Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P0C0L4 (CO4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C4-A
Alternative name(s):
Acidic complement C4
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2
Gene names
Name:C4A
Synonyms:CO4, CPAMD2
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 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.19 Ref.21

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.19 Ref.21

Subunit structure

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

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.23

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.

N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. Ref.24 Ref.31 Ref.33

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. 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.23). C4A6 allotype is deficient in hemolytic activity. Allotype C4A13 is infrequent.

Involvement in disease

Complement component 4A deficiency (C4AD) [MIM:614380]: 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.20

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.22 Ref.28

Sequence similarities

Contains 1 anaphylatoxin-like domain.

Contains 1 NTR domain.

Sequence caution

The sequence AAB59537.1 differs from that shown. Reason: During cDNA synthesis, the 5' end has been inverted (Ref.6).

The sequence BAE06071.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P0C0L4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P0C0L4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1458-1503: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Chain20 – 675656Complement C4 beta chain
PRO_0000005966
Propeptide676 – 6794
PRO_0000005967
Chain680 – 1446767Complement C4-A alpha chain
PRO_0000005968
Chain680 – 75677C4a anaphylatoxin
PRO_0000005969
Chain757 – 1446690C4b-A
PRO_0000005970
Chain957 – 1336380C4d-A
PRO_0000042698
Propeptide1447 – 14537
PRO_0000005971
Chain1454 – 1744291Complement C4 gamma chain
PRO_0000005972

Regions

Domain702 – 73635Anaphylatoxin-like
Domain1595 – 1742148NTR

Sites

Site11251Responsible for effective binding to form amide bonds with immune aggregates or protein antigens

Amino acid modifications

Modified residue14171Sulfotyrosine Ref.17
Modified residue14201Sulfotyrosine Ref.17
Modified residue14221Sulfotyrosine Ref.17
Glycosylation2261N-linked (GlcNAc...) Ref.24 Ref.29 Ref.30
Glycosylation8621N-linked (GlcNAc...) Ref.27
Glycosylation12441O-linked (GalNAc...) Ref.33
Glycosylation13281N-linked (GlcNAc...) (complex) Ref.27 Ref.29 Ref.30 Ref.31
Glycosylation13911N-linked (GlcNAc...) Ref.25 Ref.27 Ref.30
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

Alternative sequence1458 – 150346Missing in isoform 2.
VSP_046252
Natural variant1411L → V.
Corresponds to variant rs9296005 [ dbSNP | Ensembl ].
VAR_069154
Natural variant3471S → Y in allotype C4A3a, allotype C4A6. Ref.2 Ref.4 Ref.5
Corresponds to variant rs150969927 [ dbSNP | Ensembl ].
VAR_019778
Natural variant4181V → A in allotype C4A4. Ref.1
VAR_069155
Natural variant4771R → W in allotype C4A6. Ref.8
VAR_001987
Natural variant5491H → P. Ref.8
Corresponds to variant rs2229405 [ dbSNP | Ensembl ].
VAR_069156
Natural variant5641A → D.
Corresponds to variant rs35277227 [ dbSNP | Ensembl ].
VAR_069157
Natural variant7261P → L in allotype C4A3a. Ref.2
VAR_001988
Natural variant7271D → N. Ref.7
VAR_019779
Natural variant9071A → T. Ref.8
Corresponds to variant rs141302872 [ dbSNP | Ensembl ].
VAR_019780
Natural variant10731D → G in allotype C4A1, allotype C4A2. Ref.5 Ref.8 Ref.12
Corresponds to variant rs147162052 [ dbSNP | Ensembl ].
VAR_069158
Natural variant11761N → S in allotype C4A1. Ref.3 Ref.4 Ref.8 Ref.12
Corresponds to variant rs17874654 [ dbSNP | Ensembl ].
VAR_069159
Natural variant12011T → S in allotype C4A4. Ref.1
VAR_001992
Natural variant12071V → A in allotype C4A1, allotype C4A13. Ref.8 Ref.12 Ref.16
Corresponds to variant rs28357075 [ dbSNP | Ensembl ].
VAR_001993
Natural variant12101L → R in allotype C4A1, allotype C4A13. Ref.8 Ref.12 Ref.16
Corresponds to variant rs28357076 [ dbSNP | Ensembl ].
VAR_001994
Natural variant12861S → A in allotype C4A1, allotype C4A3a, allotype C4A6. Ref.2 Ref.3 Ref.4 Ref.5 Ref.12 Ref.16 Ref.35
Corresponds to variant rs201016130 [ dbSNP | Ensembl ].
VAR_001995

