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Database: UniProt
Entry: P0C0L4
LinkDB: P0C0L4
Original site: P0C0L4 
ID   CO4A_HUMAN              Reviewed;        1744 AA.
AC   P0C0L4; A6H8M8; A6NHJ5; A7E2V2; B0QZR6; B0V2C8; B2RUT6; B7ZVZ6; P01028;
AC   P78445; Q13160; Q13906; Q14033; Q14835; Q4LE82; Q5JNX2; Q5JQM8; Q6P4R1;
AC   Q6U2E5; Q6U2E8; Q6U2F0; Q6U2F3; Q6U2F4; Q6U2F6; Q6U2F8; Q6U2G0; Q96EG2;
AC   Q96SA8; Q9NPK5; Q9UIP5;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 2.
DT   23-FEB-2022, entry version 164.
DE   RecName: Full=Complement C4-A;
DE   AltName: Full=Acidic complement C4;
DE   AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2;
DE   Contains:
DE     RecName: Full=Complement C4 beta chain;
DE   Contains:
DE     RecName: Full=Complement C4-A alpha chain;
DE   Contains:
DE     RecName: Full=C4a anaphylatoxin;
DE   Contains:
DE     RecName: Full=C4b-A;
DE   Contains:
DE     RecName: Full=C4d-A;
DE   Contains:
DE     RecName: Full=Complement C4 gamma chain;
DE   Flags: Precursor;
GN   Name=C4A; Synonyms=CO4, CPAMD2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-418 AND SER-1201.
RC   TISSUE=Liver;
RX   PubMed=6546707; DOI=10.1016/0092-8674(84)90040-0;
RA   Belt K.T., Carroll M.C., Porter R.R.;
RT   "The structural basis of the multiple forms of human complement component
RT   C4.";
RL   Cell 36:907-914(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-347; LEU-726 AND
RP   ALA-1286.
RX   PubMed=1988494;
RA   Yu C.Y.;
RT   "The complete exon-intron structure of a human complement component C4A
RT   gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase
RT   gene.";
RL   J. Immunol. 146:1057-1066(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS SER-1176
RP   AND ALA-1286.
RC   TISSUE=Brain;
RA   Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA   Okazaki N., Koga H., Nagase T., Ohara O.;
RT   "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT   encoding large proteins by the ORF trap cloning method.";
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS TYR-347;
RP   SER-1176 AND ALA-1286.
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP   TYR-347; GLY-1073 AND ALA-1286.
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22 AND 1056-1225.
RX   PubMed=3838531; DOI=10.1007/bf00364869;
RA   Belt K.T., Yu C.Y., Carroll M.C., Porter R.R.;
RT   "Polymorphism of human complement component C4.";
RL   Immunogenetics 21:173-180(1985).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21, AND VARIANT ASN-727.
RX   PubMed=8012361; DOI=10.1093/hmg/3.3.481;
RA   Sargent C.A., Anderson M.J., Hsieh S.-L., Kendall E., Gomez-Escobar N.,
RA   Campbell R.D.;
RT   "Characterisation of the novel gene G11 lying adjacent to the complement
RT   C4A gene in the human major histocompatibility complex.";
RL   Hum. Mol. Genet. 3:481-488(1994).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 448-570 AND 692-1225, AND VARIANTS
RP   TRP-477; PRO-549; THR-907; GLY-1073; SER-1176; ALA-1207 AND ARG-1210.
RA   Sayer D., Puschendorf M., Wetherall J.;
RT   "Molecular genetics of complement C4: implications for MHC evolution and
RT   disease susceptibility gene mapping.";
RL   Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   PROTEIN SEQUENCE OF 680-756.
RX   PubMed=6167582;
RA   Moon K.E., Gorski J.P., Hugli T.E.;
RT   "Complete primary structure of human C4a anaphylatoxin.";
RL   J. Biol. Chem. 256:8685-8692(1981).
RN   [10]
RP   PROTEIN SEQUENCE OF 757-771 AND 980-990.
RX   PubMed=1699796; DOI=10.1016/0014-5793(90)80389-z;
RA   Hessing M., van 't Veer C., Hackeng T.M., Bouma B.N., Iwanaga S.;
RT   "Importance of the alpha 3-fragment of complement C4 for the binding with
RT   C4b-binding protein.";
RL   FEBS Lett. 271:131-136(1990).
RN   [11]
RP   PROTEIN SEQUENCE OF 957-1044.
RX   PubMed=6978711; DOI=10.1042/bj1990359;
RA   Campbell R.D., Gagnon J., Porter R.R.;
RT   "Amino acid sequence around the thiol and reactive acyl groups of human
RT   complement component C4.";
RL   Biochem. J. 199:359-370(1981).
RN   [12]
RP   PROTEIN SEQUENCE OF 957-1336, AND VARIANTS GLY-1073; SER-1176; ALA-1207;
RP   ARG-1210 AND ALA-1286.
RX   PubMed=3696167; DOI=10.1016/0161-5890(87)90165-9;
RA   Chakravarti D.N., Campbell R.D., Porter R.R.;
RT   "The chemical structure of the C4d fragment of the human complement
RT   component C4.";
RL   Mol. Immunol. 24:1187-1197(1987).
RN   [13]
RP   PROTEIN SEQUENCE OF 990-1037.
RX   PubMed=6950384; DOI=10.1073/pnas.78.12.7388;
RA   Harrison R.A., Thomas M.L., Tack B.F.;
RT   "Sequence determination of the thiolester site of the fourth component of
RT   human complement.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:7388-7392(1981).
RN   [14]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1055-1225 (ALLOTYPE C4A13).
RX   PubMed=9759862;
RA   Martinez-Quiles N., Paz-Artal E., Moreno-Pelayo M.A., Longas J.,
RA   Ferre-Lopez S., Rosal M., Arnaiz-Villena A.;
RT   "C4d DNA sequences of two infrequent human allotypes (C4A13 and C4B12) and
RT   the presence of signal sequences enhancing recombination.";
RL   J. Immunol. 161:3438-3443(1998).
