P0C0L5 (CO4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Complement C4 beta chain
2. Complement C4-B alpha chain
3. C4a anaphylatoxin
4. C4b-B
5. C4d-B
6. Complement C4 gamma chain

Gene names

Name:	C4B
Synonyms:	CO4, CPAMD3
AND
Name:	C4B_2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1744 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Complement pathway Immunity Inflammatory response Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Systemic lupus erythematosus
Domain	Signal
Molecular function	Blood group antigen
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Sulfation Thioester bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation Traceable author statement. Source: Reactome complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome negative regulation of endopeptidase activity Inferred from electronic annotation. Source: GOC regulation of complement activation Traceable author statement. Source: Reactome
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: InterPro plasma membrane Traceable author statement. Source: Reactome
Molecular_function	endopeptidase inhibitor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Chain	20 – 675	656	Complement C4 beta chain		PRO_0000042699
	Propeptide	676 – 679	4			PRO_0000042700
	Chain	680 – 1446	767	Complement C4-B alpha chain		PRO_0000042701
	Chain	680 – 756	77	C4a anaphylatoxin		PRO_0000042702
	Chain	757 – 1446	690	C4b-B		PRO_0000042703
	Chain	957 – 1336	380	C4d-B		PRO_0000042704
	Propeptide	1447 – 1453	7			PRO_0000042705
	Chain	1454 – 1744	291	Complement C4 gamma chain		PRO_0000042706
Regions
	Domain	702 – 736	35	Anaphylatoxin-like
	Domain	1595 – 1742	148	NTR
Amino acid modifications
	Modified residue	1417	1	Sulfotyrosine
	Modified residue	1420	1	Sulfotyrosine
	Modified residue	1422	1	Sulfotyrosine
	Glycosylation	226	1	N-linked (GlcNAc...) Ref.20
	Glycosylation	862	1	N-linked (GlcNAc...) Potential
	Glycosylation	1328	1	N-linked (GlcNAc...) Ref.22
	Glycosylation	1391	1	N-linked (GlcNAc...) Ref.21
	Disulfide bond	702 ↔ 728		By similarity
	Disulfide bond	703 ↔ 735		By similarity
	Disulfide bond	716 ↔ 736		By similarity
	Disulfide bond	1595 ↔ 1673		By similarity
	Disulfide bond	1618 ↔ 1742		By similarity
	Cross-link	1010 ↔ 1013		Isoglutamyl cysteine thioester (Cys-Gln)
Natural variations
	Natural variant	347	1	S → Y in allotype C4B-long. Ref.2 Ref.4 Corresponds to variant rs139889867 [ dbSNP | Ensembl ].		VAR_023729
	Natural variant	478	1	P → L in allotype C4B1-hi.		VAR_069160
	Natural variant	907	1	T → A in allotype C4B-long and allotype C4B2. Ref.2 Ref.3 Ref.4		VAR_023730
	Natural variant	1073	1	G → D in allotype C4B2 and allotype C4B5-Rg1. Ref.3 Ref.7		VAR_023731
	Natural variant	1176	1	S → N in allotype C4B1a. Ref.12 Corresponds to variant rs2746414 [ dbSNP | Ensembl ].		VAR_023732
	Natural variant	1207	1	A → V in allotype C4B5-Rg1. Ref.12 Corresponds to variant rs200888163 [ dbSNP | Ensembl ].		VAR_023734
	Natural variant	1210	1	R → L in allotype C4B5-Rg1. Ref.12 Corresponds to variant rs112683215 [ dbSNP | Ensembl ].		VAR_023735
	Natural variant	1317	1	I → F in allotype C4B1-SC01. Ref.1		VAR_069161
Experimental info
	Mutagenesis	1120	1	L → P: No effect on hemolytic activity, nor on C1-dependent binding to IgG. Ref.16
	Mutagenesis	1121	1	S → C: 30-40% decrease in hemolytic activity and C1-dependent binding to IgG. Ref.16
	Mutagenesis	1124	1	I → A: 50-60% decrease in hemolytic activity and C1-dependent binding to IgG. Ref.16
	Mutagenesis	1125	1	H → A: 20% decrease in hemolytic activity, 2-fold increase in C1-dependent binding to IgG. Ref.16
	Mutagenesis	1125	1	H → D: 2.5-3 fold-decrease in hemolytic activity, 3-fold increase in C1-dependent binding to IgG. Ref.16