Experimental info

Sequence conflict2171A → V in AAI71786. Ref.5
Sequence conflict6431A → S in AAH63289. Ref.5
Sequence conflict7291R → W in AAH63289. Ref.5
Sequence conflict10131Q → E AA sequence Ref.11
Sequence conflict10131Q → E AA sequence Ref.12
Sequence conflict10131Q → E AA sequence Ref.13
Sequence conflict1109 – 11102SQ → IA AA sequence Ref.12
Sequence conflict11821K → I in AAH63289. Ref.5
Sequence conflict12451P → Q in AAH63289. Ref.5
Sequence conflict12711H → V AA sequence Ref.12
Sequence conflict12711H → V AA sequence Ref.16
Sequence conflict13001R → V AA sequence Ref.12
Sequence conflict13001R → V AA sequence Ref.16
Sequence conflict1419 – 14213Missing in AAB59537. Ref.1
Sequence conflict16351D → G in AAH12372. Ref.5
Sequence conflict16371R → S in AAI44547. Ref.5
Sequence conflict16371R → S in AAI46850. Ref.5
Sequence conflict16781E → G in AAI71786. Ref.5
Sequence conflict17041D → E in AAH12372. Ref.5

Secondary structure

.............................. 1744
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2013. Version 2.
Checksum: 9396A4CC4DA3602C

FASTA1,744192,785
        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 
VVPTAAAAVS 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 SRDSSTWLTA 

      1090       1100       1110       1120       1130       1140 
FVLKVLSLAQ EQVGGSPEKL QETSNWLLSQ QQADGSFQDP CPVLDRSMQG GLVGNDETVA 

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

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

      1270       1280       1290       1300       1310       1320 
WIETTAYALL HLLLHEGKAE MADQASAWLT 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 

« Hide

Isoform 2 [UniParc].

Checksum: 6169C0C84E28C512
Show »

FASTA1,698187,704

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1), VARIANTS ALA-418 AND SER-1201.
Tissue: Liver.
[2]"The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene."
Yu C.Y.
J. Immunol. 146:1057-1066(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-347; LEU-726 AND ALA-1286.
[3]"Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method."
Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS SER-1176 AND ALA-1286.
Tissue: Brain.
[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; SER-1176 AND ALA-1286.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS TYR-347; GLY-1073 AND ALA-1286.
Tissue: Brain.
[6]"Polymorphism of human complement component C4."
Belt K.T., Yu C.Y., Carroll M.C., Porter R.R.
Immunogenetics 21:173-180(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22 AND 1056-1225.
[7]"Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex."
Sargent C.A., Anderson M.J., Hsieh S.-L., Kendall E., Gomez-Escobar N., Campbell R.D.
Hum. Mol. Genet. 3:481-488(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21, VARIANT ASN-727.
[8]"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] OF 448-570 AND 692-1225, VARIANTS TRP-477; PRO-549; THR-907; GLY-1073; SER-1176; ALA-1207 AND ARG-1210.
[9]"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.
[10]"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.
[11]"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.
[12]"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, VARIANTS GLY-1073; SER-1176; ALA-1207; ARG-1210 AND ALA-1286.
[13]"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.
[14]"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 C4A13).
[15]"Cloning of a human complement component C4 gene."
Carroll M.C., Porter R.R.
Proc. Natl. Acad. Sci. U.S.A. 80:264-267(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1195-1294.
[16]"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, VARIANTS ALA-1207; ARG-1210 AND ALA-1286.
[17]"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.
[18]"Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig."
Whitehead A.S., Goldberger G., Woods D.E., Markham A.F., Colten H.R.
Proc. Natl. Acad. Sci. U.S.A. 80:5387-5391(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1448-1474.
[19]"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 ASP-1125 IN IMMUNOGLOBULIN-BINDING AND HEMOLYSIS.
[20]"Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression."
Barba G., Rittner C., Schneider P.M.
J. Clin. Invest. 91:1681-1686(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN C4AD.
[21]"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.
[22]"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.
[23]"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.
[24]"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.
[25]"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.
[26]"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.
[27]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-862; ASN-1328 AND ASN-1391.
Tissue: Plasma.
[28]"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.
[29]"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry."
Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.
Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226 AND ASN-1328.
Tissue: Milk.
[30]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226; ASN-1328 AND ASN-1391.
Tissue: Liver.
[31]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-1328.
[32]"Enrichment of glycopeptides for glycan structure and attachment site identification."
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], STRUCTURE OF CARBOHYDRATES.
Tissue: Cerebrospinal fluid.
[33]"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins."
Halim A., Ruetschi U., Larson G., Nilsson J.
J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-1244, IDENTIFICATION BY MASS SPECTROMETRY.
[34]"X-ray crystal structure of the C4d fragment of human complement component C4."
van den Elsen J.M., Martin A., Wong V., Clemenza L., Rose D.R., Isenman D.E.
J. Mol. Biol. 322:1103-1115(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 957-1323.
[35]"The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect."
Anderson M.J., Milner C.M., Cotton G.H., Campbell R.D.
J. Immunol. 148:2795-2802(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-1286 (ALLOTYPE C4A6).
+Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02403 mRNA. Translation: AAB59537.1. Sequence problems.
M59815, M59816 Genomic DNA. Translation: AAA51855.1.
L26261 Genomic DNA. Translation: AAA20121.2.
AB209989 mRNA. Translation: BAE06071.1. Different initiation.
AL645922 Genomic DNA. No translation available.
AL844853 Genomic DNA. No translation available.
AL929593 Genomic DNA. No translation available.
CR936924 Genomic DNA. No translation available.
BC012372 mRNA. Translation: AAH12372.2.
BC063289 mRNA. Translation: AAH63289.1.
BC144546 mRNA. Translation: AAI44547.1.
BC146673 mRNA. Translation: AAI46674.1.
BC146849 mRNA. Translation: AAI46850.1.
BC151204 mRNA. Translation: AAI51205.1.
BC171786 mRNA. Translation: AAI71786.1.
M14824 Genomic DNA. Translation: AAA52292.1.
X77491 Genomic DNA. Translation: CAA54627.1.
AY379925 Genomic DNA. Translation: AAR89152.1.
AY379926 Genomic DNA. Translation: AAR89153.1.
AY379927 Genomic DNA. Translation: AAR89154.1.
AY379928 Genomic DNA. Translation: AAR89155.1.
AY379929 Genomic DNA. Translation: AAR89156.1.
AY379930 Genomic DNA. Translation: AAR89157.1.
AY379931 Genomic DNA. Translation: AAR89158.1.
AY379932 Genomic DNA. Translation: AAR89159.1.
AY379933 Genomic DNA. Translation: AAR89160.1.
AY379934 Genomic DNA. Translation: AAR89161.1.
AY379935 Genomic DNA. Translation: AAR89162.1.
AY379960 Genomic DNA. Translation: AAR89164.1.
AY379962 Genomic DNA. Translation: AAR89166.1.
AY379963 Genomic DNA. Translation: AAR89167.1.
AY379964 Genomic DNA. Translation: AAR89168.1.
AY379965 Genomic DNA. Translation: AAR89169.1.
AY379966 Genomic DNA. Translation: AAR89170.1.
U77886 Genomic DNA. Translation: AAK49810.1.
V00502 mRNA. Translation: CAA23760.1.
K00830 mRNA. Translation: AAA36229.1.
PIRB20807.
C4HU. I56095.
RefSeqNP_001002029.3. NM_001002029.3.
NP_001239133.1. NM_001252204.1.
NP_009224.2. NM_007293.2.
UniGeneHs.534847.
Hs.720022.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HZFX-ray2.30A957-1323[»]
4FXGX-ray3.75A/D20-675[»]
B/E680-1446[»]
C/F1454-1744[»]
4FXKX-ray3.60A20-675[»]
B680-1446[»]
C1454-1744[»]
ProteinModelPortalP0C0L4.
SMRP0C0L4. Positions 20-670, 681-1420, 1455-1744.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107181. 4 interactions.
IntActP0C0L4. 11 interactions.
STRING9606.ENSP00000364444.