RN   [15]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1195-1294.
RX   PubMed=6572000; DOI=10.1073/pnas.80.1.264;
RA   Carroll M.C., Porter R.R.;
RT   "Cloning of a human complement component C4 gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:264-267(1983).
RN   [16]
RP   PROTEIN SEQUENCE OF 1199-1304, AND VARIANTS ALA-1207; ARG-1210 AND
RP   ALA-1286.
RX   PubMed=6832377; DOI=10.1016/0014-5793(83)80188-4;
RA   Chakravarti D.N., Campbell R.D., Gagnon J.;
RT   "Amino acid sequence of a polymorphic segment from fragment C4d of human
RT   complement component C4.";
RL   FEBS Lett. 154:387-390(1983).
RN   [17]
RP   PROTEIN SEQUENCE OF 1405-1431, AND SULFATION AT TYR-1417; TYR-1420 AND
RP   TYR-1422.
RX   PubMed=3944109;
RA   Hortin G., Sims H., Strauss A.W.;
RT   "Identification of the site of sulfation of the fourth component of human
RT   complement.";
RL   J. Biol. Chem. 261:1786-1793(1986).
RN   [18]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1448-1474.
RX   PubMed=6577433; DOI=10.1073/pnas.80.17.5387;
RA   Whitehead A.S., Goldberger G., Woods D.E., Markham A.F., Colten H.R.;
RT   "Use of a cDNA clone for the fourth component of human complement (C4) for
RT   analysis of a genetic deficiency of C4 in guinea pig.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:5387-5391(1983).
RN   [19]
RP   FUNCTION, AND INVOLVEMENT OF ASP-1125 IN IMMUNOGLOBULIN-BINDING AND
RP   HEMOLYSIS.
RX   PubMed=2395880; DOI=10.1073/pnas.87.17.6868;
RA   Carroll M.C., Fathallah D.M., Bergamaschini L., Alicot E.M., Isenman D.E.;
RT   "Substitution of a single amino acid (aspartic acid for histidine) converts
RT   the functional activity of human complement C4B to C4A.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:6868-6872(1990).
RN   [20]
RP   INVOLVEMENT IN C4AD.
RX   PubMed=8473511; DOI=10.1172/jci116377;
RA   Barba G., Rittner C., Schneider P.M.;
RT   "Genetic basis of human complement C4A deficiency. Detection of a point
RT   mutation leading to nonexpression.";
RL   J. Clin. Invest. 91:1681-1686(1993).
RN   [21]
RP   FUNCTION.
RX   PubMed=8538770; DOI=10.1038/379177a0;
RA   Dodds A.W., Ren X.D., Willis A.C., Law S.K.;
RT   "The reaction mechanism of the internal thioester in the human complement
RT   component C4.";
RL   Nature 379:177-179(1996).
RN   [22]
RP   INVOLVEMENT IN SLE.
RX   PubMed=10092831;
RA   Lokki M.L., Circolo A., Ahokas P., Rupert K.L., Yu C.Y., Colten H.R.;
RT   "Deficiency of human complement protein C4 due to identical frameshift
RT   mutations in the C4A and C4B genes.";
RL   J. Immunol. 162:3687-3693(1999).
RN   [23]
RP   REVIEW, DESCRIPTION OF ALLOTYPES, AND TISSUE SPECIFICITY.
RX   PubMed=11367523; DOI=10.1016/s1567-5769(01)00019-4;
RA   Blanchong C.A., Chung E.K., Rupert K.L., Yang Y., Yang Z., Zhou B.,
RA   Moulds J.M., Yu C.Y.;
RT   "Genetic, structural and functional diversities of human complement
RT   components C4A and C4B and their mouse homologues, Slp and C4.";
RL   Int. Immunopharmacol. 1:365-392(2001).
RN   [24]
RP   GLYCOSYLATION AT ASN-226.
RX   PubMed=12754519; DOI=10.1038/nbt827;
RA   Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT   "Identification and quantification of N-linked glycoproteins using
RT   hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL   Nat. Biotechnol. 21:660-666(2003).
RN   [25]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1391.
RC   TISSUE=Plasma;
RX   PubMed=14760718; DOI=10.1002/pmic.200300556;
RA   Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT   "Screening for N-glycosylated proteins by liquid chromatography mass
RT   spectrometry.";
RL   Proteomics 4:454-465(2004).
RN   [26]
RP   STRUCTURAL BASIS OF POLYMORPHISM.
RX   PubMed=2431902; DOI=10.1002/j.1460-2075.1986.tb04582.x;
RA   Yu C.Y., Belt K.T., Giles C.M., Campbell R.D., Porter R.R.;
RT   "Structural basis of the polymorphism of human complement components C4A
RT   and C4B: gene size, reactivity and antigenicity.";
RL   EMBO J. 5:2873-2881(1986).
RN   [27]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-862; ASN-1328 AND ASN-1391.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [28]
RP   INVOLVEMENT IN SLE.
RX   PubMed=17503323; DOI=10.1086/518257;
RA   Yang Y., Chung E.K., Wu Y.L., Savelli S.L., Nagaraja H.N., Zhou B.,
RA   Hebert M., Jones K.N., Shu Y., Kitzmiller K., Blanchong C.A., McBride K.L.,
RA   Higgins G.C., Rennebohm R.M., Rice R.R., Hackshaw K.V., Roubey R.A.,
RA   Grossman J.M., Tsao B.P., Birmingham D.J., Rovin B.H., Hebert L.A.,
RA   Yu C.Y.;
RT   "Gene copy-number variation and associated polymorphisms of complement
RT   component C4 in human systemic lupus erythematosus (SLE): low copy number
RT   is a risk factor for and high copy number is a protective factor against
RT   SLE susceptibility in European Americans.";
RL   Am. J. Hum. Genet. 80:1037-1054(2007).
