ID CO5_MOUSE Reviewed; 1680 AA. AC P06684; A2AS36; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 24-JAN-2024, entry version 198. DE RecName: Full=Complement C5; DE AltName: Full=Hemolytic complement; DE Contains: DE RecName: Full=Complement C5 beta chain; DE Contains: DE RecName: Full=Complement C5 alpha chain; DE Contains: DE RecName: Full=C5a anaphylatoxin; DE Contains: DE RecName: Full=Complement C5 alpha' chain; DE Flags: Precursor; GN Name=C5; Synonyms=Hc; 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 [MRNA], AND INVOLVEMENT IN C5 DEFICIENCY. RX PubMed=2303408; DOI=10.1016/s0021-9258(19)39817-5; RA Wetsel R.A., Fleischer D.T., Haviland D.L.; RT "Deficiency of the murine fifth complement component (C5). A 2-base pair RT gene deletion in a 5'-exon."; RL J. Biol. Chem. 265:2435-2440(1990). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 41-1680. RX PubMed=2436653; DOI=10.1021/bi00377a013; RA Wetsel R.A., Ogata R.T., Tack B.F.; RT "Primary structure of the fifth component of murine complement."; RL Biochemistry 26:737-743(1987). RN [4] RP GENE STRUCTURE. RX PubMed=1711041; DOI=10.1016/s0021-9258(18)99030-7; RA Haviland D.L., Haviland J.C., Fleischer D.T., Wetsel R.A.; RT "Structure of the murine fifth complement component (C5) gene. A large, RT highly interrupted gene with a variant donor splice site and organizational RT homology with the third and fourth complement component genes."; RL J. Biol. Chem. 266:11818-11825(1991). RN [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-427. RC STRAIN=C57BL/6J; TISSUE=Plasma; RX PubMed=16944957; DOI=10.1021/pr060186m; RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.; RT "Proteome-wide characterization of N-glycosylation events by diagonal RT chromatography."; RL J. Proteome Res. 5:2438-2447(2006). RN [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-427. 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, 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: Activation of C5 by a C5 convertase initiates the spontaneous CC assembly of the late complement components, C5-C9, into the membrane CC attack complex. C5b has a transient binding site for C6. The C5b-C6 CC complex is the foundation upon which the lytic complex is assembled. CC -!- FUNCTION: [C5a anaphylatoxin]: Derived from proteolytic degradation of CC complement C5, C5a anaphylatoxin is a mediator of local inflammatory CC process. Binding to the receptor C5AR1 induces a variety of responses CC including intracellular calcium release, contraction of smooth muscle, CC increased vascular permeability, and histamine release from mast cells CC and basophilic leukocytes. C5a is also a potent chemokine which CC stimulates the locomotion of polymorphonuclear leukocytes and directs CC their migration toward sites of inflammation. CC {ECO:0000250|UniProtKB:P01031}. CC -!- SUBUNIT: C5 precursor is first processed by the removal of 4 basic CC residues, forming two chains, beta and alpha, linked by a disulfide CC bond. C5 convertase activates C5 by cleaving the alpha chain, releasing CC C5a anaphylatoxin and generating C5b (beta chain + alpha' chain). CC {ECO:0000250|UniProtKB:P01031}. CC -!- SUBUNIT: [C5a anaphylatoxin]: Interacts with C5AR1. CC {ECO:0000250|UniProtKB:P01031}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- DISEASE: Note=Murine C5 deficiency is caused by a 2 base-pairs deletion CC resulting in frameshift and premature truncation. All C5-deficient CC strains contain this mutation. {ECO:0000269|PubMed:2303408}. 