P0C0L4 (CO4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement C4-A

Alternative name(s):
Acidic complement C4
C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2

Cleaved into the following 6 chains:

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

Gene names

Name:	C4A
Synonyms:	CO4, CPAMD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. 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.
Subunit structure	Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain.
Subcellular location	Secreted.
Post-translational modification	Prior to secretion, the single-chain precursor is enzymatically cleaved to yield the 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. N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. Ref.15 Ref.16 Ref.18 Ref.20 Ref.21 Ref.22
Polymorphism	Human complement component C4 is polymorphic at two loci, C4A and C4B. 13 alleles of C4A and 22 alleles of C4B have been detected. The allele shown here is C4A4. The C4A alleles carry the Rodgers (Rg) while the C4B alleles carry the Chido (Ch) blood group antigens. The C4A6 allotype is totally deficient in hemolytic activity.
Involvement in disease	Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:120810]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=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.19
Miscellaneous	C4A allotypes react more rapidly with the amino group of peptide antigens while C4B allotypes react more rapidly with the hydroxyl group of carbohydrate antigens.
Sequence similarities	Contains 1 anaphylatoxin-like domain. Contains 1 NTR domain.

Ontologies

Keywords
Biological process	Complement pathway Immunity Inflammatory response Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation 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	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	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
Cellular component	extracellular space Inferred from electronic annotation. Source: InterPro
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_0000005966

Propeptide

676 – 679

4

PRO_0000005967

Chain

680 – 1446

767

Complement C4-A alpha chain

PRO_0000005968

Chain

680 – 756

77

C4a anaphylatoxin

PRO_0000005969

Chain

757 – 1446

690

C4b-A

PRO_0000005970

Chain

957 – 1336

380

C4d-A

PRO_0000042698

Propeptide

1447 – 1453

7

PRO_0000005971

Chain

1454 – 1744

291

Complement C4 gamma chain

PRO_0000005972

Regions

Domain

702 – 736

35

Anaphylatoxin-like

Domain

1595 – 1742

148

NTR

Region

1232 – 1244

13

O-glycosylated at one site

Amino acid modifications

Modified residue

1417

1

Sulfotyrosine Ref.13

Modified residue

1420

1

Sulfotyrosine Ref.13

Modified residue

1422

1

Sulfotyrosine Ref.13

Glycosylation

226

1

N-linked (GlcNAc...) Ref.15 Ref.20 Ref.21

Glycosylation

862

1

N-linked (GlcNAc...) Ref.18

Glycosylation

1328

1

N-linked (GlcNAc...) Ref.18 Ref.20 Ref.21

Glycosylation

1391

1

N-linked (GlcNAc...) Ref.16 Ref.18 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. Ref.2
Corresponds to variant rs392610 [ dbSNP | Ensembl ].

VAR_019778

Natural variant

477

1

R → W in allotype C4A6.

VAR_001987

Natural variant

726

1

P → L in allotype C4A3. Ref.2
Corresponds to variant rs2229408 [ dbSNP | Ensembl ].

VAR_001988

Natural variant

727

1

D → N. Ref.5

VAR_019779

Natural variant

907

1

A → T.
Corresponds to variant rs429329 [ dbSNP | Ensembl ].

VAR_019780

Natural variant

1073

1

D → G in allotype C4A1. Ref.9
Corresponds to variant rs2258218 [ dbSNP | Ensembl ].

VAR_001989

Natural variant

1176

1

N → S in allotype C4A1. Ref.9
Corresponds to variant rs2746414 [ dbSNP | Ensembl ].

VAR_001991

Natural variant

1201

1

S → T in allotype C4A6, allotype C4A3 and allotype C4A1. Ref.3 Ref.9 Ref.11 Ref.12

VAR_001992

Natural variant

1207

1

V → A in allotype C4A1. Ref.9 Ref.12
Corresponds to variant rs2229403 [ dbSNP | Ensembl ].

VAR_001993

Natural variant

1210

1

L → R in allotype C4A1. Ref.9 Ref.12
Corresponds to variant rs2229409 [ dbSNP | Ensembl ].

VAR_001994

Natural variant

1286

1

S → A in allotype C4A6, allotype C4A1, allotype C4A3. Ref.9 Ref.12 Ref.24
Corresponds to variant rs9501603 [ dbSNP | Ensembl ].

VAR_001995

Experimental info

Sequence conflict

1 – 12

12

MRLLW…IWASS → TRSAPRAASWLEDPREVRSV CLSAT in AAA52292. Ref.1

Sequence conflict

418

1

V → A in AAB59537. 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.12

Sequence conflict

1300

1

R → V AA sequence Ref.9

Sequence conflict

1300

1

R → V AA sequence Ref.12

Sequence conflict

1418 – 1420

3

Missing in AAB59537. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

1744

Helix Strand Turn

Details...