RN   [29]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226 AND ASN-1328.
RC   TISSUE=Milk;
RX   PubMed=18780401; DOI=10.1002/pmic.200701057;
RA   Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT   "Identification of N-linked glycoproteins in human milk by hydrophilic
RT   interaction liquid chromatography and mass spectrometry.";
RL   Proteomics 8:3833-3847(2008).
RN   [30]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-226; ASN-1328 AND ASN-1391.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [31]
RP   GLYCOSYLATION AT ASN-1328.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
RN   [32]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS], AND STRUCTURE OF CARBOHYDRATES.
RC   TISSUE=Cerebrospinal fluid;
RX   PubMed=19838169; DOI=10.1038/nmeth.1392;
RA   Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA   Larson G.;
RT   "Enrichment of glycopeptides for glycan structure and attachment site
RT   identification.";
RL   Nat. Methods 6:809-811(2009).
RN   [33]
RP   GLYCOSYLATION AT THR-1244, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=23234360; DOI=10.1021/pr300963h;
RA   Halim A., Ruetschi U., Larson G., Nilsson J.;
RT   "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT   of human cerebrospinal fluid glycoproteins.";
RL   J. Proteome Res. 12:573-584(2013).
RN   [34]
RP   PHOSPHORYLATION AT SER-918.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted phosphoproteome.";
RL   Cell 161:1619-1632(2015).
RN   [35]
RP   POLYMORPHISM, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=26814963; DOI=10.1038/nature16549;
RG   Schizophrenia Working Group of the Psychiatric Genomics Consortium;
RA   Sekar A., Bialas A.R., de Rivera H., Davis A., Hammond T.R., Kamitaki N.,
RA   Tooley K., Presumey J., Baum M., Van Doren V., Genovese G., Rose S.A.,
RA   Handsaker R.E., Daly M.J., Carroll M.C., Stevens B., McCarroll S.A.;
RT   "Schizophrenia risk from complex variation of complement component 4.";
RL   Nature 530:177-183(2016).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 957-1323.
RX   PubMed=12367531; DOI=10.1016/s0022-2836(02)00854-9;
RA   van den Elsen J.M., Martin A., Wong V., Clemenza L., Rose D.R.,
RA   Isenman D.E.;
RT   "X-ray crystal structure of the C4d fragment of human complement component
RT   C4.";
RL   J. Mol. Biol. 322:1103-1115(2002).
RN   [37]
RP   VARIANT ALA-1286 (ALLOTYPE C4A6).
RX   PubMed=1573268;
RA   Anderson M.J., Milner C.M., Cotton G.H., Campbell R.D.;
RT   "The coding sequence of the hemolytically inactive C4A6 allotype of human
RT   complement component C4 reveals that a single arginine to tryptophan
RT   substitution at beta-chain residue 458 is the likely cause of the defect.";
RL   J. Immunol. 148:2795-2802(1992).
CC   -!- FUNCTION: Non-enzymatic component of C3 and C5 convertases and thus
CC       essential for the propagation of the classical complement pathway.
CC       Covalently binds to immunoglobulins and immune complexes and enhances
CC       the solubilization of immune aggregates and the clearance of IC through
CC       CR1 on erythrocytes. C4A isotype is responsible for effective binding
CC       to form amide bonds with immune aggregates or protein antigens, while
CC       C4B isotype catalyzes the transacylation of the thioester carbonyl
CC       group to form ester bonds with carbohydrate antigens.
CC   -!- FUNCTION: Derived from proteolytic degradation of complement C4, C4a
CC       anaphylatoxin is a mediator of local inflammatory process. It induces
CC       the contraction of smooth muscle, increases vascular permeability and
CC       causes histamine release from mast cells and basophilic leukocytes.
CC   -!- SUBUNIT: Circulates in blood as a disulfide-linked trimer of an alpha,
CC       beta and gamma chain.
CC   -!- SUBCELLULAR LOCATION: Secreted. Cell junction, synapse
CC       {ECO:0000269|PubMed:26814963}. Cell projection, axon
CC       {ECO:0000269|PubMed:26814963}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:26814963}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P0C0L4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P0C0L4-2; Sequence=VSP_046252;
CC   -!- TISSUE SPECIFICITY: Complement component C4 is expressed at highest
CC       levels in the liver, at moderate levels in the adrenal cortex, adrenal
CC       medulla, thyroid gland, and the kidney, and at lowest levels in the
CC       heart, ovary, small intestine, thymus, pancreas and spleen. The extra-
CC       hepatic sites of expression may be important for the local protection
CC       and inflammatory response. {ECO:0000269|PubMed:11367523}.
CC   -!- PTM: Prior to secretion, the single-chain precursor is enzymatically
CC       cleaved to yield non-identical chains alpha, beta and gamma. During
CC       activation, the alpha chain is cleaved by C1 into C4a and C4b, and C4b
CC       stays linked to the beta and gamma chains. Further degradation of C4b
CC       by C1 into the inactive fragments C4c and C4d blocks the generation of
CC       C3 convertase. The proteolytic cleavages often are incomplete so that
CC       many structural forms can be found in plasma.
CC   -!- PTM: N- and O-glycosylated. O-glycosylated with a core 1 or possibly
CC       core 8 glycan. {ECO:0000269|PubMed:12754519,
CC       ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952,
CC       ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19139490,
CC       ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169,
CC       ECO:0000269|PubMed:23234360}.
