CO5_MOUSE
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 03-AUG-2022, entry version 190.
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}.
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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 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; P06684; -.
DR PeptideAtlas; P06684; -.
DR PRIDE; P06684; -.
DR ProteomicsDB; 283598; -.
DR ABCD; P06684; 2 sequenced antibodies.
DR Antibodypedia; 15836; 763 antibodies from 41 providers.
DR DNASU; 15139; -.
DR Ensembl; ENSMUST00000028233; ENSMUSP00000028233; ENSMUSG00000026874.
DR GeneID; 15139; -.
DR KEGG; mmu:15139; -.
DR UCSC; uc008jjn.2; mouse.
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; YVEQNQN; -.
DR OrthoDB; 20179at2759; -.
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 72 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 54 other tissues.
DR ExpressionAtlas; P06684; baseline and differential.
DR Genevisible; P06684; MM.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0005579; C:membrane attack complex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0006956; P:complement activation; ISO:MGI.
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:0019835; P:cytolysis; 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: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:0050778; P:positive regulation of immune response; IC:ComplexPortal.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI.
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; IPR041425; C3/4/5_MG1.
DR InterPro; IPR037562; Complement_C5.
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; PTHR11412:SF83; 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; 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; SSF47686; SSF47686; 1.
DR SUPFAM; SSF48239; SSF48239; 1.
DR SUPFAM; SSF49410; SSF49410; 1.
DR SUPFAM; SSF50242; SSF50242; 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; 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