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; M35525; AAA37349.1; -; mRNA. DR EMBL; M35526; AAA37348.1; -; mRNA. DR EMBL; AL845534; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS15957.1; -. DR PIR; A35530; C5MS. DR RefSeq; NP_034536.2; NM_010406.2. DR PDB; 4P3A; X-ray; 1.40 A; A/B/C/D=679-755. DR PDB; 4P3B; X-ray; 2.10 A; A/B/C/D=679-754. DR PDB; 4WB2; X-ray; 1.80 A; A/B/C=679-755. DR PDB; 4WB3; X-ray; 2.00 A; A/B/C=679-754. DR PDBsum; 4P3A; -. DR PDBsum; 4P3B; -. DR PDBsum; 4WB2; -. DR PDBsum; 4WB3; -. DR AlphaFoldDB; P06684; -. DR SMR; P06684; -. DR BioGRID; 200226; 4. DR ComplexPortal; CPX-6202; Membrane attack complex. DR IntAct; P06684; 3. DR STRING; 10090.ENSMUSP00000028233; -. DR MEROPS; I39.952; -. DR GlyCosmos; P06684; 4 sites, No reported glycans. DR GlyGen; P06684; 4 sites. DR iPTMnet; P06684; -. DR PhosphoSitePlus; P06684; -. DR CPTAC; non-CPTAC-3698; -. DR CPTAC; non-CPTAC-4025; -. DR MaxQB; P06684; -. DR PaxDb; 10090-ENSMUSP00000028233; -. DR PeptideAtlas; P06684; -. DR ProteomicsDB; 283598; -. DR ABCD; P06684; 2 sequenced antibodies. DR Antibodypedia; 15836; 994 antibodies from 41 providers. DR DNASU; 15139; -. DR Ensembl; ENSMUST00000028233.7; ENSMUSP00000028233.4; ENSMUSG00000026874.11. DR GeneID; 15139; -. DR KEGG; mmu:15139; -. DR UCSC; uc008jjn.2; mouse. DR AGR; MGI:96031; -. DR CTD; 15139; -. DR MGI; MGI:96031; Hc. DR VEuPathDB; HostDB:ENSMUSG00000026874; -. DR eggNOG; KOG1366; Eukaryota. DR GeneTree; ENSGT00940000155670; -. DR HOGENOM; CLU_001634_4_2_1; -. DR InParanoid; P06684; -. DR OMA; YKRIIAC; -. DR OrthoDB; 4033541at2759; -. DR PhylomeDB; P06684; -. DR TreeFam; TF313285; -. DR Reactome; R-MMU-166665; Terminal pathway of complement. DR Reactome; R-MMU-174577; Activation of C3 and C5. DR Reactome; R-MMU-375276; Peptide ligand-binding receptors. DR Reactome; R-MMU-418594; G alpha (i) signalling events. DR Reactome; R-MMU-977606; Regulation of Complement cascade. DR BioGRID-ORCS; 15139; 3 hits in 77 CRISPR screens. DR ChiTaRS; Hc; mouse. DR PRO; PR:P06684; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P06684; Protein. DR Bgee; ENSMUSG00000026874; Expressed in left lobe of liver and 55 other cell types or tissues. DR ExpressionAtlas; P06684; baseline and differential. DR GO; GO:0005615; C:extracellular space; IEA:InterPro. DR GO; GO:0005579; C:membrane attack complex; ISO:MGI. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro. DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW. DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW. DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW. DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; ISO:MGI. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI. DR CDD; cd00017; ANATO; 1. DR CDD; cd02896; complement_C3_C4_C5; 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; -; 1. 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; IPR011625; A2M_N_BRD. DR InterPro; IPR011626; Alpha-macroglobulin_TED. DR InterPro; IPR000020; Anaphylatoxin/fibulin. DR InterPro; IPR018081; Anaphylatoxin_comp_syst. DR InterPro; IPR041425; C3/4/5_MG1. DR InterPro; IPR048843; C5_CUB. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR001599; Macroglobln_a2. 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:SF83; COMPLEMENT C5; 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; PF21309; C5_CUB; 1. DR Pfam; PF17790; MG1; 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 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; 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; PS01177; ANAPHYLATOXIN_1; 1. DR PROSITE; PS01178; ANAPHYLATOXIN_2; 1. DR PROSITE; PS50189; NTR; 1. DR Genevisible; P06684; MM. PE 1: Evidence at protein level; KW 3D-structure; Cleavage on pair of basic residues; KW Complement alternate pathway; Complement pathway; Cytolysis; KW Disulfide bond; Glycoprotein; Immunity; Inflammatory response; KW Innate immunity; Membrane attack complex; Reference proteome; Secreted; KW Signal. FT SIGNAL 1..18 FT CHAIN 19..674 FT /note="Complement C5 beta chain" FT /id="PRO_0000005991" FT PROPEP 675..678 FT /id="PRO_0000005992" FT CHAIN 679..1680 FT /note="Complement C5 alpha chain" FT /id="PRO_0000005993" FT