Helix

997 – 1001

5

Helix

1011 – 1030

20

Helix

1041 – 1057

17

Helix

1076 – 1089

14

Helix

1090 – 1092

3

Helix

1097 – 1107

11

Helix

1108 – 1110

3

Helix

1126 – 1132

7

Helix

1137 – 1153

17

Turn

1158 – 1161

4

Helix

1162 – 1185

24

Helix

1190 – 1202

13

Helix

1207 – 1218

12

Helix

1259 – 1275

17

Helix

1280 – 1292

13

Helix

1302 – 1319

18

Sequences

	Sequence		Length	Mass (Da)
	P0C0L4 [UniParc]. Last modified November 8, 2005. Version 1. Checksum: D718DCDF5DA3602D	FASTA	1,744	192,771
	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 SLTKAPVDLL 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

References

	« Hide 'large scale' referencesShow '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: 6546707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 1988494] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-347 AND LEU-726 (ALLOTYPE C4A3).
[3]	"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: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-1201.
[4]	"Polymorphism of human complement component C4." Belt K.T., Yu C.Y., Carroll M.C., Porter R.R. Immunogenetics 21:173-180(1985) [PubMed: 3838531] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22 AND 1056-1225.
[5]	"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: 8012361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21, VARIANT ASN-727.
[6]	"Complete primary structure of human C4a anaphylatoxin." Moon K.E., Gorski J.P., Hugli T.E. J. Biol. Chem. 256:8685-8692(1981) [PubMed: 6167582] [Abstract] Cited for: PROTEIN SEQUENCE OF 680-756.
[7]	"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: 1699796] [Abstract] Cited for: PROTEIN SEQUENCE OF 757-771 AND 980-990.
[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: 6978711] [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: 3696167] [Abstract] Cited for: PROTEIN SEQUENCE OF 957-1336, VARIANTS GLY-1073; SER-1176; THR-1201; ALA-1207; ARG-1210 AND ALA-1286.
[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: 6950384] [Abstract] Cited for: PROTEIN SEQUENCE OF 990-1037.
[11]	"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: 6572000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1195-1294, VARIANT THR-1201.
[12]	"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: 6832377] [Abstract] Cited for: PROTEIN SEQUENCE OF 1199-1304, VARIANTS THR-1201; ALA-1207; ARG-1210 AND ALA-1286.
[13]	"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: 3944109] [Abstract] Cited for: PROTEIN SEQUENCE OF 1405-1431, SULFATION AT TYR-1417; TYR-1420 AND TYR-1422.
[14]	"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: 6577433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1448-1474.
[15]	"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: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-226.
[16]	"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: 14760718] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1391, MASS SPECTROMETRY. Tissue: Plasma.
[17]	"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: 2431902] [Abstract] Cited for: STRUCTURAL BASIS OF POLYMORPHISM.
[18]	"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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-862; ASN-1328 AND ASN-1391, MASS SPECTROMETRY. Tissue: Plasma.
[19]	"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: 17503323] [Abstract] Cited for: INVOLVEMENT IN SLE.
[20]	"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: 18780401] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226 AND ASN-1328, MASS SPECTROMETRY. Tissue: Milk.
[21]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226; ASN-1328 AND ASN-1391, MASS SPECTROMETRY. Tissue: Liver.
[22]	"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: 19838169] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS], STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[23]	"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: 12367531] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 957-1323.
[24]	"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: 1573268] [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.
M59815, M59816 Genomic DNA. Translation: AAA51855.1.
L26261 Genomic DNA. Translation: AAA20121.2.
AL645922 Genomic DNA. Translation: CAQ09284.1.
M14824 Genomic DNA. Translation: AAA52292.1.
X77491 Genomic DNA. Translation: CAA54627.1.
K00830 mRNA. Translation: AAA36229.1.
V00502 mRNA. Translation: CAA23760.1.

IPI

IPI00032258.

PIR

B20807.
C4HU. I56095.

RefSeq

NP_009224.2. NM_007293.2.

UniGene

Hs.534847.
Hs.720022.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HZF	X-ray	2.30	A	957-1323	[»]

ProteinModelPortal

P0C0L4.

SMR

P0C0L4. Positions 138-239, 683-745, 764-984, 996-1321, 1324-1743.

ModBase

Search...

Protein-protein interaction databases

IntAct

P0C0L4. 9 interactions.

STRING

P0C0L4.

PTM databases

PhosphoSite

P0C0L4.

Polymorphism databases

DMDM

81175238.

Proteomic databases

PRIDE

P0C0L4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000428956; ENSP00000396688; ENSG00000244731.

GeneID

720.

KEGG

hsa:720.

Organism-specific databases

CTD

720.

GeneCards

GC06P031954.

HGNC

HGNC:1323. C4A.

HPA

CAB009811.
CAB032603.

MIM

120790. phenotype.
120810. gene+phenotype.
152700. phenotype.

neXtProt

NX_P0C0L4.

Orphanet

169147. Immunodeficiency due to an early component of complement deficiency.

PharmGKB

PA25903.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG107123.

InParanoid

P0C0L4.

OrthoDB

EOG4JM7NW.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Genevestigator

P0C0L4.

GermOnline

ENSG00000204319. Homo sapiens.

Family and domain databases

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]

Gene3D

G3DSA:2.60.40.690. A-macroglobulin_rcpt-bd. 1 hit.
G3DSA:1.20.91.20. Anaphylatoxin. 1 hit.

KO

K03989.

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

2930.

PMAP-CutDB

P0C0L4.

SOURCE

Search...

Entry information

Entry name

CO4A_HUMAN

Accession

Primary (citable) accession number: P0C0L4
Secondary accession number(s): B0QZR6 , P01028, P78445, Q13160, Q13906, Q14033, Q14835, Q5JQM8, Q9NPK5, Q9UIP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 8, 2005
Last modified:	January 25, 2012
This is version 78 of the entry and version 1 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.