPTPAPRNP SDPMPQAPAL 

      1270       1280       1290       1300       1310       1320 
WIETTAYALL HLLLHEGKAE MADQAAAWLT RQGSFQGGFR STQDTVIALD ALSAYWIASH 

      1330       1340       1350       1360       1370       1380 
TTEERGLNVT LSSTGRNGFK SHALQLNNRQ IRGLEEELQF SLGSKINVKV GGNSKGTLKV 

      1390       1400       1410       1420       1430       1440 
LRTYNVLDMK NTTCQDLQIE VTVKGHVEYT MEANEDYEDY EYDELPAKDD PDAPLQPVTP 

      1450       1460       1470       1480       1490       1500 
LQLFEGRRNR RRREAPKVVE EQESRVHYTV CIWRNGKVGL SGMAIADVTL LSGFHALRAD 

      1510       1520       1530       1540       1550       1560 
LEKLTSLSDR YVSHFETEGP HVLLYFDSVP TSRECVGFEA VQEVPVGLVQ PASATLYDYY 

      1570       1580       1590       1600       1610       1620 
NPERRCSVFY GAPSKSRLLA TLCSAEVCQC AEGKCPRQRR ALERGLQDED GYRMKFACYY 

      1630       1640       1650       1660       1670       1680 
PRVEYGFQVK VLREDSRAAF RLFETKITQV LHFTKDVKAA ANQMRNFLVR ASCRLRLEPG 

      1690       1700       1710       1720       1730       1740 
KEYLIMGLDG ATYDLEGHPQ YLLDSNSWIE EMPSERLCRS TRQRAACAQL NDFLQEYGTQ 


GCQV 

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References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , 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.
CCDSCCDS47405.1.
PIRB20807.
RefSeqNP_001002029.3. NM_001002029.3.
NP_001229752.1. NM_001242823.2.
UniGeneHs.534847.
Hs.720022.

3D structure databases

ProteinModelPortalP0C0L5.
SMRP0C0L5. Positions 20-670, 681-1420, 1455-1744.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107182. 1 interaction.
DIPDIP-47260N.
IntActP0C0L5. 1 interaction.
STRING9606.ENSP00000412786.

Protein family/group databases

MEROPSI39.951.

PTM databases

PhosphoSiteP0C0L5.

Polymorphism databases

DMDM476007828.

2D gel databases

SWISS-2DPAGEP0C0L5.

Proteomic databases

MaxQBP0C0L5.
PaxDbP0C0L5.
PRIDEP0C0L5.

Protocols and materials databases

DNASU721.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375177; ENSP00000364321; ENSG00000228454.
ENST00000411583; ENSP00000407942; ENSG00000228267.
ENST00000435363; ENSP00000415941; ENSG00000224389.
ENST00000435500; ENSP00000412786; ENSG00000233312.
ENST00000449788; ENSP00000414200; ENSG00000236625.
GeneID100293534.
721.
KEGGhsa:100293534.
hsa:721.
UCSCuc011doy.2. human.

Organism-specific databases

CTD100293534.
721.
GeneCardsGC06P031982.
GC06P031985.
H-InvDBHIX0164690.
HIX0164691.
HIX0166073.
HIX0166340.
HIX0166869.
HIX0167127.
HIX0167359.
HIX0167360.
HGNCHGNC:1324. C4B.
HGNC:42398. C4B_2.
MIM120820. gene.
152700. phenotype.
614374. phenotype.
614379. phenotype.
neXtProtNX_P0C0L5.
Orphanet169147. Immunodeficiency due to an early component of complement deficiency.
536. Systemic lupus erythematosus.
PharmGKBPA25904.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2373.
HOVERGENHBG107123.
InParanoidP0C0L5.
KOK03989.
OMAYAPRQTV.
PhylomeDBP0C0L5.
TreeFamTF313285.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

GenevestigatorP0C0L5.

Family and domain databases

Gene3D1.20.91.20. 1 hit.
1.50.10.20. 1 hit.
2.60.40.690. 1 hit.
InterProIPR009048. 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]
PfamPF00207. 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]
PRINTSPR00004. ANAPHYLATOXN.
SMARTSM00104. ANATO. 1 hit.
SM00643. C345C. 1 hit.
[Graphical view]
SUPFAMSSF47686. SSF47686. 1 hit.
SSF48239. SSF48239. 1 hit.
SSF49410. SSF49410. 1 hit.
SSF50242. SSF50242. 1 hit.
PROSITEPS00477. ALPHA_2_MACROGLOBULIN. 1 hit.
PS01177. ANAPHYLATOXIN_1. 1 hit.
PS01178. ANAPHYLATOXIN_2. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiComplement_component_4B.
NextBio20783275.
PROP0C0L5.
SOURCESearch...

Entry information

Entry nameCO4B_HUMAN
AccessionPrimary (citable) accession number: P0C0L5
Secondary accession number(s): A2BHY4 expand/collapse secondary AC list , P01028, P78445, Q13160, Q13906, Q14033, Q14835, Q6U2E9, Q6U2G1, Q6U2I5, Q6U2L1, Q6U2L7, Q6U2L9, Q6U2M5, Q6VCV8, Q96SA7, Q9NPK5, Q9UIP5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 3, 2013
Last modified: July 9, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Blood group antigen proteins

Nomenclature of blood group antigens and list of entries