CC   -!- POLYMORPHISM: The complement component C4 is the most polymorphic
CC       protein of the complement system. It is the product of 2 closely linked
CC       and highly homologous genes, C4A and C4B. Once polymorphic variation is
CC       discounted, the 2 isotypes differ by only 4 amino acids at positions
CC       1120-1125: PCPVLD for C4A and LSPVIH for C4B. The 2 isotypes bear
CC       several antigenic determinants defining Chido/Rodgers blood group
CC       system [MIM:614374]. Rodgers determinants are generally associated with
CC       C4A allotypes, and Chido with C4B. Variations at these loci involve not
CC       only nucleotide polymorphisms, but also gene number and gene size. Some
CC       individuals may lack either C4A, or C4B gene. Partial deficiency of C4A
CC       or C4B is the most commonly inherited immune deficiency known in humans
CC       with a combined frequency over 31% in the normal Caucasian population
CC       (PubMed:11367523). C4A6 allotype is deficient in hemolytic activity.
CC       Allotype C4A13 is infrequent. Common copy-number variants of C4A and
CC       C4B affecting expression of complement component C4 in the brain have
CC       been associated with schizophrenia risk (PubMed:26814963).
CC       {ECO:0000269|PubMed:11367523, ECO:0000269|PubMed:26814963}.
CC   -!- DISEASE: Complement component 4A deficiency (C4AD) [MIM:614380]: A rare
CC       defect of the complement classical pathway associated with the
CC       development of autoimmune disorders, mainly systemic lupus with or
CC       without associated glomerulonephritis. {ECO:0000269|PubMed:8473511}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic,
CC       relapsing, inflammatory, and often febrile multisystemic disorder of
CC       connective tissue, characterized principally by involvement of the
CC       skin, joints, kidneys and serosal membranes. It is of unknown etiology,
CC       but is thought to represent a failure of the regulatory mechanisms of
CC       the autoimmune system. The disease is marked by a wide range of system
CC       dysfunctions, an elevated erythrocyte sedimentation rate, and the
CC       formation of LE cells in the blood or bone marrow.
CC       {ECO:0000269|PubMed:10092831, ECO:0000269|PubMed:17503323}.
CC       Note=Disease susceptibility is associated with variants affecting the
CC       gene represented in this entry. Interindividual copy-number variation
CC       (CNV) of complement component C4 and associated polymorphisms result in
CC       different susceptibilities to SLE. The risk of SLE susceptibility has
CC       been shown to be significantly increased among subjects with only two
CC       copies of total C4. A high copy number is a protective factor against
CC       SLE.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB59537.1; Type=Miscellaneous discrepancy; Note=During cDNA synthesis, the 5' end has been inverted (PubMed:3838531).; Evidence={ECO:0000305|PubMed:3838531};
CC       Sequence=BAE06071.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation
CC       database;
CC       URL="https://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=chrg";
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DR   EMBL; K02403; AAB59537.1; ALT_SEQ; mRNA.
DR   EMBL; M59815; AAA51855.1; -; Genomic_DNA.
DR   EMBL; M59816; AAA51855.1; JOINED; Genomic_DNA.
DR   EMBL; L26261; AAA20121.2; -; Genomic_DNA.
DR   EMBL; AB209989; BAE06071.1; ALT_INIT; mRNA.
DR   EMBL; AL645922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL844853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR936924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC012372; AAH12372.2; -; mRNA.
DR   EMBL; BC063289; AAH63289.1; -; mRNA.
DR   EMBL; BC144546; AAI44547.1; -; mRNA.
DR   EMBL; BC146673; AAI46674.1; -; mRNA.
DR   EMBL; BC146849; AAI46850.1; -; mRNA.
DR   EMBL; BC151204; AAI51205.1; -; mRNA.
DR   EMBL; BC171786; AAI71786.1; -; mRNA.
DR   EMBL; M14824; AAA52292.1; -; Genomic_DNA.
DR   EMBL; X77491; CAA54627.1; -; Genomic_DNA.
DR   EMBL; AY379925; AAR89152.1; -; Genomic_DNA.
DR   EMBL; AY379926; AAR89153.1; -; Genomic_DNA.
DR   EMBL; AY379927; AAR89154.1; -; Genomic_DNA.
DR   EMBL; AY379928; AAR89155.1; -; Genomic_DNA.
DR   EMBL; AY379929; AAR89156.1; -; Genomic_DNA.
DR   EMBL; AY379930; AAR89157.1; -; Genomic_DNA.
DR   EMBL; AY379931; AAR89158.1; -; Genomic_DNA.
DR   EMBL; AY379932; AAR89159.1; -; Genomic_DNA.
DR   EMBL; AY379933; AAR89160.1; -; Genomic_DNA.
DR   EMBL; AY379934; AAR89161.1; -; Genomic_DNA.
DR   EMBL; AY379935; AAR89162.1; -; Genomic_DNA.
DR   EMBL; AY379960; AAR89164.1; -; Genomic_DNA.
DR   EMBL; AY379962; AAR89166.1; -; Genomic_DNA.
DR   EMBL; AY379963; AAR89167.1; -; Genomic_DNA.
DR   EMBL; AY379964; AAR89168.1; -; Genomic_DNA.
DR   EMBL; AY379965; AAR89169.1; -; Genomic_DNA.
DR   EMBL; AY379966; AAR89170.1; -; Genomic_DNA.
DR   EMBL; U77886; AAK49810.1; -; Genomic_DNA.
DR   EMBL; V00502; CAA23760.1; -; mRNA.
DR   EMBL; K00830; AAA36229.1; -; mRNA.
DR   CCDS; CCDS47404.1; -. [P0C0L4-1]
DR   CCDS; CCDS59005.1; -. [P0C0L4-2]
DR   PIR; B20807; B20807.
DR   PIR; I56095; C4HU.
DR   RefSeq; NP_001002029.3; NM_001002029.3.
DR   RefSeq; NP_001239133.1; NM_001252204.1. [P0C0L4-2]
DR   RefSeq; NP_009224.2; NM_007293.2. [P0C0L4-1]
DR   PDB; 1HZF; X-ray; 2.30 A; A=957-1323.
