ID CO4B_MOUSE Reviewed; 1738 AA. AC P01029; E9QKK7; O70346; Q31201; Q3TYY1; Q3TZC9; Q61372; Q61859; Q62353; AC Q6NWV8; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 04-NOV-2026, entry version 215. DE RecName: Full=Complement C4-B; DE Contains: DE RecName: Full=Complement C4 beta chain; DE Contains: DE RecName: Full=Complement C4 alpha chain; DE Contains: DE RecName: Full=C4a anaphylatoxin; DE Contains: DE RecName: Full=Complement C4b-B; DE Contains: DE RecName: Full=Complement C4 gamma chain; DE Flags: Precursor; GN Name=C4b {ECO:0000312|MGI:MGI:88228}; Synonyms=C4; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=FM; RX PubMed=2993295; DOI=10.1016/s0021-9258(17)39125-1; RA Nonaka M., Nakayama K., Yeul Y.D., Takahashi M.; RT "Complete nucleotide and derived amino acid sequences of the fourth RT component of mouse complement (C4). Evolutionary aspects."; RL J. Biol. Chem. 260:10936-10943(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=B10.WR; RX PubMed=3862104; DOI=10.1073/pnas.82.17.5895; RA Sepich D.S., Noonan D.J., Ogata R.T.; RT "Complete cDNA sequence of the fourth component of murine complement."; RL Proc. Natl. Acad. Sci. U.S.A. 82:5895-5899(1985). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=B10.WR; RX PubMed=2777798; DOI=10.1016/s0021-9258(19)84744-0; RA Ogata R.T., Rosa P.A., Zepf N.E.; RT "Sequence of the gene for murine complement component C4."; RL J. Biol. Chem. 264:16565-16572(1989). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Inner ear; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=129; RX PubMed=14656967; DOI=10.1101/gr.1736803; RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., RA Hood L.; RT "Analysis of the gene-dense major histocompatibility complex class III RT region and its comparison to mouse."; RL Genome Res. 13:2621-2636(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and CD-1; TISSUE=Germ cell, and Neural stem cell; 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 [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-128. RC STRAIN=FM; RX PubMed=2997024; DOI=10.1111/j.1600-065x.1985.tb01146.x; RA Nonaka M., Nakayama K., Yeul Y.D., Shimizu A., Takahashi M.; RT "Molecular cloning and characterization of complementary and genomic DNA RT clones for mouse C4 and Slp."; RL Immunol. Rev. 87:81-99(1985). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21. RX PubMed=3464002; DOI=10.1073/pnas.83.20.7883; RA Nonaka M., Kimura H., Yeul Y.D., Yokoyama S., Nakayama K., Takahashi M.; RT "Identification of the 5'-flanking regulatory region responsible for the RT difference in transcriptional control between mouse complement C4 and Slp RT genes."; RL Proc. Natl. Acad. Sci. U.S.A. 83:7883-7887(1986). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 591-1738. RC STRAIN=C57BL/10 X DBA/2; RX PubMed=3008092; DOI=10.1093/nar/14.6.2539; RA Hemenway C., Kalff M., Stavenhagen J., Walthall D., Robins D.; RT "Sequence comparison of alleles of the fourth component of complement (C4) RT and sex-limited protein (Slp)."; RL Nucleic Acids Res. 14:2539-2554(1986). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 651-810 AND 924-1083. RX PubMed=6208559; DOI=10.1073/pnas.81.21.6822; RA Nonaka M., Takahashi M., Natsuume-Sakai S., Nonaka M., Tanaka S., RA Shimizu A., Honjo T.; RT "Isolation of cDNA clones specifying the fourth component of mouse RT complement and its isotype, sex-limited protein."; RL Proc. Natl. Acad. Sci. U.S.A. 81:6822-6826(1984). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 961-1290. RX PubMed=2459207; DOI=10.4049/jimmunol.141.7.2382; RA Taillon-Miller P.A., Shreffler D.C.; RT "Structural basis for the C4d.1/C4d.2 serologic allotypes of murine RT complement component C4."; RL J. Immunol. 141:2382-2387(1988). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1099-1142. RC STRAIN=B10.BR, B10.WR, C3H/He, C57BL/6J, CBA/J, and DBA/2J; RX PubMed=2387317; DOI=10.1002/eji.1830200730; RA Ogata R.T., Zepf N.E.; RT "C4 from C4-high and C4-low mouse strains have identical sequences in the RT region corresponding to the isotype-specific segment of human C4."; RL Eur. J. Immunol. 20:1607-1610(1990). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1105-1449. RX PubMed=3856857; DOI=10.1073/pnas.82.6.1746; RA Levi-Strauss M., Tosi M., Steinmetz M., Klein J., Meo T.; RT "Multiple duplications of complement C4 gene correlate with H-2-controlled RT testosterone-independent expression of its sex-limited isoform, C4-Slp."; RL Proc. Natl. Acad. Sci. U.S.A. 82:1746-1750(1985). RN [15] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1257-1376. RX PubMed=6149581; DOI=10.1098/rstb.1984.0099; RA Tosi M., Levi-Strauss M., Duponchel C., Meo T.; RT "Sequence heterogeneity of murine complementary DNA clones related to the RT C4 and C4-Slp isoforms of the fourth complement component."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 306:389-394(1984). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1360-1511. RX PubMed=6192448; DOI=10.1073/pnas.80.16.5061; RA Ogata R.T., Shreffler D.C., Sepich D.S., Lilly S.P.; RT "cDNA clone spanning the alpha-gamma subunit junction in the precursor of RT the murine fourth complement component (C4)."; RL Proc. Natl. Acad. Sci. U.S.A. 80:5061-5065(1983). RN [17] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1324. RC STRAIN=C57BL/6J; TISSUE=Plasma; RX PubMed=17330941; DOI=10.1021/pr0604559; RA Bernhard O.K., Kapp E.A., Simpson R.J.; RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing RT tryptic glycopeptides."; RL J. Proteome Res. 6:987-995(2007). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Precursor of non-enzymatic components of the classical, CC lectin and GZMK complement pathways, which consist in a cascade of CC proteins that leads to phagocytosis and breakdown of pathogens and CC signaling that strengthens the adaptive immune system. CC {ECO:0000250|UniProtKB:A0AAQ4VMX2}. CC -!- FUNCTION: [Complement C4b-B]: Non-enzymatic component of C3 and C5 CC convertases. Generated following cleavage by complement proteases (C1S, CC MASP2 or GZMK, depending on the complement pathway), it covalently CC attaches to the surface of pathogens, where it acts as an opsonin that CC marks the surface of antigens for removal. It then recruits the serine CC protease complement C2b to form the C3 and C5 convertases, which cleave CC and activate C3 and C5, respectively, the next components of the CC complement pathways. Complement C4b-A isotype is responsible for CC effective binding to form amide bonds with immune aggregates or protein CC antigens, while complement C4b-B isotype catalyzes the transacylation CC of the thioester carbonyl group to form ester bonds with carbohydrate CC antigens. {ECO:0000250|UniProtKB:P0C0L4}. CC -!