PTM databases

PhosphoSiteP0C0L4.

Polymorphism databases

DMDM476007827.

Proteomic databases

PaxDbP0C0L4.
PRIDEP0C0L4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000383325; ENSP00000372815; ENSG00000206340.
ENST00000421274; ENSP00000388662; ENSG00000227746.
ENST00000428956; ENSP00000396688; ENSG00000244731. [P0C0L4-1]
ENST00000498271; ENSP00000420212; ENSG00000244731. [P0C0L4-2]
GeneID720.
721.
KEGGhsa:720.
hsa:721.
UCSCuc011doz.2. human.

Organism-specific databases

CTD720.
721.
GeneCardsGC06P031954.
GC06Pm32059.
GC06Pn31940.
HGNCHGNC:1323. C4A.
HPACAB009811.
CAB032603.
HPA046356.
HPA048287.
HPA050103.
MIM120790. phenotype.
120810. gene.
152700. phenotype.
614374. phenotype.
614380. phenotype.
neXtProtNX_P0C0L4.
Orphanet117. Behcet disease.
169147. Immunodeficiency due to an early component of complement deficiency.
536. Systemic lupus erythematosus.
PharmGKBPA25903.
PA25904.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2373.
HOVERGENHBG107123.
InParanoidP0C0L4.
KOK03989.
OMATGCAEQT.
TreeFamTF313285.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP0C0L4.
GenevestigatorP0C0L4.

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

EvolutionaryTraceP0C0L4.
GeneWikiC4A.
NextBio13630656.
PMAP-CutDBB0QZR6.
PROP0C0L4.
SOURCESearch...

Entry information

Entry nameCO4A_HUMAN
AccessionPrimary (citable) accession number: P0C0L4
Secondary accession number(s): A6H8M8 expand/collapse secondary AC list , A6NHJ5, A7E2V2, B0QZR6, B0V2C8, B2RUT6, B7ZVZ6, P01028, P78445, Q13160, Q13906, Q14033, Q14835, Q4LE82, Q5JNX2, Q5JQM8, Q6P4R1, Q6U2E5, Q6U2E8, Q6U2F0, Q6U2F3, Q6U2F4, Q6U2F6, Q6U2F8, Q6U2G0, Q96EG2, Q96SA8, Q9NPK5, Q9UIP5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 3, 2013
Last modified: April 16, 2014
This is version 101 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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