	Sequence conflict	714	1	R → S in AAR89101. Ref.3
	Sequence conflict	729	1	R → Q in AAR89127. Ref.3
	Sequence conflict	980 – 981	2	VT → LQ in AAA99717. Ref.1
	Sequence conflict	1013	1	Q → E AA sequence Ref.8
	Sequence conflict	1013	1	Q → E AA sequence Ref.9
	Sequence conflict	1013	1	Q → E AA sequence Ref.10
	Sequence conflict	1109 – 1110	2	SQ → IA AA sequence Ref.9
	Sequence conflict	1271	1	H → V AA sequence Ref.9
	Sequence conflict	1271	1	H → V AA sequence Ref.13
	Sequence conflict	1300	1	R → V AA sequence Ref.9
	Sequence conflict	1300	1	R → V AA sequence Ref.13
	Sequence conflict	1654	1	T → RA in AAA99717. Ref.1
	Sequence conflict	1698	1	H → Q in AAA99717. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P0C0L5 [UniParc]. Last modified April 3, 2013. Version 2. Checksum: E724B85F7FA673C5	FASTA	1,744	192,751
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
[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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
+	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 , 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.
IPI	IPI00654875.
PIR	B20807.
RefSeq	NP_001002029.3. NM_001002029.3. NP_001229752.1. NM_001242823.2.
UniGene	Hs.534847. Hs.720022.
3D structure databases
ProteinModelPortal	P0C0L5.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-47260N.
IntAct	P0C0L5. 1 interaction.
Protein family/group databases
MEROPS	I39.951.
PTM databases
PhosphoSite	P0C0L5.
Polymorphism databases
DMDM	81175167.
2D gel databases
SWISS-2DPAGE	P0C0L5.
Proteomic databases
PaxDb	P0C0L5.
PRIDE	P0C0L5.
Protocols and materials databases
DNASU	721.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000411583; ENSP00000407942; ENSG00000228267. ENST00000435363; ENSP00000415941; ENSG00000224389. ENST00000449788; ENSP00000414200; ENSG00000236625.
GeneID	100293534. 721.
KEGG	hsa:100293534. hsa:721.
UCSC	uc011doy.2. human.
Organism-specific databases
CTD	100293534. 721.
GeneCards	GC06P031982.
H-InvDB	HIX0164690. HIX0164691. HIX0166073. HIX0166340. HIX0166869. HIX0167127. HIX0167359. HIX0167360.
HGNC	HGNC:1324. C4B. HGNC:42398. C4B_2.
MIM	120820. gene. 152700. phenotype. 614374. phenotype. 614379. phenotype.
neXtProt	NX_P0C0L5.
Orphanet	169147. Immunodeficiency due to an early component of complement deficiency.
PharmGKB	PA25904.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2373.
HOVERGEN	HBG107123.
InParanoid	P0C0L5.
KO	K03989.
OrthoDB	EOG4JM7NW.
PhylomeDB	P0C0L5.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P0C0L5.
Genevestigator	P0C0L5.
GermOnline	ENSG00000204319. Homo sapiens.
Family and domain databases
Gene3D	1.20.91.20. 1 hit. 2.60.40.690. 1 hit.
InterPro	IPR009048. A-macroglobulin_rcpt-bd. IPR011626. A2M_comp. IPR002890. A2M_N. IPR011625. A2M_N_2. IPR000020. Anaphylatoxin/fibulin. IPR018081. Anaphylatoxin_. IPR001840. Anaphylatoxn. 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]
Pfam	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]
PRINTS	PR00004. ANAPHYLATOXN.
SMART	SM00104. ANATO. 1 hit. SM00643. C345C. 1 hit. [Graphical view]
SUPFAM	SSF49410. AM_receptor_bind. 1 hit. SSF47686. Anaphylatoxin. 1 hit. SSF48239. Terp_cyc_toroid. 1 hit. SSF50242. TIMP_like. 1 hit.
PROSITE	PS00477. ALPHA_2_MACROGLOBULIN. 1 hit. PS01177. ANAPHYLATOXIN_1. 1 hit. PS01178. ANAPHYLATOXIN_2. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	20783275.
SOURCE	Search...

Entry information

Entry name

CO4B_HUMAN

Accession

Primary (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 history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 3, 2013
Last modified:	May 29, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.