- FUNCTION: [C4a anaphylatoxin]: Putative humoral mediator released CC following cleavage by complement proteases (C1S, MASP2 or GZMK, CC depending on the complement pathway). While it is strongly similar to CC anaphylatoxins, its role is unclear. Was reported to act as a mediator CC of local inflammatory process; however these effects were probably due CC to contamination with C3a and/C5a anaphylatoxins in biological assays. CC {ECO:0000250|UniProtKB:P0C0L4}. CC -!- SUBUNIT: In absence of complement activation, circulates in blood as a CC disulfide-linked trimer of an alpha, beta and gamma chain. CC {ECO:0000250|UniProtKB:P0C0L4}. CC -!- SUBUNIT: [Complement C4b-B]: Complement C4b is composed of complement CC C4b-A, complement C4 beta and complement C4 gamma chains that are CC associated via disulfide bonds. Non-enzymatic component of the C3 CC convertase, also named C4bC2b, composed of the serine protease CC complement C2b (C2), as well as complement C4b. Non-enzymatic component CC of the C5 convertase, also named C4bC2bC3b, composed of the serine CC protease complement C2b (C2), complement C3b, as well as complement CC C4b. {ECO:0000250|UniProtKB:P0C0L4}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P0C0L4}. CC -!- SUBCELLULAR LOCATION: [C4a anaphylatoxin]: Secreted CC {ECO:0000250|UniProtKB:P0C0L4}. CC -!- SUBCELLULAR LOCATION: [Complement C4b-B]: Secreted CC {ECO:0000250|UniProtKB:P0C0L4}. Cell surface CC {ECO:0000250|UniProtKB:P0C0L4}. Note=Covalently associated with the CC surface of pathogens: the internal thioester bond reacts with CC carbohydrate antigens on the target surface to form amide or ester CC bonds. {ECO:0000250|UniProtKB:P0C0L4}. CC -!- PTM: Prior to secretion, the single-chain precursor is enzymatically CC cleaved by plasminogen (PLG) to yield non-identical chains alpha, beta CC and gamma. During activation of the complement systems, the alpha chain CC is cleaved into C4a and C4b by different proteases depending on the CC complement pathway: C4b stays linked to the beta and gamma chains, CC while C4a is released in the plasma. The alpha chain is cleaved by C1S CC to generate C4a and C4b following activation by the classical CC complement system. The alpha chain is cleaved to generate C4a and C4b CC by MASP2 following activation by the lectin complement system. The CC alpha chain is cleaved by GZMK to generate C4a and C4b following CC activation by the GZMK complement system. Further degradation of C4b by CC C1 into the inactive fragments C4c and C4d blocks the generation of C3 CC convertase. The proteolytic cleavages often are incomplete so that many CC structural forms can be found in plasma. CC {ECO:0000250|UniProtKB:P0C0L4}. CC -!- PTM: [Complement C4b-B]: Upon activation, the internal thioester bond CC reacts with carbohydrate antigens on the target surface to form amide CC or ester bonds, leading to covalent association with the surface of CC pathogens. {ECO:0000250|UniProtKB:P0C0L4}. CC -!- PTM: [Complement C4b-B]: Complement C4b interacts with complement C3b CC via a thioester linkage. {ECO:0000250|UniProtKB:P0C0L4}. CC -!