DR   PDB; 4FXG; X-ray; 3.75 A; A/D=20-675, B/E=680-1446, C/F=1454-1744.
DR   PDB; 4FXK; X-ray; 3.60 A; A=20-675, B=680-1446, C=1454-1744.
DR   PDB; 4XAM; X-ray; 4.20 A; C/E=757-1446, D/F=1454-1744.
DR   PDB; 5JPM; X-ray; 3.75 A; A/D=20-675, B/E=680-1446, C/F=1454-1744.
DR   PDB; 5JPN; X-ray; 3.60 A; A=20-675, B=680-1446, C=1455-1744.
DR   PDB; 5JTW; X-ray; 3.50 A; A/D=20-675, B/E=757-1446, C/F=1454-1744.
DR   PDBsum; 1HZF; -.
DR   PDBsum; 4FXG; -.
DR   PDBsum; 4FXK; -.
DR   PDBsum; 4XAM; -.
DR   PDBsum; 5JPM; -.
DR   PDBsum; 5JPN; -.
DR   PDBsum; 5JTW; -.
DR   SMR; P0C0L4; -.
DR   BioGRID; 107181; 57.
DR   BioGRID; 107182; 6.
DR   ComplexPortal; CPX-5675; Classical and lectin pathway C3 convertase complex C4b2a-A.
DR   IntAct; P0C0L4; 46.
DR   STRING; 9606.ENSP00000396688; -.
DR   DrugBank; DB00028; Human immunoglobulin G.
DR   MEROPS; I39.951; -.
DR   CarbonylDB; P0C0L4; -.
DR   GlyConnect; 651; 32 N-Linked glycans (4 sites), 4 O-Linked glycans (2 sites).
DR   GlyGen; P0C0L4; 8 sites, 35 N-linked glycans (4 sites), 6 O-linked glycans (4 sites).
DR   iPTMnet; P0C0L4; -.
DR   PhosphoSitePlus; P0C0L4; -.
DR   BioMuta; C4A; -.
DR   DMDM; 476007827; -.
DR   CPTAC; CPTAC-665; -.
DR   CPTAC; CPTAC-666; -.
DR   EPD; P0C0L4; -.
DR   jPOST; P0C0L4; -.
DR   MassIVE; P0C0L4; -.
DR   MaxQB; P0C0L4; -.
DR   PaxDb; P0C0L4; -.
DR   PeptideAtlas; P0C0L4; -.
DR   PRIDE; P0C0L4; -.
DR   ProteomicsDB; 2869; -.
DR   ProteomicsDB; 52292; -. [P0C0L4-1]
DR   ProteomicsDB; 62992; -.
DR   ProteomicsDB; 774; -.
DR   Antibodypedia; 34827; 679 antibodies from 37 providers.
DR   DNASU; 721; -.
DR   Ensembl; ENST00000383325; ENSP00000372815; ENSG00000206340.
DR   Ensembl; ENST00000421274; ENSP00000388662; ENSG00000227746.
DR   Ensembl; ENST00000428956; ENSP00000396688; ENSG00000244731.
DR   Ensembl; ENST00000498271; ENSP00000420212; ENSG00000244731. [P0C0L4-2]
DR   GeneID; 720; -.
DR   GeneID; 721; -.
DR   KEGG; hsa:720; -.
DR   KEGG; hsa:721; -.
DR   MANE-Select; ENST00000428956.7; ENSP00000396688.2; NM_007293.3; NP_009224.2.
DR   UCSC; uc011doy.3; human. [P0C0L4-1]
DR   CTD; 720; -.
DR   CTD; 721; -.
DR   DisGeNET; 720; -.
DR   DisGeNET; 721; -.
DR   GeneCards; C4A; -.
DR   HGNC; HGNC:1323; C4A.
DR   HPA; ENSG00000244731; Tissue enhanced (adrenal gland, liver).
DR   MalaCards; C4A; -.
DR   MIM; 120790; phenotype.
DR   MIM; 120810; gene.
DR   MIM; 152700; phenotype.
DR   MIM; 614374; phenotype.
DR   MIM; 614380; phenotype.
DR   neXtProt; NX_P0C0L4; -.
DR   NIAGADS; ENSG00000244731; -.
DR   OpenTargets; ENSG00000244731; -.
DR   Orphanet; 300345; Autosomal systemic lupus erythematosus.
DR   Orphanet; 117; Behcet disease.
DR   Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency.
DR   Orphanet; 536; Systemic lupus erythematosus.
DR   PharmGKB; PA25903; -.
DR   PharmGKB; PA25904; -.
DR   VEuPathDB; HostDB:ENSG00000244731; -.
DR   eggNOG; KOG1366; Eukaryota.
DR   GeneTree; ENSGT00940000155739; -.
DR   HOGENOM; CLU_001634_4_1_1; -.
DR   InParanoid; P0C0L4; -.
DR   OMA; TWEIHAV; -.
DR   OrthoDB; 28894at2759; -.
DR   PhylomeDB; P0C0L4; -.
DR   TreeFam; TF313285; -.
DR   PathwayCommons; P0C0L4; -.
DR   Reactome; R-HSA-166663; Initial triggering of complement.
DR   Reactome; R-HSA-174577; Activation of C3 and C5.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-HSA-977606; Regulation of Complement cascade.
DR   SABIO-RK; P0C0L4; -.
DR   SignaLink; P0C0L4; -.
DR   SIGNOR; P0C0L4; -.
DR   BioGRID-ORCS; 720; 26 hits in 1013 CRISPR screens.
DR   BioGRID-ORCS; 721; 4 hits in 645 CRISPR screens.
DR   ChiTaRS; C4A; human.
DR   EvolutionaryTrace; P0C0L4; -.
DR   GeneWiki; C4A; -.
DR   Pharos; P0C0L4; Tbio.