CHAIN 679..755 FT /note="C5a anaphylatoxin" FT /id="PRO_0000005994" FT CHAIN 756..1680 FT /note="Complement C5 alpha' chain" FT /id="PRO_0000005995" FT DOMAIN 702..736 FT /note="Anaphylatoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00022" FT DOMAIN 1536..1679 FT /note="NTR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295" FT REGION 696..725 FT /note="Involved in C5AR1 binding" FT /evidence="ECO:0000250|UniProtKB:P01031" FT CARBOHYD 427 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16944957, FT ECO:0000269|PubMed:17330941" FT CARBOHYD 915 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1119 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1633 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 567..814 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 635..670 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 702..728 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 703..735 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 715..736 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 860..887 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 870..1531 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1105..1163 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1379..1509 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1409..1478 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1524..1529 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1536..1609 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1557..1679 FT /evidence="ECO:0000250|UniProtKB:P01031" FT DISULFID 1657..1660 FT /evidence="ECO:0000250|UniProtKB:P01031" FT HELIX 680..691 FT /evidence="ECO:0007829|PDB:4P3A" FT STRAND 694..696 FT /evidence="ECO:0007829|PDB:4P3A" FT HELIX 697..707 FT /evidence="ECO:0007829|PDB:4P3A" FT STRAND 711..713 FT /evidence="ECO:0007829|PDB:4WB2" FT HELIX 715..719 FT /evidence="ECO:0007829|PDB:4P3A" FT HELIX 726..744 FT /evidence="ECO:0007829|PDB:4P3A" SQ SEQUENCE 1680 AA; 188878 MW; 81EB5A16FAC7D95C CRC64; MGLWGILCLL IFLDKTWGQE QTYVISAPKI LRVGSSENVV IQVHGYTEAF DATLSLKSYP DKKVTFSSGY VNLSPENKFQ NAALLTLQPN QVPREESPVS HVYLEVVSKH FSKSKKIPIT YNNGILFIHT DKPVYTPDQS VKIRVYSLGD DLKPAKRETV LTFIDPEGSE VDIVEENDYT GIISFPDFKI PSNPKYGVWT IKANYKKDFT TTGTAYFEIK EYVLPRFSVS IELERTFIGY KNFKNFEITV KARYFYNKVV PDAEVYAFFG LREDIKDEEK QMMHKATQAA KLVDGVAQIS FDSETAVKEL SYNSLEDLNN KYLYIAVTVT ESSGGFSEEA EIPGVKYVLS PYTLNLVATP LFVKPGIPFS IKAQVKDSLE QAVGGVPVTL MAQTVDVNQE TSDLETKRSI THDTDGVAVF VLNLPSNVTV LKFEIRTDDP ELPEENQASK EYEAVAYSSL SQSYIYIAWT ENYKPMLVGE YLNIMVTPKS PYIDKITHYN YLILSKGKIV QYGTREKLFS STYQNINIPV TQNMVPSARL LVYYIVTGEQ TAELVADAVW INIEEKCGNQ LQVHLSPDEY VYSPGQTVSL DMVTEADSWV ALSAVDRAVY KVQGNAKRAM QRVFQALDEK SDLGCGAGGG HDNADVFHLA GLTFLTNANA DDSHYRDDSC KEILRSKRNL HLLRQKIEEQ AAKYKHSVPK KCCYDGARVN FYETCEERVA RVTIGPLCIR AFNECCTIAN KIRKESPHKP VQLGRIHIKT LLPVMKADIR SYFPESWLWE IHRVPKRKQL QVTLPDSLTT WEIQGIGISD NGICVADTLK AKVFKEVFLE MNIPYSVVRG EQIQLKGTVY NYMTSGTKFC VKMSAVEGIC TSGSSAASLH TSRPSRCVFQ RIEGSSSHLV TFTLLPLEIG LHSINFSLET SFGKDILVKT LRVVPEGVKR ESYAGVILDP KGIRGIVNRR KEFPYRIPLD LVPKTKVERI LSVKGLLVGE FLSTVLSKEG INILTHLPKG SAEAELMSIA PVFYVFHYLE AGNHWNIFYP DTLSKRQSLE KKIKQGVVSV MSYRNADYSY SMWKGASAST WLTAFALRVL GQVAKYVKQD ENSICNSLLW LVEKCQLENG SFKENSQYLP IKLQGTLPAE AQEKTLYLTA FSVIGIRKAV DICPTMKIHT ALDKADSFLL ENTLPSKSTF TLAIVAYALS LGDRTHPRFR LIVSALRKEA FVKGDPPIYR YWRDTLKRPD SSVPSSGTAG MVETTAYALL ASLKLKDMNY ANPIIKWLSE EQRYGGGFYS TQDTINAIEG LTEYSLLLKQ IHLDMDINVA YKHEGDFHKY KVTEKHFLGR PVEVSLNDDL VVSTGYSSGL ATVYVKTVVH KISVSEEFCS FYLKIDTQDI EASSHFRLSD SGFKRIIACA SYKPSKEEST SGSSHAVMDI SLPTGIGANE EDLRALVEGV DQLLTDYQIK DGHVILQLNS IPSRDFLCVR FRIFELFQVG FLNPATFTVY EYHRPDKQCT MIYSISDTRL QKVCEGAACT CVEADCAQLQ AEVDLAISAD SRKEKACKPE TAYAYKVRIT SATEENVFVK YTATLLVTYK TGEAADENSE VTFIKKMSCT NANLVKGKQY LIMGKEVLQI KHNFSFKYIY PLDSSTWIEY WPTDTTCPSC QAFVENLNNF AEDLFLNSCE //