- MISCELLANEOUS: C4 is a major histocompatibility complex class-III CC protein. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M11789; AAA39557.1; -; Genomic_DNA. DR EMBL; M11729; AAA39506.1; -; mRNA. DR EMBL; M17440; AAA39561.1; -; Genomic_DNA. DR EMBL; AK157954; BAE34280.1; -; mRNA. DR EMBL; AK158256; BAE34429.1; -; mRNA. DR EMBL; AF049850; AAC05279.1; -; Genomic_DNA. DR EMBL; CT573030; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC067394; AAH67394.1; -; mRNA. DR EMBL; BC067409; AAH67409.1; -; mRNA. DR EMBL; M12968; AAA39558.1; -; Genomic_DNA. DR EMBL; M12969; AAA39559.1; -; Genomic_DNA. DR EMBL; M14225; AAA39563.1; -; Genomic_DNA. DR EMBL; X05314; CAA28936.1; -; mRNA. DR EMBL; M12970; AAA39555.1; -; mRNA. DR EMBL; M12972; AAA39556.1; -; mRNA. DR EMBL; M23186; AAA40487.1; -; Genomic_DNA. DR EMBL; X55493; CAA39112.1; -; Genomic_DNA. DR EMBL; X55495; CAA39114.1; -; Genomic_DNA. DR EMBL; K02798; AAC42021.1; -; mRNA. DR EMBL; K02799; AAC42022.1; -; mRNA. DR EMBL; K00019; AAA39554.1; -; mRNA. DR CCDS; CCDS28657.1; -. DR PIR; A24558; A24558. DR PIR; A29176; A29176. DR RefSeq; NP_033910.2; NM_009780.2. DR AlphaFoldDB; P01029; -. DR SMR; P01029; -. DR BioGRID; 198420; 18. DR ComplexPortal; CPX-6198; Classical and lectin pathway C3 convertase complex C4b2a-B. DR FunCoup; P01029; 67. DR STRING; 10090.ENSMUSP00000069418; -. DR MEROPS; I39.951; -. DR GlyConnect; P01029; 2 N-Linked glycans (1 site). DR GlyCosmos; P01029; 6 sites, 6 glycans. DR GlyGen; P01029; 7 sites, 6 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P01029; -. DR PhosphoSitePlus; P01029; -. DR SwissPalm; P01029; -. DR CPTAC; non-CPTAC-3339; -. DR jPOST; P01029; -. DR PaxDb; 10090-ENSMUSP00000069418; -. DR ProteomicsDB; 279132; -. DR Pumba; P01029; -. DR DNASU; 12268; -. DR Ensembl; ENSMUST00000069507.9; ENSMUSP00000069418.9; ENSMUSG00000073418.5. DR GeneID; 12268; -. DR KEGG; mmu:12268; -. DR UCSC; uc008cdk.2; mouse. DR AGR; MGI:88228; -. DR CTD; 721; -. DR MGI; MGI:88228; C4b. DR VEuPathDB; HostDB:ENSMUSG00000073418; -. DR eggNOG; KOG1366; Eukaryota. DR GeneTree; ENSGT00940000155739; -. DR HOGENOM; CLU_001634_4_1_1; -. DR InParanoid; P01029; -. DR OMA; AAFSHYY; -. DR OrthoDB; 6359008at2759; -. DR PhylomeDB; P01029; -. DR Reactome; R-MMU-166663; Initial triggering of complement. DR Reactome; R-MMU-174577; Activation of C3 and C5. DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation. DR Reactome; R-MMU-977606; Regulation of Complement cascade. DR BioGRID-ORCS; 12268; 3 hits in 78 CRISPR screens. DR PRO; PR:P01029; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; P01029; protein. DR Bgee; ENSMUSG00000073418; Expressed in epididymal fat pad and 59 other cell types or tissues. DR ExpressionAtlas; P01029; baseline and differential. DR GO; GO:0030424; C:axon; ISO:GO_Central. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005601; C:classical-complement-pathway C3/C5 convertase complex; ISO:GO_Central. DR GO; GO:0030425; C:dendrite; ISO:GO_Central. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:GO_Central. DR GO; GO:0106139; C:symbiont cell surface; ISS:UniProtKB. DR GO; GO:0045202; C:synapse; ISO:GO_Central. DR GO; GO:0003823; F:antigen binding; ISS:UniProtKB. DR GO; GO:0030246; F:carbohydrate binding; ISO:GO_Central. DR GO; GO:0001848; F:complement binding; ISO:GO_Central. DR GO; GO:0001849; F:complement component C1q complex binding; ISO:GO_Central. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro. DR GO; GO:0006956; P:complement activation; IMP:MGI. DR GO; GO:0006958; P:complement activation, classical pathway; ISS:UniProtKB. DR GO; GO:0160257; P:complement activation, GZMK pathway; ISS:UniProtKB. DR GO; GO:0001867; P:complement activation, lectin pathway; ISS:UniProtKB. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI. DR GO; GO:0006954; P:inflammatory response; IEA:InterPro. DR CDD; cd00017; ANATO; 1. DR CDD; cd02896; complement_C3_C4_C5; 1. DR FunFam; 2.60.40.10:FF:000155; complement C3 isoform X1; 1. DR FunFam; 1.20.91.20:FF:000006; Complement C4; 1. DR FunFam; 2.60.40.690:FF:000002; Complement C4 isoform-A; 1. DR FunFam; 1.50.10.20:FF:000010; Complement C4-A; 1. DR FunFam; 2.20.130.20:FF:000002; Complement C4-A; 1. DR FunFam; 2.40.50.120:FF:000009; Complement C4-A; 1. DR FunFam; 2.60.120.1540:FF:000001; Complement C4-A; 1. DR FunFam; 2.60.40.10:FF:000803; Complement C4-A; 1. DR FunFam; 2.60.40.1930:FF:000004; Complement C4-A; 1. DR FunFam; 2.60.40.1930:FF:000007; Complement C4-A; 1. DR FunFam; 2.60.40.1930:FF:000005; complement C4-A isoform X3; 1. DR FunFam; 2.60.40.1940:FF:000001; Complement component C3; 1. DR FunFam; 2.60.120.1540:FF:000006; MHC-linked complement C4; 1. DR Gene3D; 1.50.10.20; -; 1. DR Gene3D; 2.20.130.20; -; 1. DR Gene3D; 2.40.50.120; -; 1. DR Gene3D; 2.60.120.1540; -; 2. DR Gene3D; 2.60.40.1930; -; 3. DR Gene3D; 2.60.40.1940; -; 1. DR Gene3D; 6.20.50.160; -; 1. DR Gene3D; 2.60.40.690; Alpha-macroglobulin, receptor-binding domain; 1. DR Gene3D; 1.20.91.20; Anaphylotoxins (complement system); 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR009048; A-macroglobulin_rcpt-bd. DR InterPro; IPR036595; A-macroglobulin_rcpt-bd_sf. DR InterPro; IPR050473; A2M/Complement_sys. DR InterPro; IPR011625; A2M_N_BRD. DR InterPro; IPR047565; Alpha-macroglob_thiol-ester_cl. 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; IPR048847; C4_MG1. DR InterPro; IPR054587; CO4A-B_CUB_C. 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; 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; COMPLEMENT C4-A-RELATED; 1. DR PANTHER; PTHR11412; MACROGLOBULIN / COMPLEMENT; 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; PF21145; C4_MG1; 1. DR Pfam; PF22661; CO4A-B_CUB_C; 1. DR Pfam; PF01835; MG2; 1. DR Pfam; PF17791; MG3; 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 SMART; SM01419; Thiol-ester_cl; 1. DR SUPFAM; SSF49410; Alpha-macroglobulin receptor domain; 1. DR SUPFAM; SSF47686; Anaphylotoxins (complement system); 1. DR SUPFAM; SSF48239; Terpenoid cyclases/Protein prenyltransferases; 1. DR SUPFAM; SSF50242; TIMP-like; 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 Cleavage on pair of basic residues; Complement pathway; Disulfide bond; KW Glycoprotein; Immunity; Inflammatory response; Innate immunity; KW Phosphoprotein; Reference proteome; Secreted; Signal; Sulfation; KW Thioester bond. FT SIGNAL 1..19 FT CHAIN 20..1738 FT /note="Complement C4-B" FT /id="PRO_0000462546" FT CHAIN 20..673 FT /note="Complement C4 beta chain" FT /id="PRO_0000005973" FT PROPEP 674..677 FT /id="PRO_0000005974" FT CHAIN 678..1443 FT /note="Complement C4 alpha chain" FT /id="PRO_0000005975" FT CHAIN 678..753 