DR   PRO; PR:P0C0L4; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P0C0L4; protein.
DR   Bgee; ENSG00000244731; Expressed in right lobe of liver and 114 other tissues.
DR   Genevisible; P0C0L4; HS.
DR   GO; GO:0030424; C:axon; IDA:UniProtKB.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0005601; C:classical-complement-pathway C3/C5 convertase complex; IPI:ComplexPortal.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR   GO; GO:0001849; F:complement component C1q complex binding; IDA:BHF-UCL.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0006956; P:complement activation; IDA:ComplexPortal.
DR   GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:2000427; P:positive regulation of apoptotic cell clearance; IGI:BHF-UCL.
DR   CDD; cd00017; ANATO; 1.
DR   Gene3D; 2.40.50.120; -; 1.
DR   Gene3D; 2.60.40.10; -; 2.
DR   Gene3D; 2.60.40.690; -; 1.
DR   InterPro; IPR009048; A-macroglobulin_rcpt-bd.
DR   InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf.
DR   InterPro; IPR011625; A2M_N_BRD.
DR   InterPro; IPR011626; Alpha-macroglobulin_TED.
DR   InterPro; IPR000020; Anaphylatoxin/fibulin.
DR   InterPro; IPR018081; Anaphylatoxin_comp_syst.
DR   InterPro; IPR001840; Anaphylatoxn_comp_syst_dom.
DR   InterPro; IPR037569; Complement_C4A.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR001599; Macroglobln_a2.
DR   InterPro; IPR019742; MacrogloblnA2_CS.
DR   InterPro; IPR002890; MG2.
DR   InterPro; IPR041555; MG3.
DR   InterPro; IPR040839; MG4.
DR   InterPro; IPR001134; Netrin_domain.
DR   InterPro; IPR018933; Netrin_module_non-TIMP.
DR   InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   PANTHER; PTHR11412:SF86; PTHR11412:SF86; 1.
DR   Pfam; PF00207; A2M; 1.
DR   Pfam; PF07703; A2M_BRD; 1.
DR   Pfam; PF07677; A2M_recep; 1.
DR   Pfam; PF01821; ANATO; 1.
DR   Pfam; PF01835; MG2; 1.
DR   Pfam; PF17791; MG3; 1.
DR   Pfam; PF17789; MG4; 1.
DR   Pfam; PF01759; NTR; 1.
DR   Pfam; PF07678; TED_complement; 1.
DR   PRINTS; PR00004; ANAPHYLATOXN.
DR   SMART; SM01360; A2M; 1.
DR   SMART; SM01359; A2M_N_2; 1.
DR   SMART; SM01361; A2M_recep; 1.
DR   SMART; SM00104; ANATO; 1.
DR   SMART; SM00643; C345C; 1.
DR   SUPFAM; SSF47686; SSF47686; 1.
DR   SUPFAM; SSF48239; SSF48239; 1.
DR   SUPFAM; SSF49410; SSF49410; 1.
DR   SUPFAM; SSF50242; SSF50242; 1.
DR   PROSITE; PS00477; ALPHA_2_MACROGLOBULIN; 1.
DR   PROSITE; PS01177; ANAPHYLATOXIN_1; 1.
DR   PROSITE; PS01178; ANAPHYLATOXIN_2; 1.
DR   PROSITE; PS50189; NTR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Blood group antigen; Cell junction;
KW   Cell projection; Cleavage on pair of basic residues; Complement pathway;
KW   Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW   Immunity; Inflammatory response; Innate immunity; Phosphoprotein;
KW   Reference proteome; Secreted; Signal; Sulfation; Synapse;
KW   Systemic lupus erythematosus; Thioester bond.
FT   SIGNAL          1..19
FT   CHAIN           20..675
FT                   /note="Complement C4 beta chain"
FT                   /id="PRO_0000005966"
FT   PROPEP          676..679
FT                   /evidence="ECO:0000269|PubMed:6167582"
FT                   /id="PRO_0000005967"
FT   CHAIN           680..1446
FT                   /note="Complement C4-A alpha chain"
FT                   /id="PRO_0000005968"
FT   CHAIN           680..756
FT                   /note="C4a anaphylatoxin"
FT                   /id="PRO_0000005969"
FT   CHAIN           757..1446
FT                   /note="C4b-A"
FT                   /id="PRO_0000005970"
FT   CHAIN           957..1336
FT                   /note="C4d-A"
FT                   /id="PRO_0000042698"
FT   PROPEP          1447..1453
FT                   /id="PRO_0000005971"
FT   CHAIN           1454..1744
FT                   /note="Complement C4 gamma chain"
FT                   /id="PRO_0000005972"
FT   DOMAIN          702..736
FT                   /note="Anaphylatoxin-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00022"
FT   DOMAIN          1595..1742
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   SITE            1125
FT                   /note="Responsible for effective binding to form amide
FT                   bonds with immune aggregates or protein antigens"
FT   MOD_RES         918
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039"
FT   MOD_RES         1417
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:3944109"
FT   MOD_RES         1420
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:3944109"
FT   MOD_RES         1422
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:3944109"
FT   CARBOHYD        226
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:12754519,
FT                   ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19159218"
FT   CARBOHYD        862
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952"
FT   CARBOHYD        1244
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   CARBOHYD        1328
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19139490,
FT                   ECO:0000269|PubMed:19159218"
FT   CARBOHYD        1391
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14760718,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT   DISULFID        702..728
FT                   /evidence="ECO:0000250"
FT   DISULFID        703..735
FT                   /evidence="ECO:0000250"
FT   DISULFID        716..736
FT                   /evidence="ECO:0000250"
FT   DISULFID        1595..1673
FT                   /evidence="ECO:0000250"
FT   DISULFID        1618..1742
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        1010..1013
FT                   /note="Isoglutamyl cysteine thioester (Cys-Gln)"
FT   VAR_SEQ         1458..1503
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_046252"
FT   VARIANT         141
FT                   /note="L -> V (in dbSNP:rs9296005)"
FT                   /id="VAR_069154"
FT   VARIANT         347
FT                   /note="S -> Y (in allotype C4A3a, allotype C4A6;
FT                   dbSNP:rs392610)"
FT                   /evidence="ECO:0000269|PubMed:14574404,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1988494"
FT                   /id="VAR_019778"
FT   VARIANT         418
FT                   /note="V -> A (in allotype C4A4)"
FT                   /evidence="ECO:0000269|PubMed:6546707"
FT                   /id="VAR_069155"
FT   VARIANT         477
FT                   /note="R -> W (in allotype C4A6)"
FT                   /evidence="ECO:0000269|Ref.8"
FT                   /id="VAR_001987"
FT   VARIANT         549
FT                   /note="H -> P (in dbSNP:rs2229405)"
FT                   /evidence="ECO:0000269|Ref.8"
FT                   /id="VAR_069156"
FT   VARIANT         726
FT                   /note="P -> L (in allotype C4A3a; dbSNP:rs1215093373)"
FT                   /evidence="ECO:0000269|PubMed:1988494"
FT                   /id="VAR_001988"
FT   VARIANT         727
FT                   /note="D -> N"
FT                   /evidence="ECO:0000269|PubMed:8012361"
FT                   /id="VAR_019779"
FT   VARIANT         907
FT                   /note="A -> T (in dbSNP:rs429329)"
FT                   /evidence="ECO:0000269|Ref.8"
FT                   /id="VAR_019780"
FT   VARIANT         1073
FT                   /note="D -> G (in allotype C4A1, allotype C4A2;
FT                   dbSNP:rs147162052)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:3696167, ECO:0000269|Ref.8"
FT                   /id="VAR_069158"
FT   VARIANT         1176
FT                   /note="N -> S (in allotype C4A1; dbSNP:rs17874654)"
FT                   /evidence="ECO:0000269|PubMed:14574404,
FT                   ECO:0000269|PubMed:3696167, ECO:0000269|Ref.3,
FT                   ECO:0000269|Ref.8"
FT                   /id="VAR_069159"
FT   VARIANT         1201
FT                   /note="T -> S (in allotype C4A4)"
FT                   /evidence="ECO:0000269|PubMed:6546707"
FT                   /id="VAR_001992"
FT   VARIANT         1207
FT                   /note="V -> A (in allotype C4A1, allotype C4A13;
FT                   dbSNP:rs28357075)"
FT                   /evidence="ECO:0000269|PubMed:3696167,
FT                   ECO:0000269|PubMed:6832377, ECO:0000269|Ref.8"
FT                   /id="VAR_001993"
FT   VARIANT         1210
FT                   /note="L -> R (in allotype C4A1, allotype C4A13;
FT                   dbSNP:rs28357076)"
FT                   /evidence="ECO:0000269|PubMed:3696167,
FT                   ECO:0000269|PubMed:6832377, ECO:0000269|Ref.8"
FT                   /id="VAR_001994"
FT   VARIANT         1286
FT                   /note="S -> A (in allotype C4A1, allotype C4A3a, allotype
FT                   C4A6; dbSNP:rs201016130)"
FT                   /evidence="ECO:0000269|PubMed:14574404,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1988494,
FT                   ECO:0000269|PubMed:3696167, ECO:0000269|PubMed:6832377,
FT                   ECO:0000269|Ref.3"
FT                   /id="VAR_001995"
FT   CONFLICT        217
FT                   /note="A -> V (in Ref. 5; AAI71786)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        643
FT                   /note="A -> S (in Ref. 5; AAH63289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        729
FT                   /note="R -> W (in Ref. 5; AAH63289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1013
FT                   /note="Q -> E (in Ref. 11; AA sequence, 12; AA sequence and
FT                   13; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1109..1110
FT                   /note="SQ -> IA (in Ref. 12; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1182
FT                   /note="K -> I (in Ref. 5; AAH63289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1245
FT                   /note="P -> Q (in Ref. 5; AAH63289)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1271
FT                   /note="H -> V (in Ref. 12; AA sequence and 16; AA
FT                   sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1300
FT                   /note="R -> V (in Ref. 12; AA sequence and 16; AA
FT                   sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1419..1421
FT                   /note="Missing (in Ref. 1; AAB59537)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1635
FT                   /note="D -> G (in Ref. 5; AAH12372)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1637
FT                   /note="R -> S (in Ref. 5; AAI44547/AAI46850)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1678
FT                   /note="E -> G (in Ref. 5; AAI71786)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1704
FT                   /note="D -> E (in Ref. 5; AAH12372)"
FT                   /evidence="ECO:0000305"
FT   STRAND          22..32
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          37..45
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          51..59
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          67..69
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          72..77
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          82..87
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           91..97
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           99..101
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          107..113
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           116..119
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          126..135
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          139..146
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          155..163
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          167..169
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          174..179
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          181..183
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          185..191
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          194..203
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          210..221
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          228..233
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          240..253
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          262..270
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          278..287
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          289..291
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          293..295
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          301..304
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          309..314
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           316..325
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           330..332
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          337..346
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   TURN            347..349
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          352..357
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          361..364
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          366..370
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          372..374
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          382..392
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          395..397
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          402..409
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          412..414
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          417..424
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          430..436
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          442..450
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          452..454
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          456..463
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          472..476
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          488..498
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          504..511
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          514..522
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          527..532
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   TURN            535..537
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          539..549
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          552..561
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          571..575
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          586..605
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           607..611
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           621..628
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           629..631