FT /note="C4a anaphylatoxin" FT /id="PRO_0000005976" FT CHAIN 754..1443 FT /note="Complement C4b-B" FT /id="PRO_0000462547" FT PROPEP 1444..1447 FT /id="PRO_0000005977" FT CHAIN 1448..1738 FT /note="Complement C4 gamma chain" FT /id="PRO_0000005978" FT DOMAIN 700..734 FT /note="Anaphylatoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022" FT DOMAIN 1589..1736 FT /note="NTR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295" FT SITE 753..754 FT /note="Cleavage; by C1S, MASP2 and GZMK" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT MOD_RES 1413 FT /note="Sulfotyrosine" FT /evidence="ECO:0000250|UniProtKB:P0C0L5" FT MOD_RES 1416 FT /note="Sulfotyrosine" FT /evidence="ECO:0000250|UniProtKB:P0C0L5" FT MOD_RES 1417 FT /note="Sulfotyrosine" FT /evidence="ECO:0000250|UniProtKB:P0C0L5" FT CARBOHYD 224 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 743 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1324 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17330941" FT CARBOHYD 1387 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 66..95 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 565 FT /note="Interchain (with C-818)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 633..667 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 700..726 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 701..733 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 714..734 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 818 FT /note="Interchain (with C-565)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 874 FT /note="Interchain (with C-1584)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1390 FT /note="Interchain (with C-1560)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1465..1529 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1560 FT /note="Interchain (with C-1390)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1577..1582 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1584 FT /note="Interchain (with C-874)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1589..1667 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1612..1736 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT DISULFID 1712..1721 FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT CROSSLNK 1006..1009 FT /note="Isoglutamyl cysteine thioester (Cys-Gln)" FT /evidence="ECO:0000250|UniProtKB:P0C0L4" FT CONFLICT 132 FT /note="F -> Y (in Ref. 1; AAA39557)" FT /evidence="ECO:0000305" FT CONFLICT 177 FT /note="E -> G (in Ref. 4; BAE34429)" FT /evidence="ECO:0000305" FT CONFLICT 283 FT /note="A -> V (in Ref. 4; BAE34429)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="G -> E (in Ref. 1; AAA39557)" FT /evidence="ECO:0000305" FT CONFLICT 440 FT /note="E -> K (in Ref. 7; AAH67394/AAH67409)" FT /evidence="ECO:0000305" FT CONFLICT 570 FT /note="Q -> E (in Ref. 1; AAA39557 and 4; BAE34280)" FT /evidence="ECO:0000305" FT CONFLICT 604 FT /note="M -> T (in Ref. 1; AAA39557, 2; AAA39506, 3; FT AAA39561, 4; BAE34280/BAE34429 and 7; AAH67394/AAH67409)" FT /evidence="ECO:0000305" FT CONFLICT 639 FT /note="D -> G (in Ref. 4; BAE34429)" FT /evidence="ECO:0000305" FT CONFLICT 758 FT /note="M -> I (in Ref. 4; BAE34280)" FT /evidence="ECO:0000305" FT CONFLICT 838 FT /note="P -> R (in Ref. 1; AAA39557)" FT /evidence="ECO:0000305" FT CONFLICT 916 FT /note="V -> I (in Ref. 4; BAE34280)" FT /evidence="ECO:0000305" FT CONFLICT 1077 FT /note="F -> S (in Ref. 7; AAH67394/AAH67409)" FT /evidence="ECO:0000305" FT CONFLICT 1119 FT /note="V -> A (in Ref. 14; AAC42021)" FT /evidence="ECO:0000305" FT CONFLICT 1190 FT /note="A -> T (in Ref. 14; AAC42021)" FT /evidence="ECO:0000305" FT CONFLICT 1206 FT /note="R -> Q (in Ref. 4; BAE34280/BAE34429, 7; FT AAH67394/AAH67409 and 12; AAA40487)" FT /evidence="ECO:0000305" FT CONFLICT 1290 FT /note="S -> N (in Ref. 15; AAC42022)" FT /evidence="ECO:0000305" FT CONFLICT 1324 FT /note="N -> K (in Ref. 2; AAA39506, 3; AAA39561 and 14; FT AAC42021)" FT /evidence="ECO:0000305" FT CONFLICT 1365 FT /note="K -> E (in Ref. 4; BAE34429)" FT /evidence="ECO:0000305" FT CONFLICT 1401 FT /note="G -> S (in Ref. 16; AAA39554)" FT /evidence="ECO:0000305" FT CONFLICT 1442 FT /note="R -> K (in Ref. 1; AAA39557)" FT /evidence="ECO:0000305" FT CONFLICT 1453 FT /note="V -> A (in Ref. 2; AAA39506, 3; AAA39561, 4; FT BAE34429 and 16; AAA39554)" FT /evidence="ECO:0000305" FT CONFLICT 1456 FT /note="Q -> R (in Ref. 4; BAE34429)" FT /evidence="ECO:0000305" FT CONFLICT 1586 FT /note="E -> Q (in Ref. 10; CAA28936)" FT /evidence="ECO:0000305" FT CONFLICT 1611 FT /note="A -> T (in Ref. 5; AAC05279)" FT /evidence="ECO:0000305" SQ SEQUENCE 1738 AA; 192915 MW; FCC7580209029E88 CRC64; MRLLWGLAWV FSFCASSLQK PRLLLFSPSV VNLGTPLSVG VQLLDAPPGQ EVKGSVFLRN PKGGSCSPKK DFKLSSGDDF VLLSLEVPLE DVRSCGLFDL RRAPHIQLVA QSPWLRNTAF KATETQGVNL LFSSRRGHIF VQTDQPIYNP GQRVRYRVFA LDQKMRPSTD FLTITVENSH GLRVLKKEIF TSTSIFQDAF TIPDISEPGT WKISARFSDG LESNRSTHFE VKKYVLPNFE VKITPWKPYI LMVPSNSDEI QLDIQARYIY GKPVQGVAYT RFALMDEQGK RTFLRGLETQ AKLVEGRTHI SISKDQFQAA LDKINIGVRD LEGLRLYAAT AVIESPGGEM EEAELTSWRF VSSAFSLDLS RTKRHLVPGA HFLLQALVQE MSGSEASNVP VKVSATLVSG SDSQVLDIQQ STNGIGQVSI SFPIPPTVTE LRLLVSAGSL YPAIARLTVQ APPSRGTGFL SIEPLDPRSP SVGDTFILNL QPVGIPAPTF SHYYYMIISR GQIMAMGREP RKTVTSVSVL VDHQLAPSFY FVAYFYHQGH PVANSLLINI QSRDCEGKLQ LKVDGAKEYR NADMMKLRIQ TDSKALVALG AVDMALYAVG GRSHKPLDMS KVFEVINSYN VGCGPGGGDD ALQVFQDAGL AFSDGDRLTQ TREDLSCPKE KKSRQKRNVN FQKAVSEKLG QYSSPDAKRC CQDGMTKLPM KRTCEQRAAR VPQQACREPF LSCCKFAEDL RRNQTRSQAH LARNNHNMLQ EEDLIDEDDI LVRTSFPENW LWRVEPVDSS KLLTVWLPDS MTTWEIHGVS LSKSKGLCVA KPTRVRVFRK FHLHLRLPIS IRRFEQFELR PVLYNYLNDD VAVSVHVTPV EGLCLAGGGM MAQQVTVPAG SARPVAFSVV PTAAANVPLK VVARGVFDLG DAVSKILQIE KEGAIHREEL VYNLDPLNNL GRTLEIPGSS DPNIVPDGDF SSLVRVTASE PLETMGSEGA LSPGGVASLL RLPQGCAEQT MIYLAPTLTA SNYLDRTEQW SKLSPETKDH AVDLIQKGYM RIQQFRKNDG SFGAWLHRDS STWLTAFVLK ILSLAQEQVG NSPEKLQETA SWLLAQQLGD GSFHDPCPVI HRAMQGGLVG SDETVALTAF VVIALHHGLD VFQDDDAKQL KNRVEASITK ANSFLGQKAS AGLLGAHAAA ITAYALTLTK ASEDLRNVAH NSLMAMAEET GEHLYWGLVL GSQDKVVLRP TAPRSPTEPV PQAPALWIET TAYALLHLLL REGKGKMADK AASWLTHQGS FHGAFRSTQD TVVTLDALSA YWIASHTTEE KALNVTLSSM GRNGLKTHGL HLNNHQVKGL EEELKFSLGS TISVKVEGNS KGTLKILRTY NVLDMKNTTC QDLQIEVKVT GAVEYAWDAN EDYEDYYDMP AADDPSVPLQ PVTPLQLFEG RRSRRRREAP KVVEEQESRV QYTVCIWRNG KLGLSGMAIA DITLLSGFHA LRADLEKLTS LSDRYVSHFE TDGPHVLLYF DSVPTTRECV GFGASQEVVV GLVQPSSAVL YDYYSPDHKC SVFYAAPTKS QLLATLCSGD VCQCAEGKCP RLLRSLERRV EDKDGYRMRF ACYYPRVEYG FTVKVLREDG RAAFRLFESK ITQVLHFRKD TMASIGQTRN FLSRASCRLR LEPNKEYLIM GMDGETSDNK GDPQYLLDSN TWIEEMPSEQ MCKSTRHRAA CFQLKDFLME FSSRGCQV //