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           643..650
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          652..655
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          657..660
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   TURN            666..668
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          780..782
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          786..798
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          804..814
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   TURN            815..817
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          818..821
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          825..829
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          832..836
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          849..851
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          854..857
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          859..861
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          863..869
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          875..877
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           878..880
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          885..889
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          893..896
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          899..903
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          906..921
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          924..934
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          936..948
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          951..961
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          974..982
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           997..1001
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1011..1030
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1034..1036
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1041..1057
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   TURN            1062..1064
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1076..1089
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1090..1092
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1097..1107
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1108..1110
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   STRAND          1113..1115
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1126..1132
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1137..1153
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   TURN            1158..1161
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1162..1185
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1190..1202
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1207..1218
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   STRAND          1225..1228
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1259..1275
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1280..1292
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   HELIX           1294..1297
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1302..1319
FT                   /evidence="ECO:0007829|PDB:1HZF"
FT   STRAND          1327..1335
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1338..1346
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1348..1350
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1356..1359
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1364..1373
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1376..1386
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1395..1405
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1409..1411
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1465..1475
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1484..1489
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1494..1496
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1498..1506
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1511..1518
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1521..1527
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1534..1544
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1552..1560
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1564..1570
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1573..1575
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1581..1584
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1587..1590
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1613..1618
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1624..1637
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1640..1652
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1664..1670
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1681..1687
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   STRAND          1708..1711
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1716..1719
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1721..1723
FT                   /evidence="ECO:0007829|PDB:5JTW"
FT   HELIX           1726..1740
FT                   /evidence="ECO:0007829|PDB:5JTW"
SQ   SEQUENCE   1744 AA;  192785 MW;  9396A4CC4DA3602C CRC64;
     MRLLWGLIWA SSFFTLSLQK PRLLLFSPSV VHLGVPLSVG VQLQDVPRGQ VVKGSVFLRN
     PSRNNVPCSP KVDFTLSSER DFALLSLQVP LKDAKSCGLH QLLRGPEVQL VAHSPWLKDS
     LSRTTNIQGI NLLFSSRRGH LFLQTDQPIY NPGQRVRYRV FALDQKMRPS TDTITVMVEN
     SHGLRVRKKE VYMPSSIFQD DFVIPDISEP GTWKISARFS DGLESNSSTQ FEVKKYVLPN
     FEVKITPGKP YILTVPGHLD EMQLDIQARY IYGKPVQGVA YVRFGLLDED GKKTFFRGLE
     SQTKLVNGQS HISLSKAEFQ DALEKLNMGI TDLQGLRLYV AAAIIESPGG EMEEAELTSW
     YFVSSPFSLD LSKTKRHLVP GAPFLLQALV REMSGSPASG IPVKVSATVS SPGSVPEVQD
     IQQNTDGSGQ VSIPIIIPQT ISELQLSVSA GSPHPAIARL TVAAPPSGGP GFLSIERPDS
     RPPRVGDTLN LNLRAVGSGA TFSHYYYMIL SRGQIVFMNR EPKRTLTSVS VFVDHHLAPS
     FYFVAFYYHG DHPVANSLRV DVQAGACEGK LELSVDGAKQ YRNGESVKLH LETDSLALVA
     LGALDTALYA AGSKSHKPLN MGKVFEAMNS YDLGCGPGGG DSALQVFQAA GLAFSDGDQW
     TLSRKRLSCP KEKTTRKKRN VNFQKAINEK LGQYASPTAK RCCQDGVTRL PMMRSCEQRA
     ARVQQPDCRE PFLSCCQFAE SLRKKSRDKG QAGLQRALEI LQEEDLIDED DIPVRSFFPE
     NWLWRVETVD RFQILTLWLP DSLTTWEIHG LSLSKTKGLC VATPVQLRVF REFHLHLRLP
     MSVRRFEQLE LRPVLYNYLD KNLTVSVHVS PVEGLCLAGG GGLAQQVLVP AGSARPVAFS
     VVPTAAAAVS LKVVARGSFE FPVGDAVSKV LQIEKEGAIH REELVYELNP LDHRGRTLEI
     PGNSDPNMIP DGDFNSYVRV TASDPLDTLG SEGALSPGGV ASLLRLPRGC GEQTMIYLAP
     TLAASRYLDK TEQWSTLPPE TKDHAVDLIQ KGYMRIQQFR KADGSYAAWL SRDSSTWLTA
     FVLKVLSLAQ EQVGGSPEKL QETSNWLLSQ QQADGSFQDP CPVLDRSMQG GLVGNDETVA
     LTAFVTIALH HGLAVFQDEG AEPLKQRVEA SISKANSFLG EKASAGLLGA HAAAITAYAL
     TLTKAPVDLL GVAHNNLMAM AQETGDNLYW GSVTGSQSNA VSPTPAPRNP SDPMPQAPAL
     WIETTAYALL HLLLHEGKAE MADQASAWLT RQGSFQGGFR STQDTVIALD ALSAYWIASH
     TTEERGLNVT LSSTGRNGFK SHALQLNNRQ IRGLEEELQF SLGSKINVKV GGNSKGTLKV
     LRTYNVLDMK NTTCQDLQIE VTVKGHVEYT MEANEDYEDY EYDELPAKDD PDAPLQPVTP
     LQLFEGRRNR RRREAPKVVE EQESRVHYTV CIWRNGKVGL SGMAIADVTL LSGFHALRAD
     LEKLTSLSDR YVSHFETEGP HVLLYFDSVP TSRECVGFEA VQEVPVGLVQ PASATLYDYY
     NPERRCSVFY GAPSKSRLLA TLCSAEVCQC AEGKCPRQRR ALERGLQDED GYRMKFACYY
     PRVEYGFQVK VLREDSRAAF RLFETKITQV LHFTKDVKAA ANQMRNFLVR ASCRLRLEPG
     KEYLIMGLDG ATYDLEGHPQ YLLDSNSWIE EMPSERLCRS TRQRAACAQL NDFLQEYGTQ
     GCQV
//
DBGET